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Hepatitis C protease inhibitor therapy cost-effective in some circumstances
Michael Carter Source-nam aidsmap
Published: 21 February 2012
“Our study supports the important role of protease inhibitors in treating chronic HCV [hepatitis C virus] for patients with advanced fibrosis as part of a first-line regimen,” write the authors.
Read more here...
NATAP Updates-
Presented at the 22nd Conference of the Asian Pacific Association for the Study of the Liver (APASL)
Taipei, Taiwan
February 16-19, 2012
APASL: DRUG INTERACTION PROFILE OF TELAPREVIR -
Alisporivir Formally (Debio 025)
APASL: ALISPORIVIR (ALV) PLUS Peg-IFN/RBV (PR) HAS 100% SVR IN IL28B rs12979860 CC ALLELE AND SUPERIOR EFFICACY IN CHRONIC HEPATITIS C GENOTYPE (G) 1 TREATMENT-NAIVE PATIENTS COMPARED WITH PR: THE ESSENTIAL STUDY
APASL: Alisporivir, a Host-targeting Antiviral, in Combination with Peg-IFNα2a and Ribavirin Results in Superior SVR and No Viral Breakthrough in HCV Genotype 1 Treatment-naïve Patients of IL28B CC Genotype: Results from the Phase IIb ESSENTIAL Study -
APASL: Vertex QUAD Therapy Yielded 83-93% SVR with 12 weeks duration of therapy: VX-222/TELAPREVIR IN COMBINATION WITH PEGINTERFERON-ALFA-2A AND RIBAVIRIN IN TREATMENT-NAï VE GENOTYPE 1 HCV PATIENTS TREATED FOR 12 WEEKS: ZENITH STUDY, SVR12 INTERIM ANALYSIS -
APASL: DIFFERENT LIKELIHOOD OF ACHIEVING SVR ON A TELAPREVIR-CONTAINING REGIMEN AMONG NULL RESPONDERS, PARTIAL RESPONDERS AND RELAPSERS IRRESPECTIVE OF SIMILAR RESPONSESAFTER A PEGINTERFERON/RIBAVIRIN 4-WEEK LEAD-IN PHASE: REALIZE STUDY SUBANALYSIS: "When examining this population of TVR-treated patients as a whole, there was a clear relationship between Week 4 response and SVR rates" -
APASL: RETREATMENT WITH TELAPREVIR + PEGINTERFERON/RIBAVIRIN AFTER A SHORT EXPOSURE TO TELAPREVIR IN PHASE 1 STUDIES: INTERIM RESULTS FROM A PHASE 3B ROLLOVER TRIAL (C219) -
APASL: IMPACT OF ANEMIA AND RIBAVIRIN DOSE REDUCTION ON SVR TO A TELAPREVIR-BASED REGIMEN IN PATIENTS WITH HCV GENOTYPE 1 AND PRIOR PEGINTERFERON/RIBAVIRIN TREATMENT FAILURE IN THE PHASE 3 REALIZE STUDY
APASL: EFFICACY AND SAFETY OF TELAPREVIR-BASED REGIMENS IN CIRRHOTIC PATIENTS WITH HCV GENOTYPE 1 AND PRIOR PEGINTERFERON/RIBAVIRIN TREATMENT FAILURE: SUBANALYSIS OF THE REALIZE PHASE 3 STUDY
APASL: FOLLOW-UP OF SVR DURABILITY AND VIRAL RESISTANCE IN PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH TELAPREVIR-BASED REGIMENS: INTERIM ANALYSIS OF THE EXTEND STUDY -
DIFFERENT LIKELIHOOD OF ACHIEVING SVR ON A TELAPREVIR-CONTAINING REGIMEN AMONG NULL RESPONDERS, PARTIAL RESPONDERS AND RELAPSERS IRRESPECTIVE OF SIMILAR RESPONSESAFTER A PEGINTERFERON/RIBAVIRIN 4-WEEK LEAD-IN PHASE: REALIZE STUDY SUBANALYSIS: "When examining this population of TVR-treated patients as a whole, there was a clear relationship between Week 4 response and SVR rates" -
Hepatitis C and Baby Boomers
Uploaded by wpahs on Feb 22, 2012
Dr. Jose Oliva, Allegheny General Hospital hepatologist and medical director of the liver transplant program, was interviewed on NBC Nightly News by Dr. Nancy Snyderman about the Hepatitis C epidemic and how it is affecting baby boomers. A patient at AGH's Center for Digestive Health was also interviewed about her experience.
Birth Cohort Testing for HCV Saves Lives, Study Suggests
Yael Waknine
February 21, 2012 — Birth cohort testing and treatment for hepatitis C viral infection (HCV) in the primary care setting is cost-effective and could save thousands of lives each year, suggests a study from the US Centers for Disease Control and Prevention (CDC) published online November 4 and in the February 21 issue of Annals of Internal Medicine.
HCV infection is most prevalent among Americans born between 1945 and 1965, and 50% to 75% of those infected are unaware of their status. HCV caused between 7000 and 13,000 deaths in 2005. Experts project that this number will climb to 35,000 a year by 2030 if new case identification strategies are not implemented.
At this time, the CDC recommends HCV-antibody screening only for individuals with known risk factors such as a history of injecting drugs, requiring a blood transfusion before 1992, or receiving chronic hemodialysis.
Using a computer model, David Rein, PhD, principal research scientist, Public Health Research Department, National Opinion Research Center at the University of Chicago, Illinois, and colleagues estimate that screening of the population born between 1945 and 1965, followed by standard treatment for infected individuals with pegylated interferon and ribavirin (PEG-IFN + R), would reduce deaths by 82,300 compared with risk-based screening. The estimated cost of birth cohort screening and treatement is $15,700 per quality-adjusted life-year (QALY) gained.
Adding a direct-acting antiviral drug (DAA) to the treatment of patients identified with genotype 1 disease would prevent 121,000 deaths compared with risk-based screening, at a cost of $35,700 per QALY gained.
"The important things to remember about birth cohort screening are that, first, the strategy would identify over 800,000 people with hepatitis C if it were fully implemented, and second, the strategy is at least as cost-effective as many routinely administered preventive practices such as breast cancer screening or colorectal screening," Dr. Rein said in a news release.
Birth Cohort Screening Identifies More Than 800,000 New Cases
For the study, researchers developed a computer model to simulate the cost-effectiveness of 4 scenarios: no screening or treatment, risk-based screening and treatment with PEG-IFN + R, a 1-time birth cohort screening of people born from 1945 through 1965 with PEG-IFN + R, and birth cohort screening with PEG-IFN + R for patients with HCV genotypes 2 or 3 and PEG-IFN + R and DAA for those with genotype 1 disease, which is the most prevalent in the United States.
The researchers found that birth cohort screening during an annual primary care visit led to the identification of 808,580 more cases than risk-based screening, at a cost of $2874 per diagnosis.
With no screening, an estimated 618,000 birth cohort members would develop decompensated cirrhosis (DCC) or hepatocellular carcinoma (HCC) and die of hepatitis. Under risk-based screening, 14.8 million individuals were tested, 135,000 were treated, and 53,000 achieved sustained virologic response (SVR); 592,000 developed DCC or HCC and died of HCV-related disease.
In contrast, birth cohort screening with standard treatment led to the identification of 1,070,840 new cases among 60.4 million people tested; 552,000 patients were treated, and 229,000 achieved SVR, reducing the death toll to 509,000 (a drop of 82,000 compared with risk-based screening).
Birth cohort screening with DAA plus standard therapy also increased the number of identified cases but increased the number of patients achieving SVR by 311,000 and reduced the number of HCV-related deaths to 470,000 (a decrease of 121,000 deaths vs risk-based screening).
Compared with risk-based screening, birth cohort screening with PEG-IFN + R therapy increased QALYs by 348,000 and medical costs by $5.5 billion, for an incremental cost-effectiveness ratio (ICER) of $15,700 per QALY gained (95% credible interval [CI], $11,500 - $30,100).
Birth cohort screening and treatment with PEG-IFN + R plus DAA as needed led to a 532,000 increase in QALYs at a cost of $19.0 billion, for an ICER of $35,700 per QALY saved (95% CI, $28,200 - $47,200).
"This is a phenomenal incremental cost-effectiveness ratio and will only improve as sustained treatment efficacy increases with newer regimens," write Harvey J. Alter, MD, and T. Jake Liang, MD, from the National Institutes of Health in Bethesda, Maryland, in an accompanying editorial, noting that unlike HIV, HCV is not integrated in the host genome, and therefore is eradicable after only 6 to 12 months of antiviral therapy.
Study limitations include the lack of real-world data on the efficacy of newer HCV drugs; exclusion of uninsured, institutionalized, and homeless patients; and the capping of disease duration at 20 years, making the screening intervention seem slightly less cost-effective.
Identification of Asymptomatic HCV Is Key
"As innovative treatments for hepatitis C follow their now-destined progression, the most burning question will not be whether to treat, but rather how to identify the many chronic HCV carriers who are unaware of their infection and are at risk for cirrhosis, end-stage liver disease, or hepatocellular carcinoma," note Dr. Alter and Dr. Liang.
Effective national implementation of programs for prevention and care similar to that employed to combat the AIDS epidemic is key to achieving a reduction in HCV mortality over time, they note, adding that HCV deaths now outstrip those associated with HIV.
Expansion of HCV screening practices to include routine testing of individuals born between 1945 and 1965 represents a cost-effective strategy and should be implemented as a national health policy, Dr. Alter and Dr. Liang conclude.
The study was supported by grants from the US Centers for Disease Control and Prevention's Division of Viral Hepatitis. The authors and editorialists have disclosed no relevant financial relationships.
Ann Intern Med. 2012;156:263-270, 317-319
Journalist
Yael Waknine
Yael Waknine is a freelance writer for Medscape.
Updates @ GastroHep News
Mortality and the risk of malignancy in autoimmune liver diseases
February's issue of Hepatology investigates mortality and the risk of malignancy in autoimmune liver diseases.
Population-based quantitative data on the mortality and cancer incidence of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis are scarce.
Dr Catherine Stedman and colleagues from New Zealand systematically investigated the survival and risk of malignancy on population-based cohorts of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis.
Multiple case-finding methods were employed, including searches of all public and private, adult and pediatric outpatient clinics, hospital notes, laboratory, radiology, and pathology reports.
Cases that fulfilled standardized diagnostic criteria were included.
A receiver operating characteristic curve analysis showed sensitivity of 91%
Hepatology
Kaplan-Meier survival estimates, standardized mortality ratios, and standard incidence ratios for malignancy were calculated.
A total of 130 autoimmune hepatitis, 70 primary biliary cirrhosis, and 81 primary sclerosing cholangitis patients were included contributing to 1,156, 625, and 613 person-years at risk, respectively.
For autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis cohorts, standardized mortality ratios for all-cause mortality were 2.1, and 4.1.
The team found that the standardized mortality ratios for hepatobiliary mortality were 42, 71, and 117 for autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis cohorts.
The research team noted that the standard incidence ratios for all cancers were 3, 1.6, and 5.2 for autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis cohorts.
The standard incidence ratios for extrahepatic malignancy were 2.7, 1.6, and 3.0, for autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis cohorts, respectively.
Dr Stedman and colleagues comment, "This is the first population-based study to examine and compare the survival and cancer incidence in autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis in the same population."
"The mortality for all 3 cohorts was significantly increased due to liver-related death, demonstrating the inadequacy of current management strategies."
"The risk of hepatic and extrahepatic malignancy was significantly increased in autoimmune hepatitis and primary sclerosing cholangitis patients."
| Hepatology 2012: 55(2): 522–529 21 February 2012 |
Exercise test to predict survival after liver transplantation
Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver transplantation, reports this month's Liver Transplantation.
Liver transplantation has a significant early postoperative mortality rate.
An accurate preoperative assessment is essential for minimizing mortality and optimizing limited donor organ resources.
Dr James Prentis and colleagues from the United Kingdom assessed the feasibility of preoperative submaximal cardiopulmonary exercise testing for determining the cardiopulmonary reserve in patients being assessed for liver transplantation.
In addition, the team investigated its potential for predicting 90-day posttransplant survival.
The team found that 182 patients underwent cardiopulmonary exercise testing as part of their preoperative assessment for elective liver transplantation.
The 90-day mortality rate, critical care length of stay, and hospital length of stay were determined during the prospective posttransplant follow-up.
The research team noted that 91% of patients successfully completed cardiopulmonary exercise testing.
The researchers defined this as the ability to determine a submaximal exercise parameter, termed the anerobic threshold.
A receiver operating characteristic curve analysis showed sensitivity of 91%
Liver Transplantation
The team observed that 33% underwent liver transplantation, and the mortality rate was 10%.
The mean anerobic threshold value was significantly higher for survivors versus nonsurvivors.
Logistic regression revealed that anerobic threshold, donor age, blood transfusions, and fresh frozen plasma transfusions were significant univariate predictors of outcomes.
The researchers found that only anerobic threshold was retained as a significant predictor of mortality.
A receiver operating characteristic curve analysis demonstrated sensitivity and specificity of 91% and 83%, respectively, with good model accuracy.
The optimal anerobic threshold level for survival was defined to be more than 9.0 mL/minute/kg.
The research team found that the predictive value was improved when the ideal weight was substituted for the actual body weight of a patient with refractory ascites, even after a correction for the donor's age.
Dr Prentis' team concludes, "In conclusion, the preoperative cardiorespiratory reserve is a sensitive and specific predictor of early survival after liver transplantation."
"The predictive value of cardiopulmonary exercise testing requires further evaluation."
| Liver Transplant 2012: 18(2): 152-159 21 February 2012 |
Risk factors for hepatitis C virus acquisition by ethnicity
A study in February's issue of the Journal of Viral Hepatitis identifies risk factors for hepatitis C virus acquisition by Caucasian, Hispanic, and Asian American patients.
Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos.
Dr Nguyen and colleagues from California, USA hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics.
The team surveyed risk factors in HCV-infected patients in these ethnic groups in a prospective study.
The most common risk factors in Asians were blood transfusions, and acupuncture
Journal of Viral Hepatitis
The team reported that 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008.
Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics.
The laboratory profiles were similar, and genotype 1 was the most common infection in all groups.
The great majority of Caucasians and Hispanics identified with commonly known risk factors, which was in contrast to 67% of Asians.
The team found that the most common risk factors in Asians were blood transfusions, and acupuncture.
In addition, the team observed that 74% of Caucasians and 66% of Hispanics identified more than 1 major risk factor, while only 20% of Asians reported having more than 1 risk factor.
Dr Nguyen's team concluded, "Survey for established risk factors for acquisition of HCV may be more appropriate for risk assessment of Caucasians and Hispanics, but not for Asian Americans."
"These findings may guide the development of HCV screening in our increasingly diverse population."
| J Vir Hep 2012: 19(2): e105–e111 22 February 2012 |
Discussion Only
Full Text
Hepatitis C is a major health risk and economic burden, which could be alleviated by the delivery of therapy and cure to those infected. In Tayside there were just under 1000 individuals diagnosed with HCV, at the end of the study period: of those, over 70% have attended at least one appointment at the specialist treatment services and of those 40% have been successfully commenced on treatment. This is considerably higher than the pyramid of care reported by National Institute of Clinical Excellence and other surveys.[11] Clearly, this proportionately large unselected treatment cohort will accurately reflect real world issues and include those with ongoing issues around drug misuse. Indeed given the relative ease with which this part of the population at risk of HCV infection can be identified they are frequently over represented in unselected cohorts. If treatment for HCV infection is to make a difference to the natural history of the HCV epidemic at a population level then those infected with HCV must be brought into therapy with no bias against the IDU population. Therapy for HCV is regarded as cost-effective,[12–14] but this evaluation is critically dependent on the success of the therapy, the SVR, and this is highly dependent on adherence to therapy. This concern over lack of adherence reducing the efficacy of therapy has been the traditional reason for exclusion of those patients with an IDU background from therapy. This study seeks to answer this question: is the concern over the treatment of IDU patients with chronic hepatitis C justified on the basis of SVR?
We have assessed the treatment outcome in 291 consecutively treated, predominately treatment-naive patients who received pegylated interferon and ribavarin for HCV. In contrast to much of the UK, due to record linkage, we know this represents 31.4% of the total diagnosed population in our community. They represent a typical unbiased clinic cohort. Of the three groups the non-IDU cohort was older and slightly overweight. As expected they had a higher number of cirrhotic individuals, though this does achieve significance when compared to the IDU group (Ex and active).
The sustained virological response was the highest in the non-IDU group with 61.5%, followed by 54.8% in the ex-IDU patients, with active IDU patients achieving an SVR of 47.1% of patients. This represents the worse case scenario as those patients with missing SVR data were regarded as treatment failures. This outcome was particularly common in the active IDU group, which contained a much higher number of prisoners, who upon liberation were lost to our care, as they did not reside in Tayside. These patients had fully completed therapy and could be expected to have high SVR rates. We therefore performed an analysis excluding these missing values. Unsurprisingly this improved the SVR rates for all groups and narrowed differences between the groups, which continued to show no significant differences other than ex and active IDU with nongenotype 1 infection. The overall SVR rates are slightly lower than the landmark randomized control trials (RCTs) however none of the trials treated active drug users and ex-IDU were only included if stable for >12 months.[5,6] Secondly our non-G1 patients are almost exclusively genotype 3, which will have a worse outcome compared to that of the non-genotype 1 RCT groups which have a large genotype 2 cohort. It has been shown in various cost effectiveness analysis that combination therapy prolongs life, improves quality of life and is cost-effective.[15] But these analyses were based on the results of the RCTs as models and hence excluded patients with intravenous drug use. These studies are based on patients with chronic HCV achieving overall SVRs of 55% (95% CI 52–58%) and for genotype 1 SVRs of 36–46% and for nongenotype 1 of 61–76%.[4–6] The results of our investigation fall within this range with the exception of the ex-IDU genotype 1 subgroup, which had an excess of cirrhotic patients, however the reported values in this study are still within the range to make the therapy cost effective. Clearly genotype is the most significant predictor of SVR. When this is taken into account the reassuring theme that comes across is whether it is genotype 1 with the longer treatment course where the SVR rate in the active drug user was 42.3%, or the relatively shorter treatment of non-G1, where the active IDU had treatment success in 56.6%, these results lie in the SVR range that has been demonstrated to be cost-effective. The regression analysis performed found the usual predictors of SVR such as genotype and age, but did not find significant reductions in chance of SVR in those from IDU backgrounds, while the confidence intervals in the analysis are wide due to sample size, the sample did identify genotype and age as factors reducing the chance of SVR and we still offer therapy to older genotype 1 patients. Overall the results do not differ significantly in the non-IDU group, thus confirming the message: active IDU is not a barrier to treatment or a successful achievement of SVR.
Another key question is: What is the additional patient support needed to achieve the SVRs reported in this paper? A local redesign of HCV treatment services introduced a new referral pathway in 2004, implementing strategies to improve attendance and outreach clinics within the Tayside Drug Problems Service. This model utilizes existing staff working smarter in an extended role, minimising additional staffing costs. This led to an increase in referral rates. These changes in services generated a large number of patients in the early stages of drug addiction treatment coming forward for assessment of HCV. This provided us the opportunity to assess efficacy of therapy in such a group of patients.[10] In essence, the pathway is dependent upon nurse specialists delivering the anti-viral therapy; this would now be regarded as the standard of care for HCV therapy. The care pathway is patient focussed, so for patients in active treatment for addiction the HCV therapy is co-delivered with their addiction therapy, thus minimizing the need for the patient to travel to other clinics and intimately involving the drug key worker as well as the nurse specialist in the patient's treatment. This involves the nurse specialist in outreach work but requires little additional expenditure on staff other than minimal transport costs, particularly as several patients can be seen in one session.
Our results do show that with simple support provided by a dedicated team of nurses, drug addiction workers, social services and physicians working in partnership can result in SVR rates in the active drug user group comparable with non-IDU infected individuals. This maintains the cost effectiveness of antiviral therapy for HCV in these patient groups. The intervention is designed around existing staff working smarter, rather than expensive alternatives hence a generalizable solution for the National Health Service and possibly throughout the world. Finally, it offers the patient the prospect of a better chance of cure and a positive healthcare experience.
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