HEPATOLOGY WATCH®

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

AUGUST 2004

PRIMARY BILIARY CIRRHOSIS (PBC)

Patterns of autoimmunity and characteristics of asymptomatic disease.  The etiology of PBC is unknown, however reports of an association with autoimmune diseases indicate that autoimmunity may play a role in the development of PBC.  Additionally, an inherited immunogenetic susceptibility is suggested by previously reported findings of an increased risk for PBC among relatives of PBC patients.  More recently, the results of a geographic cohort study of PBC patients (n=160) conducted by FE Watt and coworkers at the University of Newcastle were published, and it was observed that 53% of PBC patients had at least one additional autoimmune condition.  In addition, 63% of PBC patients had serum antibodies other than AMA or ANA.  Scleroderma represented the most commonly associated autoimmune disease (8% of patients), and autoimmune diseases were present in 14% of the first-degree relatives.  These observations support an autoimmune etiology and possible genetic basis for PBC.  A second study from the University of Newcastle performed by MI Prince et al. investigated the clinical features of PBC patients who present with asymptomatic disease.  They reviewed medical records of a large cohort of patients with PBC (n=770).  Sixty-one percent (n=469) of patients were identified as being asymptomatic at diagnosis.  While the asymptomatic patients had less advanced disease than patients who were initially symptomatic, the median survival times were similar for both groups of patients (9.6 vs. 8.0 years, respectively).  Most initially asymptomatic patients developed symptoms during the course of their disease (95% after 20 years), and 20% of initially asymptomatic patients died of liver disease or required liver transplantation by the end of follow-up.  The data from this large cohort study indicated that PBC patients who were asymptomatic at diagnosis did not have a better prognosis than patients presenting with symptomatic disease.  (Watt FE, et al. QJM 2004;97:397-406 and Prince MI, et al. Gut 2004;53:865-870)

 

PRIMARY SCLEROSING CHOLANGITIS (PSC)

Magnetic resonance cholangiography (MRC) vs. endoscopic retrograde cholangiopancreatography (ERCP).  Jayant Talwalker and others from the Mayo Clinic in Rochester reported that MRC, compared to ERCP, has similar accuracy and is less expensive when used as the initial test for the diagnosis of PSC.  ERCP was performed within 24 hours of MRC in 73 patients with suspected biliary disease, and the prevalence of PSC was 32%.  The sensitivity and specificity of MRC for the diagnosis of PSC were 82% and 98%, respectively.  The average MRC cost per correct diagnosis of PSC was $724 vs. $793 for ERCP, and the average cost of managing ERCP-related complications was $2902 per patient.  (Talwalker JA, et al. Hepatology 2004;40:39-45)

 

VIRAL HEPATITIS

Interferon-based therapies.  Andrew Muir and colleagues administered peginterferon alfa-2b and ribavirin for 48 weeks to 100 black patients and 100 white (non-Hispanic) patients with chronic HCV infection.  Ninety-eight percent of patients in both treatment groups had genotype 1 infection.  Sustained virological response (SVR) was achieved in a greater proportion of white patients than black patients (52% vs. 19%).  Multivariable analyses identified only black race to be a poor prognostic predictor for SVR.  In a second study, Patrizia Farci et al examined the long-term benefit of interferon (IFN) α-2a therapy in patients with chronic hepatitis D (HDV) infection, which leads to cirrhosis in 80% of patients.  In the current study, chronic HDV patients were randomized to receive high-dose (9 MU) or low-dose (3 MU) daily IFN or no treatment.  Among patients alive at ≥12 years of follow-up, biochemical responses were observed in the IFN-treated patients (7 of 12 high-dose patients and 2 of 4 low-dose patients) but not in the control group.  Patients treated with high-dose IFN experienced sustained decreases in HDV replication, clearance of HDV RNA, and improvement of liver histology.  In addition, long-term survival was greater in the high-dose IFN group compared to both the control group and the low-dose IFN group.  These data showed that IFN α-2a therapy of chronic HDV patients was associated with improved outcomes.  (Muir AJ, et al. N Engl J Med 2004;350: 2265-2271 and Farci P, et al. Gastroenterology 2004;126:1740-1749)

 

AUTOIMMUNE HEPATITIS (AIH)

Progressive fibrosis during corticosteroid therapy.  Hepatic fibrosis and cirrhosis may develop in patients with AIH during corticosteroid therapy.  Albert Czaja and Herschel Carpenter examined liver tissue specimens obtained from 73 corticosteroid-treated patients with AIH followed at the Mayo Clinic in Rochester.  Fibrosis scores increased in 18 patients (25%) and cirrhosis developed in 5 patients (7%).  In contrast, 55 patients (75%) had stable or improved fibrosis scores.  HLA DR3/DR4 and worsening histological activity was associated with progressive fibrosis.  These findings demonstrated that progressive fibrosis occurred in a minority of AIH patients treated with corticosteroids.  (Czaja AJ and Carpenter HA. Hepatology 2004;39:1631-1638)

 

NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)

Does weight loss improve liver histology?  John Dixon and colleagues at the Alfred Hospital in Melbourne, Australia examined paired liver biopsies from 36 obese patients with NAFLD.  The first biopsy was obtained at the time of laparoscopic gastric band placement and the second biopsy was obtained after weight loss.  Initial biopsies demonstrated NASH in 23 patients and steatosis in 12 patients.  Mean weight loss was 34 kg, and repeat biopsies were performed at an average of 25.6 ± 10 months after band placement.  Major improvements in lobular steatosis, necroinflammatory changes, and fibrosis were realized following weight loss.  Patients with the metabolic syndrome (n=23) had the greatest improvement with weight loss.  Only 4 of the follow-up biopsies fulfilled criteria for a diagnosis for a diagnosis of NASH.  These findings demonstrated that weight loss resulted in significant improvement in liver histology for obese patients with NAFLD.  (Dixon JB, et al. Hepatology 2004;39:1647-1654)

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