Controversy exists about whether antiviral therapy (AVT) should be recommended for compensated cirrhosis patients with chronic hepatitis B virus (HBV) infection and detectable, but low, serum HBV-DNA levels. A retrospective cohort of 385 treatmentna€ ıve, HBV-related compensated cirrhosis patients (mean age: 51.1 6 9.7 years; 66% male) with low HBV-DNA levels (<2,000 IU/mL) was assessed for the development of hepatocellular carcinoma (HCC). During a median of 5.6 years of follow-up, HCC had developed in 37 (9.6%) patients. The 5-year cumulative HCC incidence rate was 2.2%, 8.0%, and 14.0% for patients with undetectable HBV DNA (<12 IU/mL), low HBV-DNA levels plus normal alanine aminotransferase (ALT) levels, and low HBV-DNA levels plus elevated ALT levels at baseline (P 5 0.011). During follow-up, 71 patients maintained undetectable HBV-DNA levels, and 126 experienced HBV-DNA elevation over 2,000 IU/mL. AVT was initiated in 77 patients. In patients without AVT, the 5-year cumulative HCC incidence rates were 13.3%, 8.8%, and 1.4% for those who experienced HBV-DNA elevation, those who maintained detectable, but low, HBV-DNA levels, and those who maintained undetectable HBV-DNA levels, respectively. The 5-year cumulative HCC incidence rate was 5.9% for patients who started AVT; longer AVT duration and longer complete virological response (<12 IU/mL) duration was associated with lower HCC risk. Conclusion: Compensated cirrhosis patients with detectable, but low, viral load were not at low risk for HCC, and AVT was associated with lower HCC risk, suggesting that prompt AVT should be considered for these patients. (HEPATOLOGY 2015;62:694-701) H epatitis B virus (HBV) is a major public health problem worldwide; roughly 30% of the world's population show serological evidence of current or past infection. 1 Chronic HBV infection can evolve into cirrhosis and/or hepatocellular carcinoma (HCC), 2 and as many as 40% of men and 15% of women with perinatally acquired HBV die of liver cirrhosis or HCC. 1 Unfortunately, there are no effective cures for HBV; currently available treatments, such as interferons (IFNs) and nucleoside/nucleotide analogs (NUCs), can suppress viral replication, but cannot eradicate the virus. 1 Therefore, decision to treat should be individualized based on balancing the risk (i.e., untreated natural course, side effects from treatments, and cost) and benefit of treatment.Opinions differ as to whether patients with compensated cirrhosis (i.e., the early stage of cirrhosis, during which patients experience few or no symptoms) and detectable, but low, serum HBV-DNA levels should undergo antiviral treatment (AVT). Guidelines put forth Abbreviations: AASLD, American Association for the Study of Liver Diseases; AFP, alpha-fetoprotein; ALT, alanine aminotransferase; APASL, Asian Pacific Association for the Study of the Liver; AST, aspartate aminotransferase; AVT, antiviral therapy; CVR, complete virological response; EASL, European Association for the Study of the Liver;

Sometimes, hepatitis B virus (HBV)-related cirrhotic patients with normal aminotransferase levels are closely followed-up for the elevation of aminotransferase levels instead of prompt antiviral therapy (AVT). We analyzed the long-term hepatocellular carcinoma (HCC) risk according to the aminotransferase levels in a retrospective cohort of 1,468 treatment-naïve, HBV-related, compensated cirrhosis patients with elevated HBV DNA levels (≥2,000 IU/mL). Based on aminotransferase levels, patients were categorized into normal (< 40 U/L, n = 364) and elevated group (≥40 U/L, n = 1,104). During a median of 5.3 yr of follow-up (range: 1.0-8.2 yr), HCC developed in 296 (20%) patients. The 5-yr cumulative HCC incidence rate was higher in patients with elevated aminotransferase level, but was not low in normal aminotransferase level (17% vs. 14%, P = 0.004). During the follow-up, 270/364 (74%) patients with normal aminotransferase levels experienced elevation of aminotransferase levels, and AVT was initiated in 1,258 (86%) patients. Less patients with normal aminotransferase levels received AVT (70% vs. 91%, P < 0.001) and median time to start AVT was longer (17.9 vs. 2.4 months, P < 0.001). AVT duration was an independent factor associated with HCC, and median duration of AVT was shorter (4.0 vs. 2.6 yr, P < 0.001) in patients with normal aminotransferase levels. The HCC risk of compensated cirrhosis patients with normal aminotransferase level is not low, and AVT duration is associated with lowered HCC risk, indicating that prompt AVT should be strongly considered even for those with normal aminotransferase levels.

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