HEPATOLOGY WATCHTM
Timely Information for Practicing Physicians

November 1998

CIRRHOSIS

Risk of cancer. Dr. Henrik Sorensen and coworkers investigated the risk of cancer in 11,605 cirrhotic patients who had survived at least 1 year after being entered into the Danish National Registry of Patients from 1977 to 1989. Among these patients 1,447 cancers were diagnosed compared to an expected incidence of 708 cancers. The risk of hepatic carcinomas was especially elevated (59.9-fold increase for hepatocellular carcinoma and 10-fold increase for cholangiocarcinoma). In addition, the risk of several extrahepatic cancers (e.g., cancers of the lung, breast, colon, kidney, head and neck, pancreas, and urinary bladder) was also found to be elevated. The authors conclude that cirrhosis is not only an important factor for the development of hepatic cancers, but may also play a role in the carcinogenesis of many other neoplasms. (Sorensen HT, et al. Hepatology 1998; 28: 921-925)

Effects of ursodeoxycholate. Dr. Masahito Kano and colleagues assessed the expression of phospholipase A₂ (PLA₂) subtypes in selected patients with cholesterol stones who had received or not received ursodeoxycholate (UDC) therapy because PLA₂ may play a role in gallbladder mucosal inflammation. They studied 48 patients with multiple cholesterol stones, 19 of whom had randomly received UDC treatment. Group IIA-PLA₂ expression (protein mass from gallbladder tissue and bile levels) were decreased in the UDC treated patients (P<0.01). In addition, mRNA PLA₂ group V levels and mucin concentration were also reduced in the gallbladders of the UDC patients. The authors conclude that the effects of UDC on PLA₂ levels may be a mechanism for the reported efficacy of UDC therapy in cholesterol gallstone disease. (Kano M, et al. Hepatology 1998; 28: 302-313).

Impact of alcohol on clinical course. Dr. Thelma Wiley and colleagues retrospectively reviewed the medical records and liver biopsies of 176 hepatitis C virus (HCV) patients to evaluate the effect of moderate alcohol intake on the histologic and clinical progression of disease. There were 86 HCV only patients and 90 HCV/alcohol patients. There was a 2-3 fold greater risk of cirrhosis and decompensated liver disease in the alcohol patients (P<0.05). Furthermore, the rate at which cirrhosis developed was faster in the alcohol group (58% vs 10% of patients were cirrhotic in the HCV/alcohol vs HCV only patients, respectively, by the second decade). The authors conclude that alcohol intake is a risk factor for progression of HCV infection. (Wiley TE, et al. Hepatology 1998; 28: 805-809)

Interferon alfa therapy. Dr. Daryl Lau and colleagues at the NIH evaluated the long-term outcome (follow-up, 6-13 years) of 10 chronic hepatitis C (CHC) patients who were treated with interferon alfa-2b (Intron® A) for 52 ± 6 weeks between the years 1984 and 1987. Five patients had achieved a 6-month sustained response after interferon therapy. All of these patients remained serum HCV RNA negative, and at the last follow-up the serum aminotransferase levels were normal in 4 patients and minimally elevated in 1 patient. Additionally, liver biopsy specimens were non-reactive for HCV RNA and showed histological improvement for each patient. In contrast, the 5 patients without a sustained interferon response had symptoms of CHC, were serum HCV RNA positive, had persistently elevated serum aminotransferase levels, and had liver biopsies which showed progressive fibrosis or cirrhosis. The authors conclude that patients with a 6-month post-treatment response to interferon-a have a favorable long-term outcome. (Lau DT-Y, et al. Hepatology 1998; 28: 1121-1127)

Vaccine research. Dr. Pablo Sarobe and colleagues have found that a key element in developing a vaccine for hepatitis C is to understand and define subunits of the vaccine that may be immunogenic. In this study, the authors were aware that although cytotoxic T lymphocytes against hepatitis C are found in patients, these cytotoxic cells do not appear to confer protection. To further potential cytotoxicity, the group modified peptides found in HCV that were responsive in a common human genotype HLA-A2.1. They discovered that modified peptide conferred greater immune responses and therefore has the potential to be incorporated in a subunit vaccine similar to hepatitis B. (Sarobe, P, et al. J. Clin. Invest. 1998; 102: 1239-1248)

Effect of transjugular intrahepatic portosystemic shunt. Dr. Monica Guevara and coworkers prospectively evaluated the effects of transjugular intrahepatic portosystemic shunts (TIPS) on renal function in 7 patients with cirrhosis and hepatorenal syndrome. The insertion of TIPS was associated with an improvement of renal function in 6 of 7 patients. This improvement was manifested by a mean reduction of the portal pressure gradient (P<0.05), an increase in the mean GFR (P<0.05), and a decrease of the mean serum creatinine and blood urea nitrogen levels (P<0.05). In addition, these renal effects were associated with a reduction (P<0.05) of plasma renin, aldosterone, and norepinephrine activity. The authors conclude that TIPS insertion improves renal function and reduces the activity of the renin-angiotensin system in cirrhotic patients with hepatorenal syndrome (Guevera M, et al. Hepatology 1998; 28: 416-422)