Effect of vitamin E on serum aminotransferase and thioredoxin levels in patients with viral hepatitis C.

OBJECTIVES: Oxidative stress induces cellular responses such as cell death, gene activation and cell proliferation, in the liver. Vitamin E (Vit. E) has been found to protect the liver against oxidative stress in animal experiments. Thioredoxin (TRX) is a stress inducible, multifunctional protein, secreted during oxidative stress. This study evaluated effects of Vit. E on serum TRX and aminotransferase levels in hepatitis C virus (HCV) patients, partly non-responsive to initial interferon (IFN), with higher than average level of serum alanine aminotransferase (ALT) after receiving anti-inflammatory drug treatment. METHODS: Seventeen HCV patients (male = 3; female = 14) of age 62 +/- 7.65 years receiving anti-inflammatory drug therapy, at least 6 months prior to Vit. E administration, were given d-alpha-tocopherol 500 mg/day, orally, for a period of 3 months. ALT, aspartate aminotransferase (AST), TRX and Vit. E were measured at 0, 1, 2 and 3 months and 1 month after end of treatment. As controls, the same patients biochemical data, 3 months from the start of therapy were used. Patients were divided into three categories: total patients "T", low ALT group "L" (ALT < 70 IU/l) and high ALT group "H" (ALT > 70 IU/l), respectively. RESULTS: The ALT level was lowered, significantly in group H, in the 1st, 2nd, 3rd and 1-month post therapy, compared to the initial value. But group L showed little or no change in ALT. Post Vit. E therapy, in groups T and H, the TRX level was elevated but remained below initial levels, whereas in group L, TRX level remained significantly lower than the pretreatment value. Groups T and L, showed significant reduction (p < 0.05) in serum TRX levels in the 2nd and 3rd month. Group H showed a tendency towards TRX reduction, but not significantly. Serum Vit. E levels increased significantly (p < 0.0001) from the 1st to 3rd month in all three T, H and L groups. CONCLUSION: Oxidative stress induced liver damage is reduced by Vit. E in patients with viral hepatitis C, particularly those with initial ALT levels > 70 IU/l. Vit. E treatment causes reduction of oxidative stress markers as TRX and ALT in sera. Therefore, Vit. E can act as a supportive therapy to combat liver damage caused by oxidative stress, in such patients with continuously high levels of ALT even after anti-viral and anti-inflammatory drug therapy.

Long term follow-up of a group of chronic hepatitis C patients treated with anti-inflammatory drugs following initial interferon therapy.

BACKGROUND: A relationship between hepatocellular carcinoma (HCC) recurrence and serum alanine aminotransferase (ALT) in a group of hepatectomized patients has been reported. Another study suggested the development of HCC is more rapid in a high ALT group of hepatitis C virus (HCV)-associated cirrhotic patients. To find a relationship between ALT and HCC occurrence, we observed changes in ALT over a period of 6 years, in a group of non-cirrhotic, chronic hepatitis C (CHC) patients treated with anti-inflammatory drugs post interferon (IFN) therapy. METHOD: Eighty three CHC patients, with fibrosis stage 1, 2, 3 (F1, F2, F3) who had a partial (PR) or non-response (NR) to initial IFN therapy, were treated with anti-inflammatory drugs for 6 years. Over a period of 6 years HCC developed in nine patients. Of them, one belonged to F2 and eight to F3. Within the first 2 years HCC developed among two patients in F3. Multivariate analysis revealed that in F3, the 6 year average ALT activity (odds ratio 5.59; P<0.05) was the only significant variable associated with HCC occurrence. All other variables remained insignificant. Among the six F3 patients in whom HCC developed, the likelihood of HCC occurrence was found to be significantly higher (odds ratio 1.89; P<0.001) in patients who showed elevated ALT activity (>80 IU) two or more times during the 6 year period, compared to those with ALT (>80 IU) for less than 2 years. CONCLUSION: These findings suggest that continuous elevation of ALT seems to be important for HCC diagnosis. Patients with ALT >==80 IU for 2 years or more are at a greater risk of HCC development. It is necessary to continue treatment with anti-inflammatory drugs, following initial IFN therapy to suppress ALT below 80 IU, to prevent HCC occurrence or delay the time of HCC occurrence in order to prolong life.

Clinical significance of intrahepatic interleukin-8 in chronic hepatitis C patients.

Background/AIM: Interleukin-8 (IL-8) is known as a chemotactic and angiogenetic cytokine and is a potential mediator of host response to injury or inflammation. In order to identify the role of IL-8 in the pathogenesis of chronic hepatitis C (CHC), we assessed semiquantitatively the messenger RNA (mRNA) expression of IL-8 and other cytokines in liver biopsy specimens of CHC patients. METHOD: Liver biopsy specimens were obtained under peritoneoscopy from 35 patients with CHC. The mRNA expression of IL-8 and other cytokines in the liver were determined by real-time PCR and the correlation between the mRNA expression and histological classification of liver were studied. Liver histology was classified by both staging of fibrosis (F0-F4) and grading of activity (A1, mild; A2, moderate and A3, severe). RESULTS: Patients were classified into F1, 8; F2, 9; F3, 9 and F4, 9 and A1, 6; A2, 14 and A3, 15, by staging of fibrosis and grading of activity, respectively. Expression of IL-8 mRNA increased with staging of fibrosis (F1, 0.402+/-0.65; F2, 0.413+/-0.246; F3, 1.388+/-2.166; F4, 1.991+/-1.879) and grading of activity (A1, 0.560+/-0.808; A2, 0.780+/-1.268; A3, 1.548+/-1.957). The mRNA expressions of IL-2, IL-1alpha, IL-1beta, IL-15 and TNF-alpha were found to be closely correlated with IL-8 mRNA (R=0.638; 0.522; 0.487; 0.465 and 0.495, respectively, in all P<0.05). CONCLUSION: In CHC, intra-hepatic expression of both IL-8 and IL-2 increased with fibrosis and inflammatory activity. Positive correlations were found between IL-8 and other cytokines and between cytokines themselves. These findings suggest that these interacting cytokines play an active role in the pathogenesis of CHC, and maybe involved in the upregulation or induction of one and other.