Editorial Board: Emmet B. Keeffe, MD (Chair); M. Eric Gershwin, MD;

Ira S. Goldman, MD; John L. Gollan, MD, PhD; Kris V. Kowdley, MD;

Paul Martin, MD; Marion G. Peters, MD

HEPATOLOGY WATCH®

APRIL 2003

 

HEPATITIS B VIRUS (HBV )

Adefovir dipivoxil therapy.  Adefovir dipivoxil is a nucleotide analogue that has potent antiviral activity against HBV.  Stephanos Hadziyannis et al. from the Adefovir Dipivoxil 438 Study Group conducted a double-blind study in which 185 patients with HBeAg-negative chronic hepatitis B were randomized in a 2:1 ratio to receive 10 mg of adefovir or placebo daily for 48 weeks.  At week 48, 64% of adefovir-treated patients versus 33% of patients in the placebo group had improvement of histological liver abnormalities as measured by the Knodell necroinflammatory score, and ALT levels normalized in 72% versus 29% of patients, respectively.  Moreover, HBV DNA levels became undetectable in 51% and 0% of patients treated with adefovir and placebo, respectively.  Patrick Marcellin et al. from the Adefovir Dipivoxil 437 Study Group performed a second double-blind study in which 515 patients with HBeAg-positive chronic hepatitis B were equally randomized to receive 10 mg of adefovir, 30 mg of adefovir, or placebo daily for 48 weeks.  At week 48, significantly greater percentages of 10 mg or 30 mg adefovir-treated patients compared to placebo patients had improvement of histological liver abnormalities (53%, 59%, and 25%, respectively), normalization of serum ALT levels (48%, 55%, and 16%, respectively), HBeAg seroconversion (12%, 14%, and 6%, respectively), and undetectable serum levels of HBV DNA (21%, 39%, and 0%, respectively).  No HBV polymerase mutations associated with resistance to adefovir were identified in either study.  (Hadziyannis SJ, et al. N Engl J Med 2003;348:800-807; Marcellin P, et al. N Engl J Med 2003;348:808-816)

 

HEPATITIS C VIRUS (HCV)

Coinfection with HIV.  Mark Sulkowski and David Thomas conducted a literature review of published studies of HCV infection in HIV-infected patients.  The studies show that infection with HIV adversely affects the outcome of HCV, and medical management is complicated by immune suppression, potential drug interactions and toxicities, and other concomitant liver diseases.  There are little data published concerning treatment of HCV in coinfected patients with currently available agents.  The authors conclude that large prospective studies to determine optimal therapy are needed.  (Sulkowski MS, Thomas DL. Ann Intern Med 2003;138:197-207)

 

HCV infection after liver retransplantation.  Marina Berenguer et al. from Valencia, Spain report their experience with retransplantation in patients in whom HCV-related cirrhosis developed in the first graft.  Thirty-one of 49 transplant recipients with HCV-related allograft cirrhosis had hepatic decompensation that met criteria for retransplantation.  Eighteen patients were accepted for retransplantation; however 6 patients died while waiting for an appropriate donor.  Among the 12 patients who underwent retransplantation, 8 patients (67%) died after a median of 8 months due to the following causes: surgical complications (n = 3); HCV-related cirrhosis of the second graft (n = 2); fibrosing cholestatic hepatitis (n = 1); lymphoproliferative disorder (n = 1); and endocarditis (n = 1).  Four patients remained alive after 1.9 years of follow-up.  These results indicate that the outcome of retransplantation for HCV-related cirrhosis of the first graft is poor.  (Berenguer M, et al. Liver Transpl 2003;9:228-235)

 

ASCITES

Transjugular intrahepatic portosystemic shunt (TIPS).  Arun Sanyal and others of The North American Study for the Treatment of Refractory Ascites performed a multicenter, prospective trial in which 109 patients with refractory ascites were randomized to receive either medical therapy alone (sodium restriction, diuretics, and total paracenteses) or medical therapy plus TIPS.  Although medical therapy plus TIPS more successfully prevented recurrent ascites than medical therapy alone, transplant-free and overall survival rates were similar in the 2 treatment groups.  Moreover, the incidence of moderate to severe encephalopathy was greater in TIPS-treated patients, and there was no difference in the number of patients who developed disease-related complications between the 2 groups.  These findings demonstrated that TIPS therapy was not associated with improvements in survival, hospitalization rates, or quality of life.  (Sanyal AJ, et al. Gastroenterology 2003;124:634-641)

 

LIVER TRANSPLANTATION

Model for End-Stage Liver Disease (MELD). The MELD score, based on serum creatinine, serum total bilirubin, and INR, has been used to predict mortality in patients with cirrhosis.  Russell Wiesner and colleagues prospectively applied the MELD score to estimate the 3-month mortality of 3,437 adult liver transplant candidates listed with UNOS at status 2A or 2B.  Among these candidates, 412 (12%) patients died within a 3-month follow-up period.  Patients having a MELD score <9 had a 3-month mortality rate of 1.9% while those with a MELD score ³40 had a 3-month mortality rate of 71.3%.  The area under the receiver operating characteristic curve, with 3-month mortality as the endpoint, was significantly greater for the MELD score compared to the Child-Turcotte-Pugh score (0.83 vs. 0.76).  Furthermore, in a retrospective cohort study of 760 patients on a liver transplant waiting list, Robert Merion et al. at the University of Michigan found that serial MELD scores more accurately predicted mortality risk for liver transplant candidates than a single MELD measurement or medical urgency status.  The magnitude and direction of change of the MELD score during a 30-day period was an independent predictor of mortality, and increases of >5 points over 30 days was associated with a 3-fold greater mortality risk.  These data indicate that the MELD score can be used to accurately predict mortality among patients on the liver transplantation waiting list and are reasonable to use for a national liver policy for allocation of donor livers.  (Wiesner R, et al. Gastroenterology 2003;124:91-99 and Merion RM, et al. Liver Transpl 2003;9:12-18) 

Hepatology Watch is produced through educational grant from

Hepatology Watch is a registered trademark of Market Development Group

Back to Issues Archive