Nuc-Gemcitabine

Oral antiviral therapy to hepatitis B virus (HBV) with nucleos(t)ide analogues (NUCs) is effective in suppressing the viral load leading to improved clinical outcomes. However, functional cure of HBV, indicated by hepatitis B surface antigen (HBsAg) clearance from the serum, is rare. Although safety and adherence may represent minor issues in long-term treatment with the available NUCs, more efficacious treatments with finite treatment duration for patients with chronic hepatitis B (CHB) are currently undergoing active clinical investigation. Available data suggest that HBsAg loss can be achieved in 10% to 20% of patients after NUC discontinuation, at the cost of about 50% to 80% virological relapse and 40% to 55% retreatment with NUC. With this, NUC treatment in patients with cirrhosis should not be stopped to avoid detrimental risk of hepatic decompensation and death. Viral and immune biomarkers, which may be potentially useful in stratifying the patients at risk of relapse after stopping NUC therapy, are under investigation. In the era of personalized medicine aided by artificial intelligence tools, tight monitoring of viral kinetics and algorithmic modeling appear a promising strategy to assist in individualized decision and conclude the optimal timing of the NUC treatment discontinuation.

Notable advances have been made in immune checkpoint inhibitors (ICIs) for cancer treatment. However, the adverse effects of ICIs, especially hepatotoxicity, remain a challenging problem. Whether patients in hepatitis B virus (HBV)‐endemic areas are prone to developing hepatic adverse events during ICI treatment warrants further exploration.

From 2014 to 2020, the data of all patients with cancer who received ICI treatment at Taipei Veterans General Hospital were retrospectively reviewed. The incidence of and risk factors for hepatic adverse events, including hepatitis flare, immune‐related hepatitis (irHepatitis) and HBV reactivation (HBVr), were analysed through a Cox proportional hazard regression model.

A total of 1283 patients with cancer (190 hepatocellular carcinoma [HCC] patients and 1093 patients with non‐HCC malignancies) were eligible for analysis, of whom 283 (22.1%) were HBsAg‐positive. The incidence of hepatitis flare events of any grade was significantly higher in HCC patients than in non‐HCC patients (45.8% vs. 25.6%, p < 0.001). HCC and baseline alanine aminotransferase (ALT) > 40 U/L were independent risk factors for ≥ grade 3 hepatitis flare events. No difference was observed in irHepatitis risk between HCC patients and non‐HCC patients. ALT > 40 U/L was an independent risk factor for irHepatitis. Among 283 HBsAg‐positive patients, six patients (2.1%) experienced HBVr. HCC patients had a higher risk of HBVr than non‐HCC patients (4.4% vs. 0.6%). No specific risk factor for HBVr could be identified. However, none of the patients under nucleos/tide analogue (NUC) prophylaxis experienced HBVr in this study.

Under ICI treatment, HCC patients had a higher risk of hepatitis flare events than non‐HCC patients. Abnormal baseline ALT levels are a risk factor for hepatic adverse events. NUC prophylaxis can minimise the risk of HBVr.