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Background: Although an increase in hepatitis C virus (HCV) prevalence from Northern to Southern Italy has been reported, the burden of asymptomatic individuals in different Italian regions is currently unknown., Methods: A probabilistic approach, including a Markov chain for liver disease progression, was applied to estimate current HCV viraemic burden. The model defined prevalence by geographic area using an estimated annual historical HCV incidence by age, treatment rate, and migration rate from the Italian National database. Viraemic infection by age group was estimated for each region by main HCV transmission routes of individuals for stage F0-F3 (i.e. patients without liver cirrhosis and thus potentially asymptomatic) and F4 (patients with liver cirrhosis, thus potentially symptomatic)., Results: By January 2020, it was estimated that there were 409,184 Italian individuals with HCV (prevalence of 0.68%; 95% CI: 0.54-0.82%), of which 300,171 (0.50%; 95% CI: 0.4-0.6%) were stage F0-F3. Considering all individuals with HCV in stage F0-F3, the geographical distributions (expressed as the proportion of HCV infected individuals by macroarea within the overall estimated number of F0-F3 individuals and prevalence values, expressed as the percentage of individuals with HCV versus the overall number of individuals for each macroarea) were as follows: North 42.1% (0.45%; 95% CI: 0.36-0.55%), Central 24.1% (0.61%; 95% CI: 0.48-0.74%), South 23.2% (0.50%; 95% CI: 0.4-0.61%), and the Isles 10.6% (0.49%; 95% CI: 0.39-0.59%). The population of people who inject drugs accounted for 50.4% of all individuals infected (F0-F3). Undiagnosed individuals (F0-F3) were ~ 15 years younger (⁓ 50 years) compared with patients with stage F4 (⁓ 65 years), with similar age distributions across macroareas. In contrast to what has been reported on HCV epidemiology in Italy, an increasing trend in the proportion of potentially undiagnosed individuals with HCV (absolute number within the F0-F3) from South (23.2%) to North (42.1%) emerged, independent of similar regional prevalence values., Conclusion: This targeted approach, which addresses the specific profile of undiagnosed individuals, is helpful in planning effective elimination strategies by region in Italy and could be a useful methodology for other countries in implementing their elimination plans., (© 2022. The Author(s).)

Background: The universal treatment of diagnosed patients with chronic HCV infection has been widely conducted in Italy since 2017. However, the pool of individuals diagnosed but yet to be treated in Italy has been estimated to end around 2025, leaving a significant proportion of infected individuals undiagnosed/without care. Estimates of this population are currently unknown., Methods: A probabilistic modelling approach was applied to estimate annual historical HCV incident cases by their age-group (0-100 years) distribution from available literature and Italian National database (1952 to October 2019). Viraemic infection rates were modelled on the main infection routes in Italy: people who inject drugs (PWID), tattoos, sexual transmission, glass syringe use, blood transfusion and vertical transmission. Annual liver fibrosis stage transition probabilities were modelled using a Markov model. The number of HCV viraemic asymptomatic (fibrosis stage F0-F3:potentially undiagnosed/unlinked to care) and symptomatic (fibrosis stage F4: potentially linked to care) individuals was estimated., Results: By October 2019, total viraemic HCV individuals in Italy (excluding treated patients since 1992) were estimated to be 410,775 (0.68 % of current population of Italy; 95 % CI: 0.64-0.71%, based on the current Italian population), of which 281,809 (0.47 %; 95 % CI:0.35-0.60%) were fibrosis stage F0-F3. Among different high risk groups in stage F0-F3, the following distribution was estimated: PWID; 52.0 % (95 % CI:37.9-66.6 %), tattoo; 28.8 % (95 % CI:23-32.3 %), sexual transmission; 12.0 % (95 % CI:9.6-13.7 %), glass syringe and transfusion; 6.4 % (95 % CI:2.4-17.8 %), and vertical transmission; 0.7 % (95 % CI:0.4-1.2 %)., Conclusion: Under the assumption that most untreated HCV-infected individuals with stage F0-F3 are undiagnosed, more than 280,000 individuals are undiagnosed and/or unlinked to care in Italy. Marked heterogeneity across the major routes of HCV transmission was estimated. This modelling approach may be a useful tool to characterise the HCV epidemic profile also in other countries, based on country specific epidemiology and HCV main transmission routes., (Copyright © 2021. Published by Elsevier B.V.)

Aim: To describe recent trends in hospital admission rates for alcoholic liver disease (ALD) in the Veneto region of Italy., Methods: This retrospective cohort study is based on anonymous hospital discharge records (HDRs) for 2000-2017 from all public and accredited private hospitals operating within the context of the Regional (Veneto) Health Services that are conserved in National/Regional database. It examined the HDR's of all the hospitalizations of the residents of the Veneto region that were registered under an ALD diagnosis. These were classified under three subheadings: acute alcoholic hepatitis Alcoholic liver cirrhosis and 'other ALD'., Results: During 2000-2017, 30,089 hospital admissions (out of a total regional population of 4,900,000) were registered for ALD. Hospitalization stratified by age showed that the percentage attributable to acute alcoholic hepatitis is higher in younger age groups: 42% in 15-24-year-old (odds ratios (ORs): 14.74; CI95%: 7-30.86; P < 0.000) and 15% in the 25-44-year-old (OR: 3.51; CI95%: 3.12-3.94; P < 0.000). A longitudinal analysis of hospitalization patterns showed a 7% increase in average age in both sexes (from 58.8 ± 9.2 to 62.4 ± 9.7) and a substantial decrease (63.5%) in standardized hospitalization rates (HRs, χ2 trend: 4099.827; P < 0.000) and a smaller decrease (47%) in standardized mortality rates (χ2 trend: 89.563; P < 0.000)., Conclusions: The fall in the overall ALD-related HR in the Veneto region can be explained by a decrease in population alcohol consumption. Increase in the HRs for acute alcoholic hepatitis in the age group 15-44 suggests an ongoing need for strategies to prevent alcohol abuse by young people., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Objective: Screening for HBV among groups at risk, such as migrant populations, has proved to be a cost-effective strategy. With a view to advising local policy-makers, the cost-consequences of HBV screening was assessed using a modeling approach., Methods: This cost-consequence analysis of an HBV screening strategy was conducted in a cohort of adult migrants in the province of Padua, northern Italy., Results: The population targeted for screening consisted of 65 405 migrants, among whom the weighted rate for the prevalence of HBV was 0.04972, with 3251 people infected. Over a period of 5 years, the screening strategy prevented 565 cases/year of chronic hepatitis, 141 of compensated cirrhosis, 9 of decompensated cirrhosis, 14 hepatocellular carcinomas and 12 deaths. The above data revealed that the incremental cost of the screening strategy compared to no screening strategy was € 7 974 959 over the five year period. The cost per life saved amounted to € 676 709., Conclusions: The present study provides useful information to policy-makers at local and regional levels.

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Pegylated interferon (PEG-IFN) and ribavirin is the most effective treatment for chronic hepatitis C virus (HCV) hepatitis, but the rate of sustained virological response (SVR) remains approximately 50%, and 15-20% of all treated patients have a virological relapse after completing the treatment. Studies on the SVR have failed to discriminate between non-responders and relapsers., Aims: To identify the risk factors for relapse among patients with an end-of-treatment response (ETR)., Methods: We retrospectively analyzed 281 patients consecutively treated with PEG-IFN and ribavirin with a follow-up period of at least 24 weeks. The baseline details collected on each patient included demographic data, histological features, and biochemical profiles., Results: Forty-six patients (16.4%) relapsed during the first 6 months of follow-up after discontinuing the therapy. Relapser patients were significantly older, had more steatosis, fibrosis, and showed significantly lower rapid virological response (RVR) rates compared with SVR patients. By logistic regression analysis, only the absence of RVR was found to be significantly associated with relapses in both subgroups of patients with genotypes 1 and 4 (p < 0.004) and those with genotypes 2 and 3 (p < 0.006). Severe fibrosis was also predictive of relapsing disease, but only for genotypes 2 and 3 patients (p < 0.003). During the treatment, serum HCV-RNA decreased more rapidly in patients with SVR compared to non-responder and relapser patients (p < 0.001). Interestingly, relapser patients exhibited an intermediate serum HCV-RNA decay during the first 4 weeks of therapy., Conclusion: Among HCV patients treated with PEG-IFN and ribavirin, the absence of RVR was the most important independent predictor of relapse, independent of the HCV genotype. In the subgroup of genotypes 2 and 3 patients, the severity of fibrosis was also an important factor associated with the relapse rate.

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.

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.

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.

Hepatitis delta virus (HDV) was responsible for a high proportion of cases of acute and chronic liver disease in Southern Europe during the 1970s. Some data suggest that by the 1990s HDV circulation had substantially declined. We have assessed the prevalence of HDV infection and its clinical impact in 834 Italian hepatitis B surface antigen (HBsAg) carriers in 1997. Anti-HDV antibodies were sought in all consecutive chronic HBsAg carriers observed in 14 referral liver units throughout Italy. Risk factors for anti-HDV positivity were evaluated. Anti-HDV antibodies were found in 69 of 834 (8.3%) HBsAg-positive patients. Cohabitation with an anti-HDV-positive subject, intravenous drug addiction, residence in the South of the country, and the presence of cirrhosis were independently associated with the presence of anti-HDV antibodies. The overall prevalence of anti-HDV antibodies was lower than those observed in 2 multicenter surveys performed in 1987 and 1992 (23% and 14%, respectively). By 1997, the percentage of anti-HDV-positive subjects had sharply decreased in the 30 to 50 years age group, whereas it was almost unchanged in subjects over 50 years of age. The highest prevalence of anti-HDV antibodies (11.7%) was found in patients with cirrhosis. This prevalence was as high as 40% in the 1987 study. The circulation of HDV sharply decreased in Italy, by 1.5% per year, from 1987 to 1997. This decrease resulted mainly from the reduction in chronic HDV infections in the young, for whom high morbidity and mortality rates were recorded in the past. The results anticipate the almost complete control of HDV infection in the near future.

Background: Cirrhosis of viral etiology due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a risk factor for hepatocellular carcinoma (HCC). The current study evaluated the rate of incidence of HCC in patients with compensated cirrhosis of viral etiology., Methods: Two hundred fifty-nine cirrhotic patients (66 hepatitis B surface antigen [HBsAg] positive, 166 HCV positive, and 27 HBsAg/HCV positive) were longitudinally examined every 6 months by serum alpha-fetoprotein test and liver ultrasonography. The rates of incidence of HCC were calculated by the person-years method. The Kaplan-Meier method was used to estimate the cumulative probability of HCC development. Differences in survival time were evaluated by a log rank test. Independent predictors of HCC development were estimated by Cox proportional hazard regression analysis., Results: During a mean follow-up of 64.5 months, HCC developed in 51 (19.7%) patients: in 34 of 166 HCV positive subjects (20.5%) (mean follow-up, 66.3 months), in 6 of 66 of those HBsAg positive (9.1%) (mean follow-up, 55.06 months), and in 11 of 27 of those with dual HBsAg/HCV infection (40.7%) (mean follow-up, 76.4 months). The rate of incidence of HCC per 100 person-years of follow-up was 3.7 in HCV positive subjects, 2.0 in those HBsAg positive, and 6.4 in those with dual infection. Cumulative HCC appearance rates in HBsAg positive, HCV positive, and HBsAg/HCV positive subgroups were 10%, 21%, and 23% at 5 years, 16%, 28%, and 45% at 10 years, and 16%, 40%, and 55% at 13 years, respectively. Multivariate analysis indicated that age >50 years (hazard risk [HR], 4.5; 95% confidence interval [CI] = 2.1-9.4), male gender (HR, 2.8; 95% CI = 1.1-5.3), and HBsAg/HCV coinfection (HR, 2.3; 95% CI = 1.1-4.6) were independent predictors of HCC development., Conclusions: These findings confirm that male gender and more advanced age (>50 years) are risk factors for HCC in patients with cirrhosis. Furthermore, the data indicate that subjects with dual HBsAg/HCV infection are at highest risk for HCC. Surveillance programs for early detection of HCC should focus especially on these patients.

Rationale: Because of its antifibrotic and anti-inflammatory effects, colchicine has been proposed as a treatment for liver disease. Early in vitro studies have demonstrated that colchicine blocks mitosis in the metaphase and inhibits DNA synthesis., Aim: A pilot study of hepatitis B virus (HBV)-related/HBV-DNA+ve chronic liver disease., Patients: Nine biopsy-proven chronic hepatitis patients (three with cirrhosis) entered the study. Two of them were HBeAg+ve and seven were antiHBe+. All patients were HBV-DNA+ve/antiHBc IgM+ve (index values of anti-HBc IgM ranged from 0.370 to 1.200). All of them had a major contraindication to interferon therapy or refused antiviral treatment. The known persistence of positive HBsAg ranged from 2 to 21 years., Methods: After informed consent, the patients received 1 mg colchicine a day orally for 5 days-a-week over 6 months. Testing for liver enzymes and viral markers was performed at the baseline and after 3 and 6 months., Results: None of the patients experienced side-effects during the treatment. The two HBeAg+ve patients seroconverted to anti-HBe with a normalization of AST/ALT during therapy. Among the seven antiHBe+ve patients, four had a complete normalization of transaminases (one patient cleared the HBsAg with seroconversion to anti-HBs). Six of the nine patients were HBV-DNA-ve at the end of therapy and were still negative after 12 months of follow-up., Conclusion: These preliminary results suggest that colchicine might have an antiviral activity in HBV-DNA+ve chronic liver disease, and it could be regarded as an alternative therapy to interferon.

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.