entecavir and Liver-Failure--Acute

Despite a decline in cases of acute hepatitis B and the low hepatitis B virus (HBV) chronicity rates in adults, still some patients progress to HBV-related fulminant liver failure. In this review, we discuss treatment options that may prevent the progression of severe acute hepatitis B to fulminant liver failure and death. In severe acute HBV with prolonged prothrombin time and increased bilirubin, interferon failed to be effective while antiviral treatment, particularly with lamivudine, appears to improve survival (mean survival almost 80%). Outcome without antiviral therapy has remained considerably poor, whereas there is no convincing evidence of amelioration of HBV-targeted immunity. Of note, most patients who died or required transplantation despite lamivudine therapy, were started on lamivudine at advanced stages compared with those survived. This suggests that prompt and timely antiviral therapy is crucial. Owing to the abovementioned results the design of randomized placebo-control trials in the setting of severe acute hepatitis B seems unethical. On the contrary, the design of multicentre double-blind randomized trials to compare the efficacy between lamivudine and entecavir or even tenofovir in acute severe HBV cases is ideally needed, but these studies appear to be very difficult to perform considering that these cases are not frequent and therefore, it is almost impossible to have two arms adequately numerous and homogenous for statistical evaluation. Thus, in the absence of solid evidence based data, the hepatologists could treat their patients with severe acute hepatitis B with lamivudine or the most potent antivirals entecavir or tenofovir.

Topics: Adenine; Antiviral Agents; Guanine; Hepatitis B; Humans; Interferons; Lamivudine; Liver Failure, Acute; Organophosphonates; Tenofovir

Topics: Acute Disease; Antiviral Agents; Carrier State; Cyclosporine; Drug Therapy, Combination; Guanine; Hemodiafiltration; Hepatitis B; Humans; Immunosuppressive Agents; Lamivudine; Liver Failure, Acute; Liver Transplantation; Methylprednisolone; Plasma Exchange; Prognosis; Pulse Therapy, Drug

To investigate the efficacy of antiviral treatment on patients with acute-on-chronic hepatitis B liver failure with low viral load.. 352 patients with acute-on-chronic hepatitis B liver failure including 175 cases of low HBV viral load and 177 cases of high HBV viral load were enrolled into this study. The patients were divided into the antiviral group which received antiviral therapy (Lamivudine, Entecavir or Telbivudine) plus routine supportive therapy and the control group which received supportive therapy only. The clinical features and the 24-week short-term efficacy of antiviral therapy were assessed.. At week 24,total survival rate in antiviral group was higher than that in control group (P = 0.010). The survival rate of patients with low viral load in the antiviral group was higher than that in the control group (P = 0.001). But there was no significant difference between the antiviral group and the control group with high viral load (P = 0.856). But in the antiviral group, there was no significant difference in survival rate between the patients with high HBV viral load and those with low viral load (P = 0.755).. Antiviral therapy can significantly improve survival rate of patients of acute-on-chronic hepatitis B liver failure with low viral load. Liver failure;

Topics: Adult; Antiviral Agents; End Stage Liver Disease; Female; Guanine; Hepatitis B, Chronic; Humans; Lamivudine; Liver Failure, Acute; Male; Middle Aged; Nucleosides; Pyrimidinones; Telbivudine; Thymidine; Viral Load

Objective Patients with acute hepatitis B sometimes develop acute liver failure (ALF), which has a poor prognosis. The efficacy of nucleoside analogue (NA) monotherapy for ALF due to transient hepatitis B virus infection (HBV-ALF) remains controversial. Further investigations are necessary in nations with a shortage of donor livers for liver transplantation. In the present study, we aimed to clarify the efficacy of combination therapy with corticosteroid (CS) and NA in the treatment HBV-ALF. Patients We examined the clinical and biochemical features of 19 patients with HBV-ALF who were treated in the early stage of the disease between 2000 and 2015. Results Fourteen patients received CS and NA (CS + NA group) and 5 received NA monotherapy (NA group). Eleven patients (58%) survived and 8 (42%) died. The survival rates in the CS + NA and NA groups were 64% and 40%, respectively (p=0.60). The mean alanine aminotransferase (ALT) levels declined significantly at week 2 in both groups. The mean PT activities improved significantly at weeks 1 and 2 in the CS + NA group (p<0.05) but not in the NA group. None of the surviving patients developed persistent infection. Conclusion Combination therapy with CS and NA induces the rapid resolution of inflammation leading to a rapid recovery of the liver function. When it is administered at a sufficiently early stage, it would have a survival benefit and prevent persistent infection in HBV-ALF.

Topics: Adult; Alanine Transaminase; Antiviral Agents; Drug Therapy, Combination; Female; Glucocorticoids; Guanine; Hepatitis B; Hepatitis B virus; Humans; Inflammation; Lamivudine; Liver Failure, Acute; Male; Methylprednisolone; Middle Aged; Prednisolone; Retrospective Studies; Survival Rate; Time-to-Treatment

Although new hepatitis B virus (HBV) infections are decreasing due to improving vaccination coverage, patients without vaccination coverage can still suffer from manifestation of acute hepatitis B with jaundice and (although rarely) liver failure. No treatment is indicated for mild acute hepatitis B; however, antiviral therapy should be initiated for patients showing signs of significant liver impairment as exemplified by deterioration of prothrombin time to an equivalent of 1.5 or 50% of the 'Quick test'. For fulminant hepatitis, there is no complete agreement on whether antiviral treatment would alter the course, but it should still be started, as it would reduce the risk of reinfection in case there is a need for liver transplantation. Patients in danger of progression towards acute liver failure should be referred to transplant centers as early as possible.

Topics: Antiviral Agents; Guanine; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Hepatitis B virus; Humans; Interferon-alpha; Lamivudine; Liver; Liver Failure, Acute; Liver Transplantation; Polyethylene Glycols; Recombinant Proteins; Reverse Transcriptase Inhibitors; Telbivudine; Thymidine

Selection of drugs for antiviral therapy of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remains difficult. This study was undertaken to evaluate the short-term efficacy of entecavir versus lamivudine on hepatitis B e antigen (HBeAg)-negative patients with ACLF.. The data of 182 HBeAg-negative patients with ACLF were retrospectively collected from patient profiles of the hospital. In these patients, 93 HBeAg-negative patients with ACLF were treated orally with 0.5 mg of entecavir and 89 were treated orally with 100 mg of lamivudine every day. The gender and age were matched between the two groups. Biochemical items, the model for end-stage liver disease (MELD) score, and HBV DNA level were matched at baseline between the two groups and monitored during treatment. The 3-month mortalities of the two groups were compared.. No significant differences were found in biochemical items, MELD score, and HBV DNA level at baseline (P>0.05). HBV DNA level decreased within 3 months in both groups (P<0.05), regardless of the pretreatment MELD score. In patients with the same range of pretreatment MELD scores, treatment duration, posttreatment HBV DNA levels, percentage of HBV DNA level <2.7 lg copies/mL, biochemical items, MELD scores and 3-month mortality were similar in the two groups (all P>0.05). Pretreatment MELD score was not related to posttreatment HBV DNA levels (P>0.05), but related to a 3-month mortality in both groups (both P<0.001).. In HBeAg-negative patients with ACLF, the short-term efficacy of entecavir versus lamivudine was similar. The degree of pretreatment liver failure significantly affected the outcome of treatment.

Topics: Administration, Oral; Adult; Analysis of Variance; Antiviral Agents; Biomarkers; Chi-Square Distribution; DNA, Viral; Drug Administration Schedule; End Stage Liver Disease; Female; Guanine; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Liver Failure, Acute; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome

Lamivudine, adefovir, telbivudine, and entecavir are nucleoside analogues that can inhibit hepatitis B virus replication and are licensed in China by the Food and Drug Administration. This study presents the cases of 2 patients who were chronically infected with HBV and suffered hepatic failure resulting from withdrawal of telbivudine and adefovir, respectively.

Topics: Adenine; Adult; Antiviral Agents; Guanine; Hepatitis B, Chronic; Histocytochemistry; Humans; Lamivudine; Liver Failure, Acute; Liver Transplantation; Male; Medication Adherence; Necrosis; Organophosphonates; Telbivudine; Thymidine

To investigate optimal timing for therapeutic efficacy of entecavir for acute-on-chronic hepatitis B liver failure (ACLF-HBV) in hepatitis B e antigen (HBeAg)-negative patients.. A total of 109 inpatients with ACLF-HBV were recruited from the Department of Infectious Diseases of the Third Affiliated Hospital, Sun Yat-sen University from October 2007 to October 2010. Entecavir 0.5 mg/d was added to each patient's comprehensive therapeutic regimen. Patients were divided into three groups according to model for end-stage liver disease (MELD) score: high (≥ 30, 20 males and 4 females, mean age 47.8 ± 13.5 years); intermediate (22-30, 49 males and 5 females, 45.9 ± 12.4 years); and low (≤ 22, 28 males and 3 females, 43.4 ± 9.4 years). Statistical analysis were performed using SPSS 11.0 software. Data with normal distribution were expressed as mean ± SD and comparisons were made with Student's t tests. A value of P < 0.05 was considered statistically significant. Viral loads were related exponentially and logarithmic data were used for analysis.. For 24 patients with MELD score ≥ 30, treatment lasted 17.2 ± 16.5 d. Scores before and after treatment were significantly different (35.97 ± 4.87 and 40.48 ± 8.17, respectively, t = -2.762, P = 0.011); HBV DNA load was reduced (4.882 ± 1.847 copies log(10)/mL to 3.685 ± 1.436 copies log(10)/mL); and mortality rate was 95.83% (23/24). Of 54 patients with scores of 22-30, treatment lasted for 54.0 ± 43.2 d; scores before and after treatment were 25.87 ± 2.33 and 25.82 ± 13.92, respectively (t = -0.030, P = 0.976); HBV DNA load decreased from 6.308 ± 1.607 to 3.473 ± 2.097 copies log(10)/mL; and mortality was 51.85% (28/54). Of 31 patients with scores ≤ 22, treatment lasted for 66.1 ± 41.9 d; scores before and after treatment were 18.88 ± 2.44 and 12.39 ± 7.80, respectively, (t = 4.860, P = 0.000); HBV DNA load decreased from 5.841 ± 1.734 to 2.657 ± 1.154 copies log(10)/mL; and mortality was 3.23% (1/31).. For HBeAg-negative patients with ACLF-HBV, when entecavir was added to comprehensive therapy, a MELD score ≥ 30 predicted very poor prognosis due to fatal liver failure.

Topics: Adult; Antiviral Agents; DNA, Viral; Dose-Response Relationship, Drug; End Stage Liver Disease; Female; Guanine; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Humans; Liver Failure, Acute; Male; Middle Aged; Predictive Value of Tests; Prognosis; Severity of Illness Index; Survival Rate; Treatment Outcome; Viral Load

Topics: Antiviral Agents; DNA, Viral; Fatal Outcome; Guanine; Hepatitis B e Antigens; Hepatitis B, Chronic; Humans; Liver Failure, Acute; Liver Function Tests; Male; Middle Aged; Multiple Organ Failure; Prognosis

Topics: Adenine; Antiviral Agents; End Stage Liver Disease; Guanine; Hepatitis B, Chronic; Humans; Liver Failure, Acute; Organophosphonates; Tenofovir

It is well known that the reactivation of hepatitis B virus (HBV) may occur as an acute hepatitis after chemotherapy or immunosuppressive therapy. Although most of these cases have been reported in HBsAg-positive patients, there have been a few reports of HBV reactivation in HBsAg-negative patients. There have been concerns for the need to screen the reactivation as well as anti-viral prophylaxis in HBsAg-negative patients with possible HBV occult infection who are planning to undergo chemotherapy or immunosuppressive therapy. Rituximab, an anti-CD20 monoclonal antibody, is effective in the treatment of non-Hodgkins lymphoma. However, rituximab can affect the immunity against HBV, consequently increasing viral replication. In fact, there have been reports of HBV reactivation after treatment with rituximab. Here, we report a case of HBV reactivation following rituximab plus systemic chemotherapy in diffuse large B cell lymphoma patient who was HBsAg negative, anti-HBs positive, and anti-HBc positive, ultimately leading to treatment-unresponsive fulminant hepatic failure.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antiviral Agents; DNA, Viral; Female; Guanine; Hepatitis B; Hepatitis B virus; Humans; Liver Failure, Acute; Lymphoma, Large B-Cell, Diffuse; Recurrence; Rituximab

Acute hepatitis B virus (HBV) infection is followed by high viral replication rates leading to hepatocyte death and ultimately, in some cases, to acute liver failure (ALF) necessitating liver transplantation. Thus, the objective of treating HBV-induced ALF is to eliminate or significantly suppress HBV replication.. This prospective study (02/2008-02/2009) included 6 patients (1 female and 5 males, median age 35.5 years). HBV DNA and hepatitis B surface antigen (HBsAg) levels were detected, and hepatocyte death was quantified in patients' sera by (a) M65 ELISA and (b) M30 ELISA. All patients received entecavir treatment at 1 mg daily within 1-18 days after admission. Upon treatment, pathologic parameters rapidly decreased and returned to normal values or trace amounts (HBV DNA) within 3 months in all of the cases. A seroconversion to anti-HBsAg was achieved in 5 out of 6 patients; one patient with late onset of treatment did not seroconvert. M65 and the difference of M65-M30 as a marker for cell necrosis dropped significantly within 1 week of treatment.. This preliminary series of 6 patients reveals that immediate treatment of HBV-induced ALF with entecavir is well tolerated and beneficially affects the course of the disease.

Topics: Adult; Antiviral Agents; Biomarkers; Cell Death; DNA, Viral; Female; Guanine; Hepatitis B; Hepatitis B Surface Antigens; Humans; Liver Failure, Acute; Male; Prospective Studies; Virus Replication; Young Adult