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The clinical outcome of cirrhotic patients with hepatocellular carcinoma (HCC) depends both on the residual liver function and tumor characteristics. However, the relative prognostic weight of these variables is not well defined. The aims of this study were to verify the value of known prognostic factors and to devise a prognostic index more sensitive than the commonly used Okuda stage. A retrospective analysis of the cases of HCC diagnosed at 16 Italian institutions from 1990 to 1992 was performed. Overall survival was the only end point used in the analysis. The Cox model, stratified by locoregional treatment, was used for multivariate analyses. The final model was derived from 10 randomly chosen training samples, and the prognostic validity of the Cancer of the Liver Italian Program (CLIP) score was assessed on the corresponding testing samples. Four hundred thirty-five cases of HCC were collected. As of January 1997, 313 patients (72%) were deceased. Overall median survival was 20 months. At multivariate analysis, independent predictive factors of survival were Child-Pugh stage, tumor morphology, alpha-fetoprotein (AFP), and portal vein thrombosis. A simple scoring system (CLIP score) was thus produced, assigning linear scores (0/1/2) to the covariates. Compared with Okuda stage, the CLIP score, structured as a six-category tool, has a greater discriminant ability, revealing a class of patients with an impressively more favorable prognosis and another class with a relatively shorter life expectancy. The CLIP score is a new prognostic system that accounts for both liver function and tumor characteristics. It is easy to calculate and appears to give more precise information than the Okuda stage.

Hepatitis B virus (HBV), hepatitis D virus (HDV), and hepatitis C virus (HCV) are responsible for the majority of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) cases worldwide. 1-4 Multiple HBV and HDV infection has been extensively investigated in past years and found to be associated with a fulminant course of acute hepatitis, with the more severe forms of chronic liver disease, and with a rapid progression to liver cirrhosis. 5-8 An inhibitory effect exerted by HDV on HBV replication has also been shown. 9 The prevalence of patients with HCV and HBV coinfection has been described as high in geographic areas where a high endemic level of both infections is reported, such as Western Asia and the Mediterranean Basin. 10-14 The interaction between HCV and HBV has so far been poorly investigated. Little is known on the clinical presentation, the natural history, and the response to antiviral treatment of liver diseases associated with HBV and HCV coinfection. However, small pilot studies have prompted the hypothesis that HCV may have an inhibitory effect on HBV replication [15][16][17][18][19] and that multiple HBV and HCV infection may be associated with a more severe clinical presentation. 10,[20][21][22][23][24][25] The interaction between HDV and HCV in hepatitis B surface antigen (HBsAg) chronic carriers has not as yet been investigated.In this article we report the data from an Italian multicenter case-control study with incident cases, performed on a high number of patients with chronic hepatitis from a multiple hepatitis virus infection who were compared with patients with chronic hepatitis caused by a single virus. We investigated the interference between viruses, the clinical impact of a multiple virus infection compared with a single HBV or HCV infection, and tested the hypothesis that anti-HCV-positive/ anti-hepatitis B core antigen (HBc)-positive patients lacking both HBsAg and anti-hepatitis B surface antigen (HBs) might be a subgroup of patients with a multiple HBV and HCV infection. MATERIALS AND METHODSPatients. Seven liver units in different geographic areas of Italy, 1 in the north (Padua), 1 in the center (Rome), 2 in the south (Naples and Bari), 1 in Sardinia (Sassari), and 2 in Sicily (Palermo and Messina), participated in the study. These liver units had participated in numerous multicenter studies on chronic hepatitis in the past 2 decades and had been using similar criteria for the clinical approach and the histologic diagnosis. The investigation was planned as a cross-sectional case-control study with incident cases during a preliminary consensus meeting of the senior investigators from the participating centers.Chronic hepatitis was diagnosed on the basis of high serum transaminase values for at least 6 months.

Objective: The objective of this review was to define a core set of recommendations for the treatment of HCVassociated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. Methods: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. Results: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A lowantigencontent diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. Conclusion: Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.

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