Hep B surface antigen clearance may not lower HCC risk

Last Updated: 2016-05-13

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Patients with chronic hepatitis B virus (HBV) infection who achieve HB surface antigen (HBsAg) seroclearance may not lower their risk for hepatocellular carcinoma (HCC), and doctors should continue to monitor them, new research indicates.

"Resolving chronic HBV infection does not represent a cure because HBV persists as integrated HBV DNA in hepatocytes, resulting in lifelong elevated risk for HCC," said lead author Dr. Prabhu P. Gounder, consulting physician and medical epidemiologist with the Centers for Disease Control and Prevention in Anchorage, Alaska.

"The study results confirmed our hypothesis that resolving chronic HBV infection would not reduce risk for HCC because the damage predisposing to HCC occurs early in the course of the disease, such as high HBV DNA levels in the blood leading to viral integration in the host hepatocyte genome," he told Reuters Health by email. "Clinical practice guidelines recommend HCC surveillance for HBV-infected persons at high risk for HCC such as those with cirrhosis or a family history of HCC."

Using the HBV clinical registry maintained by the Alaska Tribal Health System, Dr. Gounder and colleagues compared HCC risk in Alaska Native patients with and without HBsAg seroclearance in a case-control study; the patients were followed between 1982 and 2013.

The names of those with HBV infection were cross-referenced with the Alaska Area Specimen Bank, which contains over 266,000 biological specimens from persons who have participated in research studies since 1961. The researchers tested any serum specimens they found from these persons for HBsAg to more precisely estimate their date of infection.

Among 238 cases, four developed HCC compared to nine among 435 controls. Cases and controls were not significantly different in age, sex or HBV genotype, although cases had longer follow-up than controls (11.7 vs. 10.1 years; p=0.04).

There was no significant difference in HCC rates per 100,000 persons between cases and controls (p=0.65), the researchers report in Alimentary Pharmacology and Therapeutics, online April 8.

Person-years of followup for case-patients began on the date of HBsAg resolution and for controls began on the date equivalent to the cohort entry date plus the years of HBsAg duration for their corresponding case-patient. The researchers compared HCC risk using a Cox proportional hazards model.

The adjusted hazard ratio for HCC did not differ significantly between cases and controls (0.7; 95% CI: 0.2 to 2.4); however, it increased with each one-year increment of age at cohort entry (1.1, p<0.01) and it was greater if the initial HBeAg was positive (3.5, p=0.03).

"Our study population represents the largest and longest-followed population-based cohort of persons with chronic HBV infection. It provides the best available opportunity to evaluate the question of HCC risk after resolving HBV infection," Dr. Gounder said.

Dr. Kathleen Viveiros, director of hepatology at Tufts Medical Center in Boston, told Reuters Health, "This was a very well-monitored study with very accurate data that tried to answer an interesting question that has been looked at with often confusing and conflicting results."

"The limitations are that this unique population of Alaskan natives may not be generalizable to many people being cared for," added Dr. Viveiros, who was not involved in the work. "Also, HCC is very rare so the study may not have included enough patients to accurately conclude that there is no difference between the two groups. Lastly, other factors that influence the incidence of HCC - diabetes, obesity and family history of HCC - may not have been identified and universally accounted for."

"Hepatitis B affects almost 300,000,000 people worldwide and the number of resources available to assess these patients, like ultrasound and blood work, is limited. So more ways to clearly identify risk factors in patients with hepatitis B with either resolved or continued infections, to screen them effectively, need to be found," she said.

SOURCE: http://bit.ly/1OrPuII

Aliment Pharmacol Ther 2016.