Hepatitis mortality in Brazil and regions, 2001-2020: temporal trend and spatial analysis.

OBJECTIVE: To analyze the spatial distribution and the temporal trend of the hepatitis mortality rate in Brazil from 2001 to 2020. METHODS: Ecological, temporal, and spatial study on mortality from hepatitis in Brazil with data from the Mortality Information System (Sistema de Informações sobre Mortalidade - SIM/DATASUS). Information was stratified by year of diagnosis, region of the country, municipalities (of residence). Standardized mortality rates (SMR) were calculated. The temporal trend was estimated by Prais-Winsten regression and the spatial distribution by the Global Moran Index (GMI). RESULTS: The highest SMR means in Brazil were for Chronic viral hepatitis with 0.88 deaths per 100,000 inhabitants (SD=0.16), followed by Other viral hepatitis with 0.22/100,000 (SD=0.11). In Brazil, the temporal trend of mortality from Hepatitis A was -8.11% per year (95%CI -9.38; -6.82), while for Hepatitis B it was -4.13% (95%CI -6.03; -2.20), of Other viral hepatitis of -7.84% (95%CI -14.11; -1.11) and of Unspecified Hepatitis -5.67% per year (95%CI -6.22; -5.10). Mortality due to chronic viral hepatitis increased by 5.74% (95%CI 3.47; 8.06) in the North and 4.95% in the Northeast (95%CI 0.27; 9.85). The Moran Index (I) for Hepatitis A was 0.470 (p<0.001), for Hepatitis B 0.846 (p<0.001), Chronic viral hepatitis=0.666 (p<0.001), other viral hepatitis=0.713 (p<0.001), and Unspecified Hepatitis=0.712 (p<0.001). CONCLUSION: The temporal trend of hepatitis A, B, other viral, and unspecified hepatitis was decreasing in Brazil, while mortality from chronic hepatitis was increasing in the North and Northeast.

Low Hemoglobin-to-Red Cell Distribution Width Ratio Is Associated with Mortality in Patients with HBV-Related Decompensated Cirrhosis.

BACKGROUND: The prognostic role of hemoglobin-to-red blood cell distribution width ratio (HRR) in HBV-related decompensated cirrhosis (HBV-DeCi) has not been established. The present study is aimed at determining the potential of HRR as a predictive factor for the prognosis of HBV-DeCi patients. METHODS: The study included 177 HBV-DeCi patients. The clinical outcome was death at 30 days. Multivariate regression analysis and receiver operating characteristic curve analysis were applied to assess the predictive value of HRR for poor outcomes. RESULTS: A total of 26 patients (14.7%) had died by 30 days. Patients with unfavorable outcomes had lower HRR than patients with favorable outcomes. Multivariate analysis revealed that HRR and Model for End-Stage Liver Disease (MELD) score were independently associated with poor outcomes. Combination of HRR and MELD score may improve prognostic accuracy in HBV-DeCi. CONCLUSIONS: The present findings indicate that low HRR may be a promising predictor for mortality in HBV-DeCi patients.

The impact of the timely birth dose vaccine on the global elimination of hepatitis B.

In 2016 the World Health Organization set the goal of eliminating hepatitis B globally by 2030. Horizontal transmission has been greatly reduced in most countries by scaling up coverage of the infant HBV vaccine series, and vertical transmission is therefore becoming increasingly dominant. Here we show that scaling up timely hepatitis B birth dose vaccination to 90% of new-borns in 110 low- and middle-income countries by 2030 could prevent 710,000 (580,000 to 890,000) deaths in the 2020 to 2030 birth cohorts compared to status quo, with the greatest benefits in Africa. Maintaining this could lead to elimination by 2030 in the Americas, but not before 2059 in Africa. Drops in coverage due to disruptions in 2020 may lead to 15,000 additional deaths, mostly in South-East Asia and the Western Pacific. Delays in planned scale-up could lead to an additional 580,000 deaths globally in the 2020 to 2030 birth cohorts.

Prognostic impact of hepatitis B virus infection in patients with primary cervical cancer.

BACKGROUND: Hepatitis B virus (HBV) infection has been associated with an increased risk of a few malignancies. However, the prognostic impact of HBV infection remains unclear in cervical cancer. OBJECTIVE: To explore the association between HBV infection and survival outcomes of patients with primary cervical cancer, using overall survival (OS) and disease-free survival (DFS) as primary endpoints. METHODS: This analysis was performed retrospectively with newly diagnosed cervical cancer patients admitted to the Department of Gynecologic Oncology at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from June 2013 to October 2019, who were enrolled and followed up. The Kaplan-Meier method and Cox proportional hazard analysis were used to examine the performance of HBV infection in predicting OS and DFS. RESULTS: Patients were followed up for a median of 37.17 months (95% CI, 34.69-39.65). Among the 695 patients, 87 (12.5%) were serologically positive for hepatitis B surface antigen (HBsAg), and 276 (39.7%) had a prior history of HBV infection. There was no significant difference between HBsAg-positive group and HBsAg-negative patients concerning OS or DFS. Multivariate analysis showed prior HBV infection was an independent favorable prognosticator for OS (HR, 0.335; 95% CI, 0.153-0.0.734; p = 0.006) and DFS (HR, 0.398; 95% CI, 0.208-0.691; p = 0.002). CONCLUSION: We provide the first clinical evidence that suggests prior HBV infection as an independent favorable prognostic factor for patients with primary cervical cancer.

Overweight with HBV infection limited the efficacy of TACE in hepatocellular carcinoma by inhibiting the upregulated HMGB1.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective treatment for patients with hepatocellular carcinoma (HCC). However, the impact of hepatitis B viral (HBV) infection and body mass index (BMI) on TACE is controversial. The present study aimed to compare the influence of HBV and high BMI on TACE outcomes in advanced HCC. METHODS: Based on HBV infection history and BMI, patients were assigned to different subgroups. Blood samples were collected and analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. The primary endpoint was progression-free survival (PFS) and the overall survival (OS) in the population. RESULTS: Compared to overweight combined HBV patients who received TACE, people with normal weight or no viral infection had significantly better OS and PFS. Sex, age, portal vein tumor thrombus, BCLC, ECOG, and tumor diameter are the main risk factors affecting PFS and OS. Except for the postoperative fever, no significant difference was detected in adverse reactions. Irrespective of TACE, the average expression of HMGB1 in hepatitis or obesity patients was higher than that in normal individuals and did not show upregulation after TACE. Patients without overweight or HBV infection had a low expression of serum HMGB1 that was substantially upregulated after TACE. CONCLUSIONS: In this study, overweight combined HBV infection patients had shorter PFS and OS than other HCC patients. Thus, HBV and BMI maybe two factors affecting the efficacy of TACE via upregulated HMGB1.

Association of Low High-Density Lipoprotein Cholesterol Levels with Poor Outcomes in Hepatitis B-Associated Decompensated Cirrhosis Patients.

BACKGROUND: Lipid levels become decreased in cirrhotic patients and are correlated with disease severity. In the present study, we investigated the impact of serum high-density lipoprotein cholesterol (HDL-C) on prognosis in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). METHODS: The medical records of 153 HBV-DeCi patients were analyzed. Patients were separated into survivors and nonsurvivors according to their 30-day survival. Univariate and multivariate analyses were performed to identify predictors of poor outcomes, and the performance of these predictors was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The 30-day mortality in the cohort was 18.9%. HDL-C levels differed markedly between survivors and nonsurvivors. On multivariate analysis, Model for End-stage Liver Disease (MELD) score and HDL-C level were identified as independent risk factors for mortality in HBV-DeCi patients. In the ROC analyses, the prognostic accuracy for mortality was similar between HDL-C (area under ROC curve: 0.785) and MELD score (area under ROC curve: 0.853). CONCLUSIONS: Low HDL-C level had a significant correlation with mortality in HBV-DeCi patients and can be used as a simple marker for risk assessment and selection of therapeutic options.

Adoption of Euvax-B vaccine in Nineveh

Hepatitis B infection is one of the most important health problems around the world. The high mortality rate of the hepatitis B encouraged research that led to the finding of an effective vaccine against it. The aim of the present study was to find out the use of the Euvax-B vaccine in sectors of Nineveh province. According to the results obtained in this study, in the next five years, the vaccination coverage for the second and third doses needs to improve(AU)

La infección por hepatitis B es uno de los más importantes problemas de salud del mundo. La alta tasa de mortalidad de la hepatitis B impulsó las investigaciones que llevaron a encontrar una vacuna eficaz contra la misma. El objetivo del presente estudio fue conocer el uso de la vacuna Euvax-B en sectores de la provincia de Nínive. De acuerdo con los resultados obtenidos, en los próximos cinco años, se debe incrementar la cobertura de inmunización de la segunda y tercera dosis de la vacuna(AU)

Sociodemographic characteristics, complications requiring hospital admission and causes of in-hospital death in patients with liver cirrhosis admitted at a district hospital in Ghana.

BACKGROUND: Chronic liver diseases including liver cirrhosis are a major cause of morbidity and mortality globally. Despite the high burden of liver cirrhosis in Ghana, data on this disease is lacking. OBJECTIVE: To determine the sociodemographic characteristics, reasons for admission, and in-hospital mortality of patients with cirrhosis of the liver seen at a district hospital in Ghana. METHODS: A prospective study was conducted involving one hundred and eighty-six (186) patients admitted on the medical wards in St. Dominic hospital with liver cirrhosis from 1st January 2018 to 24th June 2020. The patient's demographic and clinical features were documented using a standardized questionnaire. Diagnostic biochemical and haematological tests as well as abdominal ultrasound scans were performed for all patients. They were followed up until death or discharge from hospital. RESULTS: One hundred and eighty-six patients (186) with a median age of 46 years were included in the study. HBV was the main etiology of liver cirrhosis (38.7%) followed closely by alcohol consumption (38.3%). In-hospital mortality was 41.3% and the most frequent cause of death was hepatic encephalopathy (68.4%). The following were associated with death; Jaundice, weight loss, elevated bilirubin, international normalized ratio (INR), creatinine, blood urea nitrogen(BUN), Child-Pugh score, model for end-stage liver disease sodium score (MELDNa), and low sodium. However, hepatic encephalopathy, MELDNa, INR and BUN were independent predictors of in-hospital mortality on logistic regression analysis. CONCLUSIONS: In-hospital mortality in cirrhotic patients was high with the leading cause of death being hepatic encephalopathy. Timely diagnosis and adequate management of hepatic encephalopathy are necessary to prevent death from liver cirrhosis.

Everolimus Related Fulminant Hepatitis in Pancreatic Neuroendocrine Tumor With Liver Metastases: A Case Report and Literature Review.

Background: Everolimus, an immunosuppressant, is approved for the treatment of advanced renal cell carcinoma, metastatic hormone receptor-positive breast cancer, and pancreatic neuroendocrine tumors (P-NETs) but has been reported to be related to hepatitis B reactivation. Here, we present the first case of fatal fulminant hepatitis B reactivation in a man with P-NET accompanied by multiple liver metastases who received everolimus and octreotide long-acting repeatable (LAR). Case Presentation: A 45-year-old male had a history of chronic hepatitis B infection. He was found to have a complicated liver cyst incidentally, and then he underwent biopsy, which disclosed a grade 2 neuroendocrine tumor (NET). Subsequent MRI of the abdomen and PET revealed a solid mass at the pancreatic tail with numerous liver tumors favoring metastases and peripancreatic lymph node metastases. Transarterial chemoembolization (TACE) of the right lobe of the liver was performed, and he started to take 5 mg everolimus twice a day and 20 mg octreotide LAR every month 8 days after the 1st TACE. No hepatitis B virus (HBV) prophylaxis treatment was administered. He then underwent laparoscopic distal pancreatectomy and splenectomy three and half months after the initial treatment of everolimus. He continued everolimus 5 mg twice a day and octreotide 20 mg every month after the operation. Three months later, hepatic failure occurred due to acute hepatitis B flare-up-related fulminant hepatic failure since other possible causes of hepatic failure were excluded. Five days after hepatic failure presented, hepatic failure was apparent, and pulseless ventricular tachycardia occurred. The patient expired after failed resuscitation. Conclusion: A literature review of everolimus-related hepatitis B reactivation was conducted. In P-NET patients with chronic hepatitis B who will undergo everolimus treatment, HBV prophylaxis should be considered since fatal hepatitis B reactivation might occur under rare conditions.

Serum lactate level predicts 6-months mortality in patients with hepatitis B virus-related decompensated cirrhosis: a retrospective study.

The prediction of prognosis is an important part of management in hepatitis B virus (HBV)-related decompensated cirrhosis patients with high long-term mortality. Lactate is a known predictor of outcome in critically ill patients. The aim of this study was to assess the prognostic value of lactate in HBV-related decompensated cirrhosis patients. We performed a single-centre, observational, retrospective study of 405 HBV-related decompensated cirrhosis patients. Individuals were evaluated within 24 h after admission and the primary outcome was evaluated at 6-months. Multivariable analyses were used to determine whether lactate was independently associated with the prognosis of HBV-related decompensated cirrhosis patients. The area under the ROC (AUROC) was calculated to assess the predictive accuracy compared with existing scores. Serum lactate level was significantly higher in non-surviving patients than in surviving patients. Multivariable analyses demonstrated that lactate was an independent risk factor of 6-months mortality (odds ratio: 2.076, P < 0.001). Receiver operating characteristic (ROC) curves were drawn to evaluate the discriminative ability of lactate for 6-months mortality (AUROC: 0.716, P < 0.001). Based on our patient cohort, the new scores (Model For End-Stage Liver Disease (MELD) + lactate score, Child-Pugh + lactate score) had good accuracy for predicting 6-months mortality (AUROC = 0.769, P < 0.001; AUROC = 0.766, P < 0.001). Additionally, the performance of the new scores was superior to those of existing scores (all P < 0.001). Serum lactate at admission may be useful for predicting 6-months mortality in HBV-related decompensated cirrhosis patients, and the predictive value of the MELD score and Child-Pugh score was improved by adjusting lactate. Serum lactate should be part of the rapid diagnosis and initiation of therapy to improve clinical outcome.

Estimates of Cancer Mortality Attributable to Carcinogenic Infections in Italy.

Several infectious agents are ascertained causes of cancer, but the burden of cancer mortality attributable to carcinogenic infections in Italy is still unknown. To tackle this issue, we calculated the rate and regional distribution of cancer deaths due to infections sustained by seven pathogens ranked as group 1 carcinogenic agents in humans by the International Agency for Research on Cancer. Population attributable fractions related to these agents were applied to annual statistics of cancer deaths coded according to the 10th International Classification of Diseases. The estimated burden of cancer mortality attributable to carcinogenic infections in Italy during the period 2011-2015 was 8.7% of all cancer deaths registered yearly, on average. Approximately 60% of deaths occurred in men, and almost the whole burden was due to four infectious agents (Helicobacter pylori, hepatitis C virus, high-risk human papillomavirus, and hepatitis B virus). The analysis of regional distribution showed a higher number of infection-related cancer deaths in the northern regions, where the estimates reached 30 (Liguria) and 28 (Friuli Venezia Giulia) deaths per 100,000 inhabitants in 2015. Since one-twelfth of cancer deaths were attributable to these modifiable risk factors, the implementation of appropriate prevention and treatment interventions may help to reduce the impact of these infections on cancer mortality.

Depressive symptoms and risk of liver-related mortality in individuals with hepatitis B virus infection: a cohort study.

The impact of depression on the risk of liver-related mortality in individuals with hepatitis B virus (HBV) infection remains unclear. We examined the association between depression, HBV infection, and liver-related mortality. A total of 342,998 Korean adults who underwent health examinations were followed for up to 7.8 years. Depressive symptoms were defined as a Center for Epidemiologic Studies-Depression score ≥ 16. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During 1,836,508 person-years of follow-up, 74 liver-related deaths and 54 liver cancer deaths were identified (liver-related mortality rate of 4.0 per 105 person-years and liver cancer mortality rate of 2.9 per 105 person-years). Subjects with depressive symptoms had an increased risk of liver-related mortality with a corresponding multivariable aHR of 2.00 (95% CI 1.10-3.63) compared to those without depressive symptoms. This association was more evident in HBsAg-positive participants with a corresponding multivariable aHR of 4.22 (95% CI 1.81-9.88) than HBsAg-negative participants (P for interaction by HBsAg positivity = 0.036). A similar pattern was observed in relation to liver cancer mortality. In this large cohort, depressive symptoms were associated with an increased risk of liver-related mortality, with a stronger association in HBsAg-positive individuals.

Mortality trend due to Hepatitis B and C in the city of São Paulo, 2002-2016.

OBJECTIVE: To describe mortality due to hepatitis B and C as underlying cause in the municipality of São Paulo, verifying the trend of these rates, and to assess the association of these diseases with others, from 2002 to 2016. METHODS: This is a time series study on mortality due to hepatitis B and C according to sex, with data from the Sistema de Informação de Mortalidade (SIM - Mortality Information Sistem). Prais Winsten regression was used in rate trend analysis. RESULTS: The findings of this study showed a trend of decline of mortality from hepatitis B and C in recent years, particularly among males. These infections were important associated causes of liver cell carcinoma and HIV. The proportion of deaths under 70 years of age stands out. CONCLUSIONS: The study provides a baseline for research on mortality trend and the impact of interventions, given the history of expanded detection and supply of treatments, including the most recent antivirals in Brazil, since 2015.

Platelet-to-white blood cell ratio: A novel and promising prognostic marker for HBV-associated decompensated cirrhosis.

AIM: The present study aimed to investigate associations of the platelet-to-white blood cell ratio (PWR)-a novel hematological indicator of inflammatory responses-with 30-day outcomes in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). METHODS: We recruited 131 patients with HBV-DeCi for this retrospective study and extracted baseline clinical data and laboratory characteristics from medical records. Univariate and multivariate analyses were performed to determine major factors influencing 30-day mortality. Area under the receiver operating characteristic curve analyses was performed to compare the predictive values of prognostic markers. RESULTS: During the 30-day follow-up period, 15 patients died. The PWR was significantly different between nonsurvivors and survivors. Lower PWR was found to be associated with an increased risk of mortality, and PWR was found to be an independent predictor of mortality in patients with HBV-DeCi. CONCLUSIONS: Our results demonstrate that low PWR may be a predictor of poor prognosis in patients with HBV-DeCi, and this factor may be a useful supplement to standard approaches to enable effective management of these patients.

Ammonia predicts poor outcomes in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Hepatic encephalopathy (HE) is a common feature of acute liver failure and has been reported to be associated with poor outcomes. Ammonia is thought to be central to the pathogenesis of HE, but its role in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is unclear. The present study aimed to assess the prognostic role of ammonia level for patients with HBV-ACLF. METHODS: We retrospectively recruited 127 patients diagnosed with HBV-ACLF for the present study. RESULTS: Ammonia levels at the time of admission were higher among non-surviving participants than in survivors. Increased ammonia level was found to be associated with severe liver disease and was identified as an independent predictor for mortality in patients with HBV-ACLF. CONCLUSIONS: Our results suggest that high ammonia level at admission is an independent factor for predicting short-term mortality in patients with HBV-ACLF. Therefore, ammonia levels may represent a therapeutic target for this condition.

Mortality from liver diseases attributable to hepatitis B and C in the EU/EEA - descriptive analysis and estimation of 2015 baseline.

Background: WHO has set target to reduce mortality attributable to hepatitis B (HBV) and hepatitis C (HCV) by 65% by 2030, with 2015 as baseline. We aimed to describe the European Union/European Economic Area (EU/EEA) baseline mortality from liver diseases, as defined by WHO Core-10 indicator through ICD-10 codes, and estimate mortality attributable to HBV and HCV.Methods: Age-standardised mortality rates per 100,000 for hepatocellular carcinoma (HCC, ICD-10 C22.0), chronic liver disease (CLD, ICD-10 K72-K75) and chronic viral hepatitis B and C (CHB/CHC, ICD-10 B18.1-B18.3) were calculated by gender, age-group and country using 2015 Eurostat data. Because aetiology fraction (AF) estimates were lacking for HCC and CLD as defined by C10, number of deaths in EU/EEA countries in 2015 from liver cancer (ICD-10 C22) and 'cirrhosis and other chronic liver diseases' (ICD-10 B18-B18.9, I85-I85.9, I98.2, K70-K70.3, K71.7, K74-K74.9, K75.2, K75.4-K76.2, K76.4-K76.9 and K77.8) were adjusted by corresponding AF estimates from Global Burden of Disease publications.Results: In 2015, there were wide variations across countries in mortality rates from HCC, CLD and CHB/CHC. A 2015 mortality baseline of 63,927 deaths attributable to HBV and HCV is proposed, that includes 55% of liver cancer and 45% of 'cirrhosis and other chronic liver diseases' deaths.Conclusions: The HBV and HCV attributable mortality in the EU/EEA is high. Greater efforts are needed to identify HBV and HCV infections at an early stage and link cases to care to reduce mortality from liver diseases. Country-specific AF estimates are needed to accurately estimate HBV, HCV associated mortality.

Clinical Patterns and Outcome of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) may develop into liver cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to compare the clinical patterns and survival outcomes of NAFLD-related HCC patients and those of alcoholic liver disease (ALD)-related or hepatitis B virus (HBV)-related HCC patients. Methods: A total of 622 HCC patients with associated NAFLD (n = 56), ALD (n = 173), or HBV infection (n = 393) were enrolled. The clinical characteristics and survival were analyzed according to the underlying liver diseases. Results: NAFLD-related HCC patients were more commonly older women and had more metabolic risk factors but were less likely to have cirrhosis and ascites, compared to ALD-related or HBV-related HCC patients. NAFLD-related HCC more often had an infiltrative pattern (P=0.047), a larger tumor (P=0.001), more macrovascular invasion (P=0.022), and exceeded the Milan criteria (P=0.001), but was less frequently diagnosed during tumor surveillance (P=0.025). Survival analysis did not show any difference among NAFLD-related, ALD-related, and HBV-related HCC patients. Furthermore, propensity score matching analysis did not reveal a significant difference in the median survival between the different groups (NAFLD vs. ALD, 14.0 months [95% confidence interval (CI), 2.0-26.0] vs. 13.0 months [95% CI, 0-26.3]; P=0.667, NAFLD vs. HBV, 14.0 months [95% CI, 2.0-26.0] vs. 12.0 months [95% CI, 4.3-17.8]; P=0.573). Conclusions: NAFLD-related HCCs were more often detected at an advanced stage with infiltrative patterns, although they showed no significant difference in survival compared to ALD-related or HBV-related HCCs. A future prospective research should be focused on identifying NAFLD patients who require strict surveillance in order to early detect and timely treat HCC.

HBV flare associated with immunosuppressive treatments: it is still dangerous in the third-generation antivirals era.

BACKGROUND: There are limited data about the mortality and morbidity of patients with HBV flare related to immunosuppressive treatments (IST) in the third-generation antivirals era. Herein, we performed a multi-centric study in patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and evaluated their clinical course. METHODS: The study group included patients who were referred to gastroenterology or infectious disease specialists at eight different hospitals in Turkey. HBV flare was defined as at least a threefold elevation in alanine aminotransferase (ALT) levels above the upper limit of normal range. The demographic data, IST protocol, virological markers, liver tests, international normalized ratio (INR), HBV DNA, reactivation risk profile according to AGA guideline, MELD and MELD-Na scores were retrospectively evaluated. The primary aim of the study was to determine the liver-related mortality, including transplantation, at 12 weeks and factors predicting it. Secondary aims were to compare ETV and TDF with respect to mortality and time to ALT, bilirubin normalization and HBV DNA undetectability. RESULTS: The study group included 40 patients (29 males, mean age: 57 ±12 years). Twenty-five patients (62.5%) had a high risk of reactivation. Twenty-six patients received TDF and 14 patients received ETV treatment. Eight (20%) patients developed acute liver failure and one patient (2.5%) underwent living donor liver transplantation. Seven patients died due to liver-related complications, revealing a mortality rate of 17.5%. In multivariate analysis, total bilirubin levels at the onset, ALT levels and delta-MELD score at the first week were the independent risk factors for liver related mortality (HR: 1.222, 1.003, 1.253 and 95% CI: 1.096, 1.362; 1.001, 1.004 and 1.065, 1.470, respectively). There was no significant difference between the TDF and ETV groups with respect to time to normalize ALT and bilirubin levels, HBV DNA undetectability and mortality rates (16% and 21.4%, respectively). CONCLUSIONS: HBV flare associated with IST has a high mortality in the third-generation antivirals era. High total bilirubin at the onset and high ALT and delta-MELD score at the first week predict poor prognosis.