Review article: intra-arterial treatments in patients with hepatocellular carcinoma.

In Western countries, most of the patients with hepatocellular carcinoma (HCC) are not eligible for curative treatments. Intra-arterial treatments have a palliative effect that could lead to extensive tumour necrosis and therefore have been widely used. Arterial embolization, Lipiodol-targeted chemoembolization and intra-arterial injection of radioactive iodine mixed with Lipiodol provided promising results in terms of tumoral growth, but were also responsible for severe side-effects, particularly in patients with cirrhosis. Their influence on survival has been assessed by randomized trials with contradictory results. In patients with advanced cases, embolization alone has limited or no influence on survival, and chemoembolization provided a beneficial effect mostly in patients with viral liver diseases, without liver failure, and with an adequate portal flux. The effects of radioactive iodine either in the treatment of advanced cases or the prevention of recurrences after a curative treatment must be investigated further.

[Secondary sclerosing cholangitis and chemo-embolization with lipiodol]. / Cholangite sclérosante secondaire et chimio-embolisation lipiodolée.

Two cases of sclerosing cholangitis after oily arterial chemoembolization are reported. In one patient angiocholitis with liver abscesses, in the other patient gradual cholestasis were the main clinical features. In both cases, endoscopic retrograde cholangiogram showed a stricture of the common hepatic bile duct and, in one case, irregularities of intrahepatic biliary tree. Histologic examination of the liver in the two patients pointed out the involvement of small bile ducts and arteriolar endarteritis obliterans. Ischaemia is likely to be the main mechanism of these two cases of sclerosing cholangitis as well as in those described after FUDR intra-arterial chemotherapy. The prevalence of sclerosing cholangitis after arterial oily chemoembolization is probably underestimated because of a non specific clinical presentation and need to be precise by further study.

[Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients]. / Traitement de l'hépatite alcoolique par la silymarine. Une étude comparative en double insu chez 116 malades.

A randomized double-blind trial of silymarin versus placebo was carried out in 116 patients with histologically proven alcoholic hepatitis, 58 of them with cirrhosis. Patients were not included in case of hepatic encephalopathy, contraindication to percutaneous liver biopsy, hepatocellular carcinoma, evident lack of discipline or refusal to enter the trial. Fifty-seven patients received silymarin orally 420 mg/day and 59 received placebo during 3 months. Biologic parameters were assessed in the serum, and a percutaneous liver biopsy was obtained at the start of the trial and 3 months later. Histologic scores of alcoholic hepatitis and fibrosis were established on each biopsy specimen by two independent pathologists. The 2 groups were comparable at inclusion; 26 p. 100 of patients were lost to follow-up at 3 months, abstinence was obtained in 46 p. 100 of patients at the end of the trial. These percentages were similar in the two groups. Four patients died of hepatic failure during the trial, 3 in the placebo group. Significant improvement in the score of alcoholic hepatitis and serum amino transferase activity, was noted in both groups during the trial, irrespective of treatment with silymarin or placebo. No side-effects were noted. Our results suggest that silymarin 420 mg/d is not clinically relevant in the treatment of moderate alcoholic hepatitis.

Coagulation assays as diagnostic markers of hepatocellular carcinoma.

With the aim of improving the biological diagnosis of hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP) and factor V levels were assayed in 119 patients with HCC and 60 cirrhotic patients without HCC. Among the patients with HCC, increased levels of AFP (greater than 300 ng/ml) and of DCP (greater than 15 mU/ml) were observed in 36% and 69% of the cases, respectively. None of the 60 patients without HCC had increased AFP, and one had abnormal DCP; in this patient, DCP level returned to normal value after vitamin K1 injection. No significant correlation was found between increased AFP and DCP, thus indicating that the two tests complement each other for the diagnosis. A factor V level higher than expected from the reduced prothrombin time test of the patient was detected in 50% of patients with HCC and only 7% of those without HCC. No correlation was found between increased factor V and abnormal AFP or DCP. The thrombin time, fibrinogen activity to antigen ratio, and polymerization index failed to differentiate between cirrhosis and HCC. We conclude that AFP, DCP and factor V may give complementary informations in the diagnosis of HCC, one of these markers at least being positive in 88% of the patients.

[Serum and tissue concentrations of zinc after oral supplementation in chronic alcoholics with or without cirrhosis]. / Evolution des concentrations sériques et tissulaires de zinc après supplémentation orale chez des alcooliques chroniques avec et sans cirrhose.

Seric and hepatic zinc concentrations are decreased in chronic alcoholics, particularly those with cirrhosis. The purpose of this study was: 1) to assess the duration of zinc intake necessary to normalize seric and hepatic zinc concentrations; 2) to demonstrate that this supplementation did not increase zinc concentrations in other tissues (erythrocytes, leukocytes and hair) and did not induce adverse reactions. Twenty alcoholic patients with (group A: n = 13 or without (group B: n = 7) cirrhosis received zinc sulfate 600 mg daily during 10 days, 10 patients with alcoholic cirrhosis during 30 days (group C) and 7 during 60 days (group D) and were compared with a group of 30 normal subjects. Serum zinc concentrations increased to normal values in all groups of patients. Hepatic zinc increased significantly in groups B (p less than 0.05) and D (p less than 0.01). Zinc concentrations in erythrocytes, leukocytes and hair were unchanged. No adverse reactions were observed. We conclude that seric zinc concentrations reached normal values in alcoholics with or without cirrhosis by daily supplementation of 600 mg zinc sulfate during 10 days to 2 months while hepatic zinc concentrations increased but remained under normal values in some patients, particularly those with cirrhosis.

[Does oral zinc improve the cellular immunity of patients with alcoholic cirrhosis?]. / L'apport oral de zinc améliore-t-il l'immunité cellulaire des malades atteints de cirrhose alcoolique?

A depressed response to delayed hypersensitivity skin tests is frequent in patients with alcoholic cirrhosis. Immune dysfunction in these patients is presumably dependent on nutritional factors. Zinc deficiency, a common finding in alcoholic cirrhosis, inhibits cellular immunity and might be one of these factors. The aim of our study was to show that zinc supplementation may improve cellular immunity in patients with alcoholic cirrhosis. We therefore compared 2 groups of patients: patients in the treated group (n = 18) had a daily oral intake of zinc-sulfate, 200 mg, during 2 months, patients in the non treated group (n = 20) received no supplementation. Both groups had a free diet. Delayed hypersensitivity skin tests to 7 antigens were performed with the Multitest IMC System at the beginning and at the end of the study. The immunity score was determined by the number of tests producing a skin induration greater than 2 mm. The evolutive index, calculated in each patient, was the difference between the final and initial immunity scores. The 2 groups were similar for all studied parameters. Cumulated immunity scores improved from 35 to 53 in treated patients (p less than 0.02), and from 42 to 44 (NS) in non treated patients. The evolutive index was 1 +/- 1.4 in treated patients and 0.1 +/- 1 in non treated patients (p less than 0.05). We conclude that in patients with alcoholic cirrhosis, daily intake of zinc sulfate, 200 mg, improves responsiveness to delayed hypersensitivity skin tests.(ABSTRACT TRUNCATED AT 250 WORDS)