UNASSIGNED: Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients.
UNASSIGNED: Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n = 4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT.
UNASSIGNED: In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p < 0.001) and the propensity score matching cohort (77.2%/27.6%, p < 0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p < 0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7-10 had a higher 1-year survival benefit rate from LT (39.2%-64.3%) than those with score <7 or >10. These results were prospectively validated.
UNASSIGNED: COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortality and survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7-10 derived a higher net survival benefit from LT.
UNASSIGNED: This study was supported by the National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program).

UNASSIGNED: In view of limited data on the knowledge and awareness of hepatitis B virus (HBV) and the available preventive strategies at the community level, it was aimed to analyse the knowledge and awareness of HBV in the community.
UNASSIGNED: A cross-sectional questionnaire-based survey was conducted among residents of an urban slum and a social welfare home in Bhubaneswar, Odisha, from October 2019 to April 2021. The prevalence of HBV infection was also measured by testing the serum positivity for hepatitis B surface antigen using rapid point-of-care test kits. The statistical analysis was done by using the software SPSS version 20.
UNASSIGNED: A total of 370 individuals (mean age 38.7 ± 14.9 years, males: 55.1%) were assessed. Although 18.1% (67) had good knowledge, only 16.7% (62) had good awareness about HBV. Approximately 14.8% (55) knew that a vaccine is available in the country for HBV, and 6.2% (23) identified themselves as being vaccinated. Educational status was a significant independent predictor of knowledge and awareness such that people with education level of matriculation and above had odds of 11.05 (95% confidence interval: 5.3-22.7) and 14.7 (95% confidence interval: 6.5-33.1) for having good knowledge and awareness regarding HBV, respectively. A total of 10 participants tested positive for hepatitis B surface antigen contributing to a point prevalence rate of 2.7%. The proportion of individuals with an education status of matriculation and above was higher in the slum area when compared with the welfare home (67% vs 33%; P < 0.001), the knowledge (71.6% vs 28.4%; P < 0.001) and so was the awareness (71% vs 29%; P < 0.001) about HBV as well.
UNASSIGNED: The relatively low figures of knowledge and awareness identified in our study undermine the need for intensification of health education and promotion activities regarding the prevalence of hepatitis B infection on a large scale at the community level.

UNASSIGNED: Increasing incidence of hepatocellular carcinoma (HCC) in India is a matter of concern and need for adequate profiling and streamlining management strategies cannot be over-emphasized.
UNASSIGNED: This is a prospective multi-centric observational cohort study comprising of an oncology center, one university tertiary hospital with specialized hepatology service, one public hospital with gastroenterology service, and a private liver transplant center located within a 3-km radius. The demographic and clinical parameters were recorded on a prospectively maintained database. The clinical profile, demographics, characteristics of HCC and the allocated treatment were noted and compared among the four centers.
UNASSIGNED: In total, 672 patients were enrolled from June 2016 till January 2020. Abdominal pain (64.3%) and weight loss (47.3%) were the most common symptoms. Most common identified etiology was hepatitis B (39%). The cancer center received lesser patients with hepatitis C and those with advanced stage of HCC. The private transplant center reported the highest proportion of NASH, which was also significantly higher in those belonging to higher socioeconomic strata, and lowest proportion of alcoholic cirrhosis. Metastasis was seen in almost one-fifth (19%) cases at diagnosis. Portal vein thrombosis was evident in 40%. Adherence to treatment guidelines was seen in three-fourth cases (76%).
UNASSIGNED: Hepatitis B is the most common underlying cause for HCC, whereas other causes like NASH are on the rise. Etiologic profile may vary with selective specialization of centers catering to patients with HCC. Adherence to guideline while allocating treatment was high among all centers with highest non-adherence in BCLC A.

UNASSIGNED: Among people living with HBV, only a subset of individuals with chronic hepatitis is in need of treatment, and this proportion varies according to the population, region, and setting. No estimates of the proportion of people who are infected with HBV and meet the treatment eligibility criteria in France are available.
UNASSIGNED: 552 treatment-naïve individuals with chronic HBV infection referred for the first time to a hepatology reference centre between 2008 and 2012 were prospectively included. Demographic, clinical, and laboratory data were analysed.
UNASSIGNED: In total, 61.1% of patients were males, with a median age of 37.5 years. Moreover, 64% were born in an intermediate- or high-HBV endemicity country, and 90% were HBeAg-negative. At referral, median HBV DNA and HBsAg levels were 3.3 and 3.6 log IU/ml, respectively; 37.8% of patients had alanine aminotransferase >40 U/L, and 29.0% had moderate or severe fibrosis (≥F2), including 9.4% with cirrhosis. The most prevalent genotypes were D (34.7%), E (27.4%), and A (25.7%). Coinfections were rare: 2.4% were HIV-positive, 4.0% were HCV-positive, and 6.0% were HDV-positive. According to the 2017 EASL Clinical Practice Guidelines, using a single time point analysis, 2.7% of patients were classified as HBeAg-positive chronic infection, 6.1% as HBeAg-positive chronic hepatitis B, 26.5% as HBeAg-negative chronic hepatitis B, and 61.1% as HBeAg-negative chronic infection, whereas 3.6% patients could not be classified. The performance of HBsAg level quantification to identify individuals with HBeAg-negative chronic hepatitis B was poor. A total of 29.1% met the criteria for initiation of antiviral treatment, whereas 66.5% remained under routine clinical surveillance. Most eligible patients initiated recommended first-line therapies, including tenofovir (45.3%), entecavir (36.8%), or pegylated interferon alpha (11.6%).
UNASSIGNED: Of all cases, 9.4% had cirrhosis at presentation and 29.1% met the 2017 EASL Clinical Practice Guidelines treatment criteria. HBsAg levels failed to accurately identify individuals with HBeAg-negative chronic infection.
UNASSIGNED: Among French adults chronically infected with HBV referred for the first time to hepatology reference centres, about one-third had a significant liver disease. Approximately one-third of individuals met criteria for initiation of antiviral treatment based on entecavir or tenofovir or, occasionally, pegylated interferon alpha.

BACKGROUND: Cirrhosis is known to have a high prevalence and mortality worldwide. However, in Europe, the epidemiology of cirrhosis is possibly undergoing demographic changes, and etiologies may have changed due to improvements in standard of care. The aim of this population-based study was to analyze the trends and the course of liver cirrhosis and its complications in recent years in Germany.
METHODS: We analyzed the data of all hospital admissions in Germany within diagnosis-related groups from 2005 to 2018. The diagnostic records of cirrhosis and other categories of diseases were based on ICD-10-GM codes. The primary outcome measurement was in-hospital mortality. Trends were analyzed through Poisson regression of annual number of admissions. The impact of cirrhosis on overall in-hospital mortality were assessed through the multivariate multilevel logistic regression model adjusted for age, sex, and comorbidities.
RESULTS: Of the 248,085,936 admissions recorded between 2005 and 2018, a total of 2,302,171(0•94%) were admitted with the diagnosis of cirrhosis, mainly as a comorbidity. Compared with other chronic diseases, patients admitted with cirrhosis were younger, mainly male and had the highest in-hospital mortality rate. Diagnosis of cirrhosis was an independent risk factor of in-hospital mortality with the highest odds ratio (OR:6•2[95%CI:6.1-6•3]) among all diagnoses. The prevalence of non-alcoholic fatty liver disease has increased four times from 2005 to 2018, while alcoholic cirrhosis is 20 times than other etiologies. Bleeding was found to be decreasing over time, but ascites remained the most common complication and was increasing.
CONCLUSIONS: This nationwide study demonstrates that cirrhosis represents a considerable healthcare burden, as shown by the increasing in-hospital mortality, also in combination with other chronic diseases. Alcohol-related cirrhosis and complications are on the rise. More resources and better management strategies are warranted.
BACKGROUND: The funders had no influence on this study.

OBJECTIVE: Hepatitis B virus (HBV) infection is a major health problem in the world. Barbers deal with frequent abrasions/lacerations due to sharp equipment, making them a high-risk group. Determination of HBsAg positive status excludes most reservoirs of transmission in the population. However, Occult Hepatitis B continues to be a source of transmission. The aim of this study was to study the prevalence of occult HBV infection in barbers serving the armed forces clientele and evaluate their knowledge and preventive practices against HBV transmission.
METHODS: Seventy-nine HBsAg negative barbers were included in this study and interviewed for the status of immunisation and preventive practices. Anti-HBc total and HBV DNA levels were measured along with a complete haemogram, LFT, PT INR, ultrasound abdomen and Fibroscan of the liver.
RESULTS: The prevalence of occult Hepatitis B status was 3.79%. Among barbers who were anti-HBc total positive, 100% were found to have replicative HBV DNA status. All barbers (100%) were unaware of the existence and modes of HBV transmission and were never screened for HBV; 98.73% of barbers followed improper disinfection practices and were never immunised.
CONCLUSIONS: The prevalence of occult HBV infection in barbers, absence of immunisation, unawareness and improper disinfection practices are significantly at risk for transmission to the unaware clients. It is important to educate barbers, establish a universal disinfection procedure and implement a system of compulsory Hepatitis B vaccination before the commencement of their trade work.

OBJECTIVE: Functional cure of chronic HBV infection (CHB) without life-long treatment requires the restoration of defective HBV-specific humoral and cellular immunity. Therapeutic vaccines based on the major structural and non-structural proteins have been tested in patients with CHB but have shown scarce immunogenicity. BRII-179, also known as VBI-2601, is a novel formulation comprised of all 3 HBV surface envelope proteins (Pre-S1, Pre-S2, and S). Safety, antiviral activity, and immunogenicity of BRII-179 admixed with co-adjuvant interferon (IFN)-α were assessed in patients with CHB.
METHODS: This randomized, open-label, controlled phase Ib/IIa study included 2 dose levels, 20 μg BRII-179 (Part 1, n = 25) and 40 μg BRII-179 (Part 2, n = 24). Patients, virally suppressed under nucleos(t)ide analogue (NA) therapy were randomized 1:2:2 into 3 cohorts in Part 1 and 1:1 into 2 cohorts in Part 2 to receive 4 monthly intramuscular injections of BRII-179 admixed with/without 3 MIU IFN-α. Antibody and cellular responses to HBsAg, as well as evolution of circulating HBsAg were monitored.
RESULTS: Both 20 μg and 40 μg BRII-179 with/without IFN-α were well tolerated with no severe adverse events. BRII-179 induced anti-HBs responses in >30% patients in all treatment cohorts, however, moderate anti-Pre-S1 or anti-Pre-S2 antibody responses were only observed in patients receiving BRII-179 with IFN-α. BRII-179 also restored S-, Pre-S1-, Pre-S2-specific IFN-γ-producing T-cells in the majority of treated patients. Overall, no notable reduction of HBsAg was observed after BRII-179 treatment.
CONCLUSIONS: In patients with CHB under NA therapy, BRII-179 with/without IFN-α exhibited a good safety profile and induced HBV-specific B- and T-cell immune responses. These data support further clinical evaluation of BRII-179 in combination with other therapies.
BACKGROUND: ACTRN12619001210167.
BACKGROUND: BRII-179 is a therapeutic vaccine designed to improve the immune response in patients with chronic hepatitis B. In this study, BRII-179 alone or with a low dose of interferon-α was safe, well tolerated, and induced enhanced HBV-specific antibody and T-cell responses in patients with chronic hepatitis B. However, BRII-179 treatment alone had minimal effect on patient\'s virological status. The potential of BRII-179 to achieve a functional cure in conjunction with other agents is being evaluated in the clinic.

UNASSIGNED: Liver grafts from hepatitis B core antibody (anti-HBc) positive donors increase the risk of hepatitis B virus (HBV) reactivation in recipients due to posttransplant immunosuppressive therapy.
UNASSIGNED: to study the HBV reactivation in liver transplant recipients with anti-HBc-positive donors.
UNASSIGNED: This was a retrospective study. Liver transplant recipients who received grafts from anti-HBc-positive donors between January 2013 and December 2017 were included in analysis. Hospital records of all subjects for a 2-year posttransplantation period were studied to observe reactivation of hepatitis B. As per our institute protocol, prophylaxis for HBV was given to subjects with either positive hepatitis B surface antigens or hepatitis B surface antibody (anti-HBs) titre <100 mIU/ml, after transplantation with anti-HBc-positive donor grafts. Recipients with anti-HBs titre >100 mIU/mL were exempted from prophylaxis and kept on regular monitoring for HBV markers.
UNASSIGNED: Of 85 liver transplant recipients, 20 subjects who received anti-HBc-positive grafts were included in analysis. The mean age of the study population was 46 years (range 2-68 years). The most common aetiology of cirrhosis in our study population was cryptogenic followed by ethanol. Among the study population, 16 (80%) transplant recipients had anti-HBs titre less than 100 mu/ml and 4 (20%) subjects had anti-HBs > 100 miu/ml. HBV reactivation occurred in 6 (30%) subjects. Reactivation was seen even in those who received HBV prophylaxis, while none of the subjects with anti-HBs titre >100 miu/ml developed HBV reactivation despite absence of prophylaxis.
UNASSIGNED: HBV reactivation can occur even in the presence of target anti-HBs titre (i.e. >10 miu/ml) and HBV prophylaxis during postliver transplantation. However, HBV reactivation is not seen in recipients with anti-HBs titre of >100 miu/ml.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.

BACKGROUND: Hepatitis B virus (HBV) infection is an important etiology for chronic hepatitis globally, and especially so in China. HBV infection can lead to the development of cirrhosis through the pathological process of liver fibrosis. The effective suppression of HBV replication with NAs or interferon-alpha can histologically regress the fibrotic pathological process, but there remain patients who have achieved anti-viral responses and normalization of serum liver tests, but not liver fibrosis regression. This subset of patients typically presents with advanced liver fibrosis at baseline. Therefore, it is reasonable to administer the anti-fibrotic agents, coupled with antivirals for patients with advanced liver fibrosis due to HBV, in order to improve the fibrotic regression of the patients. Fuzheng Huayu (FZHY) tablet is a botanical product with evidence demonstrating its efficacy against mild to moderate liver fibrosis. The current clinical trial evaluates the efficacy and safety of the combination therapy of traditional Chinese medicine (TCM) (FZHY and herbal granule) and entecavir for HBV compensated cirrhosis. We will enroll HBV patients who presented with a good viral response after 2 years of entecavir treatment but had advanced liver fibrosis (≥Ishak F5).
METHODS: This is a single-arm clinical trial, conducted in 20 centers in mainland China over a period of 60 weeks, including 48 weeks of treatment observation and 12 weeks of follow-up. The main inclusion criteria include HBsAg positive more than 6 months, 2 years administration of entecavir, HBV DNA less than 20 IU/ml, liver fibrotic stage ≥ F5, and Child-Pugh scoring <7 (Stage A). The sample size is estimated to be about 190, considering a 20% drop-out and 60% of patient\'s compliance for the second liver biopsy so a total of 350 participants will be enrolled. All eligible participants are divided into 3 subgroups according to the TCM clinic pattern. And all patients will take 1 Entecavir tablet (0.5 mg) per day, 4 FZHY tablets (1.6 g) three times a day, and specific TCM granule three times a day, which is decided by TCM clinical patterns (CPs) differentiation. The patients were treated for 48 weeks, and follow-up visits at 12, 24, 36, 48 weeks and 60 weeks. The patients will receive the second liver biopsy at the end of 48 weeks, with a 12 weeks follow-up after that.The primary endpoint is the proportion of subjects with a 1-point improvement of liver fibrosis stage using the Ishak score from baseline to week 48 in the study, according to consensus readings evaluated by a panel of hepato-pathologists. The secondary endpoints are the brightness-mode ultrasonic, fibrotic biomarkers. The adverse events (AEs) will be recorded for 60 weeks, and the safety of the combination therapy will be evaluated. Meanwhile, the efficacy in the 3 sub-groups will be stratified and analyzed.
CONCLUSIONS: The study has been designed to test the therapeutic effects and safety of the combination therapy of FZHY and herbal granule with entecavir on persistent advanced stage fibrosis/cirrhosis following 2 years entecavir treatment, and to explore an effective integrative therapy on HBV cirrhosis.
BACKGROUND: ClinicalTrials.gov. NCT02241616. Registered on September 16, 2014.