Caterina Furlan

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM To evaluate if indolent B cell-non Hodgkins lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies. METHODS A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared. RESULTS Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related B-NHL treated with only antiviral therapy, achieved a complete response of their onco-haematological disease (55%). Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response (54%). CONCLUSION HCV genotypes and duration of HCV infection differed between B-NHL subtypes. Indolent lymphomas can be managed with antiviral treatment, while DLBCL is not affected by the HCV infection.

Ultrasound evaluation of liver fibrosis: preliminary experience with acoustic structure quantification (ASQ) software.

PurposeThe aim of our study was to assess the diagnostic accuracy of acoustic structure quantification (ASQ) ultrasound software in estimating the degree of hepatic fibrosis compared to Fibroscan and liver biopsy.Materials and methodsSeventy-seven patients with chronic viral hepatitis B and C underwent standard ultrasound examination, ASQ, Fibroscan and liver biopsy. ASQ analysis was conducted by placing a single region of interest (ROI) on each image captured, and calculating mode, average and standard deviation. The sonographic technique was developed through a preliminary evaluation of 20 healthy volunteers.ResultsThe area under the receiver operating characteristic (AUROC) curve for the diagnosis of cirrhosis (F≥4) with ASQ was 0.77, whereas for the diagnosis of any degree of fibrosis (F≥1) it was 0.71. The AUROC for the diagnosis of cirrhosis (F≥4) with Fibroscan was 0.98, while for the diagnosis of any degree of fibrosis (F≥1) it was 0.94. The difference between the AUROC was statistically significant (p<0.05).ConclusionsASQ is a promising new ultrasound software programme which offers encouraging results in the diagnosis of both liver cirrhosis (F=4) and fibrosis (F≥1). However, to date it has not attained the same level of diagnostic performance as Fibroscan.RiassuntoObiettivoScopo del nostro studio è stato valutare l’accuratezza diagnostica del software ecografico acoustic structure quantification (ASQ) nella stima del grado di fibrosi epatica, ponendolo a confronto con Fibroscan e con la biopsia epatica.Materiali e metodiSono stati arruolati 77 pazienti affetti da epatite virale cronica B e C, che sono stati sottoposti ad esame ecografico standard, ASQ, Fibroscan e biopsia epatica. L’analisi ASQ è stata condotta posizionando una singola regione di interesse (ROI) per immagine, su tutte le immagini acquisite, calcolando moda, media e deviazione standard. La tecnica ecografica è stata messa a punto attraverso una valutazione preliminare su 20 volontari sani.RisultatiL’area sottesa alla curva receiver operating characteristic (AUROC) per diagnosi di cirrosi (F≥4) con ASQ è risultata 0,77 mentre per diagnosi di fibrosi di qualsiasi grado (F≥1) è stata 0,71. L’AUROC per la diagnosi di cirrosi (F≥4) con Fibroscan è risultata 0,98 mentre per la diagnosi di fibrosi di qualsiasi grado (F≥1) è stata 0,94. La differenza tra le due AUROC è risultata statisticamente significativa (p<0,05).ConclusioniL’ASQ è un nuovo e promettente software ecografico che presenta risultati incoraggianti sia nella diagnosi di cirrosi epatica (F=4) che nella diagnosi di fibrosi (F≥1). Attualmente tuttavia ancora non sono state raggiunte le performance diagnostiche del Fibroscan.

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.

HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b.

BackgroundThe impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin.MethodsFor 48 weeks, 388 “naïve”genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000–1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR).ResultsThe rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR.ConclusionDual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance.Trial registrationClinicalTrials.gov Identifier: NCT01342003

Epidemiological and clinical scenario of chronic liver diseases in Italy: Data from a multicenter nationwide survey.

BACKGROUND The last Italian prevalence survey on chronic liver diseases (CLD) was performed in 2001. The present study evaluated the changes occurring over thirteen years. METHODS We enrolled 2,557 CLD consecutive patients in 16 Italian liver units in 2014. RESULTS HBV etiology accounted for 513 (20.2%) cases, alone in 439 and associated with HCV and/or alcohol abuse in 74. Of these 513, 11.9% were anti-HDV-positive and 7.2% HBeAg-positive. HCV alone was responsible for 50.3% of CLD and with alcohol abuse for 5.9%. HCV RNA was detected in 64.0% of the anti-HCV-positive patients tested. HCV genotyping, performed for 899 patients, showed genotype-1a, 1b, 2, 3, 4 and 5 respectively in 16.5%, 45.5%, 15.4%, 8.2%, 15.1% and 0.2%. Alcohol abuse alone was responsible for 6.4% of cases and NAFLD/NASH for 6.3%. Liver cirrhosis (p<0.001) and HCC (p<0.001) were more frequent in alcoholic than viral etiologies. HCV and alcohol etiologies were more frequent in 2001 than 2014 (from 69.9% to 59.9% and from 23.0% to 12.3%, respectively). HBV showed a similar impact. In all etiologies, the 2001 CLD cases were 10 years younger and with a significantly lower rate of cirrhosis than the 2014 cases. CONCLUSION The changes in HCV, HBV and alcohol etiologies may help apply more appropriate healthcare strategies.

Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Background and aims Increased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN). Methods sCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls. Results At baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups. Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with high sCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize. Conclusions These results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection.

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).

One course versus two courses of recombinant alpha interferon in chronic C hepatitis

Fifty-five patients with antibodies to HCV and chronic liver disease have been enrolled in the study. Thirty-four patients were treated with recombinant alpha interferon (IFN, 3 MU daily for 10 days followed by 3 MU twice/week for 3 months), and were compared to 21 untreated controls. Alanine aminotransferase (ALT) normalization was observed in a significant proportion of treated patients (52.9%), but 66.6% of them experienced a relapse after discontinuation of the therapy. The evaluation of the early ALT behavior after the 10 days priming with daily IFN administration was useful in predicting the response. The administration of a second IFN course with the same schedule and duration as the first course did not increase the efficacy of the treatment. Increased dosage and/or prolonged administration are probably required.

Boceprevir or telaprevir in hepatitis C virus chronic infection: The Italian real life experience

AIM To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings. METHODS This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL). RESULTS All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.