Antiviral therapy delays esophageal variceal bleeding in hepatitis B virus-related cirrhosis

Abstract

Aim: To investigate the effect of antiviral therapy with nucleoside analogs in hepatitis B virus (HBV)-related cirrhosis and esophageal varices.

Methods: Eligible patients with HBV-related cirrhosis and esophageal varices who consulted two tertiary hospitals in Beijing, China, the Chinese Second Artillery General Hospital and Chinese PLA General Hospital, were enrolled in the study from January 2005 to December 2009. Of 117 patients, 79 received treatment with different nucleoside analogs and 38 served as controls. Bleeding rate, change in variceal grade and non-bleeding duration were analyzed. Multivariate Cox proportional hazard regression was used to identify factors related to esophageal variceal bleeding.

Results: The bleeding rate was decreased in the antiviral group compared to the control group (29.1% vs 65.8%, P < 0.001). Antiviral therapy was an independent factor related to esophageal bleeding in multivariate analysis (HR = 11.3, P < 0.001). The mean increase in variceal grade per year was lower in the antiviral group (1.0 ± 1.3 vs 1.7 ± 1.2, P = 0.003). Non-bleeding duration in the antiviral group was prolonged in the Kaplan-Meier model. Viral load rebound was observed in 3 cases in the lamivudine group and in 1 case in the adefovir group, all of whom experienced bleeding. Entecavir and adefovir resulted in lower bleeding rates (17.2% and 28.6%, respectively) than the control (P < 0.001 and P = 0.006, respectively), whereas lamivudine (53.3%) did not (P = 0.531).

Conclusion: Antiviral therapy delays the progression of esophageal varices and reduces bleeding risk in HBV-related cirrhosis, however, high-resistance agents tend to be ineffective for long-term treatment.

Keywords: Adefovir; Cirrhosis; Entecavir; Esophageal variceal bleeding; Hepatitis B virus; Lamivudine; Nucleoside analog; Resistance.

Figure 1

Kaplan-Meier analysis of non-bleeding duration. A: Non-bleeding duration in antiviral and control cases was compared using the Kaplan-Meier survival model. Bleeding was defined as a failed event. The occurrence of bleeding was reduced and delayed in the antiviral treatment group compared to the control group. The curve of virological breakthrough cases (dashed line) was close to that of the control group, demonstrating reduced efficacy when virological breakthrough occurred; B: Non-bleeding durations for entecavir (ETV), adefovir (ADV) and lamivudine (LAM) therapy were compared using the Kaplan-Meier survival model. Bleeding was defined as a failed event. The non-bleeding durations for ETV, ADV and LAM were similar in the first 2 years, however, differences became clear following long-term treatment, which may have been due to cumulative resistance and bleeding.

Figure 2

Sketch of delayed progression of esophageal varices by antiviral therapy. Varices were scored according to the criteria of the Japanese Association of Portal Hypertension: grade I, II, and III and given a score of 1, 2 and 3, respectively. Bleeding was scored as 4. Endoscopic eradication was scored as 0. The dark line shows the development of esophageal varices in hepatitis B virus-related cirrhosis without antiviral therapy. The dashed line is the development of varices with antiviral therapy. The grade of esophageal varices increases with time and then bleeding occurs. After endoscopic eradication, the varices score increases again until bleeding recurs. Antiviral therapy delayed both the progression of varices before and after endoscopic therapy and postponed esophageal variceal bleeding. Before endo: Before endoscopic intervention; After endo: After endoscopic intervention.