LINKED CONTENT
This article is linked to Luo et al papers. To view these articles, visit https://doi.org/10.1111/apt.17124 and https://doi.org/10.1111/apt.17181
LINKED CONTENT
This article is linked to Chen et al papers. To view these articles, visit https://doi.org/10.1111/apt.17602 and https://doi.org/10.1111/apt.17767
Summary Following development of liver cirrhosis in patients with chronic hepatitis B, liver disease may continue to progress and decompensation or hepatocellular carcinoma (HCC) may occur, ...especially in those with active viral replication. Decompensation may manifest with jaundice, ascites, variceal bleeding or hepatic encephalopathy. Earlier studies have shown that the prognosis of decompensated cirrhosis is usually poor with a 5-year survival rate at 14–35% under conventional standard of care. The approval of oral antiviral agents has greatly improved the prognosis, as demonstrated in several cohort studies and randomized clinical trials involving therapy with lamivudine, adefovir dipivoxil, entecavir, telbivudine, or tenofovir disoproxil fumarate. Oral antiviral agents are effective in restoring liver function and improving survival in patients with decompensated cirrhosis especially if therapy is initiated early enough. These agents are generally well tolerated without significant side effects. However, their preventive effect in HCC development has yet to be convincingly demonstrated. Given their known resistance profiles, entecavir and tenofovir should be considered as the first-line therapy for patients with HBV-related decompensated cirrhosis.
Linked ContentThis article is linked to Liem et al and Liem and Janssen papers. To view these articles, visit https://doi.org/10.1111/apt.15098 and https://doi.org/10.1111/apt.15155.
It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).
...This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases.
In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio SHR, 0.45; 95% confidence interval CI, 0.26-0.79; P = 0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42-1.56; P = 0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n = 1,040) found no between-cohort differences in HCC incidences (P = 0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41-1.92; P = 0.77).
TDF and ETV did not significantly differ in the prevention of HCC in patients with CHB.
Linked ContentThis article is linked to Chan et al and Chan papers. To view these articles visit https://doi.org/10.1111/apt.14862 and https://doi.org/10.1111/apt.14961.
Background & Aims
Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long‐term entecavir therapy in ...reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB‐related cirrhosis patients.
Methods
The C‐TEAM (Cirrhosis‐Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective–prospective cohort study in Taiwan. We enrolled treatment‐naïve patients with CHB‐related cirrhosis and baseline HBV‐DNA≥2000 IU/mL receiving long‐term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort.
Results
In total, 1315 entecavir‐treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow‐up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28‐0.57. Additionally, an older age, the male gender, HBeAg positivity, alpha‐fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver‐related and all‐cause mortality. These findings were confirmed by propensity score‐matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1‐year virological response were predictive of HCC development.
Conclusions
Four‐year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB‐related cirrhosis.
See Editorial on Page 1752
Summary
Background/Aims
To compare the rates of hepatitis B surface antigen (HBsAg) loss after discontinuation of entecavir versus tenofovir disoproxil fumarate (TDF) in patients with chronic ...hepatitis B (CHB) without cirrhosis.
Methods
A total of 891 patients who received entecavir (n = 556) or TDF (n = 335) followed up post‐treatment for at least 12 months were retrospectively assessed. A total of 677 patients who had continued entecavir or TDF therapy for at least 4 years were enrolled as the continued group.
Results
Patients who discontinued TDF had higher rates of virological and clinical relapse and retreatment than patients who discontinued entecavir in both the HBeAg‐positive and HBeAg‐negative subgroups. In the entire discontinued cohort, the cumulative rates of HBsAg loss at 7 years were 22.6% and 35.4% in the entecavir and TDF groups respectively. Patients who discontinued TDF had significantly higher rates of HBsAg loss than patients who discontinued entecavir therapy in all (p = 0.019) and propensity score‐matched (p = 0.015) patients, especially among the subgroups who achieved a sustained response (p < 0.001). Cox regression analysis revealed that TDF, longer treatment duration and lower HBsAg levels at end of treatment were independently associated with HBsAg loss in the entire discontinued group. The incidence of HBsAg loss was significantly higher in the discontinued group than in the continued group after propensity score matching (p < 0.001), including HBeAg‐positive and HBeAg‐negative patients.
Conclusions
Patients who discontinued TDF had significantly higher rates of HBsAg loss than patients who discontinued entecavir, especially among the subgroups without HBV relapse after cessation of therapy.
Comparision of HBsAg loss rates between patients who discontined entecavir and TDF therapy after PSM.
We read with interest the article by Ahn et al in Liver International.
This study evaluated the predictive performance of various parameters at treatment baseline and 12 months of treatment with ...entecavir or tenofovir disoproxil fumarate for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) through logistic regression and machine-learning methods, and demonstrated that the logistic lasso regression algorithm using cirrhosis at baseline and alpha-fetoprotein (AFP) level and platelet count at 12 months of treatment exhibited the best performance compared with several extant HCC risk scores.
Background Interferon (IFN)-α therapy for chronic hepatitis C virus infection is frequently associated with depression. The routine prophylaxis with antidepressants might expose patients to adverse ...effects, hence, the need for alternative preventive interventions. Omega-3 polyunsaturated fatty acids are safe and effective essential nutritional compounds used for the treatment of depression, putatively through an anti-inflammatory action. In addition, lower erythrocyte levels of omega-3 polyunsaturated fatty acids have been associated with an increased risk of IFN-induced depression. Methods We conducted a 2-week, double-blind, placebo-controlled trial comparing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and placebo for the prevention of IFN-α-induced depression. A total of 162 patients consented to participate and were randomized to the study. All of the patients completed the 2-week trial; 152 participants were followed throughout the 24 weeks of IFN-α treatment and were included in the analysis. Results Compared with placebo, the incident rates of IFN-α-induced depression were significantly lower in EPA-treated but not in DHA-treated patients (10% and 28%, respectively, versus 30% for placebo, p = .037). Both EPA and DHA significantly delayed the onset of IFN-induced depression (week of onset: 12.0 and 11.7, respectively, versus 5.3 for placebo, p = .002). EPA and DHA were both well tolerated in this population. EPA treatment increased both EPA and DHA erythrocyte levels, but DHA only increased DHA erythrocyte levels. Conclusions EPA is effective in the prevention of depression in hepatitis C virus patients received IFN-α therapy. Our study confirms the notion that anti-inflammatory strategies are effective antidepressants in the context of depression associated with inflammation.
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