Journal of Gastroenterology and Hepatology
Volume 26, Issue 3, pages 419–420,
March 2011
Get PDF (106K)
Should all patients with nonalcoholic fatty liver disease undergo oral glucose tolerance test?
Vincent Wai-Sun Wong1,2,*,
Henry Lik-Yuen Chan1,2
Article first published online: 17 FEB 2011
DOI: 10.1111/j.1440-1746.2010.06594.x
Nonalcoholic Fatty Liver Disease (NAFLD) has become a global epidemic, affecting 20–40% of the general adult population.1 In some patients, the disease runs a progressive course, resulting in cirrhosis, hepatocellular carcinoma and liver-related mortality.2 Since NAFLD was first described, its association with metabolic syndrome and insulin resistance has been well recognized.3 Incident diabetes is also commonly diagnosed in NAFLD patients.4 With this background, the Asia-Pacific Working Party on NAFLD recommends anthropometric measurements and metabolic screening for all NAFLD patients.5 The question that remains is what tests clinicians should arrange. Should oral glucose tolerance test (OGTT) be part of the routine workup?
The issue of OGTT is not new. Although fasting glucose is commonly used to screen for or diagnose diabetes, it is well known that the correlation between fasting and postprandial glucose is not perfect. In particular, isolated post-challenge hyperglycemia after OGTT is more often found in male and elderly subjects.6 Using fasting glucose alone, a significant proportion of patients with diabetes or impaired glucose tolerance would be missed.
On the other hand, OGTT involves blood taking at two or more time points after oral glucose challenge. This may be inconvenient and costly to patients and clinicians. The intake of concentrated glucose drinks may also cause gastrointestinal upset and vomiting. Therefore, before one recommends OGTT as a routine test, a few questions need to be answered. How common do NAFLD patients have abnormal OGTT (i.e. number needed to screen)? Does it matter to have subclinical diabetes or impaired glucose tolerance not identified by fasting blood tests alone? Would the finding alter clinical management?
In this issue of the Journal, two studies provided important information in this area. Kimura and colleagues performed 75-g OGTT in 173 Japanese biopsy-proven NAFLD patients without prior diagnosis of type 2 diabetes.7 Overall, 60% of the subjects had abnormal OGTT. Thirty-seven percent had impaired glucose tolerance and 23% had diabetes. Although patients with different degree of liver fibrosis had similar glucose levels, those with advanced fibrosis had significantly higher plasma insulin level throughout a 3-h period. After adjusting for age and aspartate aminotransferase level, plasma insulin level at 2 h remained significantly associated with advanced fibrosis.
The similar glucose levels among patients with different fibrosis stages deviates somewhat from our usual understanding. In patients with NAFLD or viral hepatitis, cirrhosis or advanced fibrosis has consistently been associated with increased risk of diabetes.8,9 In fact, cirrhosis itself is a cause of insulin resistance. However, the lack of cirrhotic patients in Kimura's cohort might partly explain the observation.7 Besides, the mean plasma glucose level among patients with different fibrosis stages was compared using Mann–Whitney U-test. It might be helpful to report the number of patients with impaired glucose tolerance and diabetes in each fibrosis subgroup.
In the second article by Manchanayake and colleagues, OGTT was performed in 76 Australian NAFLD patients without prior diagnosis of diabetes.10 One-third of the subjects had abnormal OGTT, with 22% having impaired glucose tolerance and 9% having diabetes. Impaired fasting glucose only had 25% sensitivity in predicting abnormal OGTT. Similarly, based on plasma insulin levels at 0, 60 and 120 min, hyperinsulinemia and/or insulin resistance was almost universally found, including even patients with normal glucose tolerance. Although few patients in this cohort had liver biopsy, cirrhosis was found in 12% of patients with abnormal OGTT and 4% of those with normal glucose tolerance.
These two studies concur with previous studies showing that one-third to one-half of NAFLD patients had undiagnosed diabetes and impaired glucose tolerance.11 Thus, the number needed to screen for OGTT to detect abnormal glucose regulation is only 2 to 3. Even in NAFLD patients with normal fasting glucose, the number needed to screen is less than 5.
In cross-sectional and longitudinal studies, post-challenge hyperglycemia appears to be associated with adverse clinical outcomes. In a study of 1040 patients undergoing coronary angiogram, impaired glucose tolerance or diabetes by OGTT was associated with cardiovascular events (defined as a composite of vascular deaths, non-fatal myocardial infarctions, non-fatal strokes, percutaneous coronary interventions, bypass graftings, and revascularizations of non-coronary arteries) at a mean follow-up of 3.8 years.12 In another histological cohort, impaired glucose tolerance and diabetes were also associated with advanced liver fibrosis or cirrhosis.11 While it is unclear if post-challenge hyperglycemia itself contributes to the pathogenesis of these clinical complications, OGTT may help clinicians to identify high-risk patients for more intensive monitoring and treatment.
At present, lifestyle changes and insulin sensitizers have been shown to be useful in the treatment of impaired glucose tolerance or pre-diabetes. In the landmark Diabetes Prevention Program Study, 3234 patients with elevated fasting or post-challenge plasma glucose were randomized to placebo, metformin, or a lifestyle-modification program.13 While both treatments prevented the progression to diabetes, it was remarkable that lifestyle modification achieved even lower incidence of diabetes than metformin treatment. This highlights the importance of lifestyle intervention in patients with metabolic disorders. Recently, randomized controlled trials have confirmed that lifestyle modification is effective in reducing hepatic fat in NAFLD patients.14 The full extent of benefits will become clearer when larger clinical trials are completed.
Do we have new markers to replace OGTT? Although clinicians commonly use glycosylated hemoglobin levels to monitor glycemic control of patients with diabetes, the test has limited sensitivity and specificity in diagnosing impaired glucose tolerance. Besides, the tests for glycosylated hemoglobin have not been fully standardized, making comparison among different centers difficult. Lately, a number of adipocyte-secreted proteins, collectively known as adipokines, have been shown to have various effects on insulin sensitivity and inflammation. For example, persons with low serum level of adiponectin are more likely to suffer from NAFLD, obesity and diabetes.3,15 Further studies are required to define the diagnostic and prognostic role of testing adipokines in this context.
In summary, the studies by Kimura, Manchanayake and their respective colleagues clearly demonstrate that insulin resistance is almost universal in patients with NAFLD. Around half of these patients have undiagnosed impaired glucose tolerance or diabetes. Post-challenge hyperglycemia is often associated with adverse clinical events and is amenable to treatment by lifestyle modification and insulin sensitizers. Before new biomarkers are ready for routine clinical use, OGTT should be considered in most NAFLD patients.
Amarapurkar DN, Hashimoto E, Lesmana LA, Sollano JD, Chen PJ, Goh KL. How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? J. Gastroenterol. Hepatol. 2007; 22: 788–93.
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Wong VW, Wong GL, Choi PC et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 2010; 59: 969–74.
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Wong VW, Hui AY, Tsang SW et al. Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 2006; 4: 1154–61.
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Hui AY, Wong VW, Chan HL et al. Histological progression of non-alcoholic fatty liver disease in Chinese patients. Aliment. Pharmacol. Ther. 2005; 21: 407–13.
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Farrell GC, Chitturi S, Lau GK, Sollano JD. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J. Gastroenterol. Hepatol. 2007; 22: 775–7.
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DECODE Study Group. Age- and sex-specific prevalences of diabetes and impaired glucose regulation in 13 European cohorts. Diabetes Care 2003; 26: 61–9.
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Kimura Y, Hyogo H, Ishitobi T, Nabeshima Y, Arihiro K, Chayama K. Postprandial insulin secretion pattern is associated with the histological severity in nonalcoholic fatty liver disease patients without prior known diabetes mellitus. J. Gastroenterol. Hepatol. 2011; 26: 517–22.
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Wong VW, Wong GL, Chim AM et al. Validation of the NAFLD fibrosis score in a Chinese population with low prevalence of advanced fibrosis. Am. J. Gastroenterol. 2008; 103: 1682–8.
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Wong VW, Wong GL, Yu J et al. Interaction of adipokines and hepatitis B virus on histological liver injury in the Chinese. Am. J. Gastroenterol. 2010; 105: 132–8.
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Manchanayake J, Chitturi S, Nolan C, Farrell GC. Post-prandial hyperinsulinemia is universal in non-diabetic patients with non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol. 2011; 26: 510–6.
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Wong VW, Hui AY, Tsang SW et al. Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 2006; 24: 1215–22.
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Sourij H, Saely CH, Schmid F et al. Post-challenge hyperglycaemia is strongly associated with future macrovascular events and total mortality in angiographied coronary patients. Eur. Heart J. 2010; 31: 1583–90.
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Knowler WC, Barrett-Connor E, Fowler SE et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 2002; 346: 393–403.
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St George A, Bauman A, Johnston A, Farrell G, Chey T, George J. Effect of a lifestyle intervention in patients with abnormal liver enzymes and metabolic risk factors. J. Gastroenterol. Hepatol. 2009; 24: 399–407.
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Wong VW, Wong GL, Tsang SW et al. Genetic polymorphisms of adiponectin and tumor necrosis factor-alpha and nonalcoholic fatty liver disease in Chinese people. J. Gastroenterol. Hepatol. 2008; 23: 914–21.
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Friday, March 4, 2011
Hepatitis B;The quest for long-term viral suppression
To stop or not to stop: The quest for long-term viral suppression
Journal of Gastroenterology and Hepatology
Volume 26, Issue 3, pages 420–422, March 2011
James Fung,
Ching-Lung Lai,
Man-Fung Yuen
Article first published online: 17 FEB 2011
DOI: 10.1111/j.1440-1746.2011.06604.x
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
In patients with chronic hepatitis B (CHB), hepatitis B surface antigen (HBsAg) seroconversion is one of the ultimate goals of antiviral therapy. However, this is only achievable in a small proportion of patients receiving treatment. Other end-points that are commonly used include the normalization of alanine aminotransferase (ALT), viral suppression, and hepatitis B e antigen (HBeAg) seroconversion. However, HBeAg seroconversion is an inadequate end-point because it does not guarantee long-term remission and inactivity of the hepatitis B virus (HBV). Thus, although HBeAg seroconversion remains an important milestone in the natural history of CHB infection, a significant proportion (30–50%) of patients will either have ongoing active disease immediately after HBeAg seroclearance or undergo reactivation following a variable period of quiescence.
The exact immunological mechanism for the continuation of disease activity after HBeAg seroconversion is not known. However, the continuing viral replication might be partly explained by the spontaneous mutations in the precore or core promoter regions that reduce the production of HBeAg. It has been shown that the precore and core promoter mutations start to develop even before HBeAg seroconversion. In Asian HBeAg-negative patients with detectable HBV DNA, 50–60% have the precore mutations, and up to 70% have the core promoter mutations. However, approximately 10% still have both precore and core promoter wild-type sequences.
There are considerable differences between the current major regional treatment guidelines as to the criteria for stopping therapy in both HBeAg-positive and -negative patients with CHB. This highlights the fact that there is no consensus regarding the treatment end-points. The guidelines will continue to evolve with increasing understanding of the natural history of CHB infection.
For HBeAg-positive patients, the current European Association for the Study of the Liver (EASL) guidelines1 state that the ideal end-point of therapy is sustained HBsAg loss with or without seroconversion. In contrast, the American Association for the Study of Liver Diseases (AASLD)2 and Asian Pacific Association for the Study of the Liver (APASL) 3 guidelines view “durable” HBeAg seroconversion as an adequate end-point. The APASL guidelines also specify that the HBeAg seroconversion should be accompanied by undetectable HBV DNA.
However, the question remains whether treatment-induced HBeAg seroconversion together with virological response is truly durable. Even with pegylated interferon therapy, in a 5-year long-term follow-up study, despite the cumulative incidence of HBeAg seroconversion of up to 60%, only 29% of patients had HBV DNA less then 20 000 IU/mL, and 13% had HBV DNA less then 20 IU/mL.4 With lamivudine (LAM), an early study of 34 Korean patients who stopped LAM after HBeAg seroconversion showed a cumulative relapse rate of 49% after 2 years.5 Another study of 82 patients from Taiwan showed that 48% had relapsed by 12 months, with genotype C infections being associated with higher rates of relapse.6 A study of 132 Korean patients reported a relapse rate of 66% at 12 months after stopping LAM.7 A more recent Korean study of 178 patients who stopped LAM after achieving HBeAg seroconversion showed a lower relapse rate of 30% at 5 years.8 In 125 Chinese patients who stopped LAM after HBeAg loss or seroconversion, the 4-year cumulative relapse (defined as serum HBV DNA ≥ 2000 IU/mL) rates were 41% and 29%, respectively.9
Common to all these studies is the fact that older age and shorter duration of consolidation therapy after HBeAg seroconversion are associated with higher rates of relapse. However, it is important to note carefully the definition of relapse in the different studies. The low 5-year relapse rate of 30% in the previously-described study is likely due to the high cut-off level of more then 28 000 IU/mL used to define the reappearance of HBV DNA. When virological rebound was defined strictly as a 1 log increase in HBV DNA, the virological rebound rate was 82% at 4 years in a study of 22 patients who stopped LAM after HBeAg seroconversion. Seventy-eight percent of patients had undetectable HBV DNA at the time of last follow up in those who continued with LAM, compared to 0% in those who stopped (P less then 0.001).10 Altogether, these studies show that off-treatment response after HBeAg seroconversion is not durable.
An argument can be made for those in the younger age group in whom antiviral therapy might be stopped with a lower risk of relapse after an extended consolidation treatment period. However, there is no agreement as to the acceptable age cut-off and the length of consolidation. Soo et al. reported a 31% cumulative relapse rate after 2 years following LAM cessation in 85 CHB patients who had received at least 24 months of consolidation.11
For HBeAg-negative patients, both the EASL and AASLD guidelines recommend that treatment should be continued until HBsAg clearance is achieved.1,2 The APASL guidelines, however, are less definite, and recommend that consideration should be given to stopping treatment if HBV DNA remains undetectable on three separate occasions, 6 months apart.3 In this issue of the Journal of Gastroenterology and Hepatology, Liu and colleagues reported the relapse rates of 61 HBeAg-negative CHB patients in whom LAM was stopped.12 These patients were treated for at least 24 months, and had undetectable HBV DNA (less then 200 IU/mL) and normal ALT levels for at least 18 months. Relapse was defined as HBV DNA more then 2000 IU/mL. In their cohort, 31 (51%) patients suffered relapse, with a cumulative relapse rate of 52% after 3 years. Similar to previous studies, younger age was associated with a lower relapse rate. The authors conclude that despite the cessation criteria recommended by the APASL guidelines, the maintenance of viral suppression was not durable.
Another recent study using less stringent cessation criterion was associated with a similarly high relapse rate.13 In this study, of those who achieved a protocol-defined response (HBV DNA less then 1.4 × 105 IU/mL and ALT less then 1.25 × upper limit of normal) with entecavir or LAM at 48 weeks, seven of 257 (3%) entecavir-treated and 10 of 201 (5%) LAM-treated patients sustained HBV DNA less then 60 IU/mL at 24 weeks off treatment. In contrast, those who continued treatment into year 2 had maintenance of virological suppression
Currently, HBsAg seroclearance remains an elusive goal for the majority of patients treated with oral antiviral agents or with pegylated interferon. Despite this, durable suppression of HBV DNA is now achievable with long-term antiviral therapy. The importance of viral load on long-term outcome cannot be over-emphasized, with evidence showing that the lower the HBV DNA, the lower the risk of hepatocellular carcinoma and cirrhosis development.14–16 Early concerns regarding the development of drug-resistant mutations with long-term treatment have largely been mitigated by the availability of highly-potent antiviral agents with a high genetic barrier to resistance, such as entecavir and tenofovir. Relapse, despite continual therapy after HBeAg seroconversion, is usually preceded by the development of resistance in the majority, and is often seen in patients treated with LAM monotherapy.17
However, the resistance rate is lower than that observed in HBeAg-positive patients. After treatment-induced HBeAg seroconversion, the resistance rate was reported to be 10% after a median treatment length of 79 months.10
Virological rebound following cessation of antiviral therapy can be associated with negative consequences. First, inadequate monitoring can result in severe flares of hepatitis. Second, re-challenging the HBV with the same drug after rebound of viral load can theoretically increase the chance of drug resistance. In regions where expensive antiviral drugs might not be readily available as first-line treatment, long-term treatment with LAM might be the only option. Long-term therapy is still advisable, since the risk of relapse from stopping therapy is greater than that of resistance. The adoption of the roadmap concept, with testing of HBV DNA at week 24, might further minimize resistance.
In summary, the study by Liu and colleagues has provided further evidence that off-treatment virological response is not durable, even with adherence to strict cessation criteria. For both HBeAg-positive and -negative patients, the ideal treatment end-points in the era of potent antiviral therapy with low resistance should be the seroclearance of HBsAg.
J. Hepatol. 2009; 50: 227–42. CrossRef,
PubMed,
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Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009; 50: 661–2.
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Abstract
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Liaw YF, Leung N, Kao JH et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol. Int. 2008; 3: 263–83.
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Song BC, Suh DJ, Lee HC, Chung YH, Lee YS. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology 2000; 32: 803–6.
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Chien RN, Yeh CT, Tsai SL, Chu CM, Liaw YF. Determinants for sustained HBeAg response to lamivudine therapy. Hepatology 2003; 38: 1267–73.
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Byun KS, Kwon OS, Kim JH et al. Factors related to post-treatment relapse in chronic hepatitis B patients who lost HBeAg after lamivudine therapy. J. Gastroenterol. Hepatol. 2005; 20: 1838–42.
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Lee HW, Lee HJ, Hwang JS et al. Lamivudine maintenance beyond one year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAg-positive chronic hepatitis B. Hepatology 2010; 51: 415–21.
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Wang L, Liu F, Liu YD et al. Stringent cessation criterion results in better durability of lamivudine treatment: a prospective clinical study in hepatitis B e antigen-positive chronic hepatitis B patients. J. Viral Hepat. 2010; 17: 298–304.
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Journal of Gastroenterology and Hepatology
Volume 26, Issue 3, pages 420–422, March 2011
James Fung,
Ching-Lung Lai,
Man-Fung Yuen
Article first published online: 17 FEB 2011
DOI: 10.1111/j.1440-1746.2011.06604.x
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
In patients with chronic hepatitis B (CHB), hepatitis B surface antigen (HBsAg) seroconversion is one of the ultimate goals of antiviral therapy. However, this is only achievable in a small proportion of patients receiving treatment. Other end-points that are commonly used include the normalization of alanine aminotransferase (ALT), viral suppression, and hepatitis B e antigen (HBeAg) seroconversion. However, HBeAg seroconversion is an inadequate end-point because it does not guarantee long-term remission and inactivity of the hepatitis B virus (HBV). Thus, although HBeAg seroconversion remains an important milestone in the natural history of CHB infection, a significant proportion (30–50%) of patients will either have ongoing active disease immediately after HBeAg seroclearance or undergo reactivation following a variable period of quiescence.
The exact immunological mechanism for the continuation of disease activity after HBeAg seroconversion is not known. However, the continuing viral replication might be partly explained by the spontaneous mutations in the precore or core promoter regions that reduce the production of HBeAg. It has been shown that the precore and core promoter mutations start to develop even before HBeAg seroconversion. In Asian HBeAg-negative patients with detectable HBV DNA, 50–60% have the precore mutations, and up to 70% have the core promoter mutations. However, approximately 10% still have both precore and core promoter wild-type sequences.
There are considerable differences between the current major regional treatment guidelines as to the criteria for stopping therapy in both HBeAg-positive and -negative patients with CHB. This highlights the fact that there is no consensus regarding the treatment end-points. The guidelines will continue to evolve with increasing understanding of the natural history of CHB infection.
For HBeAg-positive patients, the current European Association for the Study of the Liver (EASL) guidelines1 state that the ideal end-point of therapy is sustained HBsAg loss with or without seroconversion. In contrast, the American Association for the Study of Liver Diseases (AASLD)2 and Asian Pacific Association for the Study of the Liver (APASL) 3 guidelines view “durable” HBeAg seroconversion as an adequate end-point. The APASL guidelines also specify that the HBeAg seroconversion should be accompanied by undetectable HBV DNA.
However, the question remains whether treatment-induced HBeAg seroconversion together with virological response is truly durable. Even with pegylated interferon therapy, in a 5-year long-term follow-up study, despite the cumulative incidence of HBeAg seroconversion of up to 60%, only 29% of patients had HBV DNA less then 20 000 IU/mL, and 13% had HBV DNA less then 20 IU/mL.4 With lamivudine (LAM), an early study of 34 Korean patients who stopped LAM after HBeAg seroconversion showed a cumulative relapse rate of 49% after 2 years.5 Another study of 82 patients from Taiwan showed that 48% had relapsed by 12 months, with genotype C infections being associated with higher rates of relapse.6 A study of 132 Korean patients reported a relapse rate of 66% at 12 months after stopping LAM.7 A more recent Korean study of 178 patients who stopped LAM after achieving HBeAg seroconversion showed a lower relapse rate of 30% at 5 years.8 In 125 Chinese patients who stopped LAM after HBeAg loss or seroconversion, the 4-year cumulative relapse (defined as serum HBV DNA ≥ 2000 IU/mL) rates were 41% and 29%, respectively.9
Common to all these studies is the fact that older age and shorter duration of consolidation therapy after HBeAg seroconversion are associated with higher rates of relapse. However, it is important to note carefully the definition of relapse in the different studies. The low 5-year relapse rate of 30% in the previously-described study is likely due to the high cut-off level of more then 28 000 IU/mL used to define the reappearance of HBV DNA. When virological rebound was defined strictly as a 1 log increase in HBV DNA, the virological rebound rate was 82% at 4 years in a study of 22 patients who stopped LAM after HBeAg seroconversion. Seventy-eight percent of patients had undetectable HBV DNA at the time of last follow up in those who continued with LAM, compared to 0% in those who stopped (P less then 0.001).10 Altogether, these studies show that off-treatment response after HBeAg seroconversion is not durable.
An argument can be made for those in the younger age group in whom antiviral therapy might be stopped with a lower risk of relapse after an extended consolidation treatment period. However, there is no agreement as to the acceptable age cut-off and the length of consolidation. Soo et al. reported a 31% cumulative relapse rate after 2 years following LAM cessation in 85 CHB patients who had received at least 24 months of consolidation.11
For HBeAg-negative patients, both the EASL and AASLD guidelines recommend that treatment should be continued until HBsAg clearance is achieved.1,2 The APASL guidelines, however, are less definite, and recommend that consideration should be given to stopping treatment if HBV DNA remains undetectable on three separate occasions, 6 months apart.3 In this issue of the Journal of Gastroenterology and Hepatology, Liu and colleagues reported the relapse rates of 61 HBeAg-negative CHB patients in whom LAM was stopped.12 These patients were treated for at least 24 months, and had undetectable HBV DNA (less then 200 IU/mL) and normal ALT levels for at least 18 months. Relapse was defined as HBV DNA more then 2000 IU/mL. In their cohort, 31 (51%) patients suffered relapse, with a cumulative relapse rate of 52% after 3 years. Similar to previous studies, younger age was associated with a lower relapse rate. The authors conclude that despite the cessation criteria recommended by the APASL guidelines, the maintenance of viral suppression was not durable.
Another recent study using less stringent cessation criterion was associated with a similarly high relapse rate.13 In this study, of those who achieved a protocol-defined response (HBV DNA less then 1.4 × 105 IU/mL and ALT less then 1.25 × upper limit of normal) with entecavir or LAM at 48 weeks, seven of 257 (3%) entecavir-treated and 10 of 201 (5%) LAM-treated patients sustained HBV DNA less then 60 IU/mL at 24 weeks off treatment. In contrast, those who continued treatment into year 2 had maintenance of virological suppression
Currently, HBsAg seroclearance remains an elusive goal for the majority of patients treated with oral antiviral agents or with pegylated interferon. Despite this, durable suppression of HBV DNA is now achievable with long-term antiviral therapy. The importance of viral load on long-term outcome cannot be over-emphasized, with evidence showing that the lower the HBV DNA, the lower the risk of hepatocellular carcinoma and cirrhosis development.14–16 Early concerns regarding the development of drug-resistant mutations with long-term treatment have largely been mitigated by the availability of highly-potent antiviral agents with a high genetic barrier to resistance, such as entecavir and tenofovir. Relapse, despite continual therapy after HBeAg seroconversion, is usually preceded by the development of resistance in the majority, and is often seen in patients treated with LAM monotherapy.17
However, the resistance rate is lower than that observed in HBeAg-positive patients. After treatment-induced HBeAg seroconversion, the resistance rate was reported to be 10% after a median treatment length of 79 months.10
Virological rebound following cessation of antiviral therapy can be associated with negative consequences. First, inadequate monitoring can result in severe flares of hepatitis. Second, re-challenging the HBV with the same drug after rebound of viral load can theoretically increase the chance of drug resistance. In regions where expensive antiviral drugs might not be readily available as first-line treatment, long-term treatment with LAM might be the only option. Long-term therapy is still advisable, since the risk of relapse from stopping therapy is greater than that of resistance. The adoption of the roadmap concept, with testing of HBV DNA at week 24, might further minimize resistance.
In summary, the study by Liu and colleagues has provided further evidence that off-treatment virological response is not durable, even with adherence to strict cessation criteria. For both HBeAg-positive and -negative patients, the ideal treatment end-points in the era of potent antiviral therapy with low resistance should be the seroclearance of HBsAg.
J. Hepatol. 2009; 50: 227–42. CrossRef,
PubMed,
Web of Science®
2
Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009; 50: 661–2.
Direct Link:
Abstract
Full Article (HTML)
PDF(51K)
References
3
Liaw YF, Leung N, Kao JH et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol. Int. 2008; 3: 263–83.
CrossRef,
Web of Science® Times Cited: 107
4
Wong VW, Wong GL, Yan KK et al. Durability of peginterferon alfa-2b treatment at 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology 2010; 51: 1945–53.
PubMed,
ChemPort,
Web of Science® Times Cited: 4
5
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Chien RN, Yeh CT, Tsai SL, Chu CM, Liaw YF. Determinants for sustained HBeAg response to lamivudine therapy. Hepatology 2003; 38: 1267–73.
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Thursday, March 3, 2011
Solving a Traditional Chinese Medicine Mystery
Solving a Traditional Chinese Medicine Mystery
Released: 3/3/2011 2:30 PM EST
Source: Johns Hopkins Medicine
--Discovery of molecular mechanism reveals antitumor possibilities
Newswise — Researchers at the Johns Hopkins School of Medicine have discovered that a natural product isolated from a traditional Chinese medicinal plant commonly known as thunder god vine, or lei gong teng, and used for hundreds of years to treat many conditions including rheumatoid arthritis works by blocking gene control machinery in the cell. The report, published as a cover story of the March issue of Nature Chemical Biology, suggests that the natural product could be a starting point for developing new anticancer drugs.
“Extracts of this medicinal plant have been used to treat a whole host of conditions and have been highly lauded for anti-inflammatory, immunosuppressive, contraceptive and antitumor activities,” says Jun O. Liu, Ph.D., a professor of pharmacology and molecular sciences at Johns Hopkins. “We’ve known about the active compound, triptolide, and that it stops cell growth, since 1972, but only now have we figured out what it does.”
Triptolide, the active ingredient purified from the plant Tripterygium wilfordii Hook F, has been shown in animal models to be effective against cancer, arthritis and skin graft rejection. In fact, says Liu, triptolide has been shown to block the growth of all 60 U.S. National Cancer Institute cell lines at very low doses, and even causes some of those cell lines to die. Other experiments have suggested that triptolide interferes with proteins known to activate genes, which gives Liu and colleagues an entry point into their research.
The team systematically tested triptolide’s effect on different proteins involved with gene control by looking at how much new DNA, RNA and protein is made in cells. They treated HeLa cells with triptolide for one hour, compared treated to untreated cells and found that triptolide took much longer to have an effect on the levels of newly made proteins and DNA, yet almost immediately blocked manufacture of new RNA. The researchers then looked more closely at the three groups of enzymes that make RNA and found that low doses of triptolide blocked only one, RNAPII.
But the RNAPII enzyme complex actually requires the assistance of several smaller clusters of proteins, according to Liu, which required more investigative narrowing down. Using a small gene fragment in a test tube, the researchers mixed in RNAPII components and in some tubes included triptolide and some not to see which combinations resulted in manufacture of new RNA. Every combination of proteins that included a cluster called TFIIH stopped working in the presence of triptolide.
But again, TFIIH is made of 10 individual proteins, many of which, according to Liu, have distinct and testable activities. Using information already known about these proteins and testing the rest to see if triptolide would alter their behaviors, the research team finally found that triptolide directly binds to and blocks the enzymatic activity of one of the 10, the XPB protein.
“We were fairly certain it was XPB because other researchers had found triptolide to bind to an unknown protein of the same size, but they weren’t able to identify it,” says Liu. “
To convince themselves that the interaction between triplotide and XPB is what stops cells from growing, the researchers made 12 chemicals related to triplotide with a wide range of activity and treated HeLa cells with each of the 12 chemicals at several different doses. By both counting cells and testing XPB activity levels, the team found that the two correlate; chemicals that were better at decreasing XPB activity were also better at stopping cell growth and vice versa.
“Triptolide’s general ability to stop RNAPII activity explains its anti-inflammatory and anticancer effects,” says Liu. “And its behavior has important additional implications for circumventing the resistance that some cancer cells develop to certain anticancer drugs. We’re eager to study it further to see what it can do for future cancer therapy.”
This research was supported in part by discretionary funds from the Johns Hopkins Department of Pharmacology and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Authors on the paper include Denis Titov, Qing-Li He, Shridhar Bhat, Woon-Kai Low, Yongjun Dang, Michael Smeaton and Jun O. Liu of Johns Hopkins; Benjamin Gilman, Jennifer Kugel and James Goodrich of the University of Colorado, Boulder; and Arnold Demain of Drew University, Madison, N.J.
http://www.newswise.com/articles/solving-a-traditional-chinese-medicine-mystery
Released: 3/3/2011 2:30 PM EST
Source: Johns Hopkins Medicine
--Discovery of molecular mechanism reveals antitumor possibilities
Newswise — Researchers at the Johns Hopkins School of Medicine have discovered that a natural product isolated from a traditional Chinese medicinal plant commonly known as thunder god vine, or lei gong teng, and used for hundreds of years to treat many conditions including rheumatoid arthritis works by blocking gene control machinery in the cell. The report, published as a cover story of the March issue of Nature Chemical Biology, suggests that the natural product could be a starting point for developing new anticancer drugs.
“Extracts of this medicinal plant have been used to treat a whole host of conditions and have been highly lauded for anti-inflammatory, immunosuppressive, contraceptive and antitumor activities,” says Jun O. Liu, Ph.D., a professor of pharmacology and molecular sciences at Johns Hopkins. “We’ve known about the active compound, triptolide, and that it stops cell growth, since 1972, but only now have we figured out what it does.”
Triptolide, the active ingredient purified from the plant Tripterygium wilfordii Hook F, has been shown in animal models to be effective against cancer, arthritis and skin graft rejection. In fact, says Liu, triptolide has been shown to block the growth of all 60 U.S. National Cancer Institute cell lines at very low doses, and even causes some of those cell lines to die. Other experiments have suggested that triptolide interferes with proteins known to activate genes, which gives Liu and colleagues an entry point into their research.
The team systematically tested triptolide’s effect on different proteins involved with gene control by looking at how much new DNA, RNA and protein is made in cells. They treated HeLa cells with triptolide for one hour, compared treated to untreated cells and found that triptolide took much longer to have an effect on the levels of newly made proteins and DNA, yet almost immediately blocked manufacture of new RNA. The researchers then looked more closely at the three groups of enzymes that make RNA and found that low doses of triptolide blocked only one, RNAPII.
But the RNAPII enzyme complex actually requires the assistance of several smaller clusters of proteins, according to Liu, which required more investigative narrowing down. Using a small gene fragment in a test tube, the researchers mixed in RNAPII components and in some tubes included triptolide and some not to see which combinations resulted in manufacture of new RNA. Every combination of proteins that included a cluster called TFIIH stopped working in the presence of triptolide.
But again, TFIIH is made of 10 individual proteins, many of which, according to Liu, have distinct and testable activities. Using information already known about these proteins and testing the rest to see if triptolide would alter their behaviors, the research team finally found that triptolide directly binds to and blocks the enzymatic activity of one of the 10, the XPB protein.
“We were fairly certain it was XPB because other researchers had found triptolide to bind to an unknown protein of the same size, but they weren’t able to identify it,” says Liu. “
To convince themselves that the interaction between triplotide and XPB is what stops cells from growing, the researchers made 12 chemicals related to triplotide with a wide range of activity and treated HeLa cells with each of the 12 chemicals at several different doses. By both counting cells and testing XPB activity levels, the team found that the two correlate; chemicals that were better at decreasing XPB activity were also better at stopping cell growth and vice versa.
“Triptolide’s general ability to stop RNAPII activity explains its anti-inflammatory and anticancer effects,” says Liu. “And its behavior has important additional implications for circumventing the resistance that some cancer cells develop to certain anticancer drugs. We’re eager to study it further to see what it can do for future cancer therapy.”
This research was supported in part by discretionary funds from the Johns Hopkins Department of Pharmacology and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Authors on the paper include Denis Titov, Qing-Li He, Shridhar Bhat, Woon-Kai Low, Yongjun Dang, Michael Smeaton and Jun O. Liu of Johns Hopkins; Benjamin Gilman, Jennifer Kugel and James Goodrich of the University of Colorado, Boulder; and Arnold Demain of Drew University, Madison, N.J.
http://www.newswise.com/articles/solving-a-traditional-chinese-medicine-mystery
Hepatitis C: Viral Load Test
Viral load is the amount of virus present in the bloodstream. It is expressed as the amount of viral genetic material (RNA) per milliliter of blood. Viral load is not related to the amount of liver damage, or to how sick someone is.
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Types of HCV Viral Load Tests
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There are two categories of HCV viral load tests:
Qualitative viral load tests — These tests determine the presence of HCV RNA in the blood. This type of test is usually used to confirm chronic infection with HCV. If viral RNA is detected, a positive result is reported; if viral RNA is not detected, the test result is negative.
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Quantitative viral load tests — These tests measure the amount of virus in one milliliter of blood. They are often used to assess whether or not treatment with interferon or interferon plus ribavirin is likely to be successful and, later, if treatment is working.
.
Types of HCV Viral Load Tests
.
There are two categories of HCV viral load tests:
Qualitative viral load tests — These tests determine the presence of HCV RNA in the blood. This type of test is usually used to confirm chronic infection with HCV. If viral RNA is detected, a positive result is reported; if viral RNA is not detected, the test result is negative.
.
Quantitative viral load tests — These tests measure the amount of virus in one milliliter of blood. They are often used to assess whether or not treatment with interferon or interferon plus ribavirin is likely to be successful and, later, if treatment is working.
Source
.
When you get back the result of your Hepatitis C RNA quantitative test, and when the lab was able to determine the amount of virus in your blood, then it is important to write down not only the number, but also in what units this number is given.
.
.
When you get back the result of your Hepatitis C RNA quantitative test, and when the lab was able to determine the amount of virus in your blood, then it is important to write down not only the number, but also in what units this number is given.
.
I) Volume
The volume of blood, that the number refers to, is usually one milliliter.
But some labs give the number for 20 microliters = 1/50 milliliter. So in these cases you have to multiply the result of the viral load by 50 to get the number for 1 milliliter.
II) Amount of Virus
Unfortunately, there are several ways to express the viral load. So, in order to be able to compare different results, you have to know how to convert these numbers to some standard format, which let’s say is just the plain number of viruses per milliliter, like 1.5 Million/ml, or 1,500,000/ml. (both of these numbers are the same).
a) Measure by weight
Sometimes, the lab reports the amount of genetic material found by its weight. 1 pg (pico-gram) of genetic material corresponds to about 1 million virus equivalents, so, if your lab result is given in picograms, just multiply the lab result by 1,000,000, and you have the number of viruses.
b) Measure by virus count
i) Plain numbers
Often the virus count is expressed as a plain number, like 1.73 million, or 1,730,000 or 1730000. Millions sometime are abbreviated by the prefix “M” (Mega). So when you see 1.73 Meq/ml, it means 1.73 Mega-equivalents/ml or again 1730000 equivalents/ml..
ii) Exponential format
Large numbers are often expressed in exponential form, that means a number, multiplied by 10 with an exponent. To convert this to normal numbers, append as many zeroes to a “1″ as the exponent says, and multiply this with the number. In some lab report, the viral load was “Hep C RNA Quant 17.3 x 10(exp) 5 equivalents/ml”. So, with 5 as exponent, you have to append 5 zeroes to a “1″, that gives 100000, and multiply this with the number 17.3, that gives 1730000 as the viral load. Normally this would be written 1.73×10(exp)6, or 1.73×106 , (which are again the same number).
17.3×105 = 1.73×106 = 1,730,000
iii) Logarthmic format
Now, recently some people express these numbers also in logarithmic form (logarithmic transformed number).
log(1730000)=6.24
6.24 is the logarithmic transformed number of the viral load of our above example. A result of 3.5 for a viral load, that someone reported, seems to be such a number (unless he forgot to write down a “10″ and an exponent). You need a calculator to convert this. You have to use the function 10x , where you have to replace x with the logarithmic number, in the above case 3.5. The result would be: 103.5 = 3162 virus equivalents per milliliter.
When you take the logarithmic number from the first example, 6.24, you have to calculate 106.24 = 1730000 , and here we have the original number of virus equivalents again. If you don’t have a calculator, you can estimate the order of magnitude of a viral load expressed as a logarithmic number. From the logarithmic number, you take the first digit (left of the point) and add 1 to this number. This gives you the number of digits that your viral load has (expressed as a plain number).
Example: Logarithmic number 6.24
Left of the point is “6″. 6+1 = 7
The number that gives the viral load is 7 digits long, that means it is between 1,000,000 and 9,999,999 (digit # 1 234 567)
The next digit (right of the point of the logarithmic number) shows whether you are high or low in the range.
In case you have a logarithmic number *and* a blood volume other than 1 ml, you have to convert the logarithmic number to a plain number *first*, and then correct it to correspond to 1 ml !
Therefore it is important to have a close look at your lab report and see in what units the result is given!
There is still no general agreement on what Viral Load is considered low and what is high in Hepatitis C. This interpretation makes sense for people not currently being treated – for someone who is 6 months into an INF + RIBA trial, even 200,000 could be considered a high titer.
(Numbers are Virus Equivalents per Milliliter)
below 200,000 very low (undetectable by *bDNA* test)
200,000 to 1,000,000 low
1,000,000 to 5,000,000 medium
5,000,000 to 25,000,000 high
above 25,000,000 very high
Once again, please note that this information is not written by an MD or medical expert. Nothing can (or should) take the place of appropriate medical care.
The volume of blood, that the number refers to, is usually one milliliter.
But some labs give the number for 20 microliters = 1/50 milliliter. So in these cases you have to multiply the result of the viral load by 50 to get the number for 1 milliliter.
II) Amount of Virus
Unfortunately, there are several ways to express the viral load. So, in order to be able to compare different results, you have to know how to convert these numbers to some standard format, which let’s say is just the plain number of viruses per milliliter, like 1.5 Million/ml, or 1,500,000/ml. (both of these numbers are the same).
a) Measure by weight
Sometimes, the lab reports the amount of genetic material found by its weight. 1 pg (pico-gram) of genetic material corresponds to about 1 million virus equivalents, so, if your lab result is given in picograms, just multiply the lab result by 1,000,000, and you have the number of viruses.
b) Measure by virus count
i) Plain numbers
Often the virus count is expressed as a plain number, like 1.73 million, or 1,730,000 or 1730000. Millions sometime are abbreviated by the prefix “M” (Mega). So when you see 1.73 Meq/ml, it means 1.73 Mega-equivalents/ml or again 1730000 equivalents/ml..
ii) Exponential format
Large numbers are often expressed in exponential form, that means a number, multiplied by 10 with an exponent. To convert this to normal numbers, append as many zeroes to a “1″ as the exponent says, and multiply this with the number. In some lab report, the viral load was “Hep C RNA Quant 17.3 x 10(exp) 5 equivalents/ml”. So, with 5 as exponent, you have to append 5 zeroes to a “1″, that gives 100000, and multiply this with the number 17.3, that gives 1730000 as the viral load. Normally this would be written 1.73×10(exp)6, or 1.73×106 , (which are again the same number).
17.3×105 = 1.73×106 = 1,730,000
iii) Logarthmic format
Now, recently some people express these numbers also in logarithmic form (logarithmic transformed number).
log(1730000)=6.24
6.24 is the logarithmic transformed number of the viral load of our above example. A result of 3.5 for a viral load, that someone reported, seems to be such a number (unless he forgot to write down a “10″ and an exponent). You need a calculator to convert this. You have to use the function 10x , where you have to replace x with the logarithmic number, in the above case 3.5. The result would be: 103.5 = 3162 virus equivalents per milliliter.
When you take the logarithmic number from the first example, 6.24, you have to calculate 106.24 = 1730000 , and here we have the original number of virus equivalents again. If you don’t have a calculator, you can estimate the order of magnitude of a viral load expressed as a logarithmic number. From the logarithmic number, you take the first digit (left of the point) and add 1 to this number. This gives you the number of digits that your viral load has (expressed as a plain number).
Example: Logarithmic number 6.24
Left of the point is “6″. 6+1 = 7
The number that gives the viral load is 7 digits long, that means it is between 1,000,000 and 9,999,999 (digit # 1 234 567)
The next digit (right of the point of the logarithmic number) shows whether you are high or low in the range.
In case you have a logarithmic number *and* a blood volume other than 1 ml, you have to convert the logarithmic number to a plain number *first*, and then correct it to correspond to 1 ml !
Therefore it is important to have a close look at your lab report and see in what units the result is given!
There is still no general agreement on what Viral Load is considered low and what is high in Hepatitis C. This interpretation makes sense for people not currently being treated – for someone who is 6 months into an INF + RIBA trial, even 200,000 could be considered a high titer.
(Numbers are Virus Equivalents per Milliliter)
below 200,000 very low (undetectable by *bDNA* test)
200,000 to 1,000,000 low
1,000,000 to 5,000,000 medium
5,000,000 to 25,000,000 high
above 25,000,000 very high
Once again, please note that this information is not written by an MD or medical expert. Nothing can (or should) take the place of appropriate medical care.
Posted at Avail Clinical On February 4th, 2011
http://www.availclinical.com/tag/hepatitis-c-treatment/
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http://www.availclinical.com/tag/hepatitis-c-treatment/
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HCV Viral Load Tests
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Alan Franciscus, Editor-in-Chief
Liz Highleyman
.
Viral load tests are blood tests that measure HCV ribonucleic acid (RNA, or genetic material) in the blood. The presence of viral RNA indicates that the virus is actively replicating (reproducing and infecting new cells). A viral load test is usually first done after a person has tested positive for exposure to HCV based on an antibody test. A blood sample is taken and the amount of HCV RNA in a milliliter of blood is measured. Viral load tests confirm whether an individual is actively infected with HCV. Viral load test results were previously measured in number of copies, but are now typically reported in terms of International Units per milliliter (IU/mL).
Types of HCV Viral Load Tests
There are two categories of HCV viral load tests:
Qualitative viral load tests — These tests determine the presence of HCV RNA in the blood. This type of test is usually used to confirm chronic infection with HCV. If viral RNA is detected, a positive result is reported; if viral RNA is not detected, the test result is negative.
Quantitative viral load tests — These tests measure the amount of virus in one milliliter of blood. They are often used to assess whether or not treatment with interferon or interferon plus ribavirin is likely to be successful and, later, if treatment is working.
There are currently three tests commonly used for HCV viral load testing:
Polymerase chain reaction (PCR) — PCR tests detect HCV RNA in the blood, which indicates current active infection. This type of quantitative PCR test is very sensitive, and can measure as few as 50 IU/mL.
Branched-chain DNA (bDNA) — The bDNA method quantitative viral load testing is easier (and cheaper) to use for a large number of samples, but only measures viral loads greater than 500 IU/mL. This means that if a person has a viral load below 500 IU/mL, HCV could be present in the blood but not detected by the test.
Transcription-mediated amplification (TMA) — TMA technology allows for the amplification and detection of nucleic acids (components of genetic material) in the blood. This test can measure as few as 5-10 IU/mL. This newer test appears easier and cheaper to use, streamlining test processing and producing consistent, reliable, and more rapid results.
Interpreting Viral Load Test Results
HCV viral load is often reported as low or high.
Expressed as copies/mL:
·Low: less than 2 million copies
·High: more than 2 million copies
Expressed as International Units (IU/mL):
·Low:less than 800,000 IU/mL
·High:more than 800,000 IU/mL
If no HCV RNA is found by a test, a person’s viral load is said to be undetectable. Note that whether viral load is undetectable depends on which test is used. PCR and TMA tests can measure viral loads much lower than those a bDNA test can detect. Importantly, the blood of an individual with a very low viral load may still contain HCV even though the current tests cannot measure it; that is, the virus may not have been truly eradicated from the body.
Viral load test results can vary depending on how a blood sample is handled and stored. Furthermore, results may vary from lab to lab. For this reason, most experts recommend that people should get their viral load testing done by the same laboratory each time, so that results are more comparable.
Changes in viral load are sometimes expressed in terms of logs. A log change is a 10-fold increase or decrease. For example, a change from 1,000,000 IU/mL to 10,000 IU/mL is a 2-log decrease.
Converting copies per milliliter to Inter-national Units
There is no standard conversion formula for converting the amount of HCV RNA reported in copies per milliliter to the amount reported in International Units. The conversion factor ranges from about one to about five HCV RNA copies per IU. Usually the lab report will list the conversion from IU/mL to copies/mL.
Alan Franciscus, Editor-in-Chief
Liz Highleyman
.
Viral load tests are blood tests that measure HCV ribonucleic acid (RNA, or genetic material) in the blood. The presence of viral RNA indicates that the virus is actively replicating (reproducing and infecting new cells). A viral load test is usually first done after a person has tested positive for exposure to HCV based on an antibody test. A blood sample is taken and the amount of HCV RNA in a milliliter of blood is measured. Viral load tests confirm whether an individual is actively infected with HCV. Viral load test results were previously measured in number of copies, but are now typically reported in terms of International Units per milliliter (IU/mL).
Types of HCV Viral Load Tests
There are two categories of HCV viral load tests:
Qualitative viral load tests — These tests determine the presence of HCV RNA in the blood. This type of test is usually used to confirm chronic infection with HCV. If viral RNA is detected, a positive result is reported; if viral RNA is not detected, the test result is negative.
Quantitative viral load tests — These tests measure the amount of virus in one milliliter of blood. They are often used to assess whether or not treatment with interferon or interferon plus ribavirin is likely to be successful and, later, if treatment is working.
There are currently three tests commonly used for HCV viral load testing:
Polymerase chain reaction (PCR) — PCR tests detect HCV RNA in the blood, which indicates current active infection. This type of quantitative PCR test is very sensitive, and can measure as few as 50 IU/mL.
Branched-chain DNA (bDNA) — The bDNA method quantitative viral load testing is easier (and cheaper) to use for a large number of samples, but only measures viral loads greater than 500 IU/mL. This means that if a person has a viral load below 500 IU/mL, HCV could be present in the blood but not detected by the test.
Transcription-mediated amplification (TMA) — TMA technology allows for the amplification and detection of nucleic acids (components of genetic material) in the blood. This test can measure as few as 5-10 IU/mL. This newer test appears easier and cheaper to use, streamlining test processing and producing consistent, reliable, and more rapid results.
Interpreting Viral Load Test Results
HCV viral load is often reported as low or high.
Expressed as copies/mL:
·Low: less than 2 million copies
·High: more than 2 million copies
Expressed as International Units (IU/mL):
·Low:less than 800,000 IU/mL
·High:more than 800,000 IU/mL
If no HCV RNA is found by a test, a person’s viral load is said to be undetectable. Note that whether viral load is undetectable depends on which test is used. PCR and TMA tests can measure viral loads much lower than those a bDNA test can detect. Importantly, the blood of an individual with a very low viral load may still contain HCV even though the current tests cannot measure it; that is, the virus may not have been truly eradicated from the body.
Viral load test results can vary depending on how a blood sample is handled and stored. Furthermore, results may vary from lab to lab. For this reason, most experts recommend that people should get their viral load testing done by the same laboratory each time, so that results are more comparable.
Changes in viral load are sometimes expressed in terms of logs. A log change is a 10-fold increase or decrease. For example, a change from 1,000,000 IU/mL to 10,000 IU/mL is a 2-log decrease.
Converting copies per milliliter to Inter-national Units
There is no standard conversion formula for converting the amount of HCV RNA reported in copies per milliliter to the amount reported in International Units. The conversion factor ranges from about one to about five HCV RNA copies per IU. Usually the lab report will list the conversion from IU/mL to copies/mL.
See Table 1 for a conversion of common viral load tests from IUs to copies.
Table 1: Conversion Chart
Assay Conversion Factor Amplicor HCV Monitor v2.0
(manual procedure) 1 IU/mL = 0.9 copies/ml Cobas Amplicor HCV Monitor v2.0
(semi-automated procedure) 1 IU/mL = 2.7 copies/ml Versant HCV RNA 3.0 Quantitative Assay 1 IU/mL = 5.2 copies/ml LCx HCV RNA Quantitatiive Assay 1 IU/mL = 3.8 copies/ml SuperQuant 1 IU/mL = 3.4 copies/ml
Uses of Viral Load Test Results
Viral load test results have many uses, such as confirming active HCV infection, and predicting and measuring HCV treatment response before, during, and after therapy. Higher HCV viral loads may be associated with a greater risk of HCV transmission, particularly transmission from mothers to infants during pregnancy or birth. Viral load has not been correlated with the risk of sexual transmission. Furthermore, a correlation between HCV viral load and disease progression has not been shown.
Confirming active HCV infection — After a person has tested positive for HCV antibodies, an HCV viral load test is usually performed to confirm active HCV infection. This test is necessary because in up to 25% of people exposed to HCV, the virus can be cleared on its own.
Before treatment — Viral load measurement can help predict how well HCV treatment will work.
The lower the pre-treatment viral load, the more likely it is that a person will respond to current HCV therapies.
During treatment — A decrease in viral load while on therapy indicates that treatment is working. A treatment is said to produce a complete virological response if it reduces viral load to an undetectable level. After 12 weeks of antiviral treatment, a 2-log drop in viral load or elimination of detectable HCV is an indication that the medications are working. If a person does not achieve a 2-log drop in viral load or elimination of detectable HCV after 12 weeks, it is unlikely that he or she will be able to eradicate HCV from his or her body. Viral load tests during treatment can also detect viral breakthrough, or increases in viral load that occur after a previous undetectable test result.
After treatment — Viral load measurements can be used after cessation of therapy to monitor for relapse—that is, to see if the virus becomes detectable again after being undetectable when treatment was completed.
http://www.hcvadvocate.org/news/newsLetter/advocate1003.html#4
New method allows human embryonic stem cells to avoid immune system rejection
New method allows human embryonic stem cells to avoid immune system rejection, study finds
BY KRISTA CONGER
Joseph Wu
A short-term treatment with three immune-dampening drugs allowed human embryonic stem cells to survive and thrive in mice, according to researchers at the Stanford University School of Medicine. Without such treatment, the animals’ immune systems quickly hunt down and destroy the transplanted cells. The finding is important because it may allow humans to accept transplanted stem cells intended to treat disease or injury without requiring the ongoing use of powerful immunosuppressant medications.
Just as it does with transplanted organs, the human body recognizes foreign cells and rejects them. Embryonic stem cells, or ES cells, and the tissues they become are by definition immunologically different from any potential recipient. Physicians also have to overcome the fact that unspecialized ES cells can form tumors when transplanted into the body.
“We are very excited about the clinical potential of this finding,” said Joseph Wu, MD, PhD, associate professor of cardiovascular medicine and of radiology at Stanford and senior author of the study, published in the March issue of Cell Stem Cell. “The immunological issue is one of the most important biological problems to solve, in my opinion. Clinicians need to make sure there is no tumor formation, and also that the cells are not rejected.”
This paper, in tandem with a previous study by Wu published in February in the Journal of Clinical Investigation, helps to recast a scientific debate over the relative benefits of embryonic stem cells as compared with iPS cells, or induced pluripotent stem cells, which can be created from a person’s own skin or other cells.
Some scientists argue that iPS cells can differentiate into other tissue as well as ES cells can — without the problem of immune system rejection. Yet others contend that although iPS cells behave very much like ES cells in a laboratory dish, they are not identical and may not be perfect stand-ins.
Wu’s paper in February sheds new light on the dissimilarities between the two cell types. “When we compared the gene expression patterns between single cells, we saw that they were actually quite different,” he said. That paper is the first to compare the gene expression patterns between iPS and ES cells on a single-cell level. In addition, although using a patient’s own cells sidesteps the problem of immune rejection, generating these tailor-made cells does have drawbacks. “Most people don’t realize that, although it’s possible to generate patient-specific iPS cells, the cost of doing so would likely be prohibitive for all but the most specialized applications,” said Wu. “It also takes time — time that a patient with an acute health problem like a stroke, heart attack, or neurological trauma may not have.”
Wu’s latest paper addresses ES cells’ problem with immune system rejection.
Currently most animal experiments involving transplanted stem cells rely on the long-term use of immunosuppressants to prevent rejection. Most ongoing human clinical trials also use the medications (with the exception of those in which the cells are transplanted into a body location, such as the eye, that is relatively protected from the immune system), which can cause hypertension, weight gain, organ damage and an increased susceptibility to infection. Wu and the study’s first author, graduate student Jeremy Pearl, wondered whether there were any other options.
To find out, they turned to a class of drugs called “co-stimulatory receptor blocking agents” that specifically block an interaction between an immune cell called a T cell and the transplanted stem cells. Normally a T cell attaches to foreign invaders in a two-step process that triggers their destruction. By preventing the second step, these medications instead teach the T cells to tolerate the new cells.
The researchers injected genetically engineered mouse ES cells into the leg muscles of mice of a different genetic background and monitored the fate of the cells over time using a technique called in vivo bioluminescent imaging. When the mice were untreated, the cells were completely rejected within 21 days. They then treated one group of mice with a combination of three of the blocking agents on days 0, 2, 4 and 6 after transplantation, and another with an ongoing course of traditional immunosuppressants. They found that the transplanted cells survived a bit longer in the mice receiving the traditional immunosuppressant — about 28 days. But the cells flourished in the mice receiving the blocking agents.
“We followed the cells for up to 100 days after transplantation and found that their numbers were in some cases increasing and in some cases remaining steady,” said Pearl. “The major advantage of our technique is that it only requires a short course of suppression. And because we’re not using traditional immunosuppressants, we avoid lasting side effects.” What’s more, Pearl showed that the temporary treatment didn’t keep the mice from subsequently rejecting other types of cells — indicating their immune systems had not been permanently compromised.
Wu and Pearl found the treatment also helped the mice accept human ES cells, mouse and human iPS cells, as well as human ES cells that had been first coaxed to become precursors of several types of tissue. Acceptance of the differentiated precursor cells is particularly important because undifferentiated ES or iPS cells can form a particular type of cancer called teratomas and wouldn’t be used clinically in humans.
The researchers are now testing whether the drug treatment works in larger animals like pigs, and trying different combinations and concentrations of drugs.
In addition to Wu and Pearl, other Stanford researchers involved in the study include graduate student Andrew Lee; postdoctoral scholars Dennis Leveson-Gower, PhD, Ning Sun, PhD, and Feng Lan, PhD; former postdoctoral scholar Zhumur Ghosh, PhD; professor of medicine Robert Negrin, MD; and professor of microbiology and immunology Mark Davis, PhD. The research was supported by the National Institutes of Health, the Howard Hughes Medical Institute and the Ellison Medical Foundation.
Wu is a member of the Stanford Cancer Center and the Bio-X program.
Related News » Immune response in mice suggests limits to embryonic stem cell therapy » Stem cell transplant can grow new immune system in certain mice
BY KRISTA CONGER
Joseph Wu
A short-term treatment with three immune-dampening drugs allowed human embryonic stem cells to survive and thrive in mice, according to researchers at the Stanford University School of Medicine. Without such treatment, the animals’ immune systems quickly hunt down and destroy the transplanted cells. The finding is important because it may allow humans to accept transplanted stem cells intended to treat disease or injury without requiring the ongoing use of powerful immunosuppressant medications.
Just as it does with transplanted organs, the human body recognizes foreign cells and rejects them. Embryonic stem cells, or ES cells, and the tissues they become are by definition immunologically different from any potential recipient. Physicians also have to overcome the fact that unspecialized ES cells can form tumors when transplanted into the body.
“We are very excited about the clinical potential of this finding,” said Joseph Wu, MD, PhD, associate professor of cardiovascular medicine and of radiology at Stanford and senior author of the study, published in the March issue of Cell Stem Cell. “The immunological issue is one of the most important biological problems to solve, in my opinion. Clinicians need to make sure there is no tumor formation, and also that the cells are not rejected.”
This paper, in tandem with a previous study by Wu published in February in the Journal of Clinical Investigation, helps to recast a scientific debate over the relative benefits of embryonic stem cells as compared with iPS cells, or induced pluripotent stem cells, which can be created from a person’s own skin or other cells.
Some scientists argue that iPS cells can differentiate into other tissue as well as ES cells can — without the problem of immune system rejection. Yet others contend that although iPS cells behave very much like ES cells in a laboratory dish, they are not identical and may not be perfect stand-ins.
Wu’s paper in February sheds new light on the dissimilarities between the two cell types. “When we compared the gene expression patterns between single cells, we saw that they were actually quite different,” he said. That paper is the first to compare the gene expression patterns between iPS and ES cells on a single-cell level. In addition, although using a patient’s own cells sidesteps the problem of immune rejection, generating these tailor-made cells does have drawbacks. “Most people don’t realize that, although it’s possible to generate patient-specific iPS cells, the cost of doing so would likely be prohibitive for all but the most specialized applications,” said Wu. “It also takes time — time that a patient with an acute health problem like a stroke, heart attack, or neurological trauma may not have.”
Wu’s latest paper addresses ES cells’ problem with immune system rejection.
Currently most animal experiments involving transplanted stem cells rely on the long-term use of immunosuppressants to prevent rejection. Most ongoing human clinical trials also use the medications (with the exception of those in which the cells are transplanted into a body location, such as the eye, that is relatively protected from the immune system), which can cause hypertension, weight gain, organ damage and an increased susceptibility to infection. Wu and the study’s first author, graduate student Jeremy Pearl, wondered whether there were any other options.
To find out, they turned to a class of drugs called “co-stimulatory receptor blocking agents” that specifically block an interaction between an immune cell called a T cell and the transplanted stem cells. Normally a T cell attaches to foreign invaders in a two-step process that triggers their destruction. By preventing the second step, these medications instead teach the T cells to tolerate the new cells.
The researchers injected genetically engineered mouse ES cells into the leg muscles of mice of a different genetic background and monitored the fate of the cells over time using a technique called in vivo bioluminescent imaging. When the mice were untreated, the cells were completely rejected within 21 days. They then treated one group of mice with a combination of three of the blocking agents on days 0, 2, 4 and 6 after transplantation, and another with an ongoing course of traditional immunosuppressants. They found that the transplanted cells survived a bit longer in the mice receiving the traditional immunosuppressant — about 28 days. But the cells flourished in the mice receiving the blocking agents.
“We followed the cells for up to 100 days after transplantation and found that their numbers were in some cases increasing and in some cases remaining steady,” said Pearl. “The major advantage of our technique is that it only requires a short course of suppression. And because we’re not using traditional immunosuppressants, we avoid lasting side effects.” What’s more, Pearl showed that the temporary treatment didn’t keep the mice from subsequently rejecting other types of cells — indicating their immune systems had not been permanently compromised.
Wu and Pearl found the treatment also helped the mice accept human ES cells, mouse and human iPS cells, as well as human ES cells that had been first coaxed to become precursors of several types of tissue. Acceptance of the differentiated precursor cells is particularly important because undifferentiated ES or iPS cells can form a particular type of cancer called teratomas and wouldn’t be used clinically in humans.
The researchers are now testing whether the drug treatment works in larger animals like pigs, and trying different combinations and concentrations of drugs.
In addition to Wu and Pearl, other Stanford researchers involved in the study include graduate student Andrew Lee; postdoctoral scholars Dennis Leveson-Gower, PhD, Ning Sun, PhD, and Feng Lan, PhD; former postdoctoral scholar Zhumur Ghosh, PhD; professor of medicine Robert Negrin, MD; and professor of microbiology and immunology Mark Davis, PhD. The research was supported by the National Institutes of Health, the Howard Hughes Medical Institute and the Ellison Medical Foundation.
Wu is a member of the Stanford Cancer Center and the Bio-X program.
Related News » Immune response in mice suggests limits to embryonic stem cell therapy » Stem cell transplant can grow new immune system in certain mice
Hepatitis C News: Was pulmonary toxicity induced by interferon therapy?
From Medscape;
Simultaneous Occurrence of Pleural Effusion and Interstitial Pneumonitis After Treatment With Pegylated Interferon for Hepatitis C Virus Infection
This patient with chronic hepatitis C presented with a rare simultaneous occurrence of pleural effusion and interstitial pneumonitis.
Was pulmonary toxicity induced by interferon therapy?
Southern Medical Journal, March 2011
Abstract and Introduction
Case Report
Discussion
Conclusion
Discussion Only/Click here for Full Data
Although pulmonary complications of interferon (IFN) are rare, the growing number of patients receiving such therapy will undoubtedly lead to an increasing number of patients with pulmonary manifestations, of which IP and sarcoidosis are the most common, while pleural effusion is rare. There are only three cases described to date in the English literature, including our case. The clinical data of the three cases are shown in the Table.
The present case is the second case in which the patient developed pleural effusion and IP during pegylated interferon-α and ribavirin therapy for HCV infection. In this patient's case, it seems highly likely that pegylated interferon-α was responsible for the onset of pulmonary toxicity. All other possible infectious or systemic causes were ruled out; ribavirin had been interrupted at week 12, and the absence of any previous pulmonary history and specificity of the results of the various investigations carried out in the context of the pleural effusion and IP showed a relationship between the pegylated interferon treatment and the onset of complications. We used the causal criteria from the World Health Organization to show the probability of adverse drug reaction.[8]
The cornerstone of management of IFN-induced pulmonary toxicity is to stop the drug immediately.[1] There was convincing evidence that steroids induce an increase of hepatitis C virus replication; whether steroids should be included in the treatment modality remains controversial.[9] Treatment with steroids was not considered initially, since pleural effusion in the other two cases[5,6] and IP in some patients recovered after discontinuation of (pegylated) IFN/ribavirin,[1] the severity of pulmonary injury was of moderate degree, and there was premature cessation of ribavirin, which is correlated with a higher risk of virus relapse. However, methylprednisolone was used due to progressive dyspnea and cough with severe pulmonary injury and subsequent hypoxemia. Steroid therapy caused a dramatic improvement of symptoms and imaging, which suggested that pulmonary toxicity is related to the immunomodulatory reactions of IFN.
HCV Advocate Newsletter, March 2011
In This Issue:
HCV Protease Inhibitor—TMC435: Phase 3 Studies
Alan Franciscus, Editor-in-Chief
Hepatitis C in Egypt
Alan Franciscus, Editor-in-Chief
HCV Snapshots
Lucinda K. Porter, RN
Liver Transplantation: An Overview
Liz Highleyman
HealthWise: The Power Is in Our Hands
Lucinda K. Porter, RNHCV Advocate
Eblast HCV Advocate;
Stay informed on the latest news ..click here to register for email alerts
Three died in one week after organs from same donor
Adrian Lowe March 3, 2011
World's largest online family history resource.+6 billion records
THREE women died within one week of each other after they received diseased organs in transplant procedures at the Austin and Royal Melbourne hospitals, an inquest has heard.
From GastroHep.com
Predictors of readmission with advanced liver disease
The latest issue of Clinical Gastroenterology & Hepatology investigates the incidence and predictors of 30-day readmission among patients hospitalized for advanced liver disease.
The rate of readmission to the hospital 30 days after discharge (30-day readmission rate) is used as a quality measure for hospitalized patients.
However, it has not been studied adequately for patients with advanced liver disease.
Dr Kenneth Berman and colleagues investigated the incidence and factors that predict this rate and its relationship with mortality at 90 days.
The researchers analyzed data from patients with advanced liver disease who were hospitalized to an inpatient hepatology service at 2 large academic medical centers in 2008.
Patients with elective admission and recipients of liver transplants were not included.
The 30-day readmission rate was 20%
Clinical Gastroenterology & Hepatology
During the study period, there were 447 patients and a total of 554 eligible admissions.
Multivariate analyses were performed to identify variables associated with 30-day readmission, and to examine its relationship with mortality at 90 days.
The researchers found that the 30-day readmission rate was 20%.
After the team adjusted for multiple covariates, readmission within 30 days was associated independently with model for end-stage liver disease scores at discharge, the presence of diabetes, and male sex.
After adjusting for age, sex, and model for end-stage liver disease score at discharge, the 90-day mortality rate was significantly higher among patients who were readmitted to the hospital within 30 days than those who were not.
Dr Berman's team concludes, "Patients with advanced liver disease frequently are readmitted to the hospital within 30 days after discharge."
"These patients have a higher 90-day mortality rate than those who are not readmitted in 30 days."
"These data might be used to develop strategies to reduce early readmission of hospitalized patients with cirrhosis."
Clin Gastroenterol Hepatol 2011: 9(3): 254-5903 March 2011
Hepatitis B
Hep B virus in the United States
This month's Annals of Internal Medicine investigates the rates of infection, exposure, and immunity in a nationally representative survey.
Up-to-date estimates of the prevalence of hepatitis B virus (HBV) infection, exposure, and immunity are necessary to assess the effectiveness of ongoing programs aimed at preventing HBV transmission.
Dr George Ioannou from Washington, USA determined the prevalence and associations of chronic hepatitis B virus infection, past exposure, and immunity in the United States from 1999 to 2008.
The research team performed a nationally representative, cross-sectional household survey in a civilian, noninstitutionalized population in the USA.
The researchers evaluated 39,787 participants in the National Health and Nutrition Examination Survey aged 2 years or older.
5% had been exposed to hepatitis B virus
Annals of Internal Medicine
Chronic hepatitis B virus infection was defined by presence of serum HBV surface antigen and past exposure by serum antibody to hepatitis B core antigen among persons aged 6 years or older.
Infant immunity was defined by presence of serum antibody to hepatitis B surface antigen among children aged 2 years.
Among persons aged 6 years or older, 0.3% had chronic Hepatitis B virus infection, and 5% had been exposed to hepatitis B virus.
The researchers noted that these estimates are lower than estimates of hepatitis B virus infection, and exposure in the United States reported from 1988 to 1994.
Infection and past exposure were very uncommon among persons aged 6 to 19 years.
The research team found that children aged 2 years have high rates of immunity.
Adults, including those at high risk for infection, have much lower rates of immunity.
The researchers reported that incarcerated and homeless persons were not sampled.
The team observed that categorization of race or ethnicity did not identify high-risk groups, such as persons of Asian and Pacific Islander descent.
Dr Ioannou's team concludes, "A cohort of children and adolescents is growing up in the United States with high rates of immunity against hepatitis B virus and very low rates of infection."
"Vaccination of high-risk adults should continue to be emphasized."
Ann Int Med 2011: 154(5): 319-32803 March 2011
Kinetics of Hep B surface antigen differ with peginterferon vs entecavir treatment
A study in March's issue of the Journal of Hepatology investigates the kinetics of hepatitis B surface antigen treatment with peginterferon and entecavir.
Dr Jurriën Reijnders and colleagues investigated serum hepatitis B surface antigen levels in patients with chronic hepatitis B virus infection during peginterferon and entecavir monotherapy.
Hepatitis B surface antigen was quantified at baseline and during antiviral therapy in hepatitis B e antigen-positive patients treated with entecavir or peginterferon and in hepatitis B surface antigen-negative patients treated with entecavir or peginterferon.
Within the hepatitis B surface antigen-positive population, patients treated with peginterferon tended to have a steeper hepatitis B surface antigen decline than entecavir-treated patients.
In Hep B surface antigen-negative patients, entecavir did not reduce antigen levels
Journal of Hepatology
The hepatitis B surface antigen decline was larger in those patients who became hepatitis B surface antigen negative, irrespective of the treatment regimen.
The researchers observed that a decline in hepatitis B surface antigen was confined to entecavir-treated patients with elevated baseline alanine aminotransferase levels, whereas hepatitis B surface antigen decline was not associated with baseline ALT in patients treated with peginterferon.
The research team found that within the hepatitis B surface antigen-negative population, peginterferon induced a significant hepatitis B surface antigen decline, while hepatitis B surface antigen did not decrease in entecavir-treated patients.
Both in hepatitis B surface antigen-positive and hepatitis B surface antigen-negative patients, the decline in serum hepatitis B virus DNA was larger in patients who received entecavir as compared to patients treated with peginterferon.
Dr Reijnders' team concludes, "In hepatitis B surface antigen-positive patients, the decline in serum hepatitis B surface antigen is mainly confined to patients who clear hepatitis B surface antigen, by either peginterferon or entecavir treatment."
"In hepatitis B surface antigen-negative patients, peginterferon therapy resulted in a significant reduction in hepatitis B surface antigen levels, whereas these did not decrease in entecavir-treated patients.
http://www.gastrohep.com/news/news.asp?id=107892
HIV
6-month drug regimen cuts HIV risk for breastfeeding infants, NIH study finds
Giving breastfeeding infants of HIV-infected mothers a daily dose of the antiretroviral drug nevirapine for six months halved the risk of HIV transmission to the infants at age 6 months compared with giving infants the drug daily for six weeks, according to preliminary clinical trial data presented today at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston. NIH/National Institute of Allergy and Infectious Diseases
From HIV and Hepatitis
ARIEL: 24-week Safety and Eefficacy of darunavir/ritonavir in Treatment-experienced Pediatric Patients Aged 3 to less then 6>
Pharmacokinetic Parameters of Once-Daily TMC278 Following Administration of Efavirenz in Healthy Volunteers
Lipid profiles of TMC278 and Efavirenz in Ttreatment-naïve, HIV-1-infected Patients: Pooled Week 48 Data from the Randomized, Double-blind, Phase III ECHO and THRIVE Trials
Neurologic and Psychiatric Safety Profile of TMC278 Compared with Eefavirenz in Treatment-naïve, HIV-1-infected Patients: Pooled Analysis from the Randomized, Double-blind, Phase III ECHO and THRIVE Trials at 48 Weeks
Change in Vitamin D Levels Smaller and Risk of Development of Severe Vitamin D Deficiency Lower Among HIV-1-Infected, Treatment-naïve Adults Receiving TMC278 Compared with Efavirenz: 48-week Results from the Phase III ECHO Trial
Chronic Illness
Survey shows patients with rare diseases and their caregivers are avid Internet users
By Lia Steakley
An earlier report by the Pew Internet & American Life Project found searching for health information is the third-most-popular activity on the web. Now new research from the nonprofit shows that when it comes to using the Internet to seek health information and support, one community outpaces all the rest: patients with rare diseases and their caregivers.
Healthy You
From Harvard World Health News
Fatigue Kills
Tom Avril(The Philadelphia Inquirer, February 28, 2011)
"Fatigue is an epidemic in this country, and experts say it is both underrecognized and dangerous -- accounting for more than 20 percent of transportation accidents, by some estimates. And while scientists can tell if a person is too tired to function well, there is no good way to evaluate anyone who can't stop what they're doing to take a test, such as pilots, truck drivers, surgeons, or astronauts. So researchers…are looking for clues."
Toxic or Not?
Karen Weintraub (The Boston Globe, February 28, 2011)
"It’s nearly impossible to prove scientifically that certain diseases are caused by household chemicals…known as endocrine disruptors…The question is how much exposure is too much…Exposures are cumulative…The trouble is no one knows how much each exposure matters. And no one knows how the chemicals might interact with each other, compounding their impact on the body. No one knows in part because chemical companies aren’t required to find out."
My Unhealthy Diet? It Got Me This Far
Henry Alford(The New York Times, February 28, 2011)
"It’s a common belief that life as we know it ends in old age. Gone are the little [culinary] joys that make existence worthwhile…all subsumed under a banner reading, 'Doctor’s Orders.' For older people, the irony of eating is that your metabolism slows down, so you need less food, but your body needs just as many nutrients, if not more. Declining health and the voices of authority only dampen the proceedings further…One trope that comes up often in conversations with older gourmands is that eating what they want is, at their age, a right or privilege."
Many Americans Have Poor Health Literacy
Sandra G. Boodman
(The Washington Post in collaboration with Kaiser Health News,
February 28, 2011)
"Regardless of their literacy skills, patients are expected to manage multiple chronic diseases, to comply with drug regimens that have grown increasingly complicated and to operate sophisticated medical devices…health literacy is the focus of unprecedented attention from government officials, hospitals and insurers who regard it as inextricably linked to implementing the health-care overhaul law and controlling medical costs."
Simultaneous Occurrence of Pleural Effusion and Interstitial Pneumonitis After Treatment With Pegylated Interferon for Hepatitis C Virus Infection
This patient with chronic hepatitis C presented with a rare simultaneous occurrence of pleural effusion and interstitial pneumonitis.
Was pulmonary toxicity induced by interferon therapy?
Southern Medical Journal, March 2011
Abstract and Introduction
Case Report
Discussion
Conclusion
Discussion Only/Click here for Full Data
Although pulmonary complications of interferon (IFN) are rare, the growing number of patients receiving such therapy will undoubtedly lead to an increasing number of patients with pulmonary manifestations, of which IP and sarcoidosis are the most common, while pleural effusion is rare. There are only three cases described to date in the English literature, including our case. The clinical data of the three cases are shown in the Table.
The present case is the second case in which the patient developed pleural effusion and IP during pegylated interferon-α and ribavirin therapy for HCV infection. In this patient's case, it seems highly likely that pegylated interferon-α was responsible for the onset of pulmonary toxicity. All other possible infectious or systemic causes were ruled out; ribavirin had been interrupted at week 12, and the absence of any previous pulmonary history and specificity of the results of the various investigations carried out in the context of the pleural effusion and IP showed a relationship between the pegylated interferon treatment and the onset of complications. We used the causal criteria from the World Health Organization to show the probability of adverse drug reaction.[8]
The cornerstone of management of IFN-induced pulmonary toxicity is to stop the drug immediately.[1] There was convincing evidence that steroids induce an increase of hepatitis C virus replication; whether steroids should be included in the treatment modality remains controversial.[9] Treatment with steroids was not considered initially, since pleural effusion in the other two cases[5,6] and IP in some patients recovered after discontinuation of (pegylated) IFN/ribavirin,[1] the severity of pulmonary injury was of moderate degree, and there was premature cessation of ribavirin, which is correlated with a higher risk of virus relapse. However, methylprednisolone was used due to progressive dyspnea and cough with severe pulmonary injury and subsequent hypoxemia. Steroid therapy caused a dramatic improvement of symptoms and imaging, which suggested that pulmonary toxicity is related to the immunomodulatory reactions of IFN.
HCV Advocate Newsletter, March 2011
In This Issue:
HCV Protease Inhibitor—TMC435: Phase 3 Studies
Alan Franciscus, Editor-in-Chief
Hepatitis C in Egypt
Alan Franciscus, Editor-in-Chief
HCV Snapshots
Lucinda K. Porter, RN
Liver Transplantation: An Overview
Liz Highleyman
HealthWise: The Power Is in Our Hands
Lucinda K. Porter, RNHCV Advocate
Eblast HCV Advocate;
Stay informed on the latest news ..click here to register for email alerts
Three died in one week after organs from same donor
Adrian Lowe March 3, 2011
World's largest online family history resource.+6 billion records
THREE women died within one week of each other after they received diseased organs in transplant procedures at the Austin and Royal Melbourne hospitals, an inquest has heard.
From GastroHep.com
Predictors of readmission with advanced liver disease
The latest issue of Clinical Gastroenterology & Hepatology investigates the incidence and predictors of 30-day readmission among patients hospitalized for advanced liver disease.
The rate of readmission to the hospital 30 days after discharge (30-day readmission rate) is used as a quality measure for hospitalized patients.
However, it has not been studied adequately for patients with advanced liver disease.
Dr Kenneth Berman and colleagues investigated the incidence and factors that predict this rate and its relationship with mortality at 90 days.
The researchers analyzed data from patients with advanced liver disease who were hospitalized to an inpatient hepatology service at 2 large academic medical centers in 2008.
Patients with elective admission and recipients of liver transplants were not included.
The 30-day readmission rate was 20%
Clinical Gastroenterology & Hepatology
During the study period, there were 447 patients and a total of 554 eligible admissions.
Multivariate analyses were performed to identify variables associated with 30-day readmission, and to examine its relationship with mortality at 90 days.
The researchers found that the 30-day readmission rate was 20%.
After the team adjusted for multiple covariates, readmission within 30 days was associated independently with model for end-stage liver disease scores at discharge, the presence of diabetes, and male sex.
After adjusting for age, sex, and model for end-stage liver disease score at discharge, the 90-day mortality rate was significantly higher among patients who were readmitted to the hospital within 30 days than those who were not.
Dr Berman's team concludes, "Patients with advanced liver disease frequently are readmitted to the hospital within 30 days after discharge."
"These patients have a higher 90-day mortality rate than those who are not readmitted in 30 days."
"These data might be used to develop strategies to reduce early readmission of hospitalized patients with cirrhosis."
Clin Gastroenterol Hepatol 2011: 9(3): 254-5903 March 2011
Hepatitis B
Hep B virus in the United States
This month's Annals of Internal Medicine investigates the rates of infection, exposure, and immunity in a nationally representative survey.
Up-to-date estimates of the prevalence of hepatitis B virus (HBV) infection, exposure, and immunity are necessary to assess the effectiveness of ongoing programs aimed at preventing HBV transmission.
Dr George Ioannou from Washington, USA determined the prevalence and associations of chronic hepatitis B virus infection, past exposure, and immunity in the United States from 1999 to 2008.
The research team performed a nationally representative, cross-sectional household survey in a civilian, noninstitutionalized population in the USA.
The researchers evaluated 39,787 participants in the National Health and Nutrition Examination Survey aged 2 years or older.
5% had been exposed to hepatitis B virus
Annals of Internal Medicine
Chronic hepatitis B virus infection was defined by presence of serum HBV surface antigen and past exposure by serum antibody to hepatitis B core antigen among persons aged 6 years or older.
Infant immunity was defined by presence of serum antibody to hepatitis B surface antigen among children aged 2 years.
Among persons aged 6 years or older, 0.3% had chronic Hepatitis B virus infection, and 5% had been exposed to hepatitis B virus.
The researchers noted that these estimates are lower than estimates of hepatitis B virus infection, and exposure in the United States reported from 1988 to 1994.
Infection and past exposure were very uncommon among persons aged 6 to 19 years.
The research team found that children aged 2 years have high rates of immunity.
Adults, including those at high risk for infection, have much lower rates of immunity.
The researchers reported that incarcerated and homeless persons were not sampled.
The team observed that categorization of race or ethnicity did not identify high-risk groups, such as persons of Asian and Pacific Islander descent.
Dr Ioannou's team concludes, "A cohort of children and adolescents is growing up in the United States with high rates of immunity against hepatitis B virus and very low rates of infection."
"Vaccination of high-risk adults should continue to be emphasized."
Ann Int Med 2011: 154(5): 319-32803 March 2011
Kinetics of Hep B surface antigen differ with peginterferon vs entecavir treatment
A study in March's issue of the Journal of Hepatology investigates the kinetics of hepatitis B surface antigen treatment with peginterferon and entecavir.
Dr Jurriën Reijnders and colleagues investigated serum hepatitis B surface antigen levels in patients with chronic hepatitis B virus infection during peginterferon and entecavir monotherapy.
Hepatitis B surface antigen was quantified at baseline and during antiviral therapy in hepatitis B e antigen-positive patients treated with entecavir or peginterferon and in hepatitis B surface antigen-negative patients treated with entecavir or peginterferon.
Within the hepatitis B surface antigen-positive population, patients treated with peginterferon tended to have a steeper hepatitis B surface antigen decline than entecavir-treated patients.
In Hep B surface antigen-negative patients, entecavir did not reduce antigen levels
Journal of Hepatology
The hepatitis B surface antigen decline was larger in those patients who became hepatitis B surface antigen negative, irrespective of the treatment regimen.
The researchers observed that a decline in hepatitis B surface antigen was confined to entecavir-treated patients with elevated baseline alanine aminotransferase levels, whereas hepatitis B surface antigen decline was not associated with baseline ALT in patients treated with peginterferon.
The research team found that within the hepatitis B surface antigen-negative population, peginterferon induced a significant hepatitis B surface antigen decline, while hepatitis B surface antigen did not decrease in entecavir-treated patients.
Both in hepatitis B surface antigen-positive and hepatitis B surface antigen-negative patients, the decline in serum hepatitis B virus DNA was larger in patients who received entecavir as compared to patients treated with peginterferon.
Dr Reijnders' team concludes, "In hepatitis B surface antigen-positive patients, the decline in serum hepatitis B surface antigen is mainly confined to patients who clear hepatitis B surface antigen, by either peginterferon or entecavir treatment."
"In hepatitis B surface antigen-negative patients, peginterferon therapy resulted in a significant reduction in hepatitis B surface antigen levels, whereas these did not decrease in entecavir-treated patients.
http://www.gastrohep.com/news/news.asp?id=107892
HIV
6-month drug regimen cuts HIV risk for breastfeeding infants, NIH study finds
Giving breastfeeding infants of HIV-infected mothers a daily dose of the antiretroviral drug nevirapine for six months halved the risk of HIV transmission to the infants at age 6 months compared with giving infants the drug daily for six weeks, according to preliminary clinical trial data presented today at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston. NIH/National Institute of Allergy and Infectious Diseases
From HIV and Hepatitis
ARIEL: 24-week Safety and Eefficacy of darunavir/ritonavir in Treatment-experienced Pediatric Patients Aged 3 to less then 6>
Pharmacokinetic Parameters of Once-Daily TMC278 Following Administration of Efavirenz in Healthy Volunteers
Lipid profiles of TMC278 and Efavirenz in Ttreatment-naïve, HIV-1-infected Patients: Pooled Week 48 Data from the Randomized, Double-blind, Phase III ECHO and THRIVE Trials
Neurologic and Psychiatric Safety Profile of TMC278 Compared with Eefavirenz in Treatment-naïve, HIV-1-infected Patients: Pooled Analysis from the Randomized, Double-blind, Phase III ECHO and THRIVE Trials at 48 Weeks
Change in Vitamin D Levels Smaller and Risk of Development of Severe Vitamin D Deficiency Lower Among HIV-1-Infected, Treatment-naïve Adults Receiving TMC278 Compared with Efavirenz: 48-week Results from the Phase III ECHO Trial
Chronic Illness
Survey shows patients with rare diseases and their caregivers are avid Internet users
By Lia Steakley
An earlier report by the Pew Internet & American Life Project found searching for health information is the third-most-popular activity on the web. Now new research from the nonprofit shows that when it comes to using the Internet to seek health information and support, one community outpaces all the rest: patients with rare diseases and their caregivers.
Healthy You
From Harvard World Health News
Fatigue Kills
Tom Avril(The Philadelphia Inquirer, February 28, 2011)
"Fatigue is an epidemic in this country, and experts say it is both underrecognized and dangerous -- accounting for more than 20 percent of transportation accidents, by some estimates. And while scientists can tell if a person is too tired to function well, there is no good way to evaluate anyone who can't stop what they're doing to take a test, such as pilots, truck drivers, surgeons, or astronauts. So researchers…are looking for clues."
Toxic or Not?
Karen Weintraub (The Boston Globe, February 28, 2011)
"It’s nearly impossible to prove scientifically that certain diseases are caused by household chemicals…known as endocrine disruptors…The question is how much exposure is too much…Exposures are cumulative…The trouble is no one knows how much each exposure matters. And no one knows how the chemicals might interact with each other, compounding their impact on the body. No one knows in part because chemical companies aren’t required to find out."
My Unhealthy Diet? It Got Me This Far
Henry Alford(The New York Times, February 28, 2011)
"It’s a common belief that life as we know it ends in old age. Gone are the little [culinary] joys that make existence worthwhile…all subsumed under a banner reading, 'Doctor’s Orders.' For older people, the irony of eating is that your metabolism slows down, so you need less food, but your body needs just as many nutrients, if not more. Declining health and the voices of authority only dampen the proceedings further…One trope that comes up often in conversations with older gourmands is that eating what they want is, at their age, a right or privilege."
Many Americans Have Poor Health Literacy
Sandra G. Boodman
(The Washington Post in collaboration with Kaiser Health News,
February 28, 2011)
"Regardless of their literacy skills, patients are expected to manage multiple chronic diseases, to comply with drug regimens that have grown increasingly complicated and to operate sophisticated medical devices…health literacy is the focus of unprecedented attention from government officials, hospitals and insurers who regard it as inextricably linked to implementing the health-care overhaul law and controlling medical costs."
Off The Cuff
From Parmalot
By Ed Silverman // March 2nd, 2011 //
Some of the biggest drugmakers do not have a good track record when it comes time for FDA inspectors to visit their plants. Overall, the FDA found violations at 54 percent of plants inspected last year, up 20 percent from a decade low in 2007, according to data obtained from the agency by Bloomberg News
By Ed Silverman // March 2nd, 2011 // 7:02 pm
The sutures are marketed under various brand names - Ethilon, Ethibond, Mersilene and Mersilk - and are used to close surgical incisions and wounds. Some of the products in the 140 lots that were recalled may not have been sealed properly, posing a risk that they could become infected, according to the notice, which you can read here. J&J tells the Associated Press that the problem was caused by “modifications of manufacturing equipment” that have since been corrected. We await a comment concerning any patients who may have been harmed.
UPDATE: A J&J Ethicon spokeswoman wrote us to say there were no adverse events reported.
Six Biggest Gripes of Employed Doctors
Medscape BuVictoria Rentel, a family physician in Columbus, Ohio, joined a hospital-owned group several years ago. At first, nearly everything went fine. There were a few glitches: she'd occasionally order tests or consults at competing facilities, either for patient convenience or because of health plan coverage. When the hospital's administrators found out, they told her it was a violation of her contract; but that didn't stop her because she knew the hospital never enforced this provision.siness of Medicine, March 2, 2011
Medscape BuVictoria Rentel, a family physician in Columbus, Ohio, joined a hospital-owned group several years ago. At first, nearly everything went fine. There were a few glitches: she'd occasionally order tests or consults at competing facilities, either for patient convenience or because of health plan coverage. When the hospital's administrators found out, they told her it was a violation of her contract; but that didn't stop her because she knew the hospital never enforced this provision.siness of Medicine, March 2, 2011
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