A tool to measure the impact of inaction toward elimination of hepatitis C: A case study in Korea.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) and its sequelae present a significant source of economic and societal burden. Introduction of highly effective curative therapies has made HCV elimination attainable. The study used a predictive model to assess the clinical and economic impact of implementing national screening and treatment policies toward HCV elimination in Korea. METHODS: A previously validated Markov disease progression model of HCV infection was employed to analyze the clinical and economic impact of various strategies for HCV diagnosis and treatment in Korea. In this analysis, the model compared the clinical and economic outcomes of current HCV-related interventions in Korea (7,000 patients treated and 4,200 patients newly diagnosed annually, starting in 2017) to four elimination scenarios: 1) initiating sufficient diagnosis and treatment interventions to meet the World Health Organization's GHSS elimination targets by 2030, 2) delaying initiation of interventions by one year, 3) delaying initiation of interventions by two years and 4) accelerating initiation of interventions to meet elimination targets by 2025. Modelled historical incidence of HCV was calibrated to match a viremic HCV prevalence of 0.44% in 2009. Elimination scenarios required 24,000 treatments and 34,000 newly diagnosed patients annually, starting in 2018, to reach the 2030 targets. RESULTS: Compared to current "status quo" interventions, elimination (or accelerated elimination by 2025) would avert 23,700 (27,000) incident cases of HCV, 1,300 (1,400) liver-related deaths (LRDs) and 2,900 (3,100) cases of end-stage liver disease (ESLD) over the 2017-2030 time period. Postponing interventions by one (or two) years would avert 21,100 (18,600) new HCV infections, 920 (660) LRDs and 2,000 (1,400) cases of ESLD by 2030. Following elimination or accelerated elimination strategies would save 860 million USD or 1.1 billion USD by 2030, respectively, compared to the status quo, requiring an up-front investment in prevention that decreases spending on liver-related complications and death. CONCLUSIONS: By projecting the impact of interventions and tracking progress toward GHSS elimination targets using modelling, we demonstrate that Korea can prevent significant morbidity, mortality and spending on HCV. Results should serve as the backbone for policy and decision-making, demonstrating how aggressive prevention measures are designed to reduce future costs and increase the health of the public.

Longitudinal assessment of alpha-fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis.

Background/aims: Cirrhosis is an important risk factor for hepatocellular carcinoma (HCC), and the surveillance of patients with cirrhosis is, therefore, highly recommended. However, the role of alpha-fetoprotein (AFP) in HCC surveillance is controversial. The aim of this study was to determine the role of AFP in HCC surveillance among patients with cirrhosis.Methods: The study population consisted of 392 patients with cirrhosis. Ultrasound (US) and laboratory tests including AFP were regularly performed to detect HCC development. The cutoff level of AFP for suspicion of HCC was 7 ng/mL.Results: During the median follow-up period of 4.7 (interquartile range, 3.4-5.6) years, HCC developed in 64 (16.3%) patients. Their mean age was 53.6 years, and they were predominantly male (63.5%). For the detection of HCCs, the sensitivity and specificity of US were 56.3% and 100%, respectively. The sensitivity and specificity of AFP were 62.5% and 94.5%, respectively. Using US and AFP in combination increased the sensitivity of surveillance to 89.1% with a specificity of 94.5%. Mean AFP levels were significantly higher in patients with than without HCC at the time of HCC diagnosis, at 6 months and 12 months before the diagnosis. The area under the receiver operating characteristic curve of AFP was highest at the time of HCC diagnosis (0.867), and also was acceptable at 6 months (0.823) and 12 months (0.792) before the diagnosis.Conclusions: These results suggest the complementary use of AFP and US to improve the effectiveness of HCC surveillance in patients with cirrhosis.

Risk assessment of hepatocellular carcinoma development for indeterminate hepatic nodules in patients with chronic hepatitis B.

BACKGROUND/AIMS: A risk prediction model for the development of hepatocellular carcinoma (HCC) from indeterminate nodules detected on computed tomography (CT) (RadCT score) in patients with chronic hepatitis B (CHB)-related cirrhosis was proposed. We validated this model for indeterminate nodules on magnetic resonance imaging (MRI). METHODS: Between 2013 and 2016, Liver Imaging Reporting and Data System (LI-RADS) 2/3 nodules on MRI were detected in 99 patients with CHB. The RadCT score was calculated. RESULTS: The median age of the 72 male and 27 female subjects was 58 years. HCC history and liver cirrhosis were found in 47 (47.5%) and 44 (44.4%) patients, respectively. The median RadCT score was 112. The patients with HCC (n=41, 41.4%) showed significantly higher RadCT scores than those without (median, 119 vs. 107; P=0.013); the Chinese university-HCC and risk estimation for HCC in CHB (REACH-B) scores were similar (both P>0.05). Arterial enhancement, T2 hyperintensity, and diffusion restriction on MRI were not significantly different in the univariate analysis (all P>0.05); only the RadCT score significantly predicted HCC (hazard ratio [HR]=1.018; P=0.007). Multivariate analysis showed HCC history was the only independent HCC predictor (HR=2.374; P=0.012). When the subjects were stratified into three risk groups based on the RadCT score (<60, 60-105, and >105), the cumulative HCC incidence was not significantly different among them (all P>0.05, log-rank test). CONCLUSION: HCC history, but not RadCT score, predicted CHB-related HCC development from LI-RADS 2/3 nodules. New risk models optimized for MRI-defined indeterminate nodules are required.

Feasibility of dynamic risk assessment for patients with repeated trans-arterial chemoembolization for hepatocellular carcinoma.

BACKGROUND: Hepatoma arterial-embolization prognostic (HAP) score and its modifications (modified HAP [mHAP] and mHAP-II), consisting of some or all of the following factors of tumor size, number, alpha-fetoprotein, bilirubin, and serum albumin, have been found to predict outcomes after trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We investigated the feasibility of using HAP-related risk scores for dynamic risk assessment during repeated TACE. METHODS: A total of 619 HCC patients treated with TACE from two institutions between 2003 and 2010 were included. RESULTS: Patients with A-B class risk scores showed significantly better survival than those with C-D class risk scores at the first (median 43.7 vs. 21.5 months for mHAP-II, 35.2 vs. 10.2 months for mHAP, and 39.8 vs. 18.6 months for HAP; all P < 0.001) and the second rounds of TACE (38.6 vs. 17.2 months for mHAP-II, 30.0 vs. 8.5 months for mHAP, and 32.6 vs. 17.3 months for HAP; all P < 0.001). Sequential assessment of risk scores at the second TACE round was applied for patients with A-B class risk scores at the first TACE round, which further identified two subgroups of A-B and C-D class risk scores with different outcomes (median survival 40.6 vs. 19.6 months for mHAP-II, 31.2 vs. 16.9 months for mHAP, and 35.8 vs. 21.0 months for HAP; all P < 0.001). Compared with mHAP and HAP, mHAP-II showed the highest likelihood ratio (22.61 vs. 14.67 and 13.97, respectively), highest linear trend (24.43 vs. 19.67 and 14.19, respectively), and lowest Akaike information criteria value (1432.51 vs. 3412.29 and 2296.98, respectively). CONCLUSIONS: All HAP-related risk scores dynamically predicted outcomes during repeated TACE. Sequential risk assessment using mHAP-II best identified optimal candidates for repeated TACE.

Predictors of Discordance in the Assessment of Skeletal Muscle Mass between Computed Tomography and Bioimpedance Analysis.

Computed tomography (CT) and bioimpedance analysis (BIA) can assess skeletal muscle mass (SMM). Our objective was to identify the predictors of discordance between CT and BIA in assessing SMM. Participants who received a comprehensive medical health check-up between 2010 and 2018 were recruited. The CT and BIA-based diagnostic criteria for low SMM are as follows: Defined CT cutoff values (lumbar skeletal muscle index (LSMI) <1 standard deviation (SD) and means of 46.12 cm²/m² for men and 34.18 cm²/m² for women) and defined BIA cutoff values (appendicular skeletal muscle/height² <7.0 kg/m² for men and <5.7 kg/m² for women). A total of 1163 subjects were selected. The crude and body mass index (BMI)-adjusted SMM assessed by CT were significantly associated with those assessed by BIA (correlation coefficient = 0.78 and 0.68, respectively; p < 0.001). The prevalence of low SMM was 15.1% by CT and 16.4% by BIA. Low SMM diagnosed by CT was significantly associated with advanced age, female gender, and lower serum albumin level, whereas low SMM diagnosed by BIA was significantly associated with advanced age, female gender, and lower BMI (all p < 0.05). Upon multivariate analysis, age >65 years, female and BMI <25 kg/m² had significantly higher risks of discordance than their counterparts (all p < 0.05). We found a significant association between SMM assessed by CT and BIA. SMM assessment using CT and BIA should be interpreted cautiously in older adults (>65 years of age), female and BMI <25 kg/m².

Multicenter Retrospective Risk Assessment of Esophageal Variceal Bleeding in Patients with Cirrhosis: An Acoustic Radiation Force Impulse Elastography-Based Prediction Model.

Background/Aims: Acoustic radiation force impulse (ARFI) elastography predicts the presence of esophageal varices (EVs). We investigated whether an ARFI-based prediction model can assess EV bleeding (EVB) risk in patients with cirrhosis. Methods: The records of 262 patients with cirrhosis who underwent ARFI elastography and endoscopic surveillance at two institutions in 2008 to 2013 were retrospectively reviewed, and ARFI-spleen diameter-to-platelet ratio scores (ASPS) were calculated. Results: The median patient age (165 men, 97 women) was 56 years. The median ARFI velocity, spleen diameter, platelet count, and ASPS were 1.7 m/sec, 10.1 cm, 145×109/L, and 1.16, respectively. During the median 38-month follow-up, 61 patients experienced EVB. Among all patients (179 without EVs and 83 with EVs), the cutoff value that maximized the sum of the sensitivity (73.1%) and specificity (78.4%) (area under receiver operating characteristic curve [AUROC], 0.824) for predicting EVB was 2.60. The cumulative EVB incidence was significantly higher in patients with ASPS ≥2.60 than in those with ASPS <2.60 (p<0.001). Among patients with EVs (n=83), 49 had high-risk EVs (HEVs), and 22 had EVB. The cumulative EVB incidence was significantly higher in HEV patients than in low-risk EV patients (p=0.037). At an ASPS of 4.50 (sensitivity, 66.7%; specificity, 70.6%; AUROC, 0.691), the cumulative EVB incidence was significantly higher in patients with a high ASPS than in those with a low ASPS (p=0.045). A higher ASPS independently predicted EVB (hazard ratio, 4.072; p=0.047). Conclusions: ASPS can assess EVB risk in patients with cirrhosis. Prophylactic management should be considered for patients with HEVs and ASPS ≥4.50.

Estimating the Cost-Effectiveness of One-Time Screening and Treatment for Hepatitis C in Korea.

BACKGROUND AND AIMS: This study aims to investigate the cost-effectiveness of a one-time hepatitis C virus (HCV) screening and treatment program in South Korea where hepatitis B virus (HBV) prevails, in people aged 40-70, compared to current practice (no screening). METHODS: A published Markov model was used in conjunction with a screening and treatment decision tree to model patient cohorts, aged 40-49, 50-59 and 60-69 years, distributed across chronic hepatitis C (CHC) and compensated cirrhosis (CC) health states (82.5% and 17.5%, respectively). Based on a published seroepidemiology study, HCV prevalence was estimated at 0.60%, 0.80% and 1.53%, respectively. An estimated 71.7% of the population was screened. Post-diagnosis, 39.4% of patients were treated with a newly available all-oral direct-acting antiviral (DAA) regimen over 5 years. Published rates of sustained virologic response, disease management costs, transition rates and utilities were utilised. RESULTS: Screening resulted in the identification of 43,635 previously undiagnosed patients across all cohorts. One-time HCV screening and treatment was estimated to be cost-effective across all cohorts; predicted incremental cost-effectiveness ratios ranged from $5,714 to $8,889 per quality-adjusted life year gained. Incremental costs associated with screening, treatment and disease management ranged from $156.47 to $181.85 million USD; lifetime costs-offsets associated with the avoidance of end stage liver disease complications ranged from $51.47 to $57.48 million USD. CONCLUSIONS: One-time HCV screening and treatment in South Korean people aged 40-70 is likely to be highly cost-effective compared to the current practice of no screening.

Risk Assessment of Hepatocellular Carcinoma Using Transient Elastography Vs. Liver Biopsy in Chronic Hepatitis B Patients Receiving Antiviral Therapy.

Liver stiffness (LS) assessed using transient elastography (TE) can assess the risk of developing hepatocellular carcinoma (HCC). We evaluated whether TE, when compared with histological data as a reference standard, can predict the risk of HCC development in chronic hepatitis B (CHB) patients starting antiviral therapy.Observational cohort database of 381 patients with CHB who underwent liver biopsy (LB) and TE were reviewed. All patients underwent surveillance for HCC development using ultrasonography and alpha-fetoprotein.During the median follow-up period of 48.1 (interquartile range 30.3-69.3) months, HCC developed in 34 (8.9%) patients. In patients with HCC development, age, proportion of diabetes mellitus, histological fibrosis stage, and LS value were significantly higher than those in patients without (all P <0.05). The cumulative incidence rates of HCC increased significantly in association with elevated LS value in 3 stratified groups (LS value <8, 8-13, and >13 kPa; log-rank test, P <0.001), and with higher histological fibrosis stage in 3 stratified groups (F0-2, F3, and F4; log-rank test, P <0.001). On multivariate analysis, along with age, LS value was an independent predictor of HCC development (hazard ratio 1.041, P <0.001), whereas histological staging was not (P >0.05).TE predicted HCC development independently in patients with CHB starting antiviral therapy. However, further investigation is needed to determine whether the current surveillance strategy can be optimized based on the LS value at the time of starting antiviral therapy.

Red cell volume distribution width-to-platelet ratio in assessment of liver fibrosis in patients with chronic hepatitis B.

BACKGROUND & AIMS: Precise assessment of liver fibrosis is necessary in patients with chronic liver disease. We investigated the performance of red cell volume distribution width-to-platelet ratio for the assessment of liver fibrosis in patients with chronic hepatitis B. METHODS: A total of 482 consecutive patients with chronic hepatitis B who underwent liver biopsy between October 2005 and May 2014 were recruited. Liver stiffness was measured using transient elastography. FIB-4 score, red cell volume distribution width-to-platelet ratio and the aspartate aminotransferase-to-platelet ratio index were also assessed. RESULTS: A total of 271 (56.2%) patients were males. The median age was 44 years. F1, F2, F3 and F4 fibrosis stages were identified in 68 (14.1%), 137 (28.4%), 64 (13.3%) and 213 (44.2%) of the patients respectively. The mean red cell volume distribution width-to-platelet ratio increased with liver fibrosis severity: F1, 0.065; F2, 0.077; F3, 0.097 and F4, 0.121 (P < 0.01). The area under the receiver operating characteristic curve of the red cell volume distribution width-to-platelet ratio for predicting significant fibrosis (≥F2) was 0.747. This result was inferior to transient elastography (0.866, P = 0.004), but comparable to FIB-4 (0.782, P = 0.427) and aspartate aminotransferase-to-platelet ratio index (0.716, P = 0.507). The area under the receiver operating characteristic curve of red cell volume distribution width-to-platelet ratio for predicting cirrhosis (F4) was 0.811, which was inferior to liver stiffness (0.915, P < 0.001), but comparable to FIB-4 (0.804, P = 0.805) and superior to aspartate aminotransferase-to-platelet ratio index (0.680, P < 0.001). CONCLUSIONS: The accuracy of red cell volume distribution width-to-platelet ratio was acceptable for the assessment of liver fibrosis in patients with chronic hepatitis B. When transient elastography is not available, red cell volume distribution width-to-platelet ratio assessment is a simple method that can be used to reduce the need for liver biopsy.

Disease duration and Medsger's severity score are associated with significant liver fibrosis in patients with systemic sclerosis.

OBJECTIVES: We investigated the prevalence and predictors of significant liver fibrosis in patients with systemic sclerosis (SSc) who had no evidences of liver diseases due to viral infection, drug, and heavy alcohol consumption. METHODS: A total of 44 SSc patients were recruited. In addition to the clinical and laboratory data, the 2013 College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria score, modified Rodnan skin score (mRSS), and Medsger's severity score (MSS) were analysed. Liver stiffness (LS) was measured using transient elastography to assess the degree of liver fibrosis and 7.4 kPa was adopted as the cut-off value for significant liver fibrosis. RESULTS: The median age of patients (38 women) was 54 years and the median disease duration was 41.0 months. The median LS value was 4.6 kPa. The median mRSS and MSS were 7.0 and 5.0, respectively. Six (13.6%) patients had significant liver fibrosis. Disease duration (standardised ß=0.375, p=0.018) and MSS (standardised ß=0.398, p=0.047) significantly correlated with LS values. In multivariate analysis, disease duration≥63 months (odds ratio (OR) 19.166, 95% confidence interval 1.090, 336.962, p=0.043) and MSS≥7 (OR 19.796, 95% confidence interval 1.439, 272.252, p=0.026) independently predicted the presence of significant liver fibrosis. CONCLUSIONS: The prevalence of significant liver fibrosis was relatively high (13.6%) and its independent predictors were disease duration and MSS.

Reimbursement policies in the Asia-Pacific for chronic hepatitis B.

BACKGROUND: There is considerable variation in reimbursement policies in Asian countries and this is likely to have an impact on treatment practice for chronic hepatitis B (CHB). Consequently a survey of leading hepatologists was performed to evaluate such policies and their impact on management of CHB in the Asia Pacific region. METHODS: A questionnaire was sent to key hepatologists in Asia Pacific for information on CHB reimbursement policy-its nature, coverage, funding source, duration, review strategy and impact on Asia Pacific Association for the Study of the Liver (APASL) CHB guidelines. The results were analysed and described. RESULTS: Leading hepatologists from 16 Asia Pacific countries responded. Almost all of the countries have reimbursement policies but eligibility varied from only a limited group (e.g. civil servants only) to universal access. In most instances reimbursement was from the central government (except China, Pakistan and Hong Kong). Reimbursement policies were usually created by Ministry of Health committees, who received input from medical professionals, although they may not be aware of the APASL guidelines. Policies were limited by available resources, funds and prioritization. Where there was a regular review this occurred between 1 and 5 years. The quantum of reimbursement varied from 50% in Singapore to 100% in the majority of other countries. The criteria for treatment reimbursement were based on doctor's opinion alone (Bangladesh, India, Pakistan, Philippines, Singapore and Vietnam) or specific clinical/laboratory criteria in the rest of the countries. In general, most countries offered unlimited duration for reimbursement except Taiwan, Indonesia and Pakistan. Monitoring tests for treatment response were reimbursed in all countries other than Vietnam. Viral resistance was diagnosed by viral or biochemical breakthrough, and viral resistance testing was uncommon. The main rescue therapy was adefovir. CONCLUSION: Reimbursement policies differed from country to country, the quantum and the proportion of patients who received reimbursement also varied significantly. Asia Pacific countries were able to follow APASL guidelines with variable success based on their reimbursement policies.

Evolution from WHO to EASL and mRECIST for hepatocellular carcinoma: considerations for tumor response assessment.

Radiological response assessment criteria in hepatocellular carcinoma (HCC) have evolved to accurately evaluate tumor responses. The WHO criteria and the subsequent Response Evaluation Criteria in Solid Tumors (RECIST) evaluate change in tumor size; however, these criteria generally ignore tumor necrosis and therefore may underestimate treatment responses. Thus, a panel of experts of the European Association for the Study of Liver (EASL) amended the response criteria to take into account tumor necrosis. In 2010, the modified RECIST (mRECIST) was developed, which consider both the concept of tumor viability based on arterial enhancement and single linear summation, ultimately simplifying EASL criteria. Currently, the mRECIST represents the gold standard for radiologically evaluating tumor response during HCC treatment. Here, the authors review application and performance of mRECIST as well as other HCC response assessment criteria and discuss unmet and open issues regarding response evaluation for HCC treatments.

Risk assessment of clinical outcomes in Asian patients with chronic hepatitis B using enhanced liver fibrosis test.

UNLABELLED: Serum fibrosis markers, such as the enhanced liver fibrosis (ELF) test, have been suggested as alternatives for liver biopsy (LB) in assessing liver fibrosis. We investigated the efficacy of the ELF test in predicting development of liver-related events (LREs) in patients with chronic hepatitis B (CHB). A total of 170 patients (103 men; 60.6%) with CHB who underwent LB and serological tests for determining ELFs were enrolled. All patients were followed up to monitor LRE development, defined as hepatic decompensation, hepatocellular carcinoma, and/or liver-related death. The mean age was 45.3 years. During the follow-up period (median, 41 months), 39 (22.9%) patients experienced LREs. In patients with LREs, age, proportion of male gender, ELF test results, age-spleen-platelet ratio (ASPRI), liver stiffness (LS) value, and proportion of histological cirrhosis were significantly higher than those in patients without LREs (all P < 0.05). Areas under the receiver operating characteristic curves to predict LRE development were 0.808 for the ELF test, 0.732 for LS value, 0.713 for histological fibrosis stages using Batts and Ludwig's scoring system, and 0.687 for ASPRI. On multivariate analysis, along with age, the ELF test was an independent predictor of LRE development (adjusted hazard ratio [HR], 1.438; P < 0.001). When we applied a three-tier stratification of our study population using cut-off ELF values of 8.10 and 10.40, patients with low (P = 0.002; adjusted HR: 0.045; 95% confidence interval [CI]: 0.006-0.330) and intermediate (P < 0.001; adjusted HR: 0.239; 95% CI: 0.122-0.469) ELF range were found less likely to develop LREs, compared to those with high ELF range. CONCLUSION: ELF is useful in a noninvasive prediction of LRE development. Transient elastography showed a statistically similar prognostic performance for LREs as the ELF, but other noninvasive tests were inferior.

Hepatocellular carcinoma specific graded prognostic assessment can predict outcomes for patients with brain metastases from hepatocellular carcinoma.

Stratifying patients with brain metastasis (BM) from hepatocellular carcinoma (HCC) by prognostic factors can be useful when making treatment decisions. Nevertheless, a diagnosis-specific graded prognostic assessment (GPA) for HCC has not been well established. We retrospectively reviewed the data from 118 HCC patients newly diagnosed with BM at the Yonsei University Health System between 1985 and 2011. After univariate and multivariate analyses of prognostic factors, those shown to significantly affect survival were used to develop a HCC-specific GPA (HCC-GPA) index. The median overall survival after BM in all patients was 6.1 weeks (95% confidence interval 4.8-7.4 weeks). Using the prognostic factors identified via multivariate analysis, we developed a HCC-GPA index, including number of brain metastases (single: 0.5, multiple: 0 points), alpha-feto protein (<400 ng/mL: 0.5, ≥400 ng/mL: 0 points), and Child-Pugh-Score (A: 3, B: 2, C: 0 points). There were no survival differences for age, sex, performance status, and time interval from initial diagnosis to development of BM. Median survival times from BM were discriminable when applying the HCC-GPA scoring system: 1.7, 3.2, 7.9, and 27.0 weeks for HCC-GPA scores of 0-1.0 (N = 16), 1.5-2.5 (N = 32), 3.0-3.5 (N = 49), and 4.0 (N = 21), respectively (P < 0.001). Although the prognoses of patients with BM from HCC are dismal, the newly developed HCC-GPA index can be used to discriminate the expected prognoses thereof. Moreover, the index may hold value as a tool for selecting patients who may be good candidates for active local treatment.

Risk assessment of liver-related events using transient elastography in patients with chronic hepatitis B receiving entecavir.

GOALS: We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB). BACKGROUND: LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease. METHODS: Between June 2007 and May 2010, a total of 162 patients with CHB who completed 2-year entecavir (ETV) treatment were evaluated. The primary endpoint was LRE development (hepatic decompensation, hepatocellular carcinoma, or liver-related death) during the 2-year ETV treatment. RESULTS: The median age of the patients (99 men, 63 women) was 51 years, and the median LS value was 14.8 kPa. During the 2-year ETV treatment, 15 (9.3%) patients experienced LREs. On univariate analysis, age, the proportion of patients with liver cirrhosis, platelet counts, and baseline LS values were significantly associated with LRE development (all P<0.05). Together with age, multivariate analysis identified baseline LS values as an independent predictor of LRE development (P=0.046; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). The cutoff LS value maximizing the sum of sensitivity and specificity was 12.0 kPa (area under the receiver operating characteristics curve, 0.736; P=0.003; sensitivity, 93.3%; specificity, 42.2%). In addition, the changes in LS values between baseline and 1-year ETV treatment showed significant correlations with LRE development (P=0.030). CONCLUSIONS: Our data suggest that LS values are predictive of LRE development during 2-year ETV treatment in patients with CHB. The potential role of LS value as a monitoring tool for predicting dynamic changes in the risk of LRE development during long-term ETV treatment should be investigated further.

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.

Digestive cancer management in Asia: position statements: a report on GI Oncology Summit in 2011.

BACKGROUND AND AIM: With the rising incidence of digestive cancers in the Asia Pacific region and the advancement in diagnosis, management and palliation in these conditions, the clinical burden on oncologists is ever increasing. This Summit meeting was called to discuss the optimal management of digestive cancers and the role of Gastroenterologists. METHOD: Experts from Asia Pacific countries in the fields of medical, oncologic, surgical and endoscopic management of cancers in the esophagus, stomach, colon/rectum and the liver reviewed the literature and their practice. 18 position statements were drafted, debated and voted. RESULTS: It was agreed that the burden on GI cancer is increasing. More research will be warranted on chemotherapy, chemoprevention, cost-effectiveness of treatment and nutrition. Cancer management guidelines should be developed in this region when more clinical data are available. In order to improve care to patients, a multi-disciplinary team coordinated by a "cancer therapist" is proposed. This cancer therapist can be a gastroenterologist, a surgeon or any related discipline who have acquired core competence training. This training should include an attachment in a center-of-excellence in cancer management for no less than 12 months. CONCLUSION: The management of GI cancer should be an integrated multi-disciplinary approach and training for GI cancer therapists should be provided for.

Risk assessment of development of hepatic decompensation in histologically proven hepatitis B viral cirrhosis using liver stiffness measurement.

BACKGROUND/AIMS: There are few studies regarding the predictive value of liver stiffness measurement (LSM) for development of hepatic decompensation. We assessed the risk of hepatic decompensations in B-viral compensated cirrhosis, using an LSM and LSM-based model (LSM-spleen diameter to platelet ratio score, LSPS = LSM × spleen diameter/platelet count) in a prospective, longitudinal study. METHODS: We analyzed 217 patients with histologically proven B-viral cirrhosis, well-preserved liver function, and no history of decompensation. The Kaplan-Meier and Cox regression method were used to examine the major endpoint, time to the first decompensation event, defined as development of ascites, hepatic encephalopathy, variceal hemorrhage, and deterioration of liver function to Child-Pugh class B/C. RESULTS: During follow-up, 26 patients experienced hepatic decompensation, ascites (n = 22), hepatic encephalopathy (n = 11), variceal hemorrhage (n = 9), and deterioration of liver function (n = 20). For risk stratification, patients were grouped as LSM <13, 13-18, and ≥18 kPa, and from multivariate analysis, patients with LSM 13-18 kPa [hazard ratio (HR) 4.547/ p = 0.044] and ≥18 kPa (HR 12.446/p < 0.001) retained independently higher risks than patients with LSM <13 kPa. Similarly, when patients were grouped as LSPS <1.1, 1.1-2.5, and ≥2.5, those with LSPS 1.1-2.5 (HR 5.796/p = 0.004) and ≥2.5 (HR 13.618/p < 0.001) retained independently higher risks than those with LSPS <1.1. CONCLUSION: LSM and LSPS are useful in risk assessment of hepatic decompensation among complication-naive B-viral cirrhotic patients.

Risk assessment of esophageal variceal bleeding in B-viral liver cirrhosis by a liver stiffness measurement-based model.

OBJECTIVES: Periodic endoscopic screening for esophageal varices (EVs) and prophylactic treatment for high-risk EVs (HEVs; (i) medium/large EVs and (ii) small EVs with red sign or decompensated cirrhosis) are recommended for cirrhotic patients. We assessed cumulative risks of future EV bleeding (EVB) using the liver stiffness measurement (LSM)-based model, LSM-spleen diameter to platelet ratio score (LSPS=LSM×spleen diameter/platelet count). METHODS: We prospectively enrolled 577 consecutive B-viral cirrhosis patients from 2005 to 2009, none of whom experienced EVB. All underwent laboratory workups, endoscopy, LSM, and ultrasonography. Those with HEVs took nonselective ß-blockers as prophylaxis for EVB after diagnosis, if not contraindicated. The major end point was the first EVB event, examined using Kaplan-Meier and Cox-regression methods. RESULTS: Among whole population, 95.9% negative- /93.5% positive-predictive value by LSPS<3.5/LSPS≥5.5 were provided for predicting the presence of HEV at enrollment, respectively. Among patients with HEV (n=150), 25 experienced their first EVBs during follow-up (median, 29 months). To differentiate EVB risk, we divided them into subgroup 1 (LSPS<6.5) and 2 (LSPS≥6.5) according to LSPS 6.5, a point with maximum sum of sensitivity and specificity from time-dependent receiver-operating characteristic (ROC) curves (area under ROC curve=0.929). EVB risk was higher in subgroup 2 than subgroup 1 (P<0.001). Multivariate analysis found higher LSPS (P=0.003) a significant predictor, alongside large variceal sizes (P=0.004) and Child-Pugh classifications B/C (P=0.001). Notably, EVB risk of subgroup 1 was as low as that of low-risk EVs (P=0.507). CONCLUSIONS: LSPS is a reliable predictor for EVB risk. According to risk stratification, different prophylactic treatments should be considered for subgroups with LSPS≥6.5.