Prognosis of advanced hepatocellular carcinoma: comparison of three staging systems in two French clinical trials.

OBJECTIVE: The objective of this study was to assess the performance of three staging systems [Okuda, Cancer of the Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer group (BCLC)], for predicting survival in patients with hepatocellular carcinoma (HCC) and to explore how to improve prognostic classification among French patients with HCC whose main etiology is alcoholic cirrhosis. METHODS: We have pooled two randomized clinical trials in palliative condition from the Fédération Francophone de Cancerologie Digestive. They had included 416 and 122 patients. Performances of Okuda, CLIP and BCLC scores have been compared using Akaike information criterion, discriminatory ability (Harrell's C and the Royston's D statistics), monotonicity of gradients and predictive accuracy (Schemper statistics Vs). To explore how to improve classifications, univariate and multivariate Cox model analyses were carried out. RESULTS: The pooled database included 538 patients. The median survival was 5.3 months (95% confidence interval 4.6-6.2). For all statistics CLIP staging system had a better prognostic ability. Performances of all staging systems were rather disappointing. World Health Organization performance status (WHO PS) for CLIP or alpha-fetoprotein for BCLC allowed a significant improvement of prognostic information. CONCLUSION: Our results indicate that CLIP staging seems to be most adapted to palliative setting and that it could be better by associating WHO PS.

Hepatitis C virus infection risk factors in patients admitted in hospital emergency departments in Picardy. Value of oriented screening based on recommendations of the 'Direction Générale de la Santé'.

OBJECTIVE AND DESIGN: Oriented hepatitis C virus (HCV) screening on the basis of transfusion, previous or current parenteral drug addiction, invasive procedures, and in family members of patients with hepatitis C, was recommended in France by the 'Direction Générale de la Santé' (DGS). The aim of this study was to estimate the frequency of these risk factors in patients admitted in hospital emergency departments in Picardy. METHODS: Between 1 June and 31 July 1996, physicians of the emergency units of seven hospitals in Picardy were asked to question admitted patients about risk factors mentioned in the DGS recommendations, and to suggest a screening test when at least one of these risk factors was present. RESULTS: Among 1648 patients, 68.7% had at least one of these risk factors. Screening was accepted by 723 patients, 58.7% of those with at least one risk factor, and more than 70% of those with history of transfusion and/or drug addiction. It was immediately performed in 451, and 2.4% had anti-HCV antibodies. The prevalence of anti-HCV antibodies was 1.5% in patients without history of transfusion or drug addiction and 7.9% in those with at least one of these two risk factors. CONCLUSION: Oriented screening based on transfusion or drug addiction history seems to have better efficiency than the screening policy recommended by the DGS. Poor reliability of answers about medical history was observed probably because of stress related to emergency circumstances. A screening test proposed to patients with these major risk factors by their usual physician would be probably more efficient.

[Hepatocellular carcinoma with cirrhosis: treatment with doxorubicin. Phase II evaluation]. / Carcinome hépatocellulaire sur cirrhose: traitement par la doxorubicine. Essai phase II.

Twelve patients with unresectable hepatocellular carcinoma associated with cirrhosis were treated with Doxorubicin which was given intravenously (30 to 50 mg/m2) every three weeks. Six patients were given only one dose of Doxorubicin. No clinical response was observed. Five patients has serum alphafoetoprotein (AFP) determination during the treatment. AFP concentration rose in 4 patients and fell in 1 patient. Survival rate after 3 and 8 months of treatment was 58 and 33 per cent. These results suggest that Doxorubicin is not an effective treatment for hepatocellular carcinoma.

[Hepatic function and significance of the increase in serum concentrations of IgA in alcoholic cirrhosis]. / Fonction hépatique et signification de l'augmentation de la concentration sérique des IgA au cours de la cirrhose alcoolique.

Elevated serum gammaglobulin concentrations are frequently observed in patients with liver cirrhosis. Predominant elevation of the IgA is generally considered as suggestive of an alcoholic aetiology. The aim of this study was to define the factors that determine the serum concentration of IgA in alcoholic cirrhosis. Twenty-seven patients with alcoholic cirrhosis were studied. Serum concentrations of IgG, IgA and IgM were measured by immunonephelometry. Hepatocellular function was assessed by the Child-Turcotte score, the prothrombin time and the intrinsic clearance of indocyanine green. The importance of intra-hepatic shunts was estimated according to the intact hepatocyte theory, and the degree of hepatic necrosis by serum levels of transaminases. It was noted that: 1) the IgA concentration correlated significantly with the Child-Turcotte score and with the decrease of the prothrombin time, intrinsic clearance and the functional fraction of hepatic blood flow; 2) there was no such correlation between the serum concentration of IgA and the total hepatic blood flow or transaminase levels; 3) there was no correlation between serum concentration of IgG or IgM and the factors studied. These results suggest that in alcoholic cirrhosis, increase in serum IgA, reflects the degree of impairment of hepatic function and intrahepatic shunting.

[Does the size of esophageal varices have a prognostic significance in alcoholic cirrhosis?]. / La taille des varices oesophagiennes a-t-elle une signification pronostique au cours des cirrhoses alcooliques?

This study was designed to determine whether the size of esophageal varices were of prognostic value in patients with alcoholic cirrhosis. Esophageal varices were classified into 2 groups according to whether their size was larger or smaller than 4 mm. There was a total of 99 patients; 56 had small varices and 43 had large varices. Of the clinical and biological data collected at the time of determination of the size of the esophageal varices, only the duration of cirrhosis and the prevalence of gastrointestinal bleeding were significantly greater in patients with large esophageal varices. The one- and two-year cumulative rates of patients with large esophageal varices were 63 +/- 7 p. 100 and 42 +/- 8 p. 100, respectively; these results were not significantly different from those in patients with small esophageal varices, i.e. 68 +/- 6 p. 100 and 61 p. 100 respectively (p less than 0.5 for one-year survival; p less than 0.08 for two-year survival). Serum bilirubin and albumin as well as the presence of ascite were of significant prognostic value concerning death at two years while the presence of esophageal varices did not significantly increase the prognostic value of the above-mentioned variables (using Cox's regression model). In conclusion, the results of our study suggest that large esophageal varices, in spite of their association with a high incidence of gastrointestinal bleeding, do not influence prognosis at two years for patients with alcoholic liver cirrhosis.

[Endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography performed during the same anesthesia session]. / Echo-endoscopie et cholangio-pancréatographie rétrograde endoscopique dans un même temps anesthésique.

OBJECTIVES: To evaluate the feasibility, results and importance of a diagnostic and therapeutic biliary and pancreatic exploration associating endoscopic ultrasonography and endoscopic retrograde cholangio-pancreatography during the same anaesthesia session. METHODS: From November 1997 to October 1998, 179 patients (83 males, 96 females), mean age 62 years (range 22 to 95 years), were investigated in our gastroenterology unit for biliary or pancreatic disorders. Two hundred and sixty two examinations were performed by a single physician for patients under general anaesthesia. In 87 cases (42%), endoscopic retrograde cholangio-pancreatography was performed immediately without prior endoscopic ultrasonography; these patients were not included. When endoscopic retrograde cholangio-pancreatography followed endoscopic ultrasonography, it was performed during the same anaesthesia session. RESULTS: In 118 cases, endoscopic ultrasonography was performed first, followed by endoscopic retrograde cholangio-pancreatography 57 times (48%). The sensitivity of endoscopic ultrasonography was 96.5% and the success of therapeutic endoscopic retrograde cholangio-pancreatography was 100%. Endoscopic retrograde cholangio-pancreatography was necessary for 83% of patients with angiocholitis, 60% with cholestasis, 45% with acute biliary pancreatitis and only 28% with common bile duct stone migration. CONCLUSION: To decrease the number of anaesthesia sessions, endoscopic ultrasonography--endoscopic retrograde cholangio-pancreatography during same anaesthesia session appears to be particularly interesting for the diagnosis and treatment of biliary and pancreatic disorders, in terms of cost, accuracy, morbidity and patient comfort.

[Hepatic involvement associated with ingestion of metapramine]. / Atteinte hépatique associée à la prise de métapramine.

The authors report the cases of 3 women who developed hepatic injury during administration of metapramine, a tricyclic antidepressant introduced in France in 1984. One patient had jaundice and pruritus; the 2 others had loss of weight. Serum alkaline phosphatase and serum transaminase activities were increased in 3 and 2 patients, respectively. Blood hypereosinophilia was found in one patient; erythrocyte sedimentation rate was elevated in 2 patients. The outcome was favorable after drug withdrawal in the 3 patients. Liver biopsy showed centrolobular cholestasis in the 3 patients. There was no rechallenge; in 2 patients, other drugs than metapramine might be implicated in hepatic injury; however, the similarity of these 3 cases suggests that metapramine, like other tricyclic antidepressants, may be responsible for hepatic injury.

[Portal hypertension and neutrocytic ascites in POEMS syndrome]. / Hypertension portale et ascite neutrocytique au cours du syndrome POEMS.

We report a case of portal hypertension and neutrocytic ascites in a 52 year old man with POEMS syndrome. POEMS syndrome is an association of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy and skin changes. Portal hypertension is rare in POEMS syndrome and this is the first time that culture negative neutrocytic ascites has been described with this syndrome.

[Hepatotoxicity of medications]. / Du nouveau dans l'hépatotoxicité des médicaments.

A TIMELY TOPIC: Liver toxicity remains a common problem despite adequate information for physicians and drug watch programs. The number of recent publications reporting severe drug-induced liver disease emphasizes the need for prudence. ACUTE AND CHRONIC HEPATOTOXICITY: Cases of acute drug-induced liver disease have been described for nearly all drug classes: a few examples concern hepatitis subsequent to administration of fluoxetin, acarbose, riluzole, coumarin, or orlistat. Fulminant hepatitis is fortunately an exceptional event but has been described after administration of ketoprofene, nimesulid, and clarithyromycin. Chronic liver disease has also resulted from the use of mesalazine, minocyclin or fibrates. Nevirapin prescribed for HIV infection can cause severe liver disease. OTHER AGENTS: Certain herbal agents, such as chelidoin for example, can cause cholestasis. Certain excipients can also be toxic for the liver. Ecstasy appears to be a frequent cause of sometimes severe liver disease in younger subjects.

[Extensive liver cancer of undetermined origin. Diagnostic procedure]. / Cancer étendu du foie d'origine indéterminée. Conduite diagnostique.

In patients with isolated malignant tumoral hepatomegaly, the investigations performed should aim at excluding a primary carcinoma of the liver and concentrate on the search for primary tumours belonging to 2 main groups: tumours responsive to hormonal treatment or chemotherapy, and obstructive tumours amenable to local palliative measures. In all cases where simple, essentially clinical examinations fail to indicate the cause of the tumoral liver enlargement, further investigations should be based on the histopathological features of the metastases.

Hepatocellular carcinoma--what's new?

The increasing incidence of hepatocellular carcinoma (HCC) has led several countries to standardize and update its management. This review aims at summarizing these evolutions through six questions focusing on diagnosis and treatment. The radiological diagnosis of this tumor has been refined. Besides being hypervascular at the arterial phase, the "washout" in particular at the late phase of injection has become a prominent feature. Although routine ultrasound remains the corner stone of screening, contrast ultrasound has become a very reliable characterization tool as it allows continuous monitoring of the vascular kinetics. Biopsy of the tumor allows identification of conventional or molecular prognosis features, some of which could be used in current practice. The metabolic syndrome is an increasing etiology of HCC and carcinogenesis in this context may not always require the development of formal underlying cirrhosis. Associated (in particular cardiovascular) conditions account for an increased morbidity-mortality following surgery. Liver transplantation is the most effective treatment of early-stage tumors. The limited availability of grafts has led some countries including France to implement new allocation rules that are still evaluated and might need to be refined. Sorafenib is the first medical treatment shown to be effective in the treatment of HCC. This efficacy is however still limited and its indication is therefore restricted to Child-Pugh A, OMS 0-2 patients in whom a potentially curative treatment is contraindicated.