entecavir and Fatty-Liver

Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood.. This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression.. The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%-2.88%) and an annual rate of 0.22% (.17%-.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 [95% confidence interval, 1.80-5.49]), elevated serum alanine aminotransferase >200 U/L (3.68 [2.07-6.53]), serum bilirubin (1.11 per mg/dL; [1.06-1.17 mg/dL]), and fatty liver (1.84 [1.03-3.29]).. HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.

Topics: Alanine Transaminase; Antiviral Agents; Bilirubin; China; Cohort Studies; DNA, Viral; Fatty Liver; Female; Guanine; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Incidence; Male; Middle Aged; Tenofovir; Treatment Outcome; Viremia

The effect of hepatic steatosis on the response to antiviral therapy administered in chronic hepatitis B patients is yet to be clarified. In this study, our aim was to determine the effect of hepatic steatosis on the virological response in chronic hepatitis B patients who were treated with entecavir or tenofovir disoproxil fumarate.. This retrospective cohort study was performed using the data of liver biopsy-proven chronic hepatitis B patients with or without hepatic steatosis, who received entecavir or tenofovir disoproxil fumarate treatment between 2012 and 2017. The undetectable serum hepatitis B virus deoxyribonucleic acid level under treatment was defined as the complete virological response. The predictors of virological response were determined, and it was checked whether the virological response was affected by hepatic steatosis in chronic hepatitis B patients who have undergone entecavir or tenofovir disoproxil fumarate treatment.. A total of 324 chronic hepatitis B patients, of which 203 (63%) were males, were included in the study. The median age of the patients was 42 years (range: 35-51 years). Hepatic steatosis was observed in 25% of the patients, and steatohepatitis in 4%. The median time to complete virological response was found to be 6 months (range: 3-9 months). In the full analysis model, the log hepatitis B virus deoxyribonucleic acid was determined as the factor most associated with virological response (P < .001). No statistically signifi- cant relationship was detected between hepatic steatosis and virological response (P = .409).. Concomitant hepatic steatosis has no significant impact on the virological response in chronic hepatitis B patients who have undergone entecavir or tenofovir disoproxil fumarate treatment.

Topics: Adult; Antiviral Agents; DNA, Viral; Fatty Liver; Female; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Retrospective Studies; Tenofovir; Treatment Outcome

The influence of hepatic steatosis (HS) on chronic hepatitis B (CHB) is unclear. We evaluated the influence of the degree of HS, assessed using the controlled attenuation parameter (CAP) of transient elastography (TE), on treatment outcomes in CHB patients initiated on antiviral therapy.. A total of 334 patients who were initiated on entecavir or tenofovir between 2007 and 2016 with available TE results were recruited.. Of the total study population, 146 (43.7%) patients had HS (CAP > 238 dB/m). Three-hundred-three patients (90.7%) achieved complete virological response (CVR) (hepatitis B virus DNA<12 IU/L), and 25 patients (7.5%) developed hepatocellular carcinoma (HCC). Among hepatitis B e antigen (HBeAg)-positive patients (n=172, 51.5%), 37 (21.5%) experienced HBeAg loss. On univariate analysis, CAP value was not associated with the probability of HCC development (P=0.380). However, lower CAP value was independently associated with higher probability of HBeAg loss among HBeAg-positive patients (hazard ratio [HR]=0.991, P=0.026) and with CVR achievement in the entire study population (HR=0.996, P=0.004). The cumulative incidence of HBeAg loss among HBeAg-positive patients was significantly higher in patients without HS than in those with HS (log-rank, P=0.022).. CAP values were not correlated with HCC development in patients initiated on entecavir and tenofovir. However, CAP values were negatively correlated with the probability of HBeAg loss among HBeAg-positive patients and with CVR achievement.

Topics: Adult; Antiviral Agents; Fatty Liver; Female; Guanine; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Sustained Virologic Response; Tenofovir; Treatment Outcome

Topics: Fatty Liver; Guanine; Hepatitis B, Chronic; Humans; Tenofovir

Ground glass hepatocytes (GGHs) have been shown to predict the development of hepatocellular carcinoma (HCC). Type I GGH and type II GGH harbor hepatitis B virus (HBV) pre-S1 and pre-S2 deletion mutants, respectively. Whether anti-HBV therapy can inhibit the expression of GGHs and potentially reduce HCC development is explored in this study. Two sets of liver specimens were included: the first contained 31 paired biopsy specimens obtained from chronic HBV patients receiving oral nucleos(t)ide analogue (NA) treatment; the second contained 186 resected liver tissues obtained from HBV-related HCC patients receiving surgery: 82 received NA before surgery and 104 did not. Compared with the baseline biopsy specimens, type I (P=0.527) and type II GGH (P=0.077) were not significantly decreased after 48 weeks of NA treatment in the first set of patients. In the second set, despite suppression of viral load (P<0.001) and periportal necrosis (P=0.006) in treated patients, GGH (P=0.594), cccDNA (P=0.172) and serum pre-S mutants (p=0.401) were not significantly suppressed. A significant decrease of type I (P=0.049) and type II GGH (P=0.029) could only be observed in patients after long duration of treatment (median duration: 4.3 years). In the treated patients, the persisted type II GGH remained an independent variable associated with decreased local recurrence-free survival of HCC (P=0.019) as in non-treated patients (P=0.001). In conclusion, the persistence of GGHs could explain the residual risk of HCC development under anti-HBV treatment. Therefore, intrahepatic GGHs and pre-S mutant are potential additional targets for HCC prevention in patients already receiving anti-HBV treatment.

Topics: Adenine; Administration, Oral; Adolescent; Adult; Amino Acid Sequence; Antiviral Agents; Biopsy; Carcinoma, Hepatocellular; DNA, Circular; Drug Resistance, Viral; Fatty Liver; Female; Guanine; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Humans; Lamivudine; Liver; Liver Neoplasms; Male; Middle Aged; Necrosis; Organophosphonates; Protein Precursors; Sequence Deletion; Viral Load; Young Adult

The coexistence of HBV infection and nonalcoholic fatty liver disease (NAFLD) becomes characteristic of liver disease in China, with unknown bilateral influence. We aimed to investigate the effect of hepatic steatosis, a common hepatocyte change in NAFLD, on antiviral therapy in patients with chronic hepatitis B (CHB).. We carried out a prospective nested case control study in CHB patients receiving Entecavir for initial antiviral therapy, by recording demographic, anthropometric and clinical data at baseline, 24(wk), 48(wk) and 96(wk). Univariate analysis and multivariate logistic regression were applied to find out independent factors of hepatic steatosis and Entecavir treatment failure. The rates of HBV-DNA clearance, HBeAg seroconversion and ALT normalization were compared between CHB patients with and without steatosis by post hoc analysis. A total of 267 Chinese patients with CHB entered final analysis, with overall percentages of hepatic steatosis and HBeAg positive as 30.5% and 62.4%. Multivariate analysis showed waist circumference, serum TG and uric acid levels were independent factors of hepatic steatosis. The response rates to Entecavir were 54.9%, 63.8%, 74.2% at 24(wk), 48(wk) and 96(wk). Hepatic steatosis was revealed as an independent factor of Entecavir treatment failure by multivariate logistic regression at 24(wk), 48(wk) and 96(wk). In CHB patients with hepatic steatosis, HBV-DNA clearance and HBeAg seroconversion were both lower throughout the follow-up, but only the former reached statistical significance. Besides, ALT normalization was also significantly lower at 24(wk) and 48(wk).. Hepatic steatosis is significantly associated with Entecavir treatment failure and metabolic factors are independent factors of hepatic steatosis in CHB patients, which called for a specified antiviral strategy in CHB patients with NAFLD.

Topics: Adult; Anthropometry; Antiviral Agents; Body Mass Index; Case-Control Studies; China; Fatty Liver; Female; Guanine; Hepatitis B, Chronic; Hepatocytes; Humans; Male; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Prevalence; Prospective Studies; Regression Analysis; Treatment Outcome