Patient-reported outcomes in patients with non-alcoholic fatty liver disease: A narrative review of Chronic Liver Disease Questionnaire-non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and one of the leading causes of hepatocellular carcinoma and liver transplantation. Moreover, patients with NAFLD frequently complain of non-specific symptoms including fatigue, abdominal discomfort, as well as anxiety, and NAFLD is reported to affect patient-reported outcomes (PROs). Thus, for clarifying the total burden of NAFLD, it is crucial to assess all associated outcomes, including not only clinical and economic outcomes but also PROs. PROs are thought to reflect what is happening in one's daily life and is an important way patients and health-care professionals communicate. There are various instruments for the assessment of PROs. Recently, a NAFLD/non-alcoholic steatohepatitis (NASH)-specific instrument called "Chronic Liver Disease Questionnaire (CLDQ)-NAFLD/NASH" has been developed. CLDQ-NAFLD/NASH comprises six domains: (i) abdominal symptoms, (ii) activity/energy, (iii) emotional health, (iv) fatigue, (v) systemic symptoms, and (vi) worry. CLDQ-NAFLD/NASH has demonstrated excellent internal consistency, face validity, content validity, and test-retest reliability. It has been sufficiently validated in two international phase 3 clinical trials. In this review, we summarize features of various instruments for assessing PROs by focusing on CLDQ-NAFLD/NASH. We also examine the validity of CLDQ-NAFLD/NASH in Japanese patients and alterations in CLDQ-NAFLD/NASH score in Japanese patients with significant hepatic fibrosis. Moreover, we discuss the utility of CLDQ-NAFLD/NASH in phase 3 clinical trials and in a real-world clinical setting.

Assessment of tumor volume and density as a measure of the response of advanced hepatocellular carcinoma to sorafenib: Application of automated measurements on computed tomography scans.

BACKGROUND AND AIM: To better predict patient survival, we used automated tumor volume and density measurements to make an objective radiological assessment of the response of advanced hepatocellular carcinoma (HCC) to treatment with sorafenib. METHODS: Patients treated with sorafenib were identified retrospectively. Those who were diagnosed with Child-Pugh class A liver function, Barcelona-Clinic Liver Cancer stage C, and Eastern Cooperative Oncology Group performance status grade 0/1 were enrolled (n = 22). Reviews of contrast-enhanced computed tomography images were supported by the automated measurement of lesions using computer software. Treatment responses were assessed using volume and density criteria. Kaplan-Meier methods and multivariate Cox regression analysis were used to evaluate treatment responses and identify the most significant prognostic factors for overall survival (OS). RESULTS: After patients were dichotomized according to volume and density criteria, the median OS for those with an objective response (OR) (complete response + partial response) was 20.4 months and that for those with a non-OR (stable disease + progressive disease) was 9.3 months (P = 0.009). The best multivariate regression model for survival identified volume and density criteria (OR or non-OR) as a significant variable, along with baseline alpha-fetoprotein levels (log-rank test, P = 0.01). No other conventional criteria were identified as significant. CONCLUSIONS: Tumor volume and density assessment using automated lesion measurements may be an objective method of evaluating responses of advanced HCC to treatment with sorafenib.

Estimating the cost-effectiveness of screening for hepatitis C virus infection in Japan.

AIM: The management of hepatitis C virus (HCV) has changed with the advent of interferon (IFN)-free treatment and the declining prevalence of HCV infection, which may impact the cost-effectiveness of the screening. We aimed to compare the cost-effectiveness and clinical outcomes of three screening strategies in the Japanese general population: no screening, screening plus IFN-based therapy, and screening plus IFN-free therapy. METHODS: We developed a decision analytic Markov model for screening intervention and natural history of HCV. Model parameters were derived from published literature. A lifetime horizon and the healthcare payer perspective were taken. Subanalyses included high screening scenario with improved rates of screening and attending referral, in addition to heterogeneity analysis by age subgroup. RESULTS: In the base case, the incremental cost-effectiveness ratio in the Japanese general population aged 40-89 years was ¥1 124 482 and ¥1 085 183 per quality-adjusted life year gained for screening plus IFN-free therapy compared with no screening and screening plus IFN-based therapy, respectively. Screening plus IFN-free therapy remained cost-effective below ¥5 000 000 per quality-adjusted life year gained in sensitivity analyses. Incremental cost-effectiveness ratios were lower in the younger population. Nearly 0.2% of HCV-related deaths were avoided by 1.5% of the general population screened followed by IFN-free therapy relative to no screening; the impact was greater with improved rates of screening and attending referral. CONCLUSIONS: Screening and subsequent IFN-free therapy for HCV appears to be cost-effective. Early diagnosis and treatment would produce a favorable incremental cost-effectiveness ratio. Improved rates of screening and attending referral would result in further reduction of disease progression.

Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. METHODS: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. RESULTS: If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population. CONCLUSIONS: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. LAY SUMMARY: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.

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.

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.