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AASLD 2011: Good Response to Entecavir Reduces Risk of Hepatitis B Liver Disease Progression

Chronic hepatitis B patients who achieve HBV DNA viral load suppression on entecavir (Baraclude) have a lower risk of liver failure, hepatocellular carcinoma, and death than non-responders, according to study findings presented this month at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011) in San Francisco.

Over years or decades, chronic hepatitis B virus (HBV) infection can lead to advanced liver disease including cirrhosis and liver cancer. The nucleoside analog drug entecavir effectively inhibits HBV replication, lowers viral load, and improves liver fibrosis, but the ultimate goal of treatment is to reduce the likelihood of clinical events and premature death.

Roeland Zoutendijk from Erasmus Medical Center in Rotterdam and colleagues investigated whether entecavir-induced viral suppression is associated with improved clinical outcomes among chronic hepatitis B patients.

The researchers evaluated medical records from HBV monoinfected patients (e.g., no HIV, hepatitis C, or hepatitis delta coinfection) at 10 large European referral centers within the VIRGIL Network who were treated with entecavir monotherapy for at least 3 months.

The analysis included 372 participants; three-quarters were men, about half were white, the mean age was 43 years, and about 60% were hepatitis B "e" antigen (HBeAg) positive. About 73% had no cirrhosis, 24% had compensated cirrhosis, and 2% had decompensated cirrhosis at baseline. About one-third had previously been treated with nucleoside/nucleotide analogs, including lamivudine (Epivir-HBV) and adefovir (Hepsera), and about 20% had previously used interferon.

Virological response was defined as serum HBV DNA < 80 IU/mL. Clinical endpoints considered were liver decompensation (indicated by jaundice, ascites, bleeding varices, or hepatic encephalopathy), occurrence of hepatocellular carcinoma (HCC, a form of primary liver cancer), and death. The median follow-up period was 19 months.

Results

• Patients with compensated or decompensated cirrhosis at baseline and those without had similar likelihood of achieving virological response on entecavir.
• Patients who achieved virological response on entecavir had a significantly lower probability of disease progression compared with non-responders (hazard ratio 0.29):
  • No cirrhosis: 1 event among 222 responders (0%) vs 1 event among 52 non-responders (2%);
  • Compensated cirrhosis: 3 events among 73 responders (4%) vs 5 events among 16 non-responders (30%);
  • Decompensated cirrhosis: 1 event among 6 responders (17%) vs 2 events among 3 non-responders (67%).
• Patient age, baseline MELD score, albumin level, prothrombin time (INR), platelet count, and pre-existing cirrhosis were also significantly associated with clinical events.
• However, occurrence of clinical events was not significantly influenced by patient sex, HBeAg status, previous nucleoside/nucleotide therapy, or baseline HBV DNA.

"Probability of achieving virological response to entecavir is not influenced by severity of liver disease," the investigators concluded. "Virological response to entecavir is associated with a lower probability of disease progression (HCC, hepatic decompensation, death) for cirrhotic patients."

Investigator affiliations: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, Netherlands; Department of Hepatology, Hospices Civils de Lyon, Lyon, France; Department of Hepatology and Gastroenterology, Imperial College , London, UK; NIHR Biomedical Research Unit and Centre for Liver Research, Queen Elizabeth Hospital, Birmingham, UK; Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany; Medizinische Klinik 1, Klinikum der Johan Wolfgang Goethe-Universitat, Frankfurt am Main, Germany; Liver Unit, IFI institute, Asklepios Klinik St. Georg, Hamburg, Germany; Clinic of Infectious Diseases, University of Bari, Bari, Italy; Department of Hepatology, Hospital Vall de Hebron, Barcelona, Spain; Department of Hepatology, University Clinic Leipzig, Leipzig, Germany.

11/22/11

Reference

R Zoutendijk, JG Reijnders, F Zoulim, et al. Virological response to entecavir is associated with a lower probability of disease progression: results from 377 chronic hepatitis B patients. 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 240.