Elevated liver cancer, death rates with immune-tolerant-phase chronic HBV

Last Updated: 2017-11-20

By Will Boggs MD

NEW YORK (Reuters Health) - Patients with immune-tolerant-phase chronic hepatitis B virus (HBV) infection, who are usually not considered for treatment, face an increased risk of hepatocellular carcinoma (HCC) and death, compared with treated immune-active-phase patients, researchers from Korea report.

"Serum liver enzyme (ALT) levels have been used as the criteria to initiate treatment in chronic hepatitis B patients," Dr. Young-Suk Lim from Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, told Reuters Health by email. "However, the elevation of alanine aminotransferase (ALT) may occur at later phase of liver damage by HBV. Thus, earlier treatment guided by age and serum HBV DNA levels may prevent unnecessary cancers and deaths in chronic hepatitis B patients."

The immune-tolerant (IT) phase of chronic HBV infection is characterized by high circulating HBV DNA and normal ALT levels, where histological activity is presumed to be dormant and the risk of disease progression is presumed to be low. Recent studies, however, suggest otherwise.

In a historical cohort study, Dr. Lim's team analyzed data from 3,051 adults with chronic HBV infection to compare long-term outcomes between untreated IT-phase patients and immune-active (IA)-phase patients treated with nucleoside/nucleotide analogs. Median follow-up was 6.3 years.

The annual incidence of HCC was significantly higher in the IT-phase group (1.05%) than in the IA-phase group (0.51%), as was the annual rate of death or transplantation (0.76% vs. 0.32%), according to the November 9 Gut online report.

In multivariable analysis, the IT group had a 2.54-fold higher risk of HCC and a 3.38-fold higher risk of death or transplantation, compared with the IA group. The findings persisted in inverse-probability treatment weighting and propensity-score-matching analyses.

Patients with mildly active disease also had higher risks compared with the IA group - a 3.23-fold higher cumulative incidence of HCC and a 3.21-fold higher incidence of death or transplantation.

Factors independently associated with a significantly higher risk of clinical events included older age, male sex, lower HBV DNA levels, and lower platelet counts.

"Thus, we think that at least those who have older age >40 years and/or serum HBV DNA levels >4.0 log10 IU/mL and <8.0 log10 IU/mL may have to be treated to reduce the risks of liver cancer and death, even with normal serum liver enzyme (ALT) levels," Dr. Lim said.

"Further studies taking new emerging biomarkers for HBV infection into account would be warranted to further stratify the patients for the risk of clinical events," the researchers write. "Randomized controlled trials evaluating the long-term clinical outcomes of the IT-phase patients with or without antiviral treatment may be worthwhile."

SOURCE: http://bit.ly/2ATZco5

Gut 2017.