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

NOVEMBER 2005

CHRONIC HEPATITIS C VIRUS (HCV) INFECTION

Prevalence of cirrhosis in Asian patients. A number of studies suggest that approximately 20% of patients infected with HCV develop cirrhosis after 20 years of infection. D'Souza and associates performed a retrospective analysis of all patients with detectable HCV RNA levels who were followed in local hospitals in northeast London between 1992 and 2003. The prevalence of cirrhosis among 143 Asian adults, aged 61 to 80 years, who were presumed to have been infected early in life and have had HCV infection for many decades, was 78% whereas the prevalence of cirrhosis among 239 white patients of the same age was 25%. Multivariate analysis did not identify a unique characteristic other than prolonged infection to explain the large difference in the prevalence of cirrhosis between the two populations. In an accompanying editorial, Seeff and Everhart provided a critique of this study in which they identified the major design limitations of this retrospective, clinic-based, cross-sectional investigation: assumptions that Asian patients were infected at a young age and that the opportunity for HCV detection was the same across age groups. In addition, the analyses were insufficient to exclude factors among the Asian population known to be associated with a more rapid progression of fibrosis, such as older age at the time of infection and alcohol consumption. Seeff and Everhart further suggested that if the data presented by D'Souza et al. are an accurate reflection of the long-term impact of chronic HCV infection, treatment should be universal for all HCV-infected patients because a large majority of them are likely to develop end-stage liver disease. Additional studies are needed to confirm the results of this provocative study. (D'Souza R, et al. Clin Gastroenterol Hepatol. 2005;3:910–917; Seeff LB and Everhart JE. Clin Gastroenterol Hepatol. 2005;3:840–842.)

OSTEOPOROSIS IN PATIENTS WITH LIVER DISEASE

Alendronate therapy. Osteoporosis commonly complicates the clinical course of patients with chronic severe liver disease. This finding led Zein and colleagues to conduct a double-blind trial in which 34 patients with primary biliary cirrhosis (PBC) and a bone mineral density (BMD) t scores of less than –1.5 were randomized to receive the bisphosphonate alendronate 70 mg/wk or placebo for 1 year. At the conclusion of the study, larger improvements in vertebral BMD (P = 0.005) and femoral BMD (P = 0.046) were realized in patients treated with alendronate than in patients given placebo. BMD changes were independent of concomitant estrogen therapy. Adverse effects were similar in both treatment groups. In a second study, Millonig and others initiated vitamin D and calcium supplementation in 136 patients with end-stage liver disease awaiting liver transplantation (LT), and instituted alendronate therapy following LT. Alendronate prevented further bone loss after LT in patients with osteoporosis or osteopenia and led to an increase in BMD within 24 months. These results indicate that alendronate increases BMD in patients with liver disease. Larger studies are needed to further evaluate the efficacy and safety of alendronate in this patient population with chronic liver disease. (Zein CO, et al. Hepatology. 2005;42:762–771; Millonig G, et al. Liver Trans. 2005;11:960–966.)

PRIMARY BILIARY CIRRHOSIS (PBC)

Altered monocyte response to toll-like receptor (TLR) ligands. Mao and associates isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls to study the role of the responsiveness of the innate immune system to pathogen-associated stimuli in the pathogenesis of PBC. Their data demonstrated that patients with PBC produce more inflammation than control patients when exposed to surrogate extracts reflecting nonspecific bacterial challenges. The implication of this observation is that the innate or natural limb of the immune system in PBC is excessively armed and capable of more damage. This mechanism may also facilitate the breakdown in tolerance and the appearance of autoantibodies. In addition, Kaplan and Gershwin recently published a comprehensive review of the autoimmune responses involved in PBC and the management of the symptoms of PBC, such as pruritus, osteoporosis, hyperlipidemia, and portal hypertension, as well as management of the underlying disease with drugs, in particular ursodeoxycholic acid (UDCA), and with liver transplantation. (Mao TK, et al. Hepatology. 2005;42:802–808; Kaplan MM and Gershwin ME. N Engl J Med. 2005;353:1261–1273.)

INTRAHEPATIC CHOLESTASIS OF PREGNANCY

UDCA vs. cholestyramine. Kondrackiene and colleagues randomized 84 patients with symptomatic intrahepatic cholestasis of pregnancy to receive UDCA 8 to 10 mg/kg daily or cholestyramine 8 g/day for 14 days. Patients in the UDCA group had greater reductions of pruritic symptoms (P <0.005) and serum levels of alanine and aspartate aminotransferase (P <0.01) and bile acids (P <0.02) than patients treated with cholestyramine. In addition, newborns were delivered closer to term by mothers treated with UDCA than by mothers treated with cholestyramine. UDCA was tolerated without adverse events. This study showed that UDCA was more effective than cholestyramine in the treatment of patients with intrahepatic cholestasis of pregnancy. (Kondrackiene J, et al. Gastroenterology. 2005;129:894–901.)

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