Associations of chronic hepatitis C with metabolic and cardiac outcomes

Associations of chronic hepatitis C with metabolic and cardiac outcomes

Z. M. Younossi1,2,*, M. Stepanova1, F. Nader1, Z. Younossi2, E. Elsheikh1

Article first published online: 5 FEB 2013 DOI: 10.1111/apt.12234

© 2013 Blackwell Publishing Ltd Alimentary Pharmacology & Therapeutics

Early View (Online Version of Record published before inclusion in an issue)

 

Background

Chronic hepatitis C virus (CH-C) infection is associated with metabolic conditions such as insulin resistance and type 2 diabetes (DM) and may increase the risk of cardiovascular diseases.

Aim

To assess the association of CH-C with risk factors for cardiovascular diseases using US population data.

Methods

The National Health and Nutrition Examination Surveys (NHANES) collected between 1999 and 2010 were used.
 
Results

A total of 19 741 participants were considered eligible for the study. Of this cohort, 173 individuals (0.88%) had detectable HCV RNA and were considered to have CH-C. Compared with controls, CH-C patients were predominantly African American (23.5% vs. 10.5%, P < 0.0001), men (66.6% vs. 46.1%, P = 0.0001), more likely to be between 45 and 55 years of age (41.9% vs. 20.4%, P = 0.0001), had higher rate of insulin resistance (44.1% vs. 31.1%, P = 0.0301), hypertension (40.1% vs. 28.9%, P = 0.0201), and history of smoking (76.2% vs. 29.9%, P < 0.0001). In multivariate analysis, in addition to known risk factors for insulin resistance, CH-C was independently associated with the presence of insulin resistance [OR (95% CI) = 2.06 (1.19–3.57)], DM [OR = 2.31 (1.18–4.54)] and hypertension [OR = 2.06 (1.30–3.24)]. In addition, independent predictors of cardiovascular diseases included older age, presence of obesity and smoking. Furthermore, CH-C was independently associated with congestive heart failure subtype of cardiovascular diseases but not ischaemic heart disease and stroke.

Conclusions

Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes and hypertension) and congestive heart failure.

Introduction

Hepatitis C virus (HCV) is the most common cause of cirrhosis and hepatocellular carcinoma in the United States.[1, 2] In addition, HCV is associated with a number of important extrahepatic manifestations.[3] Of these, there is increasing evidence that HCV infection increases the risk for type 2 diabetes (DM) and insulin resistance (IR). In fact, previous data indicated that in individuals older than 39 years of age, HCV infection increases the risk of DM by almost 4 times.[4] In addition, in longitudinal studies, development of DM has been reported to be 11 times more common in those infected with HCV than those who were not.[5] Although the association of HCV with DM has been confirmed, its underlying mechanism remains unknown. Some of these mechanisms include direct interaction of HCV proteins with the hepatocyte insulin signalling cascade[6-8] or impairment of pancreatic β-cell function.[9] In addition, recent evidence suggests involvement of the striated muscle in the pathogenesis of IR in patients with CH-C.[10]
 

The consequences of IR and DM in HCV-infected patients can be divided into those that affect liver disease outcomes and those affecting nonliver related outcomes.[11] HCV patients with DM or IR tend to have more advanced hepatic fibrosis, hepatocellular carcinoma and lower efficacy of treatment regimens.[12] In addition to metabolic conditions (DM and IR), HCV has also been associated with arthrosclerosis and coronary artery disease.[13-15] Although HCV and its contribution to DM and IR can explain some of these associations, the exact underlying mechanism of how CH-C can predispose to cardiovascular complications remains unknown. The aim of this study was to assess the independent association of HCV with metabolic conditions (DM, IR, hypertension and hyperlipdaemia) as well as cardiovascular complications using a large population-representative sample.

Methods
Study sample

Our study uses the data derived from the National Health and Nutrition Examination Survey (NHANES), a nationwide survey that represents the health and nutritional status of the of the non-institutionalised civilian US population. The data were collected by the US National Center for Health Statistics (NCHS) with the Centers for Disease Control and Prevention (CDC), and it is currently publicly available. Detailed description of NHANES study design and methods are available elsewhere.[16] For the purpose of the study, we used six cycles of continuous NHANES collected between 1999 and 2010. These surveys were based on similar questionnaires and similar methods for serum and blood assays.
 

The NHANES participants were included in the study if they were age of 18 years or older, had complete demographic and relevant clinical data including HCV serologic tests and completed questionnaires with history of cardiovascular diseases. Additional data used in the study included body mass index (BMI), waist circumference and blood pressure which were measured at the time of examination by the NHANES representatives for all eligible participants. The data from a number of questionnaires and laboratory tests were also used for our study, namely, alcohol consumption and smoking history, fasting serum glucose and insulin, HDL cholesterol, LDL cholesterol and total cholesterol, AST, ALT, transferrin saturation and serologic tests for HBV (hepatitis B surface antigen, or HBsAg) and HCV (anti-HCV by ELISA followed by HCV RNA by PCR for HCV positive or indeterminate samples). Participants with insufficient data for ruling in HCV infection or ruling out chronic liver disease were excluded from the study.

Study definitions

Definitions for metabolic conditions used in the study have been previously described.[17] Briefly, insulin resistance was defined as HOMA score greater than 3.0, type II diabetes was defined as fasting blood glucose of greater than 125 mg/dL or the use of hypoglycaemic agents, and hypertension was defined as blood pressure (average of four readings) of greater than 140/90 mmHg or the use of antihypertensive medications. Furthermore, obesity (BMI ≥ 30.0) and visceral obesity (waist circumference greater than 102 cm in men or 88 cm in women) were also evaluated for all eligible participants.
 

The history of cardiovascular disease was established using a medical conditions questionnaire where NHANES participants were asked about a number of chronic conditions and if they were ever diagnosed by a healthcare provider. For the purpose of the study, ischaemic heart disease (IHD) was defined as self-reported history of coronary artery disease or heart attack. Furthermore, the history of stroke and congestive heart failure was also collected for eligible participants, and these two conditions together with IHD, as defined above, were used to establish the diagnosis of cardiovascular diseases (CVD).
 

Smoking was defined as ongoing smoking (a question SMQ040 ‘Do you now smoke cigarettes?’ answered either ‘Every day’ or ‘Some days’) and given a total number of cigarettes smoked in life exceeds one hundred. The data were collected from the Smoking and Tobacco Use questionnaire during NHANES data collection.

Chronic HCV infection

All sera from NHANES participants were tested for antibody to hepatitis C virus (anti-HCV). Sera testing positive for anti-HCV were tested further for HCV RNA. Participants with positive HCV RNA were considered to have chronic hepatitis C (CH-C). On the other hand, individuals without any evidence of chronic liver disease such as excessive alcohol consumption (defined as self-reported consumption of >20 g/day for at least a year for men, and >10 g/day for women), elevated aminotransferases (ALT > 40 U/L or AST > 37 U/L for men, AST and ALT > 31 U/L for women), elevated transferrin saturation (>50%), HBV infection (positive HBsAg) were presumed not to have chronic liver disease and were further used as controls. Patients with presumed non-alcoholic fatty liver disease (elevated liver enzymes with no evidence of other liver diseases or excessive alcohol consumption), were also excluded. Participants with data insufficient to rule-in HCV infection or rule-out CLD were excluded from the study.

Statistical analysis

The prevalence of various clinical parameters, including CVD, its subtypes and metabolic conditions, was compared between those with and without HCV infection using the stratum-specific chi-squared test for independence. Furthermore, logistic regression was used to identify independent predictors of CVD and its risk factor while adjusting for potential clinical and demographic confounders. P value <0.05 was selected to identify potentially statistically significant associations.
 

For the purpose of the study, all sampling errors were calculated by Taylor linearisation. Sampling weights calculated for each NHANES participant were used to account for nonresponse and unequal selection probabilities, so, after weighing, the study cohort is designed to be representative of the US population. Furthermore, stratification and sampling units that describe the design stages of the NHANES data collection were used to account for the complex, multi-stage probability sample design of these data. According to the NHANES Analytic and Reporting Guidelines,[16] when merging several analytic cycles, adjustment coefficients were applied to all sampling weights. All analyses were run using standalone sudaan 10.0 (SAS Institute Inc., Cary, NC, USA). The study was granted an exemption from full review by Inova Institutional Review Board (VA, USA).

Results

From NHANES 1999–2010, 19 741 individuals were considered eligible for the study. Of the study cohort, 173 (0.88%) individuals tested positive for HCV RNA and were presumed to have CH-C, and 19 568 had no evidence of chronic liver disease and, therefore, were used as controls.

The results of pairwise comparison of the CH-C cohort to controls without liver disease are summarised in Table 1. Expectedly, individuals with hepatitis C were less likely to be Caucasian (62.0% vs. 72.5%, P = 0.0202) and more likely to be African American (23.5% vs. 10.5%, P < 0.0001), predominantly men (66.6% vs. 46.1%, P = 0.0001), more likely to be between 45 and 55 years of age (41.9% vs. 20.4%, P = 0.0001) and less likely to be older than 65 (3.70% vs. 14.5%, P < 0.0001). Of the metabolic conditions known to be associated with increased cardiac risks, insulin resistance and hypertension were observed significantly more frequently in those with CH-C (44.1% vs. 31.1%, P = 0.0301 and 40.1% vs. 28.9%, P = 0.0201 respectively) (Table 1). The rate of smoking in the CH-C cohort was also significantly higher (76.2% vs. 29.8%, P < 0.0001).

Table 1. Comparison of CH-C cohort and controls without chronic liver disease
 

	CH-C	Controls	P
Caucasian, %	62.04 ± 4.91	72.55 ± 1.59	0.0202
African American, %	23.51 ± 3.66	10.50 ± 0.86	<0.0001
Non-Mexican Hispanic, %	4.78 ± 1.98	4.96 ± 0.67	0.9192
Mexican American, %	6.66 ± 1.85	7.01 ± 0.73	0.8472
Male, %	66.58 ± 4.56	46.06 ± 0.37	0.0001
Age <45, %	43.72 ± 5.68	51.91 ± 0.76	0.1408
Age 45–55, %	41.89 ± 5.42	20.40 ± 0.51	0.0001
Age 55–65, %	10.70 ± 2.13	13.23 ± 0.42	0.2582
Age >65, %	3.70 ± 1.61	14.46 ± 0.43	<0.0001
Obesity, %	22.95 ± 4.20	29.97 ± 0.62	0.1147
Visceral obesity, %	47.11 ± 4.88	48.53 ± 0.73	0.7788
Insulin resistance, %	44.10 ± 5.87	31.13 ± 0.86	0.0301
Type II diabetes, %	12.66 ± 3.50	7.36 ± 0.26	0.1354
Hypercholesterolaemia, %	58.08 ± 5.20	66.96 ± 0.59	0.1079
Hypertension, %	40.09 ± 4.76	28.91 ± 0.60	0.0201
Excessive alcohol, %	6.50 ± 2.49	8.38 ± 0.32	0.4465
Smoking, %	76.23 ± 4.92	29.85 ± 0.80	<0.0001

Older age is known to be a major contributor to the risk of cardiovascular disease. At the same time, the CH-C cohort was found to be significantly younger than average for the population: only 3.70% of those actively infected with HCV were 65 years old or older, compared to 14.46% in controls (P < 0.0001). To better separate the impact of age to the risk of CVD from that of CH-C, we evaluated the association of CH-C and CVD in different age groups separately (Table 2). A significantly higher rate of congestive heart failure (CHF) in HCV-infected individuals was found for those of 64 years of age or younger: 3.84 ± 1.50% vs. 0.89 ± 0.08% in controls of the same age, P = 0.0467. Other cardiovascular diseases were not different between those with and without HCV in all studied age groups (data not shown). Furthermore, since the rate of smoking, was found to be significantly higher in those with CH-C, we also studied smoking and nonsmoking CH-C cohorts separately. In these two separate rounds of analysis, no association of CH-C with CVD or its subtypes was found as well (all P > 0.05, data not shown).
 

Table 2. Cardiovascular diseases and CH-C according to age groups (<65 and >65)
 

	CH-C	Controls	P
Age group <65
Cardiovascular diseases	6.01 ± 1.87	3.96 ± 0.20	0.2622
Congestive heart failure	3.84 ± 1.50	0.89 ± 0.08	0.0467
Ischaemic heart disease	1.97 ± 1.04	2.89 ± 0.17	0.3889
Stroke	1.51 ± 0.68	1.14 ± 0.11	0.5913
Age group ≥65
Cardiovascular diseases	17.54 ± 12.34	24.27 ± 0.90	0.6236
Congestive heart failure	1.18 ± 1.22	6.40 ± 0.45	0.0735
Ischaemic heart disease	15.18 ± 12.01	17.82 ± 0.80	0.8322
Stroke	1.19 ± 1.28	7.14 ± 0.50	0.0720 Independent predictors of metabolic conditions and cardiovascular diseases

In multivariate analysis, after adjustment for other major contributors metabolic conditions such as older age, obesity and non-Caucasian race or ethnicity, CH-C was found to be independently associated with type II diabetes [OR (95% CI) = 2.90 (1.35–6.19)], hypertension [OR = 2.01 (1.18–3.41)] and insulin resistance [OR = 2.20 (1.16–4.17)] (Table 3), and similar associations were observed when smoking and nonsmoking cohorts were studied separately (data not shown).

Table 3. Independent predictors of insulin resistance, type II diabetes and hypertension in the US population without chronic liver disease other than CH
-C [OR (95% CI)]
 

Predictor	Type II diabetes	Insulin resistance	Hypertension
CH-C	2.31 (1.18–4.54)	2.06 (1.19–3.57)	2.06 (1.30–3.24)
Caucasian race	0.46 (0.39–0.53)	0.62 (0.54–0.72)	Not significant
African American race	Not significant	Not significant	2.33 (2.04–2.65)
Age, per year	1.06 (1.05–1.06)	1.01 (1.01–1.02)	1.09 (1.09–1.09)
Obesity	3.52 (3.00–4.12)	6.64 (5.80–7.60)	2.62 (2.36–2.92)
Hypercholesterolaemia	1.20 (1.01–1.44)	1.88 (1.64–2.15)	1.32 (1.16–1.51)
Excessive alcohol	0.60 (0.42–0.85)	0.62 (0.48–0.79)	1.41 (1.18–1.68)

In multivariate analysis, CH-C was also independently associated with congestive heart failure [OR (95% CI) = 2.49 (1.04–5.96)] after controlling for age, obesity and smoking. No other independent association between CH-C and overall CVD diagnosis or other subtypes of CVD (IHD and Stroke) could be established (Table 4).
 

Table 4. Independent predictors of cardiovascular disease in the US population without chronic liver disease other than CH-C [OR (95% CI)]
 

Predictor	CVD	CHF	IHD	Stroke
a P < 0.05.
CH-C	0.93 (0.47–1.81)	2.49 (1.04–5.96)a	0.53 (0.20–1.40)	0.58 (0.16–2.02)
Age, per year	1.08 (1.08–1.09)a	1.08 (1.07–1.09)a	1.08 (1.08–1.09)a	1.07 (1.06–1.08)a
Obesity	1.64 (1.37–1.96)a	1.86 (1.39–2.50)a	1.40 (1.11–1.77)a	1.88 (1.40–2.51)a
Smoking	2.31 (1.85–2.90)a	1.92 (1.34–2.77)a	2.48 (1.93–3.18)a	2.16 (1.58–2.94)a

Discussion

This study assesses the association of CH-C with metabolic conditions and cardiovascular diseases using a general population database. Our study shows that CH-C is independently associated with three important metabolic conditions: IR, DM and hypertension. Although the association of HCV with IR and DM has been previously reported,[18-24] the association of HCV with hypertension is a novel finding.[3, 4] In fact, in one of our previous population-based studies,[21] we reported that the association of HCV with IR and DM might have been attenuated in the last decade by the epidemics of obesity. In this study, having a larger sample from additional NHANES cycles, we confirm that the association between HCV and IR/DM, in fact, remains significant and strong at the population level.

These associations have been shown to be related both to the host factors as well as viral factors. In fact, HCV has been shown to affect glucose-insulin homeostasis as well as lipid metabolism and lipid synthesis.[7-12, 18] In addition, viral factors such as HCV genotypes and HCV core protein can have a direct impact on these interactions.[12] These are significant evidence to support the notion that HCV predisposes patients to insulin resistance and possibly other metabolic abnormalities with their potential consequences such as cardiovascular diseases.[22]
 

In addition to an increased risk for metabolic conditions, our data show that CH-C is also independently associated with an important subtype of cardiovascular disease, congestive heart failure. This association was present after controlling for important confounders associated with both metabolic conditions as well as cardiovascular diseases, namely, age, smoking and obesity. Although previous studies have suggested an increased risk of carotid atherosclerosis in patients with CH-C,[22-25] the most important association between HCV and coronary artery disease (CAD) has been reported in the HIV/HCV co-infected cohort.[26] In fact, another study reported that the risk of acute myocardial infarction in patients with CH-C was not increased.[27] However, other recent studies have suggested evidence for myocardial injury and left ventricular systolic and diastolic dysfunction in patients with CH-C.[28-30]
 

Our findings may have important clinical and public health implications. It is estimated that about 4 million people are infected with CH-C in the United States and over 130 million people are infected worldwide. The vast majority of CH-C patients have not yet been diagnosed and remain untreated. In the United States, the highest prevalence of HCV infection is in the so called ‘Baby Boomers’.[31] As this group gets older, the burden of HCV-related complications is expected to increase tremendously.[1] In addition, we believe that the metabolic and cardiovascular complications of HCV can add to this tremendous clinical and economic burden, potentially making CH-C one of the most important chronic diseases for the next few decades.
 

The main weakness of our study is the lack of follow-up for the target cohort. Since the majority of HCV-infected individuals are still younger than 65 years and therefore are relatively healthy, we may not be able to explicitly appreciate the association of metabolic and cardiovascular conditions with HCV given the low overall rate of these conditions in the predominantly middle-aged CH-C population. However, we believe that with ageing of the target CH-C population, it may become possible to highlight the impact of HCV infection to the natural history of CVD with higher significance and impact. Furthermore, we used self-reports which may have led to underestimation of the true rate of CVD in patients with CH-C and controls. However, the systematic data collection for both CH-C and the controls was the same which should minimise any real bias towards one group. Also, the study is based on a large sample representative of the non-institutionalised US population which contains extensive clinical and laboratory data collected and presented in a standardised form. Finally, our study definition may have underestimated the true prevalence of NAFLD. Despite these limitations, the study uses a very systematic approach at the population level to assess these potential associations.
 

In summary, our study confirms an association between HCV and DM and IR. In addition, it shows an association between HCV and hypertension. Furthermore, our study suggests that HCV patients are at increased risk for congestive heart failure. All of these findings emphasise the importance of assessing the true impact of HCV not only for its hepatic complications but also for its extra-hepatic manifestations.

Authorship

Guarantor of the article: Dr Zobair Younossi.

Author contributions: All authors contributed to the design of the study, data interpretation, manuscript review, editing and approved the final version of the manuscript.

Acknowledgement

 

Declaration of personal and funding interests: None.

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Ira Jacobson, MD: "Hepatitis C: Present Management and Future Directions”--Video

Ira Jacobson, MD: "Hepatitis C: Present Management and Future Directions”--Video

Department of Medicine Division of Gastroenterology presents:
January 29, 2013

"Hepatitis C: Present Management and Future Directions"
Ira Jacobson, MD

Chief of the Division of Gastroenterology and Hepatology
Vincent Astor Distinguished Professor of Medicine
The Joan Sanford I. Weill Medical College of Cornell University
Dr. Jacobson reviewed the history of treatment of chronic hepatitis C and, specifically, the role of interferon (IFN) and ribavirin as cornerstones of therapy for the past twenty years. He spent the remainder of his time noting the recent landmark studies showing improved cure, or sustained virologic response (SVR), with new protease inhibitors combined with IFN and ribavirin as well as shortened duration of treatment. He also noted recent studies showing promise with new agents that are non-inferior to current optimal therapy and may obviate the need for IFN/ribavirin-based therapies and the general optimism that a cure hepatitis C may soon be widely attainable.

View Presentation-
http://medicine.med.nyu.edu/education/grand-rounds/mgr-ira-jacobson-md-video

Related - Watch: Hepatitis C Management - Professor Ira M Jacobson

Watch: Hepatitis C Management - Professor Ira M Jacobson

ViralHepatitisTV

Published on Feb 7, 2013

Professor Jacobson considers the evolution of hepatitis C therapy.

 Related - Ira Jacobson, MD: "Hepatitis C: Present Management and Future Directions”--Video

 

Hepatitis C Virus Diversity and Hepatic Steatosis

Journal of Viral Hepatitis

 

Hepatitis C Virus Diversity and Hepatic Steatosis

 

P. Roingeard

J Viral Hepat. 2013;20(2):77-84
.
Abstract and Introduction
Abstract
Hepatitis C virus (HCV) infection is closely associated with lipid metabolism defects throughout the viral lifecycle, with hepatic steatosis frequently observed in patients with chronic HCV infection. Hepatic steatosis is most common in patients infected with genotype 3 viruses, possibly due to direct effects of genotype 3 viral proteins. Hepatic steatosis in patients infected with other genotypes is thought to be mostly due to changes in host metabolism, involving insulin resistance in particular.
Specific effects of the HCV genotype 3 core proteins have been observed in cellular models in vitro: mechanisms linked with a decrease in microsomal triglyceride transfer protein activity, decreases in the levels of peroxisome proliferator-activating receptors, increases in the levels of sterol regulatory element-binding proteins, and phosphatase and tensin homologue downregulation. Functional differences between the core proteins of genotype 3 viruses and viruses of other genotypes may reflect differences in amino acid sequences. However, bioclinical studies have failed to identify specific 'steatogenic' sequences in HCV isolates from patients with hepatic steatosis. It is therefore difficult to distinguish between viral and metabolic steatosis unambiguously, and host and viral factors are probably involved in both HCV genotype 3 and nongenotype 3 steatosis.

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Molecular Mechanisms of HCV-induced Steatosis

HCV and Insulin Resistance

HCV Sequences Involved in Steatosis

Other Potential Links Between HCV Genotype 3 and Hepatic Steatosis

Conclusion

Noninvasive fibrosis markers predictive of cardiovascular death in NAFLD patients

Updates @ Healio

Noninvasive fibrosis markers predictive of cardiovascular death in NAFLD patients
February 7, 2013

Advanced fibrosis, as indicated by noninvasive markers, is associated with increased risk for cardiovascular-related death among patients with nonalcoholic fatty liver disease, according to recent results.

Researchers evaluated data from 11,154 patients enrolled in the 1988-1994 National Health and Nutrition Examination Survey (NHANES III), with follow-up through 2006. Incidence and severity of nonalcoholic fatty liver disease (NAFLD) within the cohort were identified, along with mortality rates.
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TACE-RFA superior to RFA alone for patients with HCC
February 6, 2013

Peng Z. J Clin Oncol. 2012:doi:10.1200/JCO.2012.42.9936.

The addition of transcatheter arterial chemoembolization to radiofrequency ablation extended survival in patients with hepatocellular carcinoma, according to results of a prospective randomized study.

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Current Issue - Infectious Disease News

FISSION Study Should Support Regulatory Approval For Gilead's Hepatitis C Drug

Related @ HIV and Hepatitis
Feb 6 - Sofosbuvir Combos Match or Beat Standard Hepatitis C Therapy For All Genotypes

Press Release
Feb 4 - Gilead Announces SVR Rates from Two Phase 3 Studies of Sofosbuvir (GS-7977) for Hepatitis C

Investment commentary

FISSION Study Should Support Regulatory Approval For Gilead's Hepatitis C Drug

By Amit Cohen

Gilead Sciences (GILD) is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide.

On Monday, Gilead announced positive top‐line results from two Phase III studies (FISSION and NEUTRINO) that involve the use of sofosbuvir in combination with other agents for use in treatment‐naïve patients infected with the Hepatitis C virus (HCV).

The FISSION study enrolled approximately 500 treatment-naïve patients with HCV genotype 2 or 3 (at a 1:3 ratio) and evaluated the safety and efficacy of 12 weeks of GS-7977 + RBV vs. 24 weeks of PEG-IFN and RBV. The primary endpoint of the trial is SVR12 (sustained viral response at week 12 after treatment is completed). FISSION was a non-inferiority trial in which the bottom end of the 95% confidence interval of sofosbuvir's SVR rate had to be within 15% of the SVR rate of PEG-IFN. With the weakest part of sofosbuvir's profile being its activity in GT 3 patients, and a 3:1 ratio of GT 3 vs GT 2 in the study, there was some chance that the noninferiority margin could have been missed. In fact, the expectations for FISSION had come down significantly after the release of POSITRON data during Q4:12. In POSITRON sofosbuvir + RBV produced SVR rates of 93% in genotype 2 patients and 61% in genotype 3 patients....

Continue reading @ Seeking Alpha Page one, Page two

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CDC Recommends that Groups Get Tested For Hepatitis C

HARRISONBURG, Va. -- Doctors say Hepatitis C is a virus you may not know you have because often there are no symptoms. According to the Centers for Disease Control and Prevention, it can cause everything from liver damage to death. The CDC recommends that if you were born between 1945 to 1965, you should consider getting tested for the virus. Doctor Ganesh Kini, the Medical Director at RMH, said some of the reasons for that include certain hazards during blood transfusions thirty years ago... Continue Reading...

New Patient Focused Website - Liver Cancer Connect

Launch of New Patient-Focused Website at LiverCancerConnect.org.

To provide accurate, easy-to-understand information to people diagnosed with liver cancer, the Hepatitis B Foundation has created the first patient-focused website, www.LiverCancerConnect.org.

The website aims to help people better understand how liver cancer is diagnosed and how it can be treated or prevented.  In addition, wwwLiverCancerConnect.org includes a Drug Watch of potential new liver cancer therapies, an expanding directory of liver cancer specialists, and a clinical trials listing.

Read More @ Hepatitis B Foundation

The Foundation invites you to use www.LiverCancerConnect.org to learn about liver cancer and its treatment options, and to locate liver cancer specialists and clinical trials. We welcome your feedback and suggestions at connect@livercancerconnect.org so that we may continue to build on this valuable resource for the global liver cancer community.

Liver Cancer Connect is available on Facebook and Twitter. Join LCC on Facebook at http://www.facebook.com/LiverCancerConnect and follow LCC on twitter with the handle @LiverCancerConn.

Some Omega-3 Oils Better Than Others for Protection Against Liver Disease

Some Omega-3 Oils Better Than Others for Protection Against Liver Disease

Feb. 5, 2013 — Research at Oregon State University has found that one particular omega-3 fatty acid has a powerful effect in preventing liver inflammation and fibrosis -- common problems that are steadily rising along with the number of Americans who are overweight.

The American Liver Foundation has estimated that about 25 percent of the nation's population, and 75 percent of those who are obese, have nonalcoholic fatty liver disease. This early-stage health condition can sometimes progress to more serious, even fatal diseases, including nonalcoholic steatohepatitis, or NASH, as well as cirrhosis and liver cancer.

The study, published online in the Journal of Nutrition, was one of the first to directly compare the effects of two of the omega-3 fatty acids often cited for their nutritional value, DHA and EPA.
In research with laboratory animals, it found that EPA had comparatively little effect on preventing the fibrosis, or scarring, that's associated with NASH. However, DHA supplementation reduced the proteins involved in liver fibrosis by more than 65 percent.

"A reduction of that magnitude in the actual scarring and damage to the liver is very important," said Donald Jump, a principal investigator with the Linus Pauling Institute at OSU and a professor in the College of Public Health and Human Sciences.

"Many clinical trials are being done with omega-3 fatty acids related to liver disease," Jump said. "Our studies may represent the first to specifically compare the capacity of EPA versus DHA to prevent NASH. It appears that DHA, which can also be converted to EPA in the human body, is one of the most valuable for this purpose."

The issues have taken center stage as the weight of Americans continues to rise, with a related increase in the incidence of fatty liver disease and liver damage.

NASH is a progressive form of liver disease that is associated with chronic inflammation and oxidative stress, resulting from excess fat storage in the liver. Chronic inflammation can eventually lead to fibrosis, cirrhosis, or even liver cancer. While management of lifestyle, including weight loss and exercise, is one approach to control the onset and progression of fatty liver disease, other approaches are needed to prevent and treat it.

About 30-40 percent of people with nonalcoholic fatty liver disease progress to NASH, which in turn can result in cirrhosis, a major risk factor for liver cancer. While this research studied the prevention of fatty liver disease, Jump said, ongoing studies are examining the capacity of DHA to be used in NASH therapy.

The levels of omega-3 oils needed vary with the health concern, officials say.

"Omega-3 fatty acids are typically recommended for the prevention of cardiovascular disease," Jump said. "Recommended intake levels of omega-3 fatty acids in humans for disease prevention are around 200-500 milligrams of combined DHA and EPA per day."

Levels used in therapy to lower blood triglycerides, also a risk factor for cardiovascular disease, are higher, about 2-4 grams of combined EPA and DHA per day. The OSU studies with mice used DHA at levels comparable to the triglyceride therapies.

"DHA was more effective than EPA at attenuating inflammation, oxidative stress, fibrosis and hepatic damage," the researchers wrote in their conclusion. "Based on these results, DHA may be a more attractive dietary supplement than EPA for the prevention and potential treatment of NASH in obese humans."

This work was the result of a four-year study supported by the USDA National Institute of Food and Agriculture, as well as the National Institutes of Health. Co-authors on the paper included Christopher M. Depner and Kenneth A. Philbrick, both graduate students in the Nutrition Graduate Program at OSU.

http://www.sciencedaily.com/releases/2013/02/130205123758.htm

Hemorrhagic ascites leads to worse outcomes in cirrhotic patients

Hemorrhagic ascites leads to worse outcomes in cirrhotic patients

Urrunaga NH. J Hepatol. 2013;doi:10.1016/j.jhep.2013.01.015.

 February 6, 2013

The presence of hemorrhagic ascites is predictive of poor outcome in patients with cirrhosis, according to recent results.In a retrospective case-control study, researchers evaluated the records of 1,113 patients with cirrhosis and ascites who received paracentesis at a single hospital between 2003 and 2010. Hemorrhagic ascites (HA) was identified in 214 cases, and outcomes within this group were compared with those of 642 matched controls with cirrhosis and ascites.
 

HA was most frequently spontaneous, with hepatocellular carcinoma (HCC) and iatrogenic causes occurring next most commonly. Spontaneous HA was significantly more common among those with ascitic fluid red blood cell counts between 10,000 mcL and 50,000 mcL (72%) than those with 50,000 mcL or more (52%; P=.003 for difference). Patients with HA related to HCC had significantly poorer survival rates than those with HA from other causes (P=.001).

HA participants were more likely to experience acute kidney injury (P<.001), sepsis (P<.01) and spontaneous bacterial peritonitis (P<.001), and also required transfusion (P<.001), vasopressors (P<.001) and ICU-level care more frequently (P=.001) than controls. Median albumin (2.5 g/dL vs. 2.8 g/dL; P<.01) and hemoglobin levels (10.2 g/dL vs. 11.2 g/dL; P<.001) were significantly lower compared with controls, while median MELD score (18 vs. 16; P<.001), bilirubin (3.0 mg/dL vs. 2.5 mg/dL; P=.04) and creatinine (1.1 mg/dL vs. 1 mg/dL; P=.004) were higher.

Patients with HA had higher mortality rates at 1 month (87% compared with 72%), 1 year (72% vs. 50%) and 3 years (61% vs. 41%), and a shorter median survival time than controls (1 year vs. 5.6 years). Multivariate analysis indicated an independent association between mortality and HA (HR=1.34; 95% CI, 1.07-1.68), after adjusting for other predictors including MELD score, ICU-level care, hepatitis C infection and HCC.

Don C. Rockey

“Patients with hemorrhagic ascites have poorer outcomes than those without hemorrhagic ascites,” researcher Don C. Rockey, MD, Department of Internal Medicine, Medical University of South Carolina, told Healio.com. Rockey and colleagues suggested that HA and other well-defined clinical features should be included in an improved prognostic score for this patient population.

http://www.healio.com/hepatology/cirrhosis-liver-failure/news/online/%7B7BA83759-DB97-4702-B2CF-26D131C0809D%7D/Hemorrhagic-ascites-leads-to-worse-outcomes-in-cirrhotic-patients

Antioxidant and Anti-Hepatitis C Viral Activities of Commercial Milk Thistle Food Supplements

Antioxidant and Anti-Hepatitis C Viral Activities of Commercial Milk Thistle Food Supplements

Kevin Anthony 1 , Gitanjali Subramanya 2,† , Susan Uprichard 2,† , Faiza Hammouda 3 and Mahmoud Saleh 1,*

1 Department of Chemistry, Texas Southern University, Houston, TX 77004, USA 2 Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA 3 Department of Phytochemistry, National Research Center, Dokki 12311, Cairo, Egypt † Current Address: Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA.

* Author to whom correspondence should be addressed.

Received: 6 November 2012; in revised form: 27 December 2012 / Accepted: 25 January 2013 / Published: 6 February 2013

Article Source:
Antioxidant and Anti-Hepatitis C Viral Activities of Commercial Milk Thistle Food Supplements
Antioxidants 2013, 2(1), 23-36; doi:10.3390/antiox2010023 (doi registration under processing) - published online 6 February 2013

Abstract:
Milk thistle dietary supplements that contain silymarin are widely marketed and used in the USA and other countries for liver enhancement and recovery. More recently, silymarin has also been identified as a possible antiviral for the treatment of hepatitis C virus (HCV) infection. To assess different brands of commercially sold silymarin, 45 products were collected from local stores and analyzed for their silymarin content, antioxidant activities, and antiviral activity against HCV. Antioxidant activity was measured as radical scavenging activity using DPPH and by estimating their antioxidant capacity as trolox equivalent. Anti-HCV activity was measured in an HCV genotype 1b replication inhibition assay. Samples were found to vary widely in their silymarin content, with some samples having none or very low concentrations while silymarin represented higher than 80% of other samples. Both antioxidant and anti-HCV activity correlated with the overall level of silymarin.

Keywords: Silybum marianum; radical scavenger; food supplement; over the counter drugs; hepatitis C virus

Full Text Available Here......

IL28B genotype had limited effect on telaprevir response in HCV patients

IL28B genotype had limited effect on telaprevir response in HCV patients

Pol S. J Hepatol. 2013;doi:10.1016/j.jhep.2012.12.023.

February 5, 2013

Patients with interleukin 28B CC genotype had a slightly better response to hepatitis C treatment with pegylated interferon, ribavirin and telaprevir than those with the CT or TT genotypes in a recent study

Researchers performed genetic testing on 527 patients with hepatitis C genotype 1 to detect polymorphisms of the IL28B gene. All participants had been enrolled in the REALIZE study, in which patients randomly were assigned either placebo (n=105) or 750 mg telaprevir every 8 hours for 12 weeks (n=422), in addition to 180 mcg weekly of pegylated interferon alfa-2a and between 1,000 mg and 1,200 mg ribavirin daily for 48 weeks.

Sustained virologic response (SVR) occurred more frequently among treated patients compared with placebo recipients regardless of genotype. The highest rates were observed among those with CC genotype: 79% of all treated patients achieved SVR compared with 29% of controls. SVR rates were 60% vs. 16% with genotype CT patients, and 61% vs. 13% with genotype TT patients. Among prior null and partial responders who received telaprevir, those with CC genotype also had a slightly higher rate of SVR vs. other genotypes. Multivariate analysis indicated no impact of IL28B genotype on SVR (P>.16 for all comparisons between the three genotypes).

Rapid virologic response (RVR) for telaprevir recipients was slightly higher for those with CC genotype, both overall and among null or partial responders. There also was a trend toward fewer relapses or virologic breakthrough during treatment with telaprevir for CC genotype.

“This retrospective subanalysis … suggests that IL28B genotype may have limited utility in guiding the use of this therapeutic regimen in this patient population,” the researchers wrote. “It is therefore likely other factors have a greater effect in determining response to telaprevir-based therapy in this population.

This finding underscores the need for continued efforts to identify predictive biomarkers that will be clinically useful for managing patients with HCV disease in the era of [direct-acting
antivirals], particularly in the treatment-experienced population.”

Disclosure: See the study for a full list of relevant disclosures.

http://www.healio.com/hepatology/chronic-hepatitis/news/online/%7B4C90AD02-A148-4744-A289-A94CEE93E6C2%7D/IL28B-genotype-had-limited-effect-on-telaprevir-response-in-HCV-patients