Tenofovir Alafenamide versus Tenofovir Disoproxil Fumarate for Preventing Vertical Transmission in Chronic Hepatitis B Mothers: A Systematic Review and Meta-Analysis.

OBJECTIVE: International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent HBV mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the two regimens are lacking. DESIGN: In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to March 31, 2024, and extracted data from cohort studies and RCTs in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. RESULTS: We included 31 studies with 2,588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1,600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval 0.07-0.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.16-7.61). Network meta-analysis showed the equal efficacy of the two regimens in reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: 0.77 vs. 0.72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. CONCLUSION: Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.

Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir.

INTRODUCTION: Loss of HBeAg and development of anti-HBe (seroconversion) is seen as a milestone and endpoint in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB). Among patients treated with nucleos(t)ide analogs (NA), recurrent viremia is common after discontinuation of therapy. Entecavir (ETV) and tenofovir (TDF) are highly potent NA. The durability of virological response and HBeAg seroconversion in patients treated with these agents is not well studied. METHODS: We retrospectively studied the outcomes of 54 HBeAg-positive CHB patients who were treated with either ETV (n = 30) or TDF (23) or both (n = 1) that achieved virological response and underwent seroconversion and consolidation therapy before cessation of treatment. RESULTS: Only 4 (7%) patients had sustained virological, serological, and biochemical remission. Thirteen patients (24%) continued to have HBV DNA levels below 2000 IU/mL and normal alanine aminotransferase activity (ALT). Thirty-seven patients (69%) developed HBV DNA >2000 IU/mL, with 20 having elevated ALT. Among these 37 patients, 23 (62%) remained HBeAg negative/anti-HBe positive, 12 (32%) became HBeAg positive, and 2 (5%) were HBeAg and anti-HBe negative. Duration of consolidation therapy did not correlate with low versus high level of virological relapse. CONCLUSIONS: Durability of HBeAg seroconversion associated with ETV or TDF was not superior to that reported in patients treated with less potent NA. Our results, aggregated with others, suggest HBeAg seroconversion should not be considered as a treatment endpoint for most HBeAg-positive patients treated with NA. Future updates of treatment guidelines should reconsider HBeAg seroconversion as an endpoint to therapy.

Hepatitis B vaccines.

Immunization is the most effective way to prevent transmission of HBV and, hence, the development of acute or chronic hepatitis B. The national strategy to eliminate transmission of the virus in the United States includes vaccination of all newborn infants, children, adolescents, and high-risk adults. Postexposure prophylaxis is also advocated, depending on the vaccination and anti-HBs status of the exposed person. Seroprotection after vaccination, defined as anti-HBs > or = 10 mIU/mL, is achieved in over 95% of all vaccinees. The hepatitis B vaccines are very well tolerated with usually minimal adverse effects. Predictors of non-response include increasing age, male gender, obesity, tobacco smoking, and immunocompromising chronic dis-ease. For those who remain nonresponders after the second series of vaccination, adjuvants such as GM-CSF may be considered, but their results are variable.

Nucleoside analogues and other antivirals for treatment of hepatitis B in the peritransplant period.

Chronic HBV infection is a common cause of advanced liver disease that is associated with substantial mortality. Furthermore, chronic hepatitis B was historically a controversial indication for liver transplantation because of a low post-transplant survival, with graft infection being the major contributor to adverse outcomes. The initial use of hepatitis B immune globulin as prophylaxis, followed later by combined therapy with lamivudine, markedly reduced viral recurrence and improved the survival of patients transplanted for acute or chronic hepatitis B with liver failure. Lamivudine alone can also be used for long-term prophylaxis against de novo HBV infection that can be transmitted by organs from donors positive for anti-HBc or anti-HBs. When used in patients with decompensated chronic hepatitis B with cirrhosis, lamivudine has been shown to improve clinical manifestations, prolong pretransplant survival, and defer, or even obviate, the need for transplantation. Despite prophylaxis, viral mutations with breakthrough reinfection may occur and lead to liver failure. The recently approved adefovir dipivoxil, which is active against lamivudine-resistant mutation, and other nucleoside analogs that are in various phases of development, offer hope as rescue therapy for viral recurrence. Other therapeutic alternatives in the future may include gene therapy and immune interventions.

Hepatitis B vaccines.

Immunization is the most effective way to prevent transmission of HBV and, hence, the development of acute or chronic hepatitis B. The national strategy to eliminate transmission of the virus in the United States includes vaccination of all newborn infants, children, adolescents, and high-risk adults. Postexposure prophylaxis is also advocated, depending on the vaccination and anti-HBs status of the exposed person. Seroprotection after vaccination, defined as anti-HBs > or = 10 mIU/mL, is achieved in over 95% of all vaccinees. The hepatitis B vaccines are very well tolerated with usually minimal adverse effects. Predictors of non-response include increasing age, male gender, obesity, tobacco smoking, and immunocompromising chronic disease. For those who remain nonresponders after the second series of vaccination, adjuvants such as GM-CSF may be considered, but their results are variable.

Management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) ranks fifth in frequency worldwide among all malignancies and causes 1 million deaths annually. The management of HCC begins with diagnostic confirmation by radiologic imaging or histology. Staging is essential, as the choice of therapy depends on the functional state of the liver and the extent of tumor growth. Surgery, in the form of either hepatic resection or orthotopic liver transplantation, is the only potentially curative treatment. Transarterial chemoembolization is commonly used as either palliative treatment or adjunctive therapy to surgery, and a survival benefit with this therapy has just recently been demonstrated in a randomized, controlled trial. Patients with inoperable HCC may benefit from local ablative therapy that may still have curative potential in those with sufficiently small lesions and adequate liver function. For patients with advanced HCC, systemic chemotherapy has been widely employed, despite low efficacy and significant complication rate. Tamoxifen did not improve survival in large clinical trials. Gene therapy is an exciting approach to treating HCC but is still largely confined to preclinical and experimental settings.

Nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) encompasses a broad clinicopathologic spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may advance to cirrhosis and end-stage liver disease. Steatosis alone does not appear to be progressive. The prevalence of NAFLD averages 20% and that of NASH, 2% to 3%, making these conditions the most common liver diseases in the United States. NAFLD is associated with insulin resistance, which may be evident clinically with obesity, type 2 diabetes mellitus, and hypertriglyceridemia. The pathogenesis of NAFLD consists of hepatic fat accumulation and oxidative stress with formation of free radicals. The clinical diagnosis is based on the presence of the insulin resistance syndrome and exclusion of alcohol abuse as well as viral, autoimmune, genetic, and drug-induced liver diseases. Liver biopsy is essential for diagnosis but may not be necessary for clinical management. Treatment is aimed at correcting the risk factors for NAFLD and using potentially hepatoprotective agents. Ursodeoxycholic acid and betaine appear particularly promising in early trials.