Massimo De Luca

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 <or=500,000 IU/mL (52/76 [68.4%] vs 44/67 [65.7%]; P = .727) or in patients with cirrhosis (14/33 [42.4%] vs 12/26 [46.1%]; P = .774). CONCLUSIONS In patients with chronic HCV infection, peginterferon alfa-2a plus ribavirin produced a significantly higher SVR rate than peginterferon alfa-2b plus ribavirin.

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.

Mortality Risk According to Different Clinical Characteristics of First Episode of Liver Decompensation in Cirrhotic Patients: A Nationwide, Prospective, 3-Year Follow-Up Study in Italy

OBJECTIVES:The occurrence of decompensation marks a crucial turning point in the course of cirrhosis. The purpose of this study was to assess the risk of mortality according to the clinical characteristics of first decompensation, considering also the impact of acute-on-chronic liver failure (AoCLF).METHODS:We conducted a prospective nationwide inception cohort study in Italy. Decompensation was defined by the presence of ascites, either overt or detected by ultrasonography (UD), gastroesophageal variceal bleeding (GEVB), and hepatic encephalopathy (HE). AoCLF was defined according to the Asian Pacific Association for the Study of the Liver criteria. Multivariable Cox proportional hazards regression was used to analyze the risk of failure (death or orthotopic liver transplantation (OLT)).RESULTS:A total of 490 consecutive cirrhotic patients (314 males, mean age 60.9±12.6 years) fulfilled the study criteria. AoCLF was identified in 59 patients (12.0%). Among the remaining 431 patients, ascites were found in 330 patients (76.6%): in 257 (77.8%) as overt ascites and in 73 (22.2%) as UD ascites. GEVB was observed in 77 patients (17.9%) and HE in 30 patients (7.0%). After a median follow-up of 33 months, 24 patients underwent OLT and 125 died. The cumulative incidence of failure (death or OLT) after 1, 2, and 3 years was, respectively, 28, 53, and 62% in patients with AoCLF; 10, 18, and 25% in patients with UD ascites; 17, 31, and 41% in patients with overt ascites; and 8, 12, and 24% in patients with GEVB (P<0.0001).CONCLUSIONS:AoCLF is responsible for a relevant proportion of first decompensation in cirrhotic patients and is associated with the poorest outcome. Patients with UD ascites do not have a negligible mortality rate and require clinical monitoring similar to that of patients with overt ascites.

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

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.

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 (&bgr;=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.

Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross‐sectional multicenter study

The universal hepatitis B vaccination for infants and 12‐year‐old adolescents (the latter limited to the first 12 years of application) was launched in Italy in 1991. Twenty‐three years later we evaluated the impact of the vaccination campaign on the burden of HBsAg‐positive chronic liver diseases (CLD).

Characteristics of liver cirrhosis in Italy: Evidence for a decreasing role of HCV aetiology ☆

BACKGROUND Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. AIM To assess epidemiological, laboratory and clinical features of liver cirrhosis in Italy in 2014. PATIENTS Out of the 2557 consecutive subjects evaluated in 16 hospitals located throughout Italy in 2014, 832 (32.6%) had liver cirrhosis and were enrolled in this study. RESULTS The mean age of subjects was 60.3years, with a male/female ratio of 1.7; 74.9% of cases had Child A cirrhosis and 17.9% superimposed hepatocellular carcinoma. HCV infection, alone or in combination with other aetiologic agents, was responsible of 58.6% of cases, HBV aetiology accounted for the 17.6% and alcohol abuse for the 16.0%. Compared with virus-related cirrhotic patients, those alcohol-related more frequently showed decompensation (p=0.02). CONCLUSIONS Compared to previous surveys performed in 1992 and in 2001, we observe a statistically significant (p<0.05) decreasing role of both HCV infection and alcohol abuse as aetiologic agents of liver cirrhosis in Italy, explaining, at least in part, the slow, progressive decline of the mortality rate for liver cirrhosis in the last decades in this country (from 34.5 deaths/100,000 inhabitants in1980 to 10.8 in 2012).

Incidence of Side Effects During Therapy with Different Types of Alpha Interferon: A Randomised Controlled Trial Comparing Recombinant Alpha 2b Versus Leukocyte Interferon in the Therapy of Naive Patients with Chronic Hepatitis C

BACKGROUND Alpha interferon (IFN) alone or in combination with Ribavirin (RBV) is the treatment of choice for HCV related chronic liver disease. There are many types of alpha IFN and to date only few reports are available comparing different types of alpha interferon. We run a randomised controlled trial with the aim to compare tolerability and efficacy of two different types of IFN: recombinant alpha 2b interferon (IFN-R) and leukocyte alpha n-3 interferon (IFN-L) at the same dosage of 3 MU subcutaneously thrice weekly for one year. METHODS one hundred sixty eight consecutive anti-HCV positive naive patients, 34 mild chronic active hepatitis (MCH), 81 moderate-severe hepatitis (MSCR) and 53 active cirrhosis (CIRR) that met the inclusion criteria were enrolled into the study. The diagnosis of HCV chronic liver disease was established by liver biopsy performed on patients with abnormal serum alanine aminotransferase (ALT) value for at least one year. HCV serology: all patients were tested for confirmatory test RIBA II, HCV-RNA, and identification of viral genotype. Patients were randomised to receive either IFN-R or IFN-L. Follow-up continued for at least two years after stopping treatment. RESULTS no significant differences were observed between the two groups of treatment as far as the incidence of side effects is concerned. Tolerability was good: only 11 in IFN-R and 8 patients IFN-L group respectively had to stop therapy due to side effects. The two types of IFN showed a comparable efficacy: an end of therapy response was observed in 34% of IFN-R and 30% of IFN-L patients; a sustained response was seen in 16% of IFN-R and in 19% of IFN-L patients. CONCLUSIONS in the treatment of patients with chronic hepatitis C there was no statistically significant difference in tolerability and efficacy between the two IFNs tested.

Mortality from cirrhosis and hepatocellular carcinoma in Western Europe over the last 40 years

Cirrhosis (LC) and hepatocellular carcinoma (HCC) are highly prevalent in Europe, with accompanying high mortality rates and social costs. As epidemiological data on these diseases are scarce, age‐standardized death rate (ASDR) can serve as an indirect assessment of their burden.

Etiological factors of chronic hepatitis in Italy: a 2014 national survey

Background The last Italian prevalence survey on chronic hepatitis (CH) conducted in 2001 showed that the hepatitis C virus (HCV) was the main agent associated with CH. Aim The aim of this study was to evaluate epidemiological changes in CH occurring after 13 years. Patients and methods Enrollment of 1392 CH consecutive patients referred to 16 Italian liver units in 2014 scattered all over the country (four in the North, four in the Center, four in the South, and four in the Islands) was performed. Results The mean age of the patients was 58.3 years, with a sex ratio (male/female) of 1.5. HCV infection (also with other etiologies) continues to be the most prevalent etiology (58.1%). However, this prevalence was lower (P<0.01) than the corresponding figure (76.5%) for 2001. The proportion of hepatitis B virus-related cases almost doubled over time from 12.2% in 2001 to 22.5% in 2014 (P<0.01), most probably biased because of the distribution of entecavir and tenofovir free of charge at outpatient hospital clinics after 2001. Patients reporting risky alcohol intake (also with other etiologies) accounted for 12.4% of cases, a figure lower than that reported in 2001: 19.2% (P<0.01). The proportion of nonalcoholic fatty liver disease cases nearly doubled over time (3.6% in 2001 and 6.2% in 2014; P<0.05), reflecting the greater attention over time devoted to this syndrome. Conclusion The decreasing role of HCV infection as an etiologic factor of CH in Italy is good news considering the high cost of the directly acting antiviral agents for HCV eradication. Metabolic factors warrant greater attention in the near future.