Episodic Detectable Viremia Does Not Affect Prognosis in Untreated Compensated Cirrhosis With Serum Hepatitis B Virus DNA <2,000 IU/mL

Abstract

INTRODUCTION: The necessity of antiviral therapy (AVT) for hepatitis B virus (HBV)-infected compensated cirrhosis with low-level viremia (LLV) is controversial. Herein, we evaluated its natural history. METHODS:From 3 tertiary hospitals, we enrolled untreated patients with compensated cirrhosis with persistent serum HBV-DNA levels <2,000 IU/mL; LLV was defined as having at least 1 detectable serum HBV-DNA (20-2,000 IU/mL) episode, whereas maintained virological response (MVR) was defined as having persistently undetectable serum HBV-DNA (<20 IU/mL). When serum HBV-DNA was ‡2,000 IU/mL during follow-up, AVT was administered according to guidelines. Study end points were development of cirrhotic complication event (CCE) or hepatocellular carcinoma (HCC). RESULTS:Among 567 patients analyzed, cumulative HCC risk at 3, 5, and 7 years was comparable between LLV (n 5 391) vs MVR (n 5 176) groups (5.7%, 10.7%, and 17.3% vs 7.2%, 15.5%, and 19.4%, respectively [P 5 0.390]). CCE risk was also comparable between 2 groups (7.5%, 12.8%, and 13.7% vs 7.8%, 12.3%, and 14.6%, respectively [P 5 0.880]). By multivariate analysis, LLV (vs MVR) was not associated with HCC or CCE risks, with adjusted hazard ratios of 1.422 (95% confidence interval [CI] 0.694-2.913; P 5 0.336) and 1.816 (95% CI: 0.843-3.911; P 5 0.128), respectively. Inverse probability of treatment weighting analysis yielded comparable outcomes between 2 groups, regarding HCC and CCE risks with hazard ratios of 0.903 (95% CI: 0.528-1.546; P 5 0.711) and 1.192 (95% CI: 0.675-2.105; P 5 0.545), respectively. DISCUSSION:Episodic LLV among untreated patients with compensated cirrhosis does not increase the risk of disease progression compared with MVR status. Thus, the benefits of AVT for episodic LLV should be reevaluated.

Low Level of Hepatitis B Viremia Compared With Undetectable Viremia Increases the Risk of Hepatocellular Carcinoma in Patients With Untreated Compensated Cirrhosis

“…Sinn et al (11) showed that patients with LLV had a significantly increased risk of HCC than those with undetectable HBV DNA. By contrast, a recent study suggested that episodic LLV may not affect the risk of HCC in untreated compensated cirrhosis because the risk was similar between the LLV and undetectable groups (12). However, LLV and undetectability were defined differently across the 2 studies.…”

“…Because serum HBV DNA levels may change during follow-up, several definitions of LLV may exist based on the frequency, pattern, and highest level, as addressed by Lee et al (12). Therefore, we assessed the risk of HCC according to various LLV definitions.…”

“…Unfortunately, no prospective or randomized clinical trials have demonstrated the efficacy of antiviral treatment for patients with compensated cirrhosis and LLV. Furthermore, few observational studies have examined the necessity of antiviral treatment in preventing HCC development in these patients (11,12). Sinn et al (11) showed that patients with LLV had a significantly increased risk of HCC than those with undetectable HBV DNA.…”

“…Thus, the role of antiviral treatment in patients with LLV may be justified in reducing the risk of HCC to the same level as that of patients with undetectable HBV DNA. By contrast, another study reported that LLV does not affect the long-term prognosis of untreated compensated cirrhosis with LLV (12).…”

KASL clinical practice guidelines for management of chronic hepatitis B

“…These data support prompt antiviral therapy for compensated cirrhosis with low-level viremia. However, in a recent study from Korea, the incidence rate of HCC of compensated cirrhotic patients was not different between those with HBV DNA <2,000 IU/mL without antiviral treatment and those with complete virological response to antiviral treatment [ 205 ]. However, until now, there have not been any randomized controlled trials that can assess the benefits and risks of prompt antiviral therapy for compensated cirrhosis patients showing lowlevel viremia.…”