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^®

JUNE 2003

FULMINANT HEPATIC FAILURE (FHF)

Serum phosphorus levels predict outcome. PY Chung and associates at the University of Chicago reviewed the incidence of hypophosphatemia in 38 patients with FHF referred for orthotopic liver transplantation (OLT) from January 1991 to May 2002. Hypophosphatemia (<2.5 mg/dL) developed in 87% of patients within 10 days of referral. The median nadir serum phosphorus level was lower in patients who recovered compared to those who required OLT or died. A serum phosphorus level >2.5 mg/dL was a predicator of mortality equivalent to the King’s College criteria. These findings showed that hypophosphatemia occurred frequently in patients with FHF and that lower serum phosphorus levels were associated with recovery of hepatic function, possibly secondary to utilization of phosphorus by regenerating hepatocytes. (Chung PY, et al. Liver Transpl 2003;9:248-253)

CHRONIC HEPATITIS C VIRUS (HCV) INFECTION

Normal vs. elevated alanine aminotransferase (ALT) levels. Previous studies have suggested that chronic HCV patients with persistently normal ALT (PNALT) levels have only mild hepatitis. Chee-Kin Hui and colleagues studied 40 patients with PNALT levels (Group 1) and 41 patients with elevated ALT levels (Group 2) who had F0 to F2 fibrosis on initial lever biopsy. The median time to second liver biopsy was 6.3 years (range, 2.0 – 11.1 years). Progression of fibrosis was found in 9 (22.5%) Group 1 and 17 (41.5%) Group 2 patients. The probability of fibrosis progression for patients with F0 to F1 fibrosis at baseline was lower in Group 1 compared to Group 2 (7/31 [22.6%] vs. 13/31 [43.3%], respectively). These data provide further evidence that HCV carriers with PNALT levels are less prone to develop fibrosis progression. In an accompanying editorial, Claudio Puoti emphasize that controversies remain as to the definition of PNALT levels, histological features, natural history, and optimal management of HCV patients with PNALT levels. (Hui C-K, et al. J Hepatol 2003;38:511-517 and Puoti C. J Hepatol 2003;38:529-532)

CHRONIC HEPATITIS B VIRUS INFECTION (HBV)

Durability of response to lamivudine therapy. Jules Dienstag and colleagues conducted a multicenter study in which 40 chronic HBV patients with HBeAg seroconversion after lamivudine therapy were followed for durability of the serologic responses after completion of therapy. After a median follow-up of 36.6 months (range, 4.8-45.6 months), HBeAg seroconversion continued to be demonstrated in 30 (77%) of 39 evaluable patients. The authors then reviewed data from an additional 65 patients in previous trials who had HBeAg seroconversion and found the 3-year durability rate of HBeAg seroconversion following lamivudine therapy to be 64%. Seven of 8 patients who received lamivudine retreatment for reappearance of HBV markers had biochemical and/or biological improvement. No safety issues were identified. These results demonstrate that HBeAg seroconversion achieved during lamivudine treatment is durable in most patients. (Dienstag JL, et al. Hepatology 2003;37:748-755)

VARICEAL BLEEDING

Emergency sclerotherapy vs. vasoactive drugs: a meta-analysis. Gennaro D’Amico and others performed a meta-analysis of 15 randomized controlled trials comparing sclerotherapy and vasoactive drugs for variceal bleeding in cirrhosis. Vasoactive drug therapy controlled bleeding in 83% of the patients. Sclerotherapy was not found to be superior to vasoactive drugs for several outcomes including control of bleeding, rebleeding, blood transfusions, adverse events, and mortality. The authors concluded that the available evidence does not support the use of emergency sclerotherapy as first-line treatment for variceal bleeding in cirrhosis. (D’Amico G, et al. Gastroenterology 2003;124:1277-1291)

HEMOCHROMATOSIS

Serum ferritin levels predict advance fibrosis. Elizabeth Morrison and coworkers investigated 182 patients with phenotypically defined hemochromatosis. They found that only 1 of 93 patients with a serum ferritin level < 1,000 mg/L had cirrhosis while 39 of 89 patients with serum ferritin levels > 1,000 mg/L had cirrhosis (p < 0.001). The authors suggest that liver biopsy may be unnecessary in patients with hemochromatosis and serum ferritin levels < 1,000 ug/L. (Morrison ED, et al. Ann Intern Med 2003;138:627-633)

HEPATOCELLULAR CARCINOMA (HCC)

Interferon therapy after tumor ablation. Yasushi Shiratori et al. conducted a study in which 74 patients with compensated cirrhosis and £ 3 modules of HCC associated with chronic HCV infection had complete ablation of HCC modules by percutaneous ethanol injection. Following tumor ablation, patients were randomized to receive either interferon 6 million units 3 times weekly for 48 weeks (n=49) or no further treatment (n=25). Although the rate of first recurrence of new foci of HCC were similar between the treatment groups, the rates of second or third recurrences were lower in the interferon-treated compared to the untreated patients, respectively. These results indicate that interferon treatment after tumor ablation may improve prognosis in selected patients with HCC associated with chronic hepatitis C. (Shiratori Y, et al. Ann Intern Med 2003;138:299-306)

RECENT REVIEWS OF INTEREST

Budd-Chiari syndrome. Janssen HLA, et al. J Hepatol 2003;38: 364-371.

Nonalcoholic steatohepatitis. Neuschwander-Tetri B and Caldwell S. Hepatology 2003;37:1202-1219.HHHH.

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