Cost-effectiveness of universal screening for chronic hepatitis B virus infection in China: an economic evaluation.

BACKGROUND: China has the highest prevalence of hepatitis B virus (HBV) infection worldwide. Universal HBV screening might enable China to reach the WHO 2030 target of 90% diagnostics, 80% treatment, and 65% HBV-related death reduction, and eventually elimination of viral hepatitis. We evaluated the cost-effectiveness of implementing universal HBV screening in China and identified optimal screening strategies. METHODS: We used a Markov cohort model, inputting parameters based on data from previous studies and public databases, to assess the cost-effectiveness of four HBV serological screening strategies in China in different screening scenarios. We simulated universal screening scenarios in 15 adult age groups between 18 and 70 years, with different years of screening implementation (2021, 2026, and 2031) and compared to the status quo (ie, no universal screening); in total, we investigated 180 different screening scenarios. We calculated the incremental cost-effectiveness ratio (ICER) between the different screening strategies and the status quo (current screening strategy). We performed probabilistic and one-way deterministic sensitivity analyses to assess the robustness of our findings. FINDINGS: With a willingness-to-pay level of three times the Chinese gross domestic product (GDP) per capita (US$30 828), all universal screening scenarios in 2021 were cost-effective compared with the status quo. The serum HBsAg/HBsAb/HBeAg/HBeAb/HBcAb (five-test) screening strategy in people aged 18-70 years was the most cost-effective strategy in 2021 (ICER $18 295/quality-adjusted life-years [QALY] gained). This strategy remained the most cost-effective, when the willingness-to-pay threshold was reduced to 2 times GDP per capita. The two-test strategy for people aged 18-70 years became more cost-effective at lower willingness-to-pay levels. The five-test strategy could prevent 3·46 million liver-related deaths in China over the lifetime of the cohort. It remained the most cost-effective strategy when implementation was delayed until 2026 (ICER $20 183/QALY) and 2031 (ICER $23 123/QALY). Screening young people (18-30 years) will no longer be cost-effective in delayed scenarios. INTERPRETATION: The five-test universal screening strategy in people aged 18-70 years, implemented within the next 10 years, is the optimal HBV screening strategy for China. Other screening strategies could be cost-effective alternatives, if budget is limited in rural areas. Delaying strategy implementation reduces overall cost-effectiveness. Early screening initiation will aid global efforts in achieving viral hepatitis elimination. FUNDING: National Natural Science Foundation of China.

Cost-Utility of All-Oral Direct-Acting Antiviral Regimens for the Treatment of Genotype 1 Chronic Hepatitis C Virus-Infected Patients in Hong Kong.

BACKGROUND: Direct-acting antivirals (DAAs) are entering the hepatitis C virus (HCV) treatment landscape in Hong Kong, prompting the need for cost-effectiveness evaluations of these interventions to enable optimal use of healthcare resources. AIMS: This study aimed to compare the cost-effectiveness of DAAs to standard-of-care pegylated interferon plus ribavirin (RBV) in treatment-naïve patients without significant liver fibrosis and to compare different DAAs in patients who are treatment-experienced and/or have advanced liver disease. METHODS: A Markov model was constructed to evaluate cost-effectiveness over a lifetime time horizon from the payer perspective. The target population was treatment-naïve and treatment-experienced HCV genotype 1 patients, stratified by degree of liver fibrosis. The model consists of 16 health states encompassing METAVIR fibrosis score (F0-F4), treatment success or failure, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and liver-related death. The proportions of patients achieving sustained virologic response were obtained from clinical trials. Other inputs were obtained from published and local data. The primary outcome was incremental cost-utility ratio for each DAA versus pegylated interferon + ribavirin and among different DAAs. RESULTS: In treatment-naïve F0-2 HCV patients, all DAAs were cost-effective in genotype 1a and daclatasvir + asunaprevir, elbasvir/grazoprevir, ledipasvir/sofosbuvir, and glecaprevir/pibrentasvir were cost-effective compared to pegylated interferon + ribavirin in genotype 1b. In genotypes 1a and 1b, treatment-experienced patients, and F3-4 patients, elbasvir/grazoprevir was the least costly DAA and economically dominant over most other DAAs. CONCLUSIONS: DAAs can be a cost-effective option for the treatment of genotype 1 HCV patients in Hong Kong, and elbasvir/grazoprevir is cost-effective.

Novel developments of hepatitis B: treatment goals, agents and monitoring tools.

INTRODUCTION: Chronic hepatitis B (CHB) infection causes considerable morbidity and mortality and hence should be a target for global elimination. In recent years, advances have been made in understanding the disease pathophysiology and the relationship to clinical outcome. Novel treatment targets are actively being sought in the hope of improving the treatment outlook. Areas covered: We discussed the cascade of cure of CHB with respect to the degree of persistence of viral genome and proteins. Several novel antiviral agents either targeting the virus or the host are in different clinical phases of development. Serum hepatitis B core-related antigen and HBV RNA are novel markers, which might have a role in the prediction of specific clinical outcomes such as development of hepatocellular carcinoma or virological relapse after cessation of antiviral therapy. These markers may also be used to monitor treatment response in the drug trials. Expert commentary: Global elimination of CHB is challenged by extremely low awareness of illness and poor access to care. CHB and its related complications can be reduced by birth dose vaccine, antiviral therapy, and alleviated by complication screening. Treatment options for CHB will expand in the next decade and early functional cure is not an impractical goal.

Global Epidemiology, Prevention, and Management of Hepatocellular Carcinoma.

The incidence rate of hepatocellular carcinoma (HCC) is rising. It is one of the most common cancers worldwide and accounts for substantial morbidity and mortality. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, and nonalcoholic fatty liver disease (NAFLD) are the most important etiologies of HCC, and effective screening and management strategies are crucial to reduce the HCC risk. For HBV, which accounts for the majority of HCC cases, most infections were acquired via perinatal and early horizontal transmission. Universal vaccination of newborns has led to a decline in HCC incidence compared with the pre-vaccination era. Effective antiviral therapies with nucleos(t)ide analogues or pegylated interferon reduced the incidence of HCC. For HCV, the emergence of effective direct-acting antiviral (DAA) agents has substantially improved cure rates; therefore all patients with HCV should be considered for DAA treatment. The most important obstacle in eliminating HCV is access to therapy. For NAFLD, the global incidence is increasing rapidly, thus its impact on HCC incidence may be explosive. Progression to HCC in NAFLD happens particularly in those with nonalcoholic steatohepatitis (NASH) and exacerbated by metabolic syndrome, or PNPLA3 gene polymorphism. Lifestyle changes are imperative while drug therapy has yet to demonstrate substantive protective effects on HCC prevention. For management of HCC, early diagnosis via imaging surveillance among persons with HCC risk factors remains the most important strategy to identify early-stage disease appropriate for resection or transplantation.

Mechanism of entecavir resistance of hepatitis B virus with viral breakthrough as determined by long-term clinical assessment and molecular docking simulation.

The mechanism by which entecavir resistance (ETVr) substitutions of hepatitis B virus (HBV) can induce breakthrough (BT) during ETV therapy is largely unknown. We conducted a cross-sectional study of 49 lamivudine (LVD)-refractory patients and 59 naïve patients with chronic hepatitis B. BT was observed in 26.8% of the LVD-refractory group during weeks 60 to 144 of ETV therapy. A line probe assay revealed ETVr substitutions only in the LVD-refractory group, i.e., in 4.9% of patients at baseline, increasing to 14.6%, 24.4%, and 44.8% at weeks 48, 96, and 144, respectively. Multivariate logistic regression analysis adjusted for age, gender, HBV DNA levels, and LVD resistance (LVDr) (L180M and M204V, but not M204I) indicated that T184 substitutions and S202G (not S202C) were a significant factor for BT (adjusted odds ratio [OR], 141.12, and 95% confidence interval [CI], 6.94 to 2,870.20; OR, 201.25, and 95% CI, 11.22 to 3608.65, respectively). Modeling of HBV reverse transcriptase (RT) by docking simulation indicated that a combination of LVDr and ETVr (T184L or S202G) was characterized by a change in the direction of the D205 residue and steric conflict in the binding pocket of ETV triphosphate (ETV-TP), by significantly longer minimal distances (2.2 A and 2.1 A), and by higher potential energy (-117 and -99.8 Kcal/mol) for ETV-TP compared with the wild type (1.3 A; -178 Kcal/mol) and LVDr substitutions (1.5 A; -141 Kcal/mol). Our data suggest that the low binding affinity of ETV-TP for the HBV RT, involving conformational change of the binding pocket of HBV RT by L180M, M204V plus T184L, and S202G, could induce BT.

Prevalence of fibrosis and cirrhosis in chronic hepatitis B: implications for treatment and management.

OBJECTIVE: To document the prevalence and factors associated with severe fibrosis and cirrhosis in a large population of Asian chronic hepatitis B (CHB) patients. METHODS: Transient elastography was performed in unselected CHB patients. Liver stiffness score of <8.1 kPa was used as a cut-off for the presence of severe fibrosis or liver cirrhosis. RESULTS: 1315 patients were recruited, of which 951 (72%) were treatment-naive. Of these, 319 (34%) had severe fibrosis, with higher prevalence seen in males compared with females (39% vs 24% respectively, p < 0.01. Severe fibrosis was seen with increasing age from 20% in patients <25 years to 81% in those >65 years. Higher prevalence of severe fibrosis was seen in HBeAg(+) patients compared to HBeAg(-) patients age >45 years (58% vs 43% respectively, p = 0.03), in patients with HBV DNA levels >or=4 log compared with <4 log copies/ml (41% vs 27% respectively, p < 0.01), and in patients with stepwise increase of ALT levels (<0.5 x ULN vs 0.5-1 x ULN vs 1-2 x ULN; 11% vs 30% vs 48% respectively, p < 0.01). After multivariate analysis, gender, age and ALT levels were significant factors associated with severe fibrosis. Patients who received antiviral treatment had lower ALT, stiffness score and prevalence of cirrhosis compared to treatment-naive patients [25 vs 35 U/L (p < 0.01), 6.2 vs 6.7 kPa (p = 0.031) and 14% vs 22% (p = 0.008) respectively]. CONCLUSION: The overall prevalence of severe fibrosis in CHB patients was 34% with higher rates seen in older age groups, males, and in patients with higher ALT levels.

Colonoscopy demand and practice in a regional hospital over 9 years in Hong Kong: resource implication for cancer screening.

BACKGROUND: The incidence of colorectal cancer (CRC) in Hong Kong is rising. The trend of colonoscopy demand is uncertain. AIM: To investigate colonoscopy demand and practice in a Hong Kong regional hospital over the past nine years. METHODS: Colonoscopy data from 1st January 1997 to 31st August 2005 were retrieved and divided into two equal periods for comparison. Colonoscopy practice and findings between the two periods were compared. RESULTS: There was no change in the number of endoscopists and colonoscopy sessions in the two periods. The number of colonoscopy done in the two periods was 2,681 and 2,871, respectively. The indications for screening of CRC/polyp (9.3 vs. 24.7%, p < 0.0001) and surveillance of CRC/polyp (4.7 vs. 10.9%, p < 0.0001) were increased, but decreased for diarrhea (18 vs. 10.2%, p < 0.0001) and per rectal bleeding (19 vs. 8.1%, p < 0.0001). The waiting time was lengthened from 2 to 4 weeks (p < 0.0001). The percentage of colonic adenomas (19.9 vs. 27.2%, p < 0.0001) was increased. A right-shift was observed in both CRC (37 vs. 50%, p = 0.018) and adenoma (21.6 vs. 38.1%, p < 0.0001). CONCLUSION: The number of colonoscopies performed was governed by capacity partly through lengthening of waiting time to cope with demand. Ways to improve capacity for colonoscopies is needed.