Clinical Research in Liver Disease and Nutrition
This research is focused principally on chronic viral hepatitis, the porphyrias, and diseases of metal storage (hemochromatosis, Wilson's disease). As opportunities arise, we also study patients with other liver disorders (e.g., Budd-Chiari syndrome; drug induced liver injury, primary biliary cirrhosis [PBC]; primary sclerosing cholangitis [PSC]).
Recent results from our and other centers indicate that iron in the liver and perhaps other tissues plays an important role in enhancing hepatic injury in chronic viral hepatitis and that iron reduction per se often improves severity of hepatitis (Figure 2). Furthermore, preliminary results suggest that iron reduction improves the response of chronic hepatitis B or C to interferon. However, whether iron reduction will truly prove to be of lasting benefit is not yet clear. Therefore, we are carrying out two cooperative trials designed to establish whether iron reduction will increase the frequency of sustained responses to interferon therapy.
- A multicenter, randomized comparison of interferon-a alone vs iron reduction and interferon-a for initial therapy of chronic hepatitis C;
- A multicenter, randomized comparison of iron reduction alone vs iron reduction and interferon-a for retreatment of patients with chronic heaptitis C who previously failed to respond to interferon-a alone.
Other clinical studies are as follows:
- A study to identify more rapid and precise MR-based methods for estimating hepatic iron concentrations; and
- A study of low-dose combination therapy with heme plus an inhibitor of heme oxygenase for the acute porphyrias.
We also collaborate with Drs. Rothman and Ennis of the Division of Infectious Disease and Immunology on T cell functions and reactivities in patients with chronic hepatitis C and with Drs. Banner and Woda of the Department of Pathology on inflammatory markers and adhesion molecules in liver tissue of patients with chronic viral hepatitis.
Another component of our clinical studies includes the Adult Nutritional Support Service. This multi-disciplinary team is composed of a physician, two dietitians and a nurse. Ongoing studies include evaluation of the appropriateness of enteral and parenteral nutritional supplements at UMMC, nutritional intervention for acid/peptic disorders, and tests of new nutritional supplements.
FIGURE 2. A 52-year-old man with thalassemia minor and chronic HBV infection underwent liver biopsy. Biopsy showed moderately active hepatitis as well as a liver iron concentration of 2200 micrograms per gram (normal 300-1200 mcg/g). The patient underwent treatment with interferon alpha 2-B (IFN) for four months between February and June, 1992. As depicted in the Figure, the patient's serum aminotransferases did not return to normal after therapy with IFN. Starting in February, 1994, the patient has undergone phlebotomy therapy. Between February, 1994 and August, 1995 the patient has undergone 26 units of phlebotomy. With phlebotomy therapy, the patient has had a dramatic improvement in the serum aminotransferases. (From Rubin RB, et al. Dig Dis, 13:223-238,1995.)
Bonkovsky HL, et al. Treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone: A randomized, controlled trial. I. Short-term effects on liver function. II. Short-term effects of treatment on nitrogen metabolism, metabolic balance and nutrition. Am J Gastro 86:1200-1218, 1991.
Bonkovsky HL, et al. Intravenous heme-albumin in acute intermittent porphyria. Evidence for repletion of hepatic hemoproteins and regulatory heme pools. Am J Gastro 86:1050-1056, 1991.
Levey JM, Bjornsson B, Banner B, Kuhns M, Malohtra R, Whitman N, Romain PL, Cropley TG, Bonkovsky HL. Cryoglobulinemia in chronic hepatitis C infection: A clinico-pathological analysis of 10 cases and review of recent literature. Medicine (Baltimore) 73:53-67, 1994.
Nompleggi DJ, Bonkovsky HL. Nutritional supplementation in chronic liver disease. An analytic review. Hepatology 19:518-533, 1994.
Bonkovsky HL, Kane RE, Jones DP, Galinsky RE, Banner B. Acute hepatic and renal toxicity from low doses of acetaminophen in absence of alcohol abuse or malnutrition: evidence for increased susceptibility to drug toxicity due to cardioppulmonary and renal insufficiency. Hepatology 19:1141-1148, 1994.
Clifford B, Donahue DG, Smith L, Cable EE, Luttig B, Manns M, Bonkovsky HL. High prevalence of serologic markers of auto-immunity in patients with chronic hepatitis C. Hepatology 21:613-619, 1995.
Bonkovsky HL, Liang TJ, Hasegawa K, Banner B. Chronic leukocytoclastic vasculitis complicating HBV infection. Possible role of mutant forms of HBV in pathogenesis and persistence of disease. J Clin Gastro, in press, 1995.
Barton AL, Banner BF, Cable EE, Bonkovsky HL. Distribution of iron in the liver predicts the response of chronic hepatitis C infection to interferon therapy. Am J Clin Pathol 103:419-424, 1995.
Rubin RB, Barton AL, Banner BF, Bonkovsky HL. Iron and chronic viral hepatitis: emerging evidence for an important interaction. Digestive Diseases, in press, 1995.
Bonkovsky HL, Clifford BD, Smith LJ, Allan C, Banner B. High dose interferon alfa-2b for retreatment of non-responders or relapsing patients with chronic hepatitis C: A controlled randomized trial. Dig Dis Sci, in press, 1995.