Last November, thousands of eager hepatologists descended on Boston to attend the AASLD Liver Meeting. While there was an enormous amount of hepatology information presented, one intrepid GI fellow, Ponni Perumalswami MD, has compiled a few of the most interesting presentations.
In a late-breaking abstract, major results were presented by Dr. Di Bisceglie from the HALT-C trial. This study is designed to examine the effect of prolonged antiviral therapy with peginterferon in prevention of the complications of advanced liver disease associated with hepatitis C. This has been a randomized, controlled trial of patients with chronic hepatitis C who received peginterferon alfa-2a (90mcg per week) for 3.5 years versus those who received no treatment. The patients, in addition to their chronic hepatitis C infection had to have advanced fibrosis and were non-responders to prior therapy with peginterferon and ribavirin. A total of 1,050 patients were randomized (517 treatment, 533 control). While treatment resulted in a significant decrease in serum ALT, HCV RNA levels and inflammation on liver biopsy, the authors found no significant effect on the most important endpoints of death, decompensation of their liver disease, development of hepaticellular carcinoma or an increase in hepatic fibrosis. Therefore, they were forced to conclude that long-term therapy with peginterferon did not reduce the rate of disease progression and that these findings do not support maintenance therapy with peginterferon in patient with chronic hepatitis C and advanced fibrosis who are nonresponders to a course of peginterferon/ribavirin therapy.
Another important presentation was given by Dr. Terrault who discussed the unique aspects of liver disease management in women. While the authors described a number of important observations, the most interesting were the findings that the risk of amenorrhea is increased in women with cirrhosis. Furthermore, in pregnant women with cirrhosis, portal hypertension is a major complication, and variceal bleeding occurs in 25-40% of such patients. He therefore concluded that prophylactic endoscopic variceal banding should be considered in anticipation of pregnancy or if bleeding occurs. TIPS should also be considered. Dr Terrault also stated that women with chronic hepatitis C have slower rates of fibrosis progression as compared to men, and that when they are treated for their disease, they are more likely to attain a sustained virologic response. All is not optimistic, though, because during their post-menopause years their HCV disease and progression to fibrosis tends to accelerate. Once these women hit the post-menopausal period, their risk of developing hepatocellular carcinoma also increases.
The natural history of hepatitis B infection is also different in women. Women with chronic HBV who are e antigen positive and who have a high viral load have increased prophylaxis failure in studies where lamivudine was used in the third trimester. During pregnancy, the patients HBV liver disease may also flare, so patients have to be followed closely. In pregnant women with primary biliary cirrhosis (PBC), there is an increased risk of developing jaundice, perhaps related to increases in estrogen. These patients also experience an increased rate of still births and premature labor with increased cholestasis.
Treatment of these patients with ursodiol seems safe, though patients may require fat soluble vitamin replacement and consideration for early delivery. In pregnant women with autoimmune hepatitis, flares are more common in the first trimester, and while treatment with prednisone seems to be well tolerated, cyclosporine may increase the risk of premature labor and low birth weight infants.
In a final presentation, Dr. Fallon described some of the pulmonary vascular complications of liver disease. He stated that pulmonary vascular complications of liver disease comprise two distinct entities: hepatopulmonary syndrome (HPS, microvascular dilatation) and portopulmonary hypertension (POPH), which involves vasoconstriction and vascular remodeling in resistance vessels. These are important entities for the following reasons, HPS is found in 15-30% of patients with cirrhosis and appears to increase mortality and risks of liver transplantation, particularly when hypoxemia is present. Furthermore, no medical therapies are available, although liver transplantation has been effective in reversing this syndrome in some patients. There are no reliable screening tests or clinical predictors for HPS and screening protocols should be a future area of development. In comparison, POPH is found rarely; but in patients undergoing liver transplantation, it is associated with a significantly increased perioperative mortality. Transthoracic echocardiography is recommended for screening and right heart catheterization is required to establish the diagnosis. Medical therapies are increasingly effective in improving pulmonary vascular hemodynamics in POPH and may result in better perioperative outcomes.