Multiple Studies on Antiviral Treatment for Chronic Hepatitis B Selected for Conference Exchange, with a Focus on the Stability of Decompensation

Editor’s Note:

From November 10th to 14th, 2023, the American Association for the Study of Liver Diseases (AASLD) Annual Meeting was grandly held in Boston, USA. In this event, Dr. Wen Xie’s team from Beijing Ditan Hospital, Capital Medical University, presented several notable research findings. One of them is a study on the stability of decompensation in patients with chronic hepatitis B and liver cirrhosis treated with entecavir (ETV) [1], which received the Outstanding Abstract Award at the conference. Hepatology Digest reports on these research findings as follows.

Study One

Study on the Stability of Decompensation in Patients with Chronic Hepatitis B and Liver Cirrhosis Treated with Entecavir

First Authors: Deng You, Kang Haiyan, Xiang Huiling; Corresponding Authors: Jia Jidong, Wen Xie, Xu Xiaoyuan

▲AASLD 2023 Poster Presentation (1440-C)

Background

Nucleos(t)ide analogs (NAs) therapy for chronic hepatitis B (CHB) has been proven to improve clinical outcomes, even in patients with decompensated liver cirrhosis. While some decompensated patients receiving treatment can achieve recompensation, the long-term stability of this state remains uncertain.

Methods

This study is based on a multicenter, prospective cohort extension study that included patients with decompensated liver cirrhosis due to CHB, with ascites as the first decompensation event. These patients received 120 weeks of entecavir treatment. At week 120, 283 patients were assessed for recompensation based on the Baveno VII criteria and criteria for stable improvement in liver function. Among them, 159 achieved recompensation, and 124 did not. Subsequently, these patients were followed up until the occurrence of a second decompensation event or until March 2023.

Results

This study is an extension of a multicenter, prospective cohort study that included patients with decompensated liver cirrhosis due to chronic hepatitis B. These patients experienced ascites as the initial decompensation event and underwent 120 weeks of entecavir treatment. At week 120, based on the Baveno VII criteria and criteria for stable improvement in liver function, an assessment of recompensation was conducted for 283 patients, with 159 achieving recompensation and 124 unable to achieve it. Subsequently, these patients continued to receive follow-up until the occurrence of a second decompensation event or until March 2023.

Conclusion

Among the initial 283 patients, 165 continued follow-up after week 120, with a median follow-up time of 240 (192-288) weeks. Among the 101 patients who achieved recompensation at week 120, 87 (86.1%) did not experience subsequent decompensation events. Additionally, among them, 4 were diagnosed with hepatocellular carcinoma, 2 experienced esophageal variceal bleeding, 2 progressed to moderate to severe ascites, and 6 died. In contrast, among the 64 patients who did not achieve recompensation at week 120, 27 (42.2%) did not experience subsequent decompensation events. Among them, 4 were diagnosed with hepatocellular carcinoma, 1 had esophageal variceal bleeding, 10 developed moderate to severe ascites, and 22 died.

Study Two

Efficacy and Safety of Tenofovir Alafenamide Fumarate in Treating Decompensated Patients with Chronic Hepatitis B and Cirrhosis

First Author: Deng You; Corresponding Author: Wen Xie

▲AASLD 2023 Poster Presentation (1416-C)

Background

Hepatitis B virus (HBV) infection is a major factor globally leading to liver cirrhosis and hepatocellular carcinoma (HCC). Tenofovir alafenamide fumarate (TAF), as a novel antiviral drug, has been approved for the treatment of chronic hepatitis B. Nevertheless, the antiviral and liver function effects of TAF on decompensated patients with chronic hepatitis B and cirrhosis still need clarification. This study aims to evaluate the efficacy and safety of TAF in treating such patients.

Methods

This study included patients with decompensated liver cirrhosis due to chronic hepatitis B, with ascites as the initial decompensation event. Patients received a daily dose of 25 mg TAF. After 24 weeks of treatment, efficacy was assessed through clinical event rates, virology, serology, and biochemical indicators.

Results

A total of 182 patients were included, and 126 completed the 24-week follow-up. By the 24th week, 56.3% of patients (71/126) achieved HBV-DNA clearance, 76.2% (96/126) normalized ALT levels, and 54.8% (69/126) had resolution of ascites. During the study period, one patient died, three developed HCC, six experienced gastric variceal bleeding, and five had hepatic encephalopathy. After 24 weeks of TAF treatment, significant improvements were observed in Child-Pugh score, MELD score, FIB-4 score, bilirubin, INR, albumin, and alanine aminotransferase. Lipid levels significantly increased, while eGFR showed no significant difference.

Conclusion

TAF treatment significantly improves virological and liver function outcomes in patients with decompensated chronic hepatitis B and cirrhosis. However, further research is needed to explore the long-term efficacy and safety of TAF.

Study Three

Impact of Nucleos(t)ide Analogs on Lipid Profiles in Treatment-Naive Patients with Chronic Hepatitis

First Author: Li Mengqi; Corresponding Author: Wen Xie

▲AASLD 2023 Poster Presentation (1446-C)

Background

International guidelines have approved entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF) as preferred oral antiviral nucleos(t)ide analogs for the treatment of chronic hepatitis B (CHB). However, the impact of these drugs on lipid metabolism remains controversial. This retrospective cohort study aimed to explore the effects of ETV, TDF, and TAF on lipid metabolism in patients with CHB.

Methods

This retrospective cohort study included 156 patients with CHB who received at least 96 weeks of treatment at Beijing Ditan Hospital, Capital Medical University, from July 2020 to March 2023. Patients used ETV, TDF, or TAF. Propensity score matching (PSM) was used to assess the effects of these treatments on lipid levels in CHB patients, with one-to-one matching using nearest-neighbor matching. Propensity scores were based on baseline characteristics, including age, gender, and lipid levels.

Results

After PSM, the study cohort was divided into three separate groups for analysis: 37:37 (TDF: ETV), 33:33 (TDF: TAF), and 48:48 (ETV: TAF). At 96 weeks, compared to the TDF group, the TAF group showed a significant increase in total cholesterol (TC) and low-density lipoprotein (LDL) [TC 4.76 (4.13–5.39) vs. 3.93 (3.47–4.63), P=0.004; LDL 2.96 (2.44–3.43) vs. 2.50 (1.92–2.99), P=0.028].

Additionally, the TAF group had significantly higher TC and triglyceride (TG) levels than the ETV group at 96 weeks [TC: 4.89 (4.52–5.45) vs. 4.54 (3.95–4.97), P=0.016; TG: 1.31 (0.92–1.85) vs. 0.94 (0.75–1.38), P=0.011]. However, there were no significant differences in lipid levels between the ETV and TDF groups at the 96-week follow-up. Moreover, among the 156 patients, no patient showed ≥3-grade lipid abnormalities at 96 weeks. Only a few patients had grade 2 lipid abnormalities, with one in the ETV group, one in the TDF group, and three in the TAF group.

Conclusion

After 96 weeks of treatment, TAF may lead to an increase in lipid levels compared to ETV and TDF. The impact of these lipid metabolism abnormalities on clinical outcomes requires further exploration.

Reference :

[1] Deng Y, Kang H, Xiang H, et al. Stable recompensation in entecavir-treated hepatitis B Patients with decompensated cirrhosis. AASLD 2023. Poster 1440-C.[2] Deng Y, Zhang S, Chen W, et al. Efficacy and safety of tenofovir alafenamide in the treatment of decompensated cirrhotic patients with chronic hepatitis B. AASLD 2023. Poster 1416-C.[3] Li M, Zhu L, Deng Y, et al. The effects of nucleos(t)ide analogues on lipid profiles in treatment naïve chronic hepatitis B patients. AASLD 2023. Poster 1446-C.