Radiofrequency ablation versus laser ablation for the treatment of small hepatocellular carcinoma in cirrhosis: a randomized trial.

BACKGROUND AND AIM: In patients with cirrhosis and small hepatocellular carcinoma (HCC), thermal ablation is currently recognized as an effective local treatment. Among thermal procedures, radiofrequency ablation (RFA) is the most diffusely used and is the standard against which any new treatment should be compared. In retrospective studies, laser ablation (LA) resulted as safe and effective as RFA. Therefore, we performed a non-inferiority randomized trial comparing RFA with LA in patients with cirrhosis and HCC within Milan criteria. METHODS: Overall, 140 patients with 157 HCC nodules were randomly assigned to receive RFA or LA. The primary end-point was the proportion of complete tumor ablation (CTA). Secondary end-points were time to local progression (TTLP) and overall survival (OS). RESULTS: Per patient CTA rates after RFA and LA were 97.4% (95% CI, 91.0-99.3) and 95.7% (88.1-98.5), respectively (difference = 1.4%, 95% CI from -6.0% to + 9.0%). Per nodule CTA rates for RFA and LA were 97.4% (91.0-99.3) and 96.3% (89.6-98.7), respectively (difference = 1.1%, from -5.7% to + 8.1%). The mean TTLP was comparable between RFA group (42.0 months; 95% CI, 36.83-47.3) and LA group (46.7 months; 95% CI, 41.5-51.9) (P = .591). The mean OS was 42 months in both groups and survival probability at 1 and 3 years was 94% and 89% in RFA group, and 94% and 80% in LA group. CONCLUSION: LA resulted not inferior to RFA in inducing the CTA of HCC nodules and therefore it should be considered as an evaluable alternative for thermal ablation of small HCC in cirrhotic patients.

Sorafenib off-target effects predict outcomes in patients treated for hepatocellular carcinoma.

AIM: Sorafenib is the standard of care in advanced hepatocellular carcinoma. This study was aimed to identify clinical parameters that may predict survival in these patients. MATERIALS & METHODS: In this observational study, a training (226 patients) and validation cohorts (54 patients) were analyzed for evaluating pretreatment and on-treatment parameters. RESULTS: At multivariate analysis, only on-treatment variables (skin toxicity, diarrhea and arterial hypertension - sorafenib off-target effects), alphafetoprotein and radiological responses predicted survival. Using the occurrence of off-target effects, a prognostic index able to distinguish three groups of patients with different survival was constructed and externally validated. CONCLUSION: In hepatocellular carcinoma patients, on-treatment variables are the best predictors of survival. Among these, sorafenib off-target effects may be the most useful indicators for prognostication in field practice.

Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection.

BACKGROUND & AIMS: Patients with chronic hepatitis C virus (HCV) infection are frequently treated with a combination of pegylated interferon (peginterferon) and ribavirin. This study compared the efficacy and safety of peginterferon alfa-2a and peginterferon alfa-2b, each in combination with ribavirin. METHODS: A total of 320 consecutive, treatment-naive, HCV RNA-positive patients with chronic hepatitis were randomly assigned to once-weekly peginterferon alfa-2a (180 microg, group A) or peginterferon alfa-2b (1.5 microg/kg, group B) plus ribavirin 1000 mg/day (body weight <75 kg) or 1200 mg/day (body weight >or=75 kg) for 48 weeks (genotype 1 or 4) or 24 weeks (genotype 2 or 3). The primary end point was sustained virological response (SVR) by intention-to-treat. RESULTS: More patients in group A than group B achieved an SVR (110/160 [68.8%] vs 87/160 [54.4%]; P = .008). Higher SVR rates were obtained in group A than group B among patients with genotype 1/4 (51/93 [54.8%] vs 37/93 [39.8%]; P = .04), with genotype 2/3 (59/67 [88.1%] vs 50/67 [74.6%]; P = .046), without cirrhosis (96/127 [75.6%] vs 75/134 [55.9%]; P = .005), and with baseline levels HCV RNA >500,000 IU/mL (58/84 [69%] vs 43/93 [46.2%]; P = .002). SVR rates in groups A and B were not statistically different among patients with baseline HCV RNA

Effect of alcohol, cigarette smoking, and diabetes on occurrence of hepatocellular carcinoma in patients with transfusion-acquired hepatitis C virus infection who develop cirrhosis.

AIM: Alcohol drinking, cigarette smoking, and diabetes have been claimed as risk factors for hepatocellular carcinoma in case-control studies. The aim of this study was to define the impact of these risk factors on the development of hepatocellular carcinoma in hepatitis C virus-related liver cirrhosis. METHODS: A historical cohort of 138 patients with posttransfusion hepatitis C virus-related cirrhosis was selected by reviewing all files of patients referred to our liver unit. Sixty-three of them (46%) developed hepatocellular carcinoma. RESULTS: At univariate analysis, risk factors for hepatocellular carcinoma were observed in patients aged above 59 years [P=0.004; relative risk (RR): 2.08, 95% confidence interval (CI): 1.19-3.68], male sex (P<0.001; RR: 2.48, 95% CI: 1.59-3.87), habit of alcohol drinking (P=0.001; RR: 1.89, 95% CI: 1.24-2.88), and duration of alcohol consumption of more than 30 years (P=0.02; RR: 2.08, 95% CI: 0.98-4.40). At Cox regression analysis, only male sex was an independent predictive factor (beta=0.86; P=0.002; hazard ratio=2.4, 95% CI: 1.3-4.1). CONCLUSION: Diabetes, smoking, and alcohol drinking were not independently related to the risk of developing hepatocellular carcinoma in hepatitis C virus-related cirrhosis.

Prognostic value of quantitative liver function tests in viral cirrhosis: a prospective study.

BACKGROUND AND AIMS: Widespread application of quantitative liver function tests as a prognostic tool is controversial. In this study we assessed the predictivity of serial evaluations of galactose elimination capacity (GEC) and the monoethylglycinexylidide (MEGX) test on survival in viral cirrhosis, and secondarily we compared these tests with Child-Turcotte-Pugh (CTP) and Model for End Stage Liver Disease (MELD) scores. METHODS: In a cohort of 35 patients with viral cirrhosis, GEC and MEGX were evaluated every 6 months for 24 months and compared with CTP and MELD scores at the same time intervals. The end points were patient death or liver transplantation. RESULTS: Statistically significant differences between dead/transplanted patients and survivors were found for basal values of GEC, MEGX, CTP and MELD. Receiver-operating characteristics curves of CTP and MELD scores showed a higher prognostic accuracy than GEC and MEGX. On multivariate analysis, neither GEC nor MEGX were independent predictors of survival. Repeated-measures analysis of GEC and MEGX did not increase the prognostic accuracy of these tests and did not add useful prognostic information on patient outcome during the following 6 months. CONCLUSIONS: Our data suggest that neither single nor repeated determinations of GEC and MEGX are superior to CTP and MELD scores in predicting prognosis of patients with viral cirrhosis.

Impact of age on toxicity and efficacy of sorafenib-targeted therapy in cirrhotic patients with hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide and the proportion of older patients with HCC is expected to steadily rise in the next years. Sorafenib is the standard of care for patients with advanced HCC but there is a lack of detailed data on how older patients with cirrhosis tolerate this drug. Therefore, we aimed to evaluate the impact of age on the effects of sorafenib-targeted therapy in patients with HCC and cirrhosis. We analyzed a consecutive cohort of HCC patients not eligible for surgery or locoregional treatment, with Child-Pugh score ≤ 7, and an Eastern Cooperative Oncology Group performance status of 0-1, treated with sorafenib. Clinical outcomes and treatment-related adverse events (AEs) were compared between younger (< 70 years) and older (≥ 70 years) patients. Overall, 150 patients, 90 in the younger (median age 60 years) and 60 in the older (median age 72 years) group, were evaluated. Treatment duration was 4 months in both groups. The median time to progression and overall survival were longer in older than in younger group (12 vs. 8 months and 16 vs. 12 months, respectively), although the differences did not reach a statistical significance. Grade 3-4 AEs were more frequently observed in younger than in older group (15.7 vs. 9.2 %, respectively; p = .0146). In field practice, sorafenib treatment in elderly patients with cirrhosis and HCC resulted at least as effective and safe as in younger patients. However, severe AEs occurred more frequently in younger patients.

Splanchnic vein thrombosis and variceal rebleeding in patients with cirrhosis.

OBJECTIVES: Splanchnic vein thrombosis (SVT) affects the short-term prognosis of acute variceal bleeding in cirrhotic patients. This study evaluated whether SVT also affects the rebleeding rate of patients included in a program of secondary prophylaxis after variceal bleeding. PATIENTS AND METHODS: A total of 387 patients with variceal bleeding were included from January 2001 to December 2010. Band ligation was carried out every 3-4 weeks. Follow-up included endoscopy at 1, 3, and every 6 months, Echo-Doppler, and biochemical examination every 6 months. From 2005, patients with SVT received anticoagulation with enoxaparin 200 UI/kg/day for at least 6 months. The therapy was started after variceal eradication. RESULTS: SVT was diagnosed in 41 patients at variceal bleeding, in eight before and in 18 patients during the follow-up. Variceal eradication was achieved in 89.2 and 86.6% in no-SVT and SVT patients. Rebleeding occurred in 9.5 and 11.9% of no-SVT and SVT patients at 12 months. Varices relapsed more frequently in SVT than in no-SVT patients (25.4 vs. 14.67%, P=0.03). The rates of variceal rebleeding and relapse were similar in patients who received or did not receive anticoagulation, but mortality was significantly lower in patients who received anticoagulation. CONCLUSION: SVT favors the relapse of esophageal varices, but rebleeding can be effectively prevented by standard scheduled band ligations. Anticoagulation does not prevent variceal relapse. The improvement in the survival of patients treated with anticoagulation needs to be confirmed in future studies.

Safety and effectiveness of sorafenib in patients with hepatocellular carcinoma in clinical practice.

BACKGROUND: Sorafenib is currently the only approved systemic treatment for hepatocellular carcinoma. AIM: to evaluate safety and effectiveness of sorafenib in the field of practice. METHODS: We report a single-centre experience on 116 advanced hepatocellular carcinoma patients treated with sorafenib between February 2008 and March 2011. Every 4 weeks, adverse events were graded using Common Toxicity Criteria version 3.0, and every 3 months tumour response was assessed according to modified Response Evaluation Criteria in Solid Tumours for hepatocellular carcinoma. RESULTS: Cirrhosis was present in 95.7% of patients (83.6% Child-Pugh A class), hepatitis C was the main etiological factor. Median therapy duration was 3 months and median daily dose was 642 mg. Median time-to-radiological progression in the per-protocol population was 12 months and median overall survival in the intention-to-treat population was 13 months. 91.4% of patients experienced mild adverse events (grade 1 or 2), the most frequent were gastrointestinal and dermatological. Jaundice and bleeding were the main causes of definitive drug discontinuation. 3-month overall disease control rate was 70.6%: stable disease in 37.2%, partial response in 30.8%, and complete response in 2.6% patients. The 3-month radiological response correlated with overall survival. CONCLUSIONS: In daily clinical practice, sorafenib confirmed its safety and efficacy in hepatocellular carcinoma patients.

Sustained virological response to antiviral therapy reduces mortality in HCV reinfection after liver transplantation.

BACKGROUND/AIMS: HCV infection recurs almost in all HCV-positive patients receiving liver transplantation and carries a poor prognosis. Aim of this study was to analyze efficacy and effect on survival of antiviral therapy in this clinical setting. METHODS: Pegylated-interferon alpha-2b and ribavirin were administered at a dose of 1 microg/kg of bwt weekly and 600-800 mg/day. Planned duration of treatment was 24 or 48 weeks according to HCV genotype. Patients who failed to respond at week 24 were considered as non-responders. RESULTS: 61 patients were enrolled. According to intention-to-treat analysis, 44 (72%) patients were considered as treatment failure (31 non-responders, 4 relapsers, 9 dropout). Sustained virological response was achieved in 17 cases (28%). Genotype 2, higher doses of antivirals and absence of histological cirrhosis were predictors of sustained virological response. In the follow up, patients with sustained virological response had a significantly lower mortality compared to patients with treatment failure (chi2=6.9; P<0.01). CONCLUSIONS: Response rate to antiviral therapy in HCV reinfection after liver transplantation is higher if a full dose of antiviral drugs is administered and if treatment starts before histological cirrhosis has developed. Sustained virological response improves patient survival.