The impact of immigration on hepatitis B burden in the United States: a modelling study.

Background: The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infections by 2030. However, the HBV prevalence in Western countries, where the historical prevalence is low and highly impacted by immigration trends, remains uncertain making planning difficult. We aimed to develop a more accurate estimate of HBV prevalence and identify key immigrant populations that need to be screened, vaccinated, and treated to achieve the elimination targets. Methods: US immigration data from 1900 forward and country-specific modeled prevalence by age and sex were used to estimate immigrated HBV infections entering the US, new infections in the US, mortality (all-cause and liver-related), and disease burden through 2030. Findings: Using a dynamic Markov model, we estimated 1.8 million (95% uncertainty interval: 1.3-2.6 million) HBV infections in 2020 in all ages, higher than the NHANES national serosurvey. Infections between ages 30-74 accounted for 82% of all cases. Furthermore, HBV infections were concentrated among immigrants. New decompensated cirrhosis, hepatocellular carcinoma, and liver related deaths are expected to increase by 20%, 31% and 25% respectively from 2019 to 2030 at current diagnosis and treatment rate. Interpretation: National serosurveys can underestimate total infections due to under-sampling in immigrant populations. To meet the WHO elimination targets, culturally appropriate screening and linkage to care programs in the immigrant populations are needed in the US. In their absence, there will be significant increases in the burden of HBV and the US will fail to meet the elimination targets by 2030. Funding: This analysis was funded by a research grant from Gilead Sciences (IN-US-988-5786) and made possible by grants from John C Martin Foundation (2019-G024), ZeShan Foundation (2021-0101-1-CDA-HEP-10), and EndHep2030 who supported country analyses.

Viral hepatitis elimination challenges in low- and middle-income countries-Uzbekistan Hepatitis Elimination Program (UHEP).

BACKGROUND & AIMS: Chronic infection with hepatitis B and C viruses (HBV & HCV) is a major contributor to liver disease and liver-related mortality in Uzbekistan. There is a need to demonstrate the feasibility of large-scale simplified testing and treatment to implement a national viral hepatitis elimination program. METHODS: Thirteen polyclinics were utilized to screen, conduct follow-up biochemical measures and treat chronic HBV and HCV infection in the general adult population. Task shifting and motivational interviewing training allowed nurses to provide rapid screening and general practitioners (GPs) to treat individuals on-site. An electronic medical system tracked individuals through the cascade of care. RESULTS: The use of rapid tests allowed for screening of 60 769 people for HCV and HBV over 6 months and permitted outdoor testing during the COVID-19 pandemic along with COVID testing. 13%-14% of individuals were lost to follow-up after the rapid test, and another 62%-66% failed to come in for their consultation. One stop testing and treatment did not result in a statistically increase in retention and lack of patient awareness of viral hepatitis was identified as a key factor. Despite training, there were large differences between GPs and patients initiating treatment. CONCLUSIONS: The current study demonstrated the feasibility of large-scale general population screening and task shifting in low- and middle-income countries. However, such programs need to be proceeded by awareness campaign to minimize loss to follow up. In addition, multiple trainings are needed for GPs to bolster their skills to talk to patients about treatment.

Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling study.

BACKGROUND: Treatment for infection with hepatitis C virus (HCV) during pregnancy has not yet been approved; however, interventions specifically targeting women, especially those of childbearing age (15-49 years), could prevent vertical transmission and community spread. To assess the impact of such interventions, improved prevalence estimates in this group are needed. We aimed to estimate the global prevalence of viraemic HCV in 2019 among women of childbearing age. METHODS: In this modelling study, we used previously developed models for 110 countries inputted with country-specific demographic and HCV epidemiology data. We did a literature review, searching PubMed, Embase, and grey literature for studies published between Jan 1, 2000, and June 30, 2018, reporting HCV antibody or viraemic prevalence in women of childbearing age. Studies from the literature review and studies in models were compared by use of a data quality scoring system and models were updated, as appropriate, when a better study was identified. We used these HCV disease burden models to calculate the 2019 prevalence of viraemic HCV in women of childbearing age. In countries without a model, prevalence was extrapolated by Global Burden of Disease (GBD) region. FINDINGS: An estimated 14 860 000 (95% uncertainty interval [UI] 9 667 000-18 282 000) women aged 15-49 years had HCV infection worldwide in 2019, corresponding to a viraemic prevalence of 0·78% (95% UI 0·62-0·86). Globally, HCV prevalence increased with age, rising from 0·25% (95% UI 0·20-0·27) in women aged 15-19 years to 1·21% (0·97-1·34) in women aged 45-49 years. China (16% of total infections) and Pakistan (15%) had the greatest numbers of viraemic infections, but viraemic prevalence was highest in Mongolia (5·14%, 95% CI 3·46-6·28) and Burundi (4·91%, 3·80-18·75). Of the countries with 500 cases or more, viraemic prevalence was lowest in Chile (0·07%, 95% UI 0·04-0·12). Among the GBD regions, eastern Europe had the highest viraemic prevalence (3·39%, 95% UI 1·88-3·54). By WHO region, the Eastern Mediterranean region had the highest viraemic prevalence (1·75%, 95% UI 1·26- 1·90). INTERPRETATION: Most research on HCV disease burden among women aged 15-49 years focuses on pregnant women. Using modelling, this analysis provides global and national estimates of HCV prevalence in all women of childbearing age. These data can inform preconception test-and-treat strategies to reduce vertical transmission and total disease burden. FUNDING: Gilead Sciences, John C Martin Foundation, private donors.

Modelling NAFLD disease burden in four Asian regions-2019-2030.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) account for an increasing proportion of liver disease in the Asia-Pacific region. Many areas in the region are experiencing epidemics of metabolic syndrome among rapidly ageing populations. AIMS: To estimate using modelling the growth in NAFLD populations, including cases with significant fibrosis that are most likely to experience advanced liver disease and related mortality. METHODS: A disease progression model was used to summarise and project fibrosis progression among the NAFLD populations of Hong Kong, Singapore, South Korea and Taiwan. For each area, changes in the adult prevalence of obesity was used to extrapolate long-term trends in NAFLD incidence. RESULTS: In the areas studied, prevalent NAFLD cases were projected to increase 6%-20% during 2019-2030, while prevalent NASH cases increase 20%-35%. Incident cases of hepatocellular carcinoma are projected to increase by 65%-85%, while incident decompensated cirrhosis cases increase 65%-100% by 2030. Likewise, NAFLD-related mortality is projected to increase between 65% and 100% from 2019 to 2030. NAFLD disease burden is expected to increase alongside rising trends in metabolic syndrome and obesity among populations in the region. This leads to more cases of advanced liver disease and associated mortality. CONCLUSIONS: Preventing the growth of diabetic and obese populations will be a key factor in reducing ongoing increases in NAFLD-related disease burden in the Asia-Pacific region.

Global prevalence of hepatitis C virus in children in 2018: a modelling study.

BACKGROUND: Hepatitis C virus (HCV) prevalence estimates for adults and high-risk groups have been widely published, but the disease burden in children is poorly understood. Direct-acting antiviral drugs, which are considered to be highly effective curative therapies for HCV, are now approved for paediatric patients as young as 3 years. Reliable prevalence estimates for this population are needed to inform scale-up of treatment and national strategies. This analysis combines past modelling and epidemiological work in 104 countries and territories to estimate global HCV prevalence in children in 2018. METHODS: In this modelling study, a comprehensive literature review for articles published between Jan 1, 2000, and March 31, 2019, was used to determine historical HCV prevalence estimates in children in all 249 countries and territories of the world. We identified published HCV prevalence estimates for children aged 0-18 years who are not at high risk of HCV infection in 39 countries and territories and inputted them into dynamic Markov disease-burden models to estimate viraemic HCV prevalence in 2018. For 25 of them, which had complete data, available information on HCV prevalence in children was used to build regression models to predict paediatric prevalence in an additional 65 countries and territories that had country-specific or territory-specific data about predictors only. Regression models were created for each 5-year paediatric age cohort from 0 to 19 years, considering several predictor variables. The data and forecasts from the 104 countries and territories for which data were available were used to calculate HCV prevalence by Global Burden of Disease region, which was then applied to the remaining 145 countries and territories to generate a global estimate. FINDINGS: The global estimate for viraemic prevalence in the paediatric population aged 0-18 years was 0·13% (95% uncertainty interval 0·08-0·16), corresponding to 3·26 million (2·07-3·90) children with HCV in 2018. HCV prevalence increased with age in all countries and territories. HCV prevalence in women of childbearing age was the strongest predictor of HCV prevalence in children aged 0-4 years (p<0·0001). Prevalence of HCV in adults was significantly associated with HCV prevalence in children aged 5-19 years (p<0·0001), and the proportion of HCV infections in people who inject drugs was significantly associated with HCV prevalence in children aged 15-19 years (p=0·036). INTERPRETATION: Most studies on HCV prevalence in children focus on high-risk groups and highly endemic geographic areas. Our analysis provides global prevalence estimates of HCV in the paediatric population. Treatment in paediatric patients requires different clinical and population health management optimisation than in adults. Because of this heterogeneity, country-specific or territory-specific and age-specific HCV prevalence estimates can help countries and territories to improve national HCV elimination strategies. FUNDING: Gilead Sciences, John C Martin Foundation, and private donors.

Global epidemiology and genotype distribution of the hepatitis C virus infection.

The treatment of chronic hepatitis C virus (HCV) infection has the potential to change significantly over the next few years as therapeutic regimens are rapidly evolving. However, the burden of chronic infection has not been quantified at the global level using the most recent data. Updated estimates of HCV prevalence, viremia and genotypes are critical for developing strategies to manage or eliminate HCV infection. To achieve this, a comprehensive literature search was conducted for anti-HCV prevalence, viraemic prevalence and genotypes for all countries. Studies were included based on how well they could be extrapolated to the general population, sample size and the age of the study. Available country estimates were used to develop regional and global estimates. Eighty-seven countries reported anti-HCV prevalence, while HCV viraemic rates were available for fifty-four countries. Total global viraemic HCV infections were estimated at 80 (64-103) million infections. Genotype distribution was available for ninety-eight countries. Globally, genotype 1 (G1) was the most common (46%), followed by G3 (22%), G2 (13%), and G4 (13%). In conclusion, the total number of HCV infections reported here are lower than previous estimates. The exclusion of data from earlier studies conducted at the peak of the HCV epidemic, along with adjustments for reduced prevalence among children, are likely contributors. The results highlight the need for more robust surveillance studies to quantify the HCV disease burden more accurately.