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BackgroundThe natural history of chronic HBV infection in sub-Saharan Africa is unknown. Data are required to inform WHO guidelines that are currently based on studies in Europe and Asia.MethodsBetween 1974 and 2008, serosurveys were repeated in two Gambian villages, and an open cohort of treatment-naive chronic HBV carriers was recruited. Participants were followed to estimate the rates of hepatitis B e (HBeAg) and surface antigen (HBsAg) clearance and incidence of hepatocellular carcinoma (HCC). In 2012–2013, a comprehensive liver assessment was conducted to estimate the prevalence of severe liver disease.Results405 chronic carriers (95% genotype E), recruited at a median age of 10.8 years, were followed for a median length of 28.4 years. Annually, 7.4% (95% CI 6.3% to 8.8%) cleared HBeAg and 1.0% (0.8% to 1.2%) cleared HBsAg. The incidence of HCC was 55.5/100 000 carrier-years (95% CI 24.9 to 123.5). In the 2012–2013 survey (n=301), 5.5% (95% CI 3.4% to 9.0%) had significant liver fibrosis. HBV genotype A (versus E), chronic aflatoxin B1 exposure and an HBsAg-positive mother, a proxy for mother-to-infant transmission, were risk factors for liver fibrosis. A small proportion (16.0%) of chronic carriers were infected via mother-to-infant transmission; however, this population represented a large proportion (63.0%) of the cases requiring antiviral therapy.ConclusionsThe incidence of HCC among chronic HBV carriers in West Africa was higher than that in Europe but lower than rates in East Asia. High risk of severe liver disease among the few who are infected by their mothers underlines the importance of interrupting perinatal transmission in sub-Saharan Africa.

Background Long-term antiviral therapy has resulted in viral suppression and biochemical response in chronic hepatitis B, although the risk of hepatocellular carcinoma has not been abolished. The Page-B score could be useful to estimate the probability of HCC. Aims To analyze the effectiveness and safety of entecavir or tenofovir for more than 4 years and the usefulness of Page-B score in the real-world setting. Methods Analysis of Caucasian chronic hepatitis B subjects treated with entecavir or tenofovir from the prospective, multicenter database CIBERHEP. Results A total of 611 patients were enrolled: 187 received entecavir and 424 tenofovir. Most were men, mean age 50 years, 32% cirrhotic and 16.5% HBeAg-positive. Mean follow-up was 55 (entecavir) and 49 (tenofovir) months. >90% achieved HBV DNA <69 IU/mL and biochemical normalization by months 12 and 36, respectively. Cumulative HBeAg loss and anti-HBe seroconversion were achieved by 33.7 and 23.8%. Four patients lost HBsAg; three HBeAg-positive. Renal function remained stable on long-term follow-up. Fourteen (2.29%) developed HCC during follow-up all of them with baseline Page-B ≥10. Nine were diagnosed within the first 5 years of therapy. This contrasts with the 27 estimated by Page-B, a difference that highlights the importance of regular HCC surveillance even in patients with virological suppression. Conclusions Entecavir and tenofovir achieved high biochemical and virological response. Renal function remained stable with both drugs. A Page-B cut-off ≥10 selected all patients at risk of HCC development.

Hepatitis B Virus (HBV) is one of the most common human infectious agents, and the mutations in its genome may cause chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). This study was designed to characterize the enhancer-II (Enh-II) region of X gene in HBV positive patients to assess the association of such mutations with CH, LC, and HCC. HBV positive samples (N = 200) with patients' demographic and clinical data were collected from different regions of Khyber Pakhtunkhwa (KP), Pakistan. The Enh-II region of the HBx gene was sequenced and zanalyzed for polymorphism associated with advanced liver disease. Univariate and logistic regression analyses were performed to evaluate potent mutations associated with a risk for LC and HCC. HBV Enh-II region sequences analysis revealed 25 different mutations. The highest frequency of mutations S101F (62.2%), A102V/R/G/I (56.25%), M103L/A (68.75%)were found in HCC, followed in LC and CH patients as 57.1%, 42.8%, 28.52% 16%, 15.2% and 18.4% respectively. H94 deletion in the α-box of the Enh-II region, associated with a high risk of HCC was found in half of the HCC patients. This deletion was present in 28.5% of LC and 6.5% of CH patients. Importantly, the high frequency of some notable mutations such as E109A/Y, A110S/K, Y111D/E, and F112L was first time reported in the entire study population. The frequencies of these mutations were high in HCC (43.75%, 37.5%, 50% and 43.75% respectively) as compared to LC (14.28%, 14.28%, 28.2% and 42.8%) and CH patients (12.8%, 15.2%, 16.8% and 16% respectively). Mutations associated with LC and HCC are prevalent in the Enh-II region in Pakistani HBV isolates. The mutations found are alarming in CH patients as these may progress to LC and HCC in a large number of patients.

YMDD variants of hepatitis B virus (HBV) emerge in some patients with chronic hepatitis B who receive lamivudine. YMDD variants were examined in 794 patients in 4 controlled studies of 1 year's duration. The long-term effects of YMDD variants were examined in a subset of patients treated up to 4 years. YMDD variants were detected by polymerase chain reaction (PCR) and restriction fragment-length polymorphism assays. After 1 year, YMDD variants were detected in 81 (24%) of 335 patients. In these patients, the median serum HBV DNA concentration at 1 year was <20% of the baseline level, and serum alanine transaminase (ALT) levels and liver histologic findings had significantly improved. In patients with YMDD variants who were treated for up to 4 years, median HBV DNA and ALT levels showed improvements. Sex, baseline body mass index, and HBV DNA level were associated with emergence of YMDD variants. Patients with YMDD variants losing clinical response with a significant increase in the HBV DNA and ALT levels may require additional therapy.

Hepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA 'Safeguard the household study' in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation. 812 participants from two South African townships Soweto and Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline. Forty-eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk 2.3; 95% CI: 1.3-4.0). More participants in Masiphumelele had HBeAg-negative disease (58% vs. 12%, p = 0.002) and HBV DNA levels ≤2000 IU/ml, (43% vs. 6% p<0.007). One third of HIV/HBV co-infected subjects had low HBV DNA levels and ALT while the majority had indicators of only mild liver disease. There were substantial regional differences in HBsAg and HbeAg prevalence in HIV/HBV co-infection between two regions in South Africa. This study highlights the absence of severe liver disease and the marked regional differences in HIV/HBV co-infection in South Africa and will inform treatment decisions in these populations.

Background The low diagnosis rate and poor access to clinical care among people with CHB is a major barrier to reducing HBV-related morbidity and mortality in Australia. One explanation for this is a lack of disease-specific knowledge among people living with CHB. Health literacy has been shown to be important for maximising engagement with medical care and adherence to recommended management. The ‘teach-back’ communication strategy has been shown to improve patient understanding in other clinical areas. This study aims to assess disease-specific knowledge; and evaluate the efficacy of the teach-back strategy for improving HBV knowledge, compared to a standard medical consultation. Method A randomized pilot study was conducted between February and June 2017. Participants were recruited from the liver clinic at an inner-city tertiary hospital. English-speaking patients aged ≥18 years and diagnosed with CHB were eligible for the study. Participants were randomised to a control group (medical specialist appointment) and intervention group (teach-back). Knowledge was assessed at baseline, immediately post-intervention and at one month using a validated questionnaire. Participants in the intervention group received a one-on-one teach-back session about CHB. The main outcome measure was a combined knowledge score of the domains assessed – transmission, natural history, epidemiology and prevention and clinical management. Results Seventy participants were recruited (control n  = 32, teach-back n  = 38). Mean baseline knowledge score was 19.1 out of 23 with 55 (79%) participants scoring ≥17.3 (defined as high knowledge) (7). Sub-analysis of CHB knowledge domains identified focal deficits concerning transmission and whether HBV is curable. Knowledge scores were found to be positively associated with English proficiency and antiviral treatment experience ( p  < 0.05). Teach-back was associated with a significant increase in CHB knowledge at early recall (22.5 vs 18.7, p  < 0.001) and at 1-month follow-up (21.9 vs 18.7, p < 0.001); there was no improvement in CHB knowledge associated with standard clinical consultant (early recall: 19.6 vs 19.4, p  = 0.49, one-month follow-up: 19.5 vs 19.4, p  = 0.94). Conclusion In a tertiary hospital liver clinic population, baseline knowledge about CHB was good, but there were focal deficits concerning transmission and potential for cure. Teach-back was associated with improvement in CHB knowledge and it is a simple communication tool suitable for incorporation into a standard medical consultation.

ObjectiveGiven significant advances in treatment of viral hepatitis and the growing epidemic of obesity, the burden of the different types of liver diseases in the USA may be changing. Our aim was to assess the shift in the prevalence of different liver disease aetiologies in the USA over the past three decades.DesignNational Health and Nutrition Examination Surveys (NHANES; cross-sectional 1988–1994 and 1999–2016) were used.ResultsA total of 58 731 adults from NHANES (1988–2016) were included. Over the study period, the prevalence of chronic hepatitis B and alcoholic liver disease remained stable: 0.3%–0.4% and 0.8%–1.0%, respectively (p>0.05). The prevalence of chronic hepatitis C decreased nearly twofold: 1.6% in 1988–1994 to 0.9% in 2013–2016 (p=0.03). In contrast, the prevalence of non-alcoholic fatty liver disease (NAFLD; by US-Fatty Liver Index) increased from 20.0% (1988–1994) to 28.3% (1999–2004) to 33.2% (2009–2012) and 31.9% (2013–2016) (p<0.0001). Furthermore, steady increases were observed in the rates of obesity (22.2% in 1988–1994 to 31.0% in 1999–2004 to 38.9% in 2013–2016), type 2 diabetes mellitus (T2DM) (from 7.2% to 8.2% to 13.5% same years), insulin resistance and hypertension (all p<0.0001). Yearly trend analyses showed that the only LD with consistently increasing prevalence was NAFLD (trend p=0.01). Multivariable regression analysis showed that obesity (OR 10.4; 95% CI 9.5 to 11.3) and T2DM (OR 3.7; 95% CI 3.2 to 4.2) were the major independent predictors of NAFLD.ConclusionsOver the past 30 years in the USA, NAFLD is the only liver disease with growing prevalence, synchronous with the increasing rates of obesity and T2DM.

ObjectiveHepatitis D virus (HDV) is a defective virus that completes its life cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has been considered as one of the most severe forms of the chronic viral hepatitis. However, there is a scarcity of data on the global burden of HDV infection.DesignWe searched PubMed, Embase, Cochrane Library and China Knowledge Resource Integrated databases from 1 January 1977 to 31 December 2016. We included studies with a minimum sample size of 50 patients. Our study analysed data from a total of 40 million individuals to estimate the prevalence of HDV by using Der-Simonian Laird random-effects model. The data were further categorised according to risk factors.ResultsFrom a total of 2717 initially identified studies, only 182 articles from 61 countries and regions met the final inclusion criteria. The overall prevalence of HDV was 0.98% (95% CI 0.61 to 1.42). In HBsAg-positive population, HDV pooled prevalence was 14.57% (95% CI 12.93 to 16.27): Seroprevalence was 10.58% (95% CI 9.14 to 12.11) in mixed population without risk factors of intravenous drug use (IVDU) and high-risk sexual behaviour (HRSB). It was 37.57% (95% CI 29.30 to 46.20) in the IVDU population and 17.01% (95% CI 10.69 to 24.34) in HRSB population.ConclusionWe found that approximately 10.58% HBsAg carriers (without IVDU and HRSB) were coinfected with HDV, which is twofold of what has been estimated before. We also noted a substantially higher HDV prevalence in the IVDU and HRSB population. Our study highlights the need for increased focus on the routine HDV screening and rigorous implementation of HBV vaccine programme.

Background Early age at infection with hepatitis B virus (HBV) increases the risk of chronic HBV infection. In addition early age at infection may further increase the risk of persistent viral replication beyond its effect on chronicity. The effects of perinatal and early postnatal transmission on the risk of prolonged hepatitis B e antigenaemia in children with chronic HBV infection are not well documented in Africa. We examine these associations using maternal HBV sero-status and the number of HBV-positive older siblings as proxy measures for perinatal and early postnatal transmission, respectively. Methods Hepatitis B e antigen (HBeAg)-positive mothers were identified in six population-based HBV sero-surveys conducted in The Gambia between 1986 and 1990. For every HBeAg-positive mother, a hepatitis B surface antigen (HBsAg)-positive HBeAg-negative mother and HBsAg-negative mother were randomly selected from the population surveyed. These mothers and their family members were tested for HBV sero-markers in a subsequent survey conducted between 1991 and 1993. Results Thirty-eight HBeAg positive mothers and the same number of HBsAg-positive HBeAg-negative mothers and HBsAg-negative mothers participated in the study. Sixty-nine percent of their children also participated. There was a non-significant positive association between HBeAg prevalence in children and the number of HBeAg-positive older siblings (64.1%, 69.2% and 83.3% in children with 0, 1 and ≥2 HBeAg-positive older siblings, respectively). After adjusting for confounders, having an HBeAg-positive mother was a risk factor for HBeAg positivity in children carrying HBsAg (adjusted OR 4.5, 95% CI: 1.0-19.5, p = 0.04), whilst the number of HBeAg-positive older siblings was not. Conclusions Maternal HBeAg was associated with positive HBeAg in children with chronic HBV infection. This suggests that interrupting mother-to-infant transmission in sub-Saharan Africa might help reduce the burden of liver disease. A timely dose of HBV vaccine within 24 hours of birth, as recommended by WHO, should be implemented in sub-Saharan Africa.

Chronic hepatitis B virus infection is a global public health threat that causes considerable liver-related morbidity and mortality. It is acquired at birth or later via person-to-person transmission. Vaccination effectively prevents infection and chronic hepatitis B virus carriage. In chronically infected patients, an elevated serum hepatitis B virus DNA concentration is the main risk factor for disease progression, although there are other clinical and viral parameters that influence disease outcomes. In addition to liver biochemistry, virological markers, and abdominal ultrasonography, non-invasive assessment of liver fibrosis is emerging as an important assessment modality. Long-term nucleos(t)ide-analogue therapy is safe and well tolerated, achieves potent viral suppression, and reduces the incidence of liver-related complications. However, a need to optimise management remains. Promising novel therapies are at the developmental stage. With current vaccines, therapies, and an emphasis on improving linkage to care, WHO's goal of eliminating hepatitis B virus as a global health threat by 2030 is achievable.