Alessandro Grasso

Serum prolyl-hydroxylase as an index of fibrogenic activity in chronic active hepatitis and cirrhosist

Objective To evaluate serum prolyl-hydroxylase, an enzyme reflecting hepatic fibrogenic activity, in healthy subjects and patients with various liver diseases. Design Serum prolyl-hydroxylase was evaluated in patients with varying degrees of liver damage and was related to standard liver function tests. Methods One hundred and thirty-one patients were studied, 25 with steatosis or chronic persistent hepatitis, 37 with chronic active hepatitis, 35 with Childs class A cirrhosis and 34 with Childs class B cirrhosis. Serum prolyl-hydroxylase was measured by means of an immune enzymatic method. Results Serum prolyl-hydroxylase was found to be (mean ± SD) 62 ±15ng/ml in 43 healthy subjects, 70 ± 20 ng/ml in patients with steatosis or chronic persistent hepatitis, 174 ± 86 ng/ml in patients with chronic active hepatitis (P > 0.01 compared with healthy and other disease groups), 124 ± 62 ng/ml (P > 0.01 compared with healthy subjects) in patients with Childs class A cirrhosis and 94 ± 55 ng/ml in those with Childs class B cirrhosis. Serum prolyl-hydroxylase was related to liver function tests in multiple regression analysis (131 patients; r = 0.643, P > 0.001) confirming the hepatic source of this enzyme in chronic liver disease. Conclusion The higher values found in chronic active hepatitis and in the early stages of cirrhosis suggest that fibrogenesis, evaluated by means of serum prolyl-hydroxylase levels, is likely to be a reaction to inflammatory damage of the liver. On the basis of these results, serum prolyl-hydroxylase seems to be a possible marker for identifying fibrogenic activity in patients with chronic liver disease and could be a possible target for the evaluation of antifibrogenic drugs.

Effects of beta-adrenoreceptor antagonists on cerebral blood flow of cirrhotic patients with portal hypertension

The current study evaluated the effect of two beta adrenergic—blocking agents, propranolol (PRP) and atenolol (ATN), versus placebo on cerebral blood flow (CBF) of three homogeneous groups of cirrhotic patients with portal hypertension. CBF was measured by the noninvasive 133‐Xenon inhalation method at rest and 1 hour after a single oral dose of PRP (40 mg), or ATN (100 mg), or placebo. Blood pressure and heart rate (HR) were measured at the beginning of each examination, and end‐tidal pCO2 (PeCO2) was monitored. The HR decreased significantly in both the PRP and ATN groups (P < .01), whereas no changes were recorded for both PeCO2 and mean arterial blood pressure (MABP). The comparisons of the CBF differences among groups (ANOVA with the significance levels adjusted by the Bonferronis correction) showed a significant increase in CBF after ATN as compared with both placebo (P < .02) and PRP (P < .01), whereas no significant differences were seen after PRP as compared with placebo. Our results confirm that PRP does not significantly affect CBF, whereas ATN induces an increase in CBF, although the underlying mechanism is difficult to explain.

HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients.

Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P = 0.033 and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

Hepatitis G virus and HCV related extrahepatic disease.

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High-dose interferon therapy in patients with chronic hepatitis C: A biochemical and virologic evaluation

Abstract Sixty patients of both sexes with biopsy-proven chronic hepatitis C were randomized to receive recombinant alpha-2b interferon 3 million IU or 10 million IU three times a week for 4 months. A 6-month follow-up period was scheduled for the end of therapy. Eighteen patients (30.0%) had normalized alanine aminotransferase (ALT) levels at the end of therapy and during the follow-up period. Of these, 10 received 3 million IU (33.3%) and 8 (26.7%) received 10 million IU. Twenty-three (38.3%) of the 60 patients relapsed during the follow-up period. No significant difference in relapse rate was observed between the two groups. The overall percentage of nonresponder patients was 31.7%. Treatment was discontinued because of noncompliance and/or side effects in 7 patients (11.7%), 1 in the 3-million IU group and 6 in the 10-million IU group. All patients were positive for hepatitis C virus—RNA at the beginning of the study, and it became undetectable in almost all responder patients. No correlation between viremia and biochemical signs of liver disease was observed in some cases. No virologic differences were found between the two treatment groups. Our study shows that 10 million IU does not increase the response or the relapse rate compared with 3 million IU in the treatment of patients with chronic hepatitis C.