Ray Kim

The impact of timing and prioritization on the cost-effectiveness of birth cohort testing and treatment for hepatitis C virus in the United States†‡

Recent United States guidelines recommend one‐time birth cohort testing for hepatitis C infection in persons born between 1945 and 1965; this represents a major public health policy undertaking. The purpose of this study was to assess the role of treatment timing and prioritization on predicted cost‐effectiveness. The MONARCH hepatitis C lifetime simulation model was used in conjunction with a testing and treatment decision tree to estimate the cost‐effectiveness of birth cohort versus risk‐based testing incorporating information on age, fibrosis stage and treatment timing. The study used a 1945‐1965 birth cohort and included disease progression, testing and treatment‐related parameters. Scenario analysis was used to evaluate the impact of hepatitis C virus (HCV) prevalence, treatment eligibility, age, fibrosis stage and timing of treatment initiation on total costs, quality‐adjusted life years (QALYs), HCV‐related complications and cost‐effectiveness. The cost‐effectiveness of birth cohort versus risk‐based testing was

Current limits and future challenges in the management of renal dysfunction in patients with cirrhosis: report from the International Club of Ascites.

28,602. Assuming 91% of the population is tested, at least 278,000 people need to be treated for birth cohort testing to maintain cost‐effectiveness. Prioritizing treatment toward those with more advanced fibrosis is associated with a decrease in total cost of

Structural frameworks and key model parameters in cost-effectiveness analyses for current and future treatments of chronic hepatitis C

7.5 billion and 59,035 fewer HCV‐related complications. Total QALYs and complications avoided are maximized when treatment initiation occurs as soon as possible after testing. Conclusion: This study confirms that birth cohort testing is, on average, cost‐effective. However, this remains true only when enough tested and HCV‐positive subjects are treated to generate sufficient cost offsets and QALY gains. Given the practical and financial challenges associated with implementing birth cohort testing, the greatest return on investment is obtained when eligible patients are treated immediately and those with more advanced disease are prioritized. (HEPATOLOGY 2013)

Assessing the Cost Utility of Response-Guided Therapy in Patients with Chronic Hepatitis C Genotype 1 in the UK Using the MONARCH Model

Advanced cirrhosis is often complicated by a multi organ failure syndrome which involves many different organs besides the liver. The high morbidity and mortality secondary to this clinical setting is often related to renal dysfunction, either alone or, more frequently, in combination with other organ dysfunction. A clear defintion of renal dysfunction, an accurate differential diagnostic process of its different phenotypes as well as of full understanding of its pathophysiological mechanisms are crucial to the development of strategies for the management of this complication. This article is based either on the more recent knowledge on renal dysfunction in advanced cirrhosis or current opinions among the members of the International Club of Ascites (ICA) on the management of this complication, obtained through a survey and discussed during the EASL‐ICA Joint Meeting in Berlin in March 2011. It reviews critically our current knowledge and it outlines future perspectives, on the management of renal dysfunction in patients with cirrhosis.

Estimating the Incidence and Prevalence of Chronic Hepatitis C Infection in Taiwan Using Back Projection

OBJECTIVES Published economic evaluations have reported available treatments for chronic hepatitis C to be cost-effective as part of the current approach to disease management, but as standards of care evolve, their approach to modeling should be reconsidered. This study aimed to review structural frameworks and key model parameters as reported in current economic evaluations for treatments for chronic hepatitis C, and model the impact of variability across parameters on results. METHODS A systematic review of studies published from 2000 to 2011 was performed. Studies were retrieved from five electronic databases using relevant search strategies. Model structures, disease progression rates, utilities, and costs were extracted from included studies, and were qualitatively reviewed and incorporated into a cost-utility model. RESULTS Thirty-four studies were appropriate for data extraction. A common pathway of six disease states was identified. In some studies the early disease stages and/or the decompensated cirrhosis state were further subdivided. Large variability in values used for disease progression rates, utilities, and costs were identified. When incorporated into a model, incremental cost-effectiveness ratios (ICERs) varied: in the least favorable scenario, peginterferon plus ribavirin was dominated by interferon plus ribavirin; and in the most favorable scenario, peginterferon plus ribavirin dominated interferon plus ribavirin (

Isoform-specific alanine aminotransferase measurement can distinguish hepatic from extrahepatic injury in humans

8,544 per quality-adjusted life year [QALY]; costs are given in 2008 US dollar amounts). Using mean values the ICER was

Risk scores for hepatocellular carcinoma in chronic hepatitis B

15,198 per QALY. CONCLUSIONS Current models use a simplistic structure resulting from the lack of available data reflecting patient heterogeneity. Key model parameters are currently based on a small number of studies and the variability across these values can affect the interpretation of results.

Model for end-stage liver disease (MELD) predicts survival in patients with variceal bleeding

BackgroundEuropean guidelines advocate the measurement of on-treatment hepatitis C virus (HCV) RNA in order to determine optimal therapy duration (response-guided therapy [RGT]) in patients with rapid virological response (RVR) or delayed virological response (DVR). Treatment response is highly dependent upon the extent of liver fibrosis yet there is little evidence quantifying the cost effectiveness of RGT particularly conditional upon fibrosis stage.ObjectiveThis study describes an economic model designed to assess the costs and benefits of RGT compared with standard duration of therapy (SDT) in hepatitis C virus genotype 1 patients.MethodsA Markov cohort simulation model with lifetime perspective was developed to undertake a cost utility analysis of RGT in the UK. Patients entered the model at Metavir disease stages F0–F4, and progressed through these stages via age and duration of HCV infection-dependent transition probabilities. Treated patients were partitioned according to virological response and shortened or extended duration of therapy was applied following European guidelines.ResultsFor all patients, SDT and RGT was associated with an increase of 2.14 and 2.20 QALYs and £2,374 and £2,270 costs, respectively, compared with no treatment. Overall, RGT was a dominant scenario being associated with a lower risk of complications, increased QALYs (0.08) and cost saving (£101). RGT across fibrosis stages was either highly cost effective or dominant; in all cases RGT was associated with an increase in QALYs, driven by a reduction in complications in DVR subjects and reduced exposure to treatment disutility in RVR subjects; costs were lower in F1 and F2 fibrosis stages. At a willingness-to-pay threshold of £20,000 per QALY, overall RGT across fibrosis stages F2–F4 were associated with the highest probability of being cost effective. At this threshold, the probability of reduced/extended therapy in RVR/DVR patients being cost effective is 0.35 and 0.88, respectively.ConclusionsThis analysis suggests that the treatment of HCV genotype 1 patients in fibrosis stage F2 has the greatest potential for maximizing health benefit and cost saving within an RGT protocol. Predicting those patients most likely to respond to treatments is important from both a clinical and cost perspective and the tailoring of treatment duration with the current standard of care is likely to remain a priority for payers with budgetary constraints.

Model for end-stage liver disease (MELD) and allocation of donor livers

OBJECTIVE Hepatitis C virus (HCV) infection is the leading cause of liver disease, and Taiwan has among the highest prevalence of HCV infection in the general population in Northeast Asia, estimated at between 2% and 4%. The aim of this study was to estimate the number of patients living with chronic HCV infection in Taiwan and quantify the expected numbers in each of the five Metavir fibrosis stages. METHODS We applied a back-projection approach, using observed hepatocellular carcinoma incidence between 1979 and 2008 and a smoothed Expectation-Maximization algorithm to maximize a Poisson likelihood to estimate the previous incidence of HCV infection. The algorithm was coded in Excel and combined with the MOdelling the NAtural histoRy and Cost-effectiveness of Hepatitis model (a hepatitis C natural history markov model) to predict the past and future numbers in each Metavir fibrosis stage. RESULTS Incident cases were predicted to have peaked in 1972 at 56,634 annually, with the prevalence peaking in 1986 at 763,737 infections and falling to 578,203 infections in 2012. It was estimated that in 2012, 127,795 (23.0%), 105,545 (19.0%), 81,211 (14.6%), 123,939 (22.3%), and 116,823 (21.1%) subjects were in fibrosis stages F0, F1, F2, F3, and F4, respectively. DISCUSSION Our study provides HCV infection prevalence estimates, stratified by Metavir fibrosis stage, in Taiwan for 2012. This has potential implications for budget planning, particularly with the availability of emerging therapies because fibrosis stage is predictive of both rapid and sustained virological response; therefore, planning expected treatment response in a given population could be enhanced with this additional information.

PIN98 Evaluating Optimal Treatment Outcomes of Antiviral Therapy in Hepatitis C for Prior Null Responders in the Era of First Generation Protease Inhibitors

Serum alanine aminotransferase (ALT) is used as a clinical marker to detect hepatic damage and hepatoxicity. Two isoforms of ALT have been identified, ALT1 and ALT2, which have identical enzymatic capacities and are detected simultaneously in human serum/plasma using classical clinical chemical assays. Differences exist in the expression patterns of the ALT1 and ALT2 proteins in different organs which suggest that changes in the proportion of ALT1 and ALT2 in plasma may arise and reflect damage to different human organs. However, this has not been previously studied due to the lack of a selective methodology that can quantify both ALT1 and ALT2 isoforms in the total ALT activity normally measured in clinical samples. To the best of our knowledge, our current study reveals for the first time, that under 3 different conditions of liver damage (non-alcoholic fatty liver disease, hepatitis C and during liver surgery) the leakage of ALT1 activity into plasma greatly exceeds that of ALT2, and that the measurement of ALT1 during liver damage is equal to the measurement of total ALT activity. By contrast, during skeletal muscle injury, induced in volunteers by physical exertion, the leakage of ALT2 exceeds that of ALT1 and the proportion of circulating ALT isoforms changes accordingly. The ALT isoform changes occurring in plasma reflect previously demonstrated relative contents of ALT1 and ALT2 activities in human liver and skeletal muscle. These data suggest that assessing the percentage contribution of ALT1 and ALT2 activities to total ALT activity in plasma may distinguish hepatic from extrahepatic injury using the same standard analytical platform.