Global Epidemiology of Cirrhosis: Changing Etiological Basis and Comparable Burden of Nonalcoholic Steatohepatitis between Males and Females.

INTRODUCTION: The etiology of liver diseases has changed significantly, but its impact on the comparative burden of cirrhosis between males and females is unclear. We estimated sex differences in the burden of cirrhosis across 204 countries and territories from 2010 to 2019. METHODS: We analyzed temporal trends in the burden of cirrhosis using the methodology framework of the 2019 Global Burden of Disease study. We estimated annual frequencies and age-standardized rates (ASRs) of cirrhosis incidence, death, and disability-adjusted life-years (DALYs) by sex, region, country, and etiology. RESULTS: In 2019, the frequency of incident cases, deaths, and DALYs due to cirrhosis was 1,206,125, 969,068, and 31,781,079 in males versus 845,429, 502,944, and 14,408,336 in females, respectively. From 2010 to 2019, the frequency of cirrhosis deaths increased by 9% in males and 12% in females. Incidence ASRs remained stable in males but increased in females, while death ASRs declined in both. Death ASRs for both sexes declined in all regions, except in the Americas where they remained stable. In 2019, alcohol was the leading cause of cirrhosis deaths in males, and hepatitis C in females. Death ASRs declined for all etiologies in both sexes, except in nonalcoholic steatohepatitis (NASH). The ratio of female-to-male incidence ASRs in 2019 was lowest in alcohol(0.5), and highest in NASH(1.3), while the ratio of female-to-male death ASRs was lowest in alcohol(0.3) and highest in NASH(0.8). CONCLUSION: The global burden of cirrhosis is higher in males. However, incidence and death ASRs from NASH cirrhosis in females are comparable to that of males.

A Diagnostic Test Meta-Analysis Evaluating Imaging-Based and Blood Biomarker-Based Assessment Tools for Fibrosis After Liver Transplantation.

Early detection of liver graft fibrosis is crucial for risk stratification to identify patients for liver biopsy and timely treatment. However, diagnostic accuracy of noninvasive tests (NITs) remains unclear. Thus, this study sought to evaluate diagnostic accuracy of NITs in assessing liver allograft fibrosis and compare the differences in specificities and sensitivities among NITs. Medline and Embase databases were searched to include articles on diagnostic tests in liver transplantation (LT) patients with fibrosis. A meta-analysis on diagnostic test accuracy was conducted in a random-effects model. Sensitivities and specificities among the diagnostic tests were compared, and threshold values were calculated where applicable. A total of 25 articles were included. Vibration-controlled transient elastography (VCTE) met the minimum diagnostic accuracy requirements, yielding sensitivity, specificity, and diagnostic odds ratios of 0.9 (CI, 0.8-1.0), 0.9 (CI, 0.8-1.0), and 379.6 (CI, 45.8-1728.7), respectively. In the threshold assessment, the optimal cutoff was 9.30 kPa with a sensitivity, specificity, and area under the curve of 0.7 (CI, 0.5-0.9), 0.9 (CI, 0.8-0.9), and 0.9 (CI, 0.8-0.9), respectively. For significant fibrosis, acoustic radiation force impulse (ARFI) was superior to FibroTest (LabCorp [Burlington, NC]) and magnetic resonance elastography (MRE) in sensitivity. VCTE was superior to FibroTest in specificity. For advanced fibrosis, ARFI was superior to the Fibrosis-4 Index (FIB-4) in sensitivity. VCTE was superior to the AST to Platelet Ratio Index (APRI), MRE, and FIB-4 in specificity. In cirrhosis, VCTE was superior to APRI in specificity (P = 0.004) with comparable sensitivity. This study demonstrates the potential of VCTE and ARFI as diagnostic tools for fibrosis in LT recipients compared with blood-based NITs, which were shown to be less optimal.

The costs of an expanded screening criteria for COVID-19: A modelling study.

OBJECTIVES: Nosocomial infection is an ongoing concern in the COVID-19 outbreak. The effective screening of suspected cases in the healthcare setting is therefore necessary, enabling the early identification and prompt isolation of cases for epidemic containment. We aimed to assess the cost and health outcomes of an extended screening strategy, implemented in Singapore on 07 February 2020, which maximizes case identification in the public healthcare system. METHODS: We explored the effects of the expanded screening criteria which allow clinicians to isolate and investigate patients presenting with undifferentiated fever or respiratory symptoms or chest x-ray abnormalities. We formulated a cost appraisal framework which evaluated the treatment costs averted from the prevention of secondary transmission in the hospital setting, as determined by a branching process infection model, and compared these to the costs of the additional testing required to meet the criteria. RESULTS: In the base case analysis, an R0 of 2.5 and incubation period of 4 days, an estimated 239 (95% CI: 201-287) cases could be averted over 150 days within the hospital setting through ESC. A corresponding $2.36 (2-2.85) million USD in costs could be averted with net cost savings of $124,000 (95% CI: -334,000 to 516,000). In the sensitivity analyses, when positive identification rates (PIR) were above 7%, regardless of R0 and incubation period, all scenarios were cost-saving. CONCLUSION: The expanded screening criteria can help to identify and promptly isolate positive COVID cases in a cost-saving manner or within acceptable cost margins where the costs incurred from the testing of negative patients could be negated by the averted costs. Outbreak control must be sustainable and effective; the proposed screening criteria should be considered to mitigate nosocomial transmission risk within healthcare facilities.

Responding to COVID-19: how an academic infectious diseases division mobilized in Singapore.

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.

Management of hepatitis C virus infection in the Asia-Pacific region: an update.

The Asia-Pacific region has disparate hepatitis C virus (HCV) epidemiology, with prevalence ranging from 0·1% to 4·7%, and a unique genotype distribution. Genotype 1b dominates in east Asia, whereas in south Asia and southeast Asia genotype 3 dominates, and in Indochina (Vietnam, Cambodia, and Laos), genotype 6 is most common. Often, availability of all-oral direct-acting antivirals (DAAs) is delayed because of differing regulatory requirements. Ideally, for genotype 1 infections, sofosbuvir plus ledipasvir, sofosbuvir plus daclatasvir, or ombitasvir, paritaprevir, and ritonavir plus dasabuvir are suitable. Asunaprevir plus daclatasvir is appropriate for compensated genotype 1b HCV if baseline NS5A mutations are absent. For genotype 3 infections, sofosbuvir plus daclatasvir for 24 weeks or sofosbuvir, daclatasvir, and ribavirin for 12 weeks are the optimal oral therapies, particularly for patients with cirrhosis and those who are treatment experienced, whereas sofosbuvir, pegylated interferon, and ribavirin for 12 weeks is an alternative regimen. For genotype 6, sofosbuvir plus pegylated interferon and ribavirin, sofosbuvir plus ledipasvir, or sofosbuvir plus ribavirin for 12 weeks are all suitable. Pegylated interferon plus ribavirin has been replaced by sofosbuvir plus pegylated interferon and ribavirin, and all-oral therapies where available, but cost and affordability remain a major issue because of the absence of universal health coverage. Few patients have been treated because of multiple barriers to accessing care. HCV in the Asia-Pacific region is challenging because of the disparate epidemiology, poor access to all-oral therapy because of availability, cost, or regulatory licensing. Until these problems are addressed, the burden of disease is likely to remain high.

The impact of hepatitis C virus outside the liver: Evidence from Asia.

Between 80 and 115 million people worldwide are chronically infected with hepatitis C virus, with 60%-90% of these being undiagnosed. Untreated chronic hepatitis C (CHC) is associated with progressive liver disease, cirrhosis, hepatocellular carcinoma and liver-related mortality. A number of extrahepatic manifestations are also reported in CHC patients, further adding to the burden of the disease. CHC also impacts patients in terms of lower health-related quality of life, higher levels of fatigue and reduced productivity. Furthermore, the later stages of disease are costly for both healthcare systems and society. Pegylated-interferon (PEG-IFN)+ribavirin (RBV), for many years the mainstay of treatment, leads to sustained virological response (SVR) in 40%-70% of patients. However, a substantial number of patients are ineligible for treatment, and many patients fail to achieve SVR with this regimen. Furthermore, PEG-IFN+RBV leads to impairment of patient-reported outcomes during treatment, and most patients suffer from adverse events, associated with poor adherence, treatment discontinuation and treatment failure. The approval of second-generation direct-acting antivirals (DAAs) has revolutionized the treatment of CHC patients. All-oral, PEG-IFN and RBV-free regimens have higher efficacy rates, shorter treatment durations, fewer adverse events, higher adherence rates and improvement in PROs from as early as Week 4, compared to PEG-IFN+RBV regimens. The aim of this article is to review the evidence for HCV infection as a systemic disease, summarizing the impact of hepatitis C and its treatments on clinical, patient and economic outcomes, with a focus on data from Asia and Japan specifically.

Cost-effectiveness of strategy-based approach to treatment of genotype 1 chronic hepatitis C.

BACKGROUND AND AIM: The high cost of chronic hepatitis C (HCV) direct-acting antivirals (DAAs) poses significant financial challenges for health payers, especially in Asia. A personalized treatment strategy based on individualized probability of virological response using oral DAAs as second-line therapy would seem practical but has not been studied. METHODS: We performed a Markov model to project health outcomes and costs for patients with genotype 1 HCV through 10 treatment strategies over a lifetime period. The implication of retreatment was also incorporated to reflect real-life situation. RESULTS: Using boceprevir and peginterferon/ribavirin (BOC/PR, the least costly treatment) as a base case, the all-oral therapies such as ombitasvir/paritaprevir/ritonavir-dasabuvir are cost-effective with an incremental cost-effective ratio of $US50 828. However, the all-oral DAAs would no longer be cost-effective compared with conventional therapies if retreatment were taken into account. A road map strategy using rapid virological response to guide use of BOC/PR and sofosbuvir/PR had the most favorable incremental cost-effective ratio ($US27 782) relative to BOC/PR. Nevertheless, the trade-off with the cost-effectiveness of the road map strategy is an increased number of liver-related deaths compared with all-oral DAAs (52 vs 10-20 per 10 000 patients) by incorporating retreatment. CONCLUSIONS: The 12-week all-oral DAAs were cost-effective options using conventional drug-to-drug comparison. However, they cease to be cost-effective when treatment strategies incorporating DAA retreatment for interferon failures are incorporated. HCV management can be optimized by adopting individualized treatment algorithm providing a practical solution to health payers to make oral DAAs accessible to those who need them most.

Hepatitis C: An Eastern Perspective.

HCV in the East is a complex scenario with prevalence rates of 0.5% to as high as 4.7%, and variable distributions of genotypes, with a dominance of genotype 1b in East Asia, genotype 3 in South Asia and South East Asia, and genotype 6 in Indochina. Approvals for the new oral directing antiviral agents (DAAs), in the East have been very slow, but ultimately will be achieved by 2019, consequently, pegylated interferon and ribavirin are still widely used. Nonetheless the main issues are the problems of screening and linkage to management, and the considerable barriers to access HCV care.

Cost effectiveness of response-guided therapy with peginterferon in the treatment of chronic hepatitis B.

BACKGROUND & AIMS: The high prevalence of chronic hepatitis B in Asian countries produces a substantial economic burden. Peginterferon has immunomodulatory effects and a finite course for treatment of hepatitis B, but also a high cost and side effects. The recent introduction of a 12-week stopping rule (stopping treatment after 12 weeks) has increased its appeal as a first-line treatment for hepatitis B. We aimed to determine the cost effectiveness of the 12-week stopping rule for peginterferon in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: We used Markov modeling, with data from the Hong Kong population, to compare the cost effectiveness of peginterferon therapy with a 12-week stopping rule vs conventional therapy (48 weeks) and with other antiviral agents. RESULTS: For HBeAg-positive patients, stopping peginterferon therapy after 12 weeks had the lowest cost-effectiveness ratio (CER), of $9501/quality-adjusted life-year (QALY), compared with no treatment, making it the most cost-effective option. Conventional (48-week) peginterferon treatment had a CER of $9664/QALY. For HBeAg-negative patients, entecavir had the lowest CER ($34,310/QALY). Entecavir was more cost effective than either peginterferon strategies (CERs of $37,423/QALY for 12 weeks of peginterferon and $38,474/QALY for 48 weeks of treatment). CONCLUSIONS: The 12-week stopping rule increases the cost effectiveness of peginterferon therapy, and is the most cost-effective treatment for HBeAg-positive patients. The need for long-term antiviral therapy for HBeAg-negative patients makes entecavir the most cost-effective strategy.

Cost-effectiveness of boceprevir co-administration versus pegylated interferon-α2b and ribavirin only for patients with hepatitis C genotype 1 in Singapore.

BACKGROUND: Patients infected with chronic HCV genotype 1 experience liver complications as the disease progresses. This study aims to project the long-term reduction of liver complications and cost-effectiveness of treatment strategies, including co-administrating boceprevir (BOC) with pegylated interferon-α2b (PEG-IFN) and ribavirin compared with standard of care (SOC) of PEG-IFN and ribavirin only. METHODS: A Markov model was created to estimate the expected costs and quality-adjusted life-years (QALYs) associated with treatment strategies outlined in the BOC package insert in Singapore. Patient characteristics were from pivotal trials, the transition probabilities and QALYs were estimated from publications, and the pharmaceutical and health status costs were obtained from a public hospital in Singapore. The threshold of cost-effectiveness was chosen as 65,000 SGD for this study. RESULTS: For treatment-naive patients, BOC is highly cost-effective compared with SOC (179 SGD/QALY) and cost-saving for patients who have failed prior treatment, due to higher QALYs from better sustained virological response (SVR) and lower costs from avoidance of complications. Sub-group analyses show that BOC is cost-effective for non-cirrhotic treatment-experienced patients and null responders. It out-performs SOC for treatment-naive non-cirrhotic and cirrhotic patients who have failed prior treatment. Even after adjusting for higher prevalence of favourable IL28B genotype in Asians, BOC is cost-effective compared with SOC. Only untreated cirrhotic patients showed inconclusive cost-effectiveness for BOC. CONCLUSIONS: Compared with SOC, BOC prevents more HCV liver complications from HCV genotype 1, particularly in patients who have failed previous SOC. Improved SVR and shortened duration of treatment result in BOC being potentially cost-saving or cost-effective in an Asian population.

Consensus cost-effectiveness model for treatment of chronic hepatitis B in Asia Pacific countries.

PURPOSE: The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party to develop a consensus cost-effectiveness model for treatment of Hepatitis B in Asia Pacific countries in March 2010. METHODS: The working party consisted of expert hepatologists, virologists and epidemiologists from 11 representative countries in the Asia Pacific region. Meetings were conducted at the 20th APASL Annual Meeting in 2010 to determine consensus estimates for modeling and at the 21st and 22nd APASL meetings in 2011 and 2012, respectively to review and approve the models. RESULTS: The consensus cost-effectiveness model used Singapore as base case analysis and was validated using actual data from the Singapore Cancer, Diseases and Death Registries. Simulation for Singapore, China, Thailand, Pakistan, Taiwan and Korea were performed. Antivirals with high resistance barriers like entecavir and tenofovir had the highest retail cost but were the most cost-effective therapy in developed countries such as Singapore, Taiwan and Korea while generic tenofovir was most cost effective in Thailand and Pakistan. The cost effectiveness of different treatment strategies varied significantly between countries and was affected by medication cost, economic affordability, access to liver transplantation and the prevailing health of the general population. CONCLUSION: Choosing treatment strategies for hepatitis B based on low retail drug cost can be misleading because more expensive drugs may be more cost effective when considering long-term health outcomes and costs. Cost-effectiveness data should be individualized to countries based on their unique socio-economic conditions. Governmental policies which subsidize more costly drugs that have lower risk of drug resistance can benefit more patients.

A cost-effectiveness analysis evaluating endoscopic surveillance for gastric cancer for populations with low to intermediate risk.

BACKGROUND: Gastric cancer (GC) surveillance based on oesophagogastroduodenoscopy (OGD) appears to be a promising strategy for GC prevention. By evaluating the cost-effectiveness of endoscopic surveillance in Singaporean Chinese, this study aimed to inform the implementation of such a program in a population with a low to intermediate GC risk. METHODS: USING A REFERENCE STRATEGY OF NO OGD INTERVENTION, WE EVALUATED FOUR STRATEGIES: 2-yearly OGD surveillance, annual OGD surveillance, 2-yearly OGD screening and 2-yearly screening plus annual surveillance in Singaporean Chinese aged 50-69 years. From a perspective of the healthcare system, Markov models were built to simulate the life experience of the target population. The models projected discounted lifetime costs ($), quality adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) indicating the cost-effectiveness of each strategy against a Singapore willingness-to-pay of $46,200/QALY. Deterministic and probabilistic sensitivity analyses were used to identify the influential variables and their associated thresholds, and to quantify the influence of parameter uncertainties respectively. RESULTS: With an ICER of $44,098/QALY, the annual OGD surveillance was the optimal strategy while the 2-yearly surveillance was the most cost-effective strategy (ICER = $25,949/QALY). The screening-based strategies were either extendedly dominated or cost-ineffective. The cost-effectiveness heterogeneity of the four strategies was observed across age-gender subgroups. Eight influential parameters were identified each with their specific thresholds to define the choice of optimal strategy. Accounting for the model uncertainties, the probability that the annual surveillance is the optimal strategy in Singapore was 44.5%. CONCLUSION: Endoscopic surveillance is potentially cost-effective in the prevention of GC for populations at low to intermediate risk. Regarding program implementation, a detailed analysis of influential factors and their associated thresholds is necessary. Multiple strategies should be considered in order to recommend the right strategy for the right population.

Screening based on risk for colorectal cancer is the most cost-effective approach.

BACKGROUND & AIMS: Performing single endoscopic examinations or selective screening based on risk might be more practical than recommended screening strategies for colorectal cancer (CRC). We investigated the cost effectiveness of these strategies, under real-life conditions of suboptimal compliance, and the societal cost perspective. METHODS: We used Markov modeling to analyze data from 787,000 individuals in Singapore, aged 50 to 75 years, with an age-standardized rate of CRC of 30 to 40/100,000 in 2009. Potential outcomes, incremental cost-effectiveness ratio, and net health benefit were compared between single sigmoidoscopy or colonoscopy and current recommended screening strategies, and also with a strategy of selective screening based on risk of CRC. RESULTS: Performing single sigmoidoscopies on individuals when they are 60 years old was the cheapest screening strategy; it would reduce CRC incidence by 19% and mortality by 16%, compared with no screening. A single colonoscopy is less cost effective than a single sigmoidoscopy, unless the proportion of right-sided lesions exceeds 65%. The fecal occult blood test (iFOBT) had the lowest incremental cost-effectiveness ratio when all strategies were compared with no screening; iFOBT and colonoscopic examinations every 10 years each had extended dominance over other strategies. Screening subjects 50 to 60 years old by iFOBT and subjects 60 to 72 years old with colonoscopies every 10 years was the most cost-effective strategy (US$25,000/quality-adjusted life-years). Risk for CRC, adherence, and cost of colonoscopy were the main determinants of cost effectiveness, based on sensitivity analysis. CONCLUSIONS: Markov modeling analysis indicates that selectively screening individuals for CRC based on risk is the most cost-effective approach; it limits the cost and number of colonoscopies needed and significantly reduces CRC mortality.

Cost-effectiveness analysis of hospital infection control response to an epidemic respiratory virus threat.

The outbreak of influenza A pandemic (H1N1) 2009 prompted many countries in Asia, previously strongly affected by severe acute respiratory syndrome (SARS), to respond with stringent measures, particularly in preventing outbreaks in hospitals. We studied actual direct costs and cost-effectiveness of different response measures from a hospital perspective in tertiary hospitals in Singapore by simulating outbreaks of SARS, pandemic (H1N1) 2009, and 1918 Spanish influenza. Protection measures targeting only infected patients yielded lowest incremental cost/death averted of 23,000 (US dollars) for pandemic (H1N1) 2009. Enforced protection in high-risk areas (Yellow Alert) and full protection throughout the hospital (Orange Alert) averted deaths but came at an incremental cost of up to $2.5 million/death averted. SARS and Spanish influenza favored more stringent measures. High case-fatality rates, virulence, and high proportion of atypical manifestations impacted cost-effectiveness the most. A calibrated approach in accordance with viral characteristics and community risks may help refine responses to future epidemics.

The economics of treating chronic hepatitis B in Asia.

Chronic hepatitis B constitutes a significant health and economic burden to Asian countries. Six medications are now approved for the treatment of chronic hepatitis B, but there is still significant uncertainty with regards to treatment outcomes, cost impact, and benefits in view of the absence of long-term outcomes data. Cost-effectiveness Markov modeling thus allows us to project and estimate long-term outcomes based on current data and compare the cost-benefit between different treatment options. However, there are limitations to these reported studies. Cost-utility indices such as cost/quality-adjusted life years (cost/QALY) may not be intuitive to clinicians and patients. These studies are also usually based on first-world economies, using a benchmark of US$50,000/QALY, and cannot be extrapolated directly to Asia-Pacific countries. Cost-effectiveness of various treatment strategies using a combination of cost-effectiveness indices may provide a more complete picture. These include cost/HBeAg seroconversion for HBeAg-positive patients (range: US$19,400-30,800) and cost/HBV DNA negative (PCR assay) for HBeAg-negative patients (range: US$14,400-32,000) over 5-year time horizon; cost per cirrhosis prevented (range: US$326,000-686,000) and cost per HCC prevented (range: US$654,000-1,380,000) over 10-year horizon using data from REVEAL study, cost per end point complication prevented in cirrhotics (US$9,630/year), and cost per HCC prevented in cirrhotics (US$ 27,600/year) over a 32-month horizon, using data from Asia Lamivudine Cirrhosis Study. More potent antivirals with low resistance appear to have lower cost/clinical end point averted. Published reports of cost-utility analysis comparing treatment using conventional cost/QALY show that all treatment modalities fall below the first-world benchmark of US$50,000/QALY but vary in modeling assumptions and in quality, making comparisons difficult. Reimbursement policies affect out-of-pocket expenses to the patient, and increases the proportion of patients who can afford therapy, but generally do not affect cost-effectiveness. In conclusion, cost-effectiveness analysis is an important tool for health care administrators, clinicians, and patients to decide on the optimal therapy for chronic hepatitis B, but the methodology permits considerable leeway for interpretation of results, thus a combination of cost-effective indices may be needed to paint a more complete picture.

Endoscopic screening for gastric cancer.

BACKGROUND & AIMS: Population endoscopic screening for gastric cancer is generally deemed not to be cost-effective except in Japan, where its prevalence is very high. However, in the absence of screening, patients present with advanced disease, and prognosis is poor. We conducted a cost utility analysis to determine whether endoscopic screening for stomach cancer in intermediate-risk population would be cost-effective and to better define the high-risk groups in the population who would benefit from such strategy. METHODS: Cost-effectiveness analysis was performed by using a Markov Model. Simulation was performed on Singapore (intermediate-risk) population and various high-risk subgroups. Comparison was made between 2-yearly endoscopic mass screening program versus no screening. Data sources were extracted from relevant studies published from 1980-2004 identified via systematic PUBMED search. Main outcome measures were deaths caused by stomach cancer averted, cost per life saved, and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life year (QALY) saved. RESULTS: Screening of high-risk group of Chinese men (age-standardized rate, 25.9/100,000) from 50-70 years old is highly cost-effective, with cost benefit of United States $26,836 per QALY. Screening this cohort of 199,000 subjects prevents 743 stomach cancer deaths and saves 8234 absolute life years. Cost of averting 1 cancer death is United States $247,600. Cost-effectiveness was most sensitive to incidence of stomach cancer and cost of screening endoscopy. CONCLUSIONS: Screening of stomach cancer in moderate to high-risk population subgroups is cost-effective. Targeted screening strategies for stomach cancer should be explored.

Prophylactic strategies for hepatitis B patients undergoing liver transplant: a cost-effectiveness analysis.

Hepatitis B immunoglobulin with lamivudine prophylaxis (LAM/HBIG) is effective in preventing Hepatitis B (HBV) recurrence posttransplant but is expensive and inconvenient. Lamivudine-resistant HBV, which has limited the usefulness of lamivudine monoprophylaxis in transplant, can now be effectively controlled with adefovir dipivoxil. We performed a cost-effectiveness analysis on the strategies of lamivudine prophylaxis with adefovir rescue(LAM/ADV) compared to combination LAM/intravenous fixed high-dose HBIG prophylaxis(LAM/ivHBIG) or LAM/intramuscular HBIG prophylaxis(LAM/imHBIG). Markov modeling was performed with analysis from societal perspective. Probability rates were derived from systematic review of the literature and cost taken from MEDICARE database. Outcome measures were incremental cost-effectiveness ratio(ICER) and cost to prevent each HBV recurrence and death. Analysis was performed at 5 years posttransplant as well as at end of life expectancy (15 years). Combination LAM/ivHBIG cost an additional USD562,000 at 15 years, while LAM/imHBIG cost an additional USD139,000 per patient compared to LAM/ADV. Although there is an estimated increase in recurrence of 53% with LAM/ADV and 7.6% increased mortality at the end of life expectancy (15 years), the ICER of LAM/ivHBIG over LAM/ADV treatment is USD760,000 per quality-adjusted life-years and for LAM/imHBIG, USD 188,000. Cost-effectiveness is most sensitive to cost of HBIG. Lamivudine prophylaxis with adefovir dipivoxil salvage offers the more cost-effective option for HBV patients undergoing liver transplant but with higher recurrence and death rate using a model that favors LAM/HBIG. Lowering the cost of HBIG maintenance will improve cost-effectiveness of LAM/HBIG strategy. In conclusion, a tailored approach based on individual risks will optimize the cost-benefit of HBV transplant prophylaxis.