Acute polymyositis during treatment of acute hepatitis C with pegylated interferon alpha-2b

Hepatitis C virus is not cleared after primary infection in 50-85% of subjects exposed to hepatitis C virus. Anti-viral treatment during the early phase of infection significantly enhances the likelihood of a sustained clearance of hepatitis C virus. Although, a variety of autoimmune-related side effects have been observed during interferon therapy for chronic hepatitis, immuno-mediated adverse reactions have not been reported during treatment of acute hepatitis C. We describe the case of a patient who developed acute hepatitis C virus infection and, while receiving pegylated interferon alpha-2b monotherapy, developed a severe polymyositis. This case illustrates the potential risk of autoimmunity by interferon, also for acute hepatitis, and underlines the importance of a prompt diagnosis and a rapid discontinuation of interferon treatment for an improvement of clinical outcomes. \ua9 2005 Editrice Gastroenterologica Italiana S.r.l

The impact of direct acting antivirals on hepatitis C virus disease burden and associated costs in four european countries

Background and Aims We assessed the clinical and economic impact of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in England, Italy, Romania and Spain.Methods An HCV progression Markov model was developed considering DAA eligibility and population data during the years 2015-2019. The period of time to recover the investment in DAAs was calculated as the cost saved by avoiding estimated clinical events for 1000 standardized treated patients. A delayed treatment scenario because of coronavirus disease (COVID-19) was also developed.Results The estimated number of avoided hepatocellular carcinoma, decompensated cirrhosis and liver transplantations over a 20-year time horizon was: 1,057 in England; 1,221 in Italy; 1,211 in Romania; and 1,103 in Spain for patients treated during 2015-2016 and 640 in England; 626 in Italy; 739 in Romania; and 643 in Spain for patients treated during 2017-2019. The cost-savings ranged from euro 45 to euro 275 million. The investment needed to expand access to DAAs in 2015-2019 is estimated to be recovered in 6.5 years in England; 5.4 years in Italy; 6.7 years in Romania; and 4.5 years in Spain. A delay in treatment because of COVID-19 will increase liver mortality in all countries.Conclusion Direct-acting antivirals have significant clinical benefits and can bring substantial cost-savings over the next 20 years, reaching a Break-even point in a short period of time. When pursuing an exit strategy from strict lockdown measures for COVID-19, providing DAAs should remain high on the list of priorities in order to maintain HCV elimination efforts

A mathematical model by route of transmission and fibrosis progression to estimate undiagnosed individuals with HCV in different Italian regions

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

Estimated prevalence of undiagnosed HCV infected individuals in Italy: A mathematical model by route of transmission and fibrosis progression

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