Nonalcoholic fatty liver disease burden: Australia, 2019-2030.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a large and growing proportion of liver disease burden globally. The burden of NAFLD/NASH manifests in increasing levels of advanced liver disease and primary liver cancer in Australia. A Markov model was used to forecast NAFLD burden in Australia through 2030. METHODS: A model was used to estimate fibrosis progression, primary liver cancer, and liver deaths among the Australian NAFLD population, with changes in incident NAFLD cases based on long-term trends for changes in the prevalence of obesity. Published estimates and surveillance data were applied to build and validate the model projections, including surveillance data for the incidence of liver cancer. RESULTS: Prevalent NAFLD cases were projected to increase 25% from the current burden (5 551 000 [4 748 000-6 306 000] cases in 2019) to 7 024 000 [5 838 000-7 886 000] cases in 2030. The projected increase in the number of NASH cases (40%) was greater than that of NAFLD cases. Incident cases of advanced liver disease are projected to increase up to 85% by 2030, and incident NAFLD liver deaths are estimated to increase 85% from 1900 (1100-3300) deaths in 2019 to 3500 (2100-6100) deaths in 2030. CONCLUSIONS: Restraining growth of the obese and diabetic populations, along with potential therapeutic options, will be essential for mitigating disease burden.

Combination of Tenofovir Disoproxil Fumarate and Peginterferon α-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B.

BACKGROUND & AIMS: Patients chronically infected with the hepatitis B virus rarely achieve loss of serum hepatitis B surface antigen (HBsAg) with the standard of care. We evaluated HBsAg loss in patients receiving the combination of tenofovir disoproxil fumarate (TDF) and peginterferon α-2a (peginterferon) for a finite duration in a randomized trial. METHODS: In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus peginterferon for 48 weeks (group A), TDF plus peginterferon for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or peginterferon for 48 weeks (group D). The primary end point was the proportion of patients with serum HBsAg loss at week 72. RESULTS: At week seventy-two, 9.1% of subjects in group A had HBsAg loss compared with 2.8% of subjects in group B, none of the subjects in group C, and 2.8% of subjects in group D. A significantly higher proportion of subjects in group A had HBsAg loss than in group C (P < .001) or group D (P = .003). However, the proportions of subjects with HBsAg loss did not differ significantly between group B and group C (P = .466) or group D (P = .883). HBsAg loss in group A occurred in hepatitis B e antigen-positive and hepatitis B e antigen-negative patients with all major viral genotypes. The incidence of common adverse events (including headache, alopecia, and pyrexia) and treatment discontinuation due to adverse events was similar among groups. CONCLUSIONS: A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone. ClinicalTrials.gov ID NCT01277601.

Feasibility of conducting a randomized control trial for liver cancer screening: is a randomized controlled trial for liver cancer screening feasible or still needed?

UNLABELLED: Screening for hepatocellular carcinoma (HCC) is commonly practiced and recommended in published guidelines, but evidence for its efficacy has been controversial. We tested the feasibility of conducting a randomized controlled trial (RCT) of HCC surveillance in patients with cirrhosis and followed up those offered screening to detect clinical outcomes. Participation was offered to patients with cirrhosis attending liver clinics at three university hospitals. Following discussion, patients received a decision aid (DA) that outlined the risks and benefits of surveillance. The proposed screening program comprised ultrasonography 6-monthly and serum alpha-fetoprotein every 3 months. We envisaged five groups of patients: those who agreed to randomization, those choosing nonrandomized screening, those wanting continuation of usual care, those who were undecided, and those refusing participation. Among 205 patients, 204 (99.5%) declined randomization. Of these, 181 (88%) elected for a nonrandomized screening program, 10% chose usual care (which typically included ad hoc screening), and two were undecided. Among 176 patients fluent in English communication skills, 160 (91%) preferred nonrandomized screening compared with 22/29 (76%) patients needing an interpreter (P < 0.026). Of 173 patients in nonrandomized screening followed up for a mean 13.5 ± 6.04 months, three developed HCC, two died from nonliver-related causes, and one underwent liver transplantation for liver failure. Eighteen of 21 patients in "usual care" received ad hoc screening. A simultaneous survey on the quality of the DA showed that the majority of participants believed that the information provided was unbiased. CONCLUSION: Although an RCT is theoretically ideal for determining the efficacy, efficiency, and cost-effectiveness of HCC screening, informed patients prefer surveillance. A randomized study of HCC screening is not feasible when informed consent is imparted.

The direct cost of managing patients with chronic hepatitis B infection in Australia.

GOALS: To estimate the average annual cost of managing a patient with chronic hepatitis B (CHB) disease in Australia. BACKGROUND: Little is known about the prevalence or economic burden of hepatitis B viral (HBV) infection in Australia, despite it being recognized as a significant cause of morbidity and mortality. STUDY: A retrospective analysis of 149 patients with CHB disease in six disease states (noncirrhotic CHB, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplantation in year 1, and liver transplantation in subsequent posttransplantation years) was conducted. The cost of palliative care for 53 patients with chronic hepatitis and hepatocellular carcinoma was also estimated, based on data from a palliative care unit. RESULTS: The average annual costs (year-2001 AUS$) for each disease state per patient were: noncirrhotic CHB, 1233 dollars (95% CI 939 dollars-1544 dollars); compensated cirrhosis, 1394 dollars (95% CI 975 dollars-1797 dollars); decompensated cirrhosis, 11,961 dollars (95% CI 6993 dollars-18,503 dollars); liver transplantation in year 1, 144,392 dollars (SD, 115,374 dollars); liver transplantation in year 2+, 23,160 dollars (SD, 19,289 dollars); and hepatocellular carcinoma, 11,753 dollars (95% CI 7385 dollars-17,159 dollars). Within the noncirrhotic CHB group, the cost of managing active disease was 1778 dollars (95% CI 1212 dollars-2374 dollars) compared with 758 dollars (95% CI 519 dollars-1045 dollars) for inactive disease. The average cost of palliative care for patients with chronic hepatitis and hepatocellular carcinoma was 6307 dollars (95% CI 4848 dollars-8187 dollars). Multivariate statistical analysis indicated that age, sex, marital status, country of birth, and duration of follow-up were not statistically significant in explaining variation in costs. CONCLUSIONS: The cost of managing patients with CHB disease varies significantly between the noncirrhotic CHB/compensated cirrhosis states and the other four disease states. Within the noncirrhotic CHB state, there is also a significant difference between the cost of managing active and inactive disease. These results will be useful in future cost-effectiveness analyses of prevention and treatment options.