Use of Nucleoside (Tide) Analogues in Patients with Hepatitis B-Related Acute Liver Failure

Abstract

Background and Aims

The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF.

Methods

The US Acute Liver Failure Study Group, a 23-site registry, prospectively enrolled 1,413 patients with ALF with different etiologies between 1998 and 2008. Of those, 105 patients were identified as HBV-ALF patients, of whom we excluded those without data on NA use or with co-infection with hepatitis C, leaving 85 patients, 43 of whom had received NA treatment. HBV-DNA on admission was quantified by real time polymerase chain reaction.

Results

The treated and untreated groups were similar in most respects but differed significantly in regard to higher aminotransferase and bilirubin levels and hepatic coma grades, all being observed in the untreated group. Median duration of NA treatment was 6 days (range, 1–21 days). Overall survival in the NA treated and untreated groups were 61 and 64%, respectively (P = 0.72). Rates of transplant-free survival were 21 and 36% in the treated and untreated groups, respectively (P = 0.42). Multivariate analysis revealed that not using a NA [odds ratio (OR) 4.4, 95% CI 1.1–18.1, P = 0.041], hepatic coma grade I or II [OR 14.4, 95% CI 3.3–62.8, P < 0.001] and prothrombin time (PT) [OR 0.59, 95% CI 0.39–0.89, P = 0.012] were predictors of improved transplant-free survival.

Conclusions

Patients who are admitted with established HBV-ALF do not appear to benefit from viral suppression using nucleoside(tide) analogues presumably because of rapid disease evolution and short treatment duration. Despite the lack of benefit, NAs should still be given to transplantation candidates since viral suppression prevents recurrence after grafting.

Appendix

Members and institutions participating in the Acute Liver Failure Study Group 1998–2006: W.M. Lee, MD (Principal Investigator), George A. Ostapowicz, MD, Frank V. Schiødt, MD, Julie Polson, MD, University of Texas Southwestern, Dallas, TX; Anne M. Larson, MD, University of Washington, Seattle, WA; Timothy Davern, MD, University of California, San Francisco, CA; Michael Schilsky, MD, Mount Sinai School of Medicine, NY, NY; Timothy McCashland, MD, University of Nebraska, Omaha, NE; J. Eileen Hay, MBBS, Mayo Clinic, Rochester, MN; Natalie Murray, MD, Baylor University Medical Center, Dallas, TX; A. Obaid S. Shaikh, MD, University of Pittsburgh, Pittsburgh, PA; Andres Blei, MD, Northwestern University, Chicago, IL; Atif Zaman, MD, University of Oregon, Portland, OR; Steven H.B. Han, MD, University of California, Los Angeles, CA; Robert Fontana, MD, University of Michigan, Ann Arbor, MI; Brendan McGuire, MD, University of Alabama, Birmingham, AL; Raymond T. Chung, MD, Massachusetts General Hospital, Boston, MA; Alastair Smith, MB, ChB, Duke University Medical Center, Durham, NC; Robert Brown, MD, Cornell/Columbia University, NY, NY; Jeffrey Crippin, MD, Washington University, St Louis, MO; Edwin Harrison, Mayo Clinic, Scottsdale, AZ; Adrian Reuben, MBBS, Medical University of South Carolina, Charleston, SC; Santiago Munoz, MD, Albert Einstein Medical Center, Philadelphia, PA; Rajender Reddy, MD, University of Pennsylvania, Philadelphia, PA; R. Todd Stravitz, MD, Virginia Commonwealth University, Richmond, VA; Lorenzo Rossaro, MD, University of California Davis, Sacramento, CA; Raj Satyanarayana, MD, Mayo Clinic, Jacksonville, FL; and Tarek Hassanein, MD, University of California, San Diego, CA. The University of Texas Southwestern Administrative Group included Grace Samuel, Ezmina Lalani, Carla Pezzia, and Corron Sanders, PhD and the Statistics and Data Management Group included Joan Reisch, PhD, Linda Hynan, PhD, Janet P. Smith, Joe W. Webster, and Mechelle Murray.