S. Lobello

Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study

BACKGROUND/AIMS This study assess prevalence, risk factors, and clinical and virological features of dual hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. METHODS We evaluated 837 hepatitis B surface antigen positive patients, prospectively enrolled in 14 Italian units. RESULTS Anti-HCV was present in 59 cases (7%); age specific prevalences were 4.5% (0-30 years), 4.4% (>30-50) and 14% (>50). Independent predictors of dual infection were age >42 years, history of I.V. drug use (IDU), blood transfusion and residence in the South of the country. The strength of the association with IDU was high, but this exposure accounted for five coinfection cases only. Cirrhosis was present in 107 of the 709 patients with HBV alone (15.1%), in 30 of 69 with hepatitis D virus coinfection (43%) and in 17 of 59 with HCV coinfection (28.8%); a light alcohol use was marginally associated with cirrhosis. Of 36 B/C coinfected patients, 16 (44.4%) had only HBV-DNA in serum, (median age=47.5 years) five (13.9%) had both HBV-DNA and HCV-RNA (age=53), nine (25%) had HCV-RNA alone (age=59) and six (16.7%) tested negative for both. CONCLUSIONS This study depicts the epidemiological and clinical burden of dual HBV/HCV infection in Italy.

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.

Intra-familial transmission of hepatitis B virus in Italy: phylogenetic sequence analysis and amino-acid variation of the core gene

BACKGROUND/AIMS Transmission of hepatitis B virus (HBV) in countries of intermediate endemicity, such as Italy, is thought to be primarily horizontal and, to a lesser extent, vertical. Most chronic carriers therefore become infected in infancy or at a very young age. The index cases in such events have been assumed to come from within the family unit or from sources outside the immediate family, with whom the affected person is in close contact. METHODS We studied a number of Italian families with multiple members chronically infected with HBV. The precore/core region of the virus was amplified from serum derived HBV-DNA, and the sequences subjected to phylogenetic tree analysis. In addition, the extent of amino-acid variation within the core region was correlated to HLA type, determined by allele-specific PCR. RESULTS The phylogenetic tree analysis provided strong evidence of intra-familial transmission of the virus. Analysis of amino-acid substitutions in the core region in relation to HLA class II alleles from members of the same family showed that these substitutions were restricted in siblings with concordant, and more diverse in those with discordant HLA haplotypes. CONCLUSIONS This is consistent with major histocompatibility complex class II mediated selection pressure on the virus.

Fatal hepatic decompensation in a bone marrow transplant recipient with HBV-related cirrhosis following lamivudine withdrawal

Lamivudine is a nucleoside analogue with a potent antiviral activity used as prophylaxis against hepatitis B virus reactivation in patients with chronic HBV infection receiving chemotherapy. No standard guidelines exist, however, for the duration of lamivudine treatment. We report a clinical case of a 56-year-old patient with HBeAg-negative cirrhosis who developed a multiple myeloma. He was treated with lamivudine for 1 year while receiving chemotherapy and a subsequent bone marrow transplant. Complete remission from multiple myeloma was achieved. Four months after lamivudine was withdrawn, he experienced HBV reactivation with jaundice, though no YMDD mutations were detected. The patient rapidly developed fatal decompensation with septicemia and renal failure. In conclusion, this case shows that physicians should avoid discontinuing nucleoside therapy in patients with HBV infection who undergo immunosuppression for concomitant neoplastic conditions.

Interferon treatment in hepatitis B surface antigen‐positive hepatitis B e antibody‐positive chronic hepatitis B: role of hepatitis B core antibody IgM titre in patient selection and treatment monitoring

Chronic hepatitis B infection with the hepatitis B e antigen (HBeAg)‐negative variant is associated with a severe clinical course and a low response rate to interferon (IFN). In an attempt to improve the chances of sustained response to interferon we designed a pilot study, using titres of IgM antibodies to hepatitis B core antigen (HBcAb IgM) to guide treatment initiation. Eighteen adults who were HBeAg‐negative with biopsy‐proven chronic active hepatitis (seven with cirrhosis) entered the study. They were followed‐up bimonthly with routine liver function tests, and HBcAb IgM titres were also determined. Treatment (lymphoblastoid IFN 5 million units (MU) m–2 three times weekly for 6 months) was started when the HBcAb IgM titre was increasing. Fifteen (83.3%) patients had normal alanine aminotransferase (ALT) levels and undetectable HBV DNA at the end of treatment. HBcAb IgM decreased in all responders. We observed a relapse in four patients (three with cirrhosis), in the first year after treatment, with an increase in ALT, HBV DNA and titre of HBcAb IgM. Eleven patients (61.1%) had a sustained response and eight of these 11 patients were followed‐up for more than 18 months; two responders cleared hepatitis B surface antigen (HBsAg). Hence, the rate of sustained response to IFN in HBeAb‐positive patients with chronic hepatitis is improved if treatment is started when HBcAb IgM levels are increasing.

S1839 Effect of Silybin in Patients With Chronic Hepatitis: Preliminary Results of a Multicentre Randomized Controlled Trial vs Placebo

A S L D A b st ra ct s levels were significantly decreased in UDCA group compared to control group. Microarray analysis revealed that gene expression of glutathione S-transferase (GST) ismarkedly increased in UDCA group compared to control group. Since Nrf2-activated genes such as glutamatecysteine ligase, catalytic subunit (Gclc), heme oxygenase 1 (HO-1) exert antioxidant effects, we next investigated mRNA expression levels of these genes by quantitative real-time PCR. Quantitative real-time PCR revealed the elevated expression of both Gclc and HO-1 in UDCA group. Conclusion : UDCA administration blocks progression of liver inflammation in NASH by inducing Nrf2-regulated antioxidant gene expression and reducing serum ROS levels.

PWE-074 Hospitality discharge for alcohol related problems in north of italy: a sixteen – years period

Background and aims WHO (2014) estimates a remarkable decline in per capita pure alcohol consumption in Italy, dropped from 18.1 to 7.1 lt in the period 1970–2013. Despite this, Italian Report on Alcohol 2016 showed an increase in drinking outside meals and a rise in consumption and binge drinking among young people (18–24, 14–17), particularly in males. The impact of these drinking styles on hospitalisation is still under-researched. This study aims to evaluate the trends of hospitality discharge for alcohol-related liver disease in the period 2000–2016 in Veneto Region in North Eastern Italy (4.8 million inhabitants). Method Retrospective cohort analysis based on Veneto Region anonymous computerised database of hospital discharges between 2000 and 2016. All Veneto residents discharge records with principal diagnosis of alcohol-related liver disease (cod. ICD9-CM: 571.0, 571.1, 571.2, 571.3) were included in the study. The principal diagnosis was chosen as it is considered the primary reason for hospital admission. Standardised Hospitalisation Ratio (SHR) per five-year age group (ref. pop. Veneto 2008) was calculated and expressed per 100.000 population. Results Over the period 2000–2016, 28.968 hospital admissions for alcohol-related diseases were recorded. Most part of subjects were males (74%) with a SHR more than double compared to females (53.3 vs. 18; OR:2.96; CI 95%:2.89–3.04 p<0,05). The longitudinal analysis of the hospitalisation trend shows a 7% increase on average age in both sexes (from 58.8±9,2 to 62.6±9,6) and a substantial decrease of 66% in SHR (X2 trend: 3933,326). In the last year of observation SHR tends to 19.5, and the greater risk for males is confirmed (30.2 vs. 8.8; OR:3.51; CI 95%:3.05–4.10; p<0.05). Considering the age groups, the highest decline in SHR can be found in the ranges 45–64 (from 69.2 to 34.1) and >65 (from 69.3 to 26.8). Interestingly, SHR shows a slightly rising trend in the group 25–44 betweeen 2013 and 2016 (p<0.05). Conclusion In Veneto Region, the reduction in alcohol intake over the last 30 years has lead to a marked decrease in hospitalisation for alcohol-related diseases. However, the changes in drinking styles occurred in the age range 25–44 may explain the upward SHR trend between 2013 and 2016. Thus, in the next few years it is likely to expect an increase in hospitalisation in this age group. Public Health strategies are needed to address the new styles of alcohol consumption, especially in young people.Abstract PWE-074 Figure 1

Sofosbuvir plus ribavirin for difficult to treat HCV-2: improved efficacy with extended treatment duration.

♦ Denotes AASLD Presidential Poster of Distinction 1 A multi-center study to define sarcopenia in patients with end-stage liver disease: From the Fitness, Life Enhancement, and Exercise in Liver Transplantation (FLEXIT) Consortium Elizabeth J. Carey1, Jennifer C. Lai2, Connie W. Wang2, Srinivasan Dasarathy3, Iryna Lobach2, Aldo J. Montano-Loza4, Michael A. Dunn5; 1Mayo Clinic Arizona, Phoenix, AZ; 2University of California San Francisco, San Francisco, CA; 3Cleveland Clinic, Cleveland, OH; 4University of Alberta, Alberta, AB, Canada; 5University of Pittsburgh, Pittsburgh, PA

Efficacy and safety of oral DAAs HCV therapy in the elderly

♦ Denotes AASLD Presidential Poster of Distinction 1 A multi-center study to define sarcopenia in patients with end-stage liver disease: From the Fitness, Life Enhancement, and Exercise in Liver Transplantation (FLEXIT) Consortium Elizabeth J. Carey1, Jennifer C. Lai2, Connie W. Wang2, Srinivasan Dasarathy3, Iryna Lobach2, Aldo J. Montano-Loza4, Michael A. Dunn5; 1Mayo Clinic Arizona, Phoenix, AZ; 2University of California San Francisco, San Francisco, CA; 3Cleveland Clinic, Cleveland, OH; 4University of Alberta, Alberta, AB, Canada; 5University of Pittsburgh, Pittsburgh, PA

YIS-4SOCIAL AND HEALTH INTEGRATED APPROACH TO ALCOHOL USE DISORDERS (AUDs) AND ALCOHOL ABUSE/DEPENDENCE: AN ITALIAN EXPERIENCE IN A SPECIALIST SERVICE

Background and Aims. In Italy, per-capita consumption is low (6.9 lt in 2009), with an increase in binge drinking, but there are not results on treatment outcomes. This study aims to evaluate the efficacy of treatment of AUDs and alcohol abuse/dependence based on integrated social-health approach to individual needs. Material …