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Background: Women represent less than 5% of the incarcerated population in Italy, with very limited data on HCV infection. Higher HCV seroprevalence and active infection rates have been described among incarcerated females in available studies. Our aim is to compare the prevalence and cascade of care of HCV between male and female populations in Italian penitentiaries., Methods: We conducted a multicentre, retrospective study comparing HCV seroprevalence, active infections, treatment, and SVR rates between female (Group A) and male (Group B) populations in Italian prison settings., Results: No significant differences were found between the two groups regarding PWIDs ( p = 0.16), nor in people living with HIV ( p = 0.35) or HBV co-infection ( p = 0.36). HCV seroprevalence was higher in Group A ( p = 0.002). There was no statistically significant difference between the two groups regarding active infections ( p = 0.41). Both groups showed a low level of fibrosis, and the dominant genotype was 3a. Almost all patients underwent antiviral treatment. All treated patients achieved SVR12., Conclusions: Our findings illuminate the importance of recognizing and addressing gender differences in HCV seroprevalence within penitentiary settings. Moving forward, addressing the unique needs of incarcerated females and optimizing HCV care for all incarcerated individuals are essential steps in the pursuit of achieving HCV micro-elimination goals.

Introduction: Migration has a direct influence on sexual health. Differences both in sexual networks and the risk of sexually transmitted diseases (STDs) between racial or ethnic minorities and the native population have been described in the literature., Methodology: We collected data on medical history, physical examination, and human immunodeficiency virus (HIV)/STDs tests. Screenings were proposed basing on Centers for Disease Control (CDC) 2018 guidelines on STDs. Patients underwent peer-to-peer counselling before screening., Results: We included data of 391 patients (both outpatients and migrants living in facility centers). The median age was 30 (range 24-38) years, and the majority were male (198/391; 50.6%). Among them, 389 (99.4%) were counselled, and 371 (94.8%) accepted the screening. We found 155 (41.7%) HBsAg/Anti-HBc positive tests, 4 (1%) HIV positive screenings, 1 (0.2%) hepatitis C virus (HCV) infection, 47 (12%) genital/perianal warts, 29 (2.3%) cases of syphilis, and 13 (3.3%) molluscum contagiosum., Conclusions: Migrants have high-risk sexual behavior. Despite this, they may have a low perception of risk and healthcare needs. An approach based on quick tests was demonstrated to be useful in increasing the screening acceptance. However, the retainment in care was low, as in previous studies. Access to HIV/STDs screening and treatment should be implemented. The development of specific retainment in care pathways is still needed to reduce the lack of follow-up., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Vito Fiore, Valentina Manca, Andrea De Vito, Agnese Colpani, Ivana Maida, Giordano Madeddu, Sergio Babudieri.)

Italy has had the highest prevalence of hepatitis C virus (HCV) infection and mortality from HCV-related liver cancer in Europe. Although direct-acting antivirals (DAA) were initially restricted to persons with advanced fibrosis, their use has since been extended to all infected individuals; more than 244 000 persons have been treated to date. HCV liver-related mortality is expected to decline by 75% by 2030, achieving the World Health Organization target for mortality. However, Italy risks failing to meet the overall goal of eliminating HCV infection by 2030. In this light, €71.5 million have been allocated for screening initially specific target populations (persons who inject drugs, prison inmates, and the 1969-1989 birth cohort). Herein, we outline the challenges and recommendations for how to move Italy toward HCV elimination, including expanding screening programs in other populations, increasing awareness through strategic communication, sustaining DAA access, and tailoring care models to meet the needs of key populations., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Hepatitis C virus (HCV) infection is more frequent among incarcerated people than in general population. In the DAAs era, the short schedules and the low risk of adverse reactions, increased the number of HCV treatments. However, the most part of literature reports lack of incarcerated women inclusion in studies on field. Our aim is to assess the screening execution, HCV prevalence, and DAAs treatment among incarcerated women. A focused insight on quick vs standard diagnosis and staging approach will be also provided., Methods: Incarcerated women from 4 Italian regions' penitentiary institutes were included. HCV screening was executed with HCV saliva test (QuickOral Test ® ) or phlebotomy. Stage of liver fibrosis was evaluated with FIB-4 value or fibroscan ® , based on physicians' decision. Treatment prescription followed national protocols., Results: We included 156 women, 89 (57%) were Italian, mean age was 41 ± 10 years, and 28 (17.9%) were people who inject drugs (PWIDs). Overall, the HCV seroprevalence was 20.5%. Being PWID and on opioid substitution therapy (OST) were significantly associated with serological status (p-value < 0.001). Of them, the 75.5% of patients had active infection, the most frequent genotype was 3a (50%). Among them, 4 (16.6%) and 6 (25%) had psychosis or alcohol abuse history. The 62.5%, 25% and 12.5% had low, intermediate, and advanced fibrosis, respectively. Out of the 24 HCV-RNA positive patients, the 75% underwent to DAAs treatment. The sustained virological response (SVR12) was achieved in 88.8% of cases. When evaluating the influence of quick diagnosis and staging methods vs standard phlebotomy and fibroscan ® on SVR12, FIB-4 use showed higher performance for retainment in treatment during prison staying (p = 0.015), while the use of quick saliva test had no influence on the outcome (p = 0.22)., Conclusion: HCV seroprevalence and active infections are very high among incarcerated women. More tailored interventions should be focused on HCV diagnosis and treatment in female prison population. The use of quick staging methods (FIB-4) is useful to increase SVR12 achievement without delays caused by the fibroscan ® awaiting., (© 2022. The Author(s).)

Although Italy has been on track for Hepatitis C Virus (HCV) elimination since 2019, it fell off track due to the decrease in the number of treated patients. HCV elimination in Italy will be possible if immediate action is taken. A health policy was implemented beginning in 2021, consisting of screening among key populations and birth cohorts (1969-1989), estimated to have a high prevalence of undiagnosed individuals. The active screening requires regional governance that manages the processes' complexity integrating a well-organized network between territory assistance and hospital to achieve an effective HCV care cascade. This document aims to support the regional decision-making process by defining paths for screening and linkage-to-care. Implementing active screening strategies beyond a risk-based approach is required as a General Practitioners' task. Simplified paths must be drawn for the key populations screening. The infrastructure built for COVID-19 vaccination could be used also for HCV screening. According to a multidisciplinary care delivery, screening should be supplemented with rapid linkage-to-care and treatment of newly diagnosed patients. The realization of the proactive screening during the first two years is vital because it will define the tracks for the whole HCV cost-effective screening of 1948-1988 birth cohorts in Italy., Competing Interests: Declaration of Competing Interest On the behalf of all authors declare no conflict of interests for the present paper, (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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).)

Objectives: Optimized diagnostic algorithms to detect active infections are crucial to achieving HCV elimination. We evaluated the cost effectiveness and sustainability of different algorithms for HCV active infection diagnosis, in a context of a high endemic country for HCV infection., Methods: A Markov disease progression model, simulating six diagnostic algorithms in the birth cohort 1969-1989 over a 10-year horizon from a healthcare perspective was used. Conventionally diagnosis of active HCV infection is through detection of antibodies (HCV-Ab) detection followed by HCV-RNA or HCV core antigen (HCV-Ag) confirmatory testing either on a second sample or by same sample reflex testing. The undiagnosed and unconfirmed rates were evaluated by assays false negative estimates and each algorithm patients' drop-off. Age, liver disease stages distribution, liver disease stage costs, treatment effectiveness and costs were used to evaluate the quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratios (ICER)., Results: The reference option was Rapid HCV-Ab followed by second sample HCV-Ag testing which produced the lowest QALYs (866,835 QALYs). The highest gains in health (QALYs=974,458) was obtained by HCV-RNA reflex testing which produced a high cost-effective ICER (€891/QALY). Reflex testing (same sample-single visit) vs two patients' visits algorithms, yielded the highest QALYs and high cost-effective ICERs (€566 and €635/QALY for HCV-Ag and HCV-RNA, respectively), confirmed in 99.9% of the 5,000 probabilistic simulations., Conclusions: Our data confirm, by a cost effectiveness point of view, the EASL and WHO clinical practice guidelines recommending HCV reflex testing as most cost effective diagnostic option vs other diagnostic pathways., (© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.)

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain-1 interacts with cellular proteins inducing pro-oncogenic pathways. Thus, we explore genetic variations in NS5A domain-1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype-1b infected DAA-naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7-82.3); p < 0.001). Focusing on HCC-group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4-6.2) log IU/mL vs. 5.3 (4.4-5.6) log IU/mL, p = 0.02) and lower ALT (35 (30-71) vs. 83 (48-108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell-cycle regulation (p53, p85-PIK3, and β-catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV-mediated oncogenesis. The role of theseNS5A domain-1 mutations in triggering pro-oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation.

Background: HCV infection among vulnerable populations is currently a major issue for HCV elimination program. Incarcerated people and people who inject drugs (PWIDs) are key population groups potentially at high risk for HCV infection. Our aim was to evaluate an extended program of screening, staging and treatment in Italian prison settings., Methods: Patients from eight prisons in five different Italian Regions were enrolled. HCV saliva test (QuickOral Test®) was offered. Data on infection awareness and illicit drug use were also collected. Positive patients underwent early HCV RNA evaluation, staging and prescription on DAAs treatment. The definition of PWID was based on self-reported injecting drug use extracted from medical records (injecting drug use during the previous six months)., Results: A total of 2,376 out of 2,687 individuals (88%) was tested. The median (IQR) age was 42 (32-50) years. PWIDs were 537out of 2,376 (23%). Prevalence of HCV antibodies was 10.4% (248/2,376). PWIDs had a lower awareness of their HCV-Ab positivity than non-PWIDs (p-value <0.001). Furthermore, PWIDs were less likely to be previously treated than non-PWIDs (78% vs 96%, p-value= 0.017). Active infection was found in 41% of patients (101/248). Overall, 61% HCV-positive were PWIDs, with 44% HCV RNA positive. HCV therapy was prescribed to 83% (84/101) of patients with active HCV infection and 67% of these (56/84) were PWIDs. Prescription for HCV treatment in PWIDs accounted for 84% (56/67) (while for non-PWIDs was 82% (28/34) p-value: 0.88. Seventeen patients were referred to a Specialist in other prisons because they were going to be transferred soon to another prison. EOT, as well as SVR12 were achieved in 98% (82/84) treated patients., Conclusions: Among patients, PWIDs had a lower awareness of their HCV-Ab positivity and had previously received less treatments. Saliva test allowed to achieve a more rapid result, stage, and treatment approach. More than 80% of patients underwent treatment, without differences between PWIDs and non-PWIDs. Linkage to care during prison transfer allowed to avoid unplanned interruptions and offered more chances to reach the end of treatment., Competing Interests: Declarations of Interest The authors have no conflict of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

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.)

Inmates have higher HCV prevalence than general population, representing a fundamental step towards HCV eradication. Our aim was to compare 8-week glecaprevir/pibrentasvir treatment in a case-control study between incarcerated and free patients. Eleven Italian prisons and six outpatient clinics were involved. Patients were matched for sex, risk factors, METAVIR grade, HIV and HBV co-infections. About 131 incarcerated (Group A) and 131 free patients (Group B) were included. Mean age was 43.0 ± 9.6 years and 42.8 ± 9.9 in Group A and B, respectively (P = .74). SVR rates were 96.2% and 99.2% in Group A and Group B respectively (P = .21). Five drop-outs occurred in Group A, one in Group B. Incarceration, being PWIDs and OST were not associated with SVR reductions (CI 95%). In conclusion, imprisonment does not influence unplanned interruptions or SVR rates when receiving short-term therapies. Short schedules with pangenotypic regimens could be a good approach to hard-to-reach populations, such as incarcerated patients., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The epidemiology of hepatocellular carcinoma (HCC) is characterized by a dynamical temporal trend of well-established and emerging risk factors., Methods: We evaluated the temporal trend of aetiological factors of HCC over the last two decades in Italy. HCC cases were recruited from two previously published national studies in 1996 and in 2008 and HCC cases were also enlisted from two national surveys in 2001 and in 2014 enrolling consecutive subjects with chronic liver disease (CLD) referring to more than 80 liver units scattered all over the country for a 6-month period., Results: Out of the 9997 subjects with CLD recruited in 2001 and the 2408 recruited in 2014, 3.3% and 5.7% (P < 0.001), respectively, had HCC. The temporal trend of HBsAg -/HCV + HCC cases significantly linearly decreased from 71.1% in 1996 to 57.2% in 2014 (P < 0.001). Conversely, that of virus-negative cases significantly linearly increased from 12.1% to 28.3% (P < 0.001). The proportion of HBV-related HCC cases showed a steady low rate, reflecting the reduced endemicity of the infection in Italy. The proportion of HCC with compensated cirrhosis (i.e., Child-Pugh A) linearly increased over time from 55.6% in 1996 to 76.0% in 2014 (P < 0.001) reflecting the growing effectiveness of semi-annual ultrasound surveillance for early detection of HCC., Conclusion: In conclusion, with decreasing viral aetiology, an overall decrease in the incidence of HCC might be expected in the future. The proportion of metabolic diseases is conversely increasing being considered as an aetiology. The growing prevalence of metabolic disorders in the general population may further increase this trend in the years to come.

Hepatitis C prevalence in prison populations is much higher than in the community. Effective hepatitis C treatment within this population does not only have a direct individual health benefit, but may lead to substantial community dividend. We reviewed available evidence on hepatitis C treatment in prison settings, with a focus on the European Union/European Economic Area. A systematic review of the literature (PubMed, EMBASE, Cochrane library) was performed and complemented with searches for conference abstracts and grey literature. Thirty-four publications were included reporting on the effectiveness, acceptability and economic aspects of hepatitis C virus treatment models of care to achieve treatment completion and sustained viral response in prison settings. Available evidence shows that hepatitis C treatment in prison settings is feasible and the introduction of direct-acting antivirals will most likely result in increased treatment completion and better clinical outcomes for the prison population, given the caveats of affordability and the need for increased funding for prison health, with the resulting benefits accruing mostly in the community., (© 2018 John Wiley & Sons Ltd.)

Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2-45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4-19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1-4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.

Background: The recent availability of direct acting antiviral drugs (DAAs) has drastically changed hepatitis C virus (HCV) treatment scenarios, due to the exceedingly high rates of sustained virological response (SVR) and excellent tolerability allowing for treatment at all disease stages., Methods: A panel of Italian experts was convened twice, in November 2016 and January 2017, to provide further support on some open issues and provide guidance for personalized HCV care, also in light of forthcoming regimens., Results and Conclusions: Treatment recommendations issued by international and national liver societies to guide clinicians in the management of HCV infection are constantly updated due to accumulating new data. Such recommendations may not be applicable to all healthcare settings for a variety of reasons. Moreover, some gaps still remain and the spectrum of patients to be treated is also evolving.

Background: Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014)., Methods: The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods., Results: The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely to show HCV infection alone (48.0% vs. 67.9%). A male preponderance was observed in HBV-related cases (1.99) and in alcoholic-related cases (2.3), a preponderance observed both in the 2001 and in 2014 cases. In HCV-related cases, however, females predominated in 2001 (M/F 0.9) and males in 2014 (M/F 1.5).The rate of cirrhosis in alcohol-related etiology was close to 36% in both genders, a finding much higher than that observed for both sexes in HBV and HCV etiologies.Both males and females enrolled in 2014 were older (p < 0.001) and with a higher rate of cirrhosis and/or HCC (p < 0.001) than those investigated in 2001. There was a remarkable increase over time in the proportion of male abstainers (36.7% in 2001 and 64.3% in 2014)., Conclusion: This study highlights important inter- and intra-gender differences in the characteristics and etiological factors of patients with CLD in Italy.

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR., Study Design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization., Results: HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p<0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted δ and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted λ, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p<0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR., Conclusions: Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis.

Background: The prevalence of HCV infection is higher among prisoners than in the general population. The introduction of HCV direct-acting antivirals (DAA) holds the potential to improve clinical outcomes also in inmates. However, treatment of hepatitis C in inmates has to face several clinical and logistical issues which are peculiar of prison environment. Recommendations on the management of HCV infection specific for the penitentiary setting in the DAA era remain scant. The Italian Society for Penitentiary Medicine and Healthcare has, therefore, issued these recommendations, to provide clinicians with a guide for the comprehensive management of HCV infection in the restriction setting, taking into account its peculiar characteristics., Results: Dedicated diagnostic and treatment procedures should be established in each prison. In particular, the use of DAAs appears crucial to provide patients with an effective therapeutic option, able to overcome the limitations of IFN-based regimens with a short period of treatment. DAA treatment should be initiated as soon as possible in all eligible subjects with the aim to cure the patient, as well as to limit the transmission of HCV infection both inside the penitentiary system and to the free community, once the inmates ends his/her release. Importantly, efforts should be made to open a discussion with regulatory bodies, to define specific regulations aimed to guarantee wide access to effective therapies of all eligible patients, to optimize the management of and the adherence to the HCV treatment, and to ensure the therapeutic continuity after discharge from prison.

Coinfection of blood-borne hepatitis B and hepatitis C viruses (HBV and HCV, respectively) in human immunodeficiency virus type 1 (HIV-1)-positive individuals frequently occurs in inmate population and peculiar viral strains and patterns of virological markers may be observed.Plasma from 69 HIV-1-positive inmates was obtained from 7 clinical centers connected with correctional centers in different towns in Italy. HIV, HBV, and HCV markers were tested by commercial assays. Virus genotyping was carried out by sequencing the protease and reverse transcriptase-encoding region (PR-RT region) for HIV and a region encompassing the NS5B gene for HCV and subsequent phylogenetic analysis.Twelve over 14 HIV-subtyped inmates were infected with HIV-1 subtype B strains. The 2 non-B strains belonged to subtype G and CRF02&#95;AG, in an Italian and a Gambian patient, respectively. Variants carrying the K103N and Y181C resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were found in 2 out of 9 patients naive for combined antiretroviral therapy (cART) (22.2%). Most HIV-positive patients (92.8%) showed evidence of past or present HBV and/or HCV infection. Prevalence of HBV and HCV was 81.2% for both viruses, whereas prevalence of HBV/HCV coinfection was 69.6%. A significantly higher presence of HCV infection was found in Italians [odds ratio (OR) 11.0; interval 1.7-80.9] and in drug users (OR 27.8; interval 4.9-186.0). HCV subtypes were determined in 42 HCV or HBV/HCV-coinfected individuals. HCV subtypes 1a, 3a, 4d, and 1b were found in 42.9%, 40.5%, 14.3%, and 2.4% of inmates, respectively. Low titers of HBV DNA in HBV DNA positive subjects precluded HBV subtyping.The high prevalence of HBV and HCV coinfections in HIV-infected inmates, as well as the heterogeneity of HIV and HCV subtypes suggest the need to adopt systematic controls in prisons to monitor both the burden and the genetic forms of blood-borne viral infections, in order to apply targeted therapeutic interventions.

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., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Underserved populations have a wide heterogeneity on healthcare provision and use. They also represent the key populations according to WHO 2030 goals for HCV micro-elimination. Our review evaluated the available literature on HCV diagnosis, staging, and treatment among underserved populations, such as incarcerated people, patients with psychiatric disorders, and migrants. A narrative review of literature was performed using key electronic databases (Scopus, Pubmed—MEDLINE) and search engines (Google Scholar). Peer-reviewed publications, grey literature on HCV, and recent models proposed for micro-elimination in underserved populations were included. An insight into the COVID-19 pandemic and its influence on HCV micro-elimination pathways will be also provided. Regarding prison settings, a progressive reduction in HCV epidemiology among incarcerated people in the last years was found (one-third of the level it had been before). People suffering from psychiatric disorders have a high anti-HCV prevalence, but there is a lack of data on active infections. A bidirectional relationship between HCV and psychiatric disorders was found. Migrants showed a very inconsistent assessment of HCV. Furthermore, available studies recorded data from populations with high heterogeneity of anti-HCV prevalence, Therefore, the reported results need caution in their evaluation. [ABSTRACT FROM AUTHOR]

Background/Aims: Patients with genotype 3 hepatitis C virus (G3-HCV) cirrhosis are very difficult to treat compared to patients with other HCV genotypes. The optimal treatment duration and drug regimen associated with ribavirin (RBV) remain unclear. To evaluate the efficacy and safety of daclatasvir (DCV)/sofosbuvir (SOF) plus a flat dose of 800 mg RBV (flat dose) compared to DCV/SOF without RBV or DCV/ SOF plus an RBV dose based on body weight (weight-based) in G3-HCV patients with compensated or decompensated cirrhosis. Methods: We analyzed data for 233 G3 cirrhotic patients. Of these, 70 (30%), 87(37%) and 76 (33%) received SOF/DCV, SOF/DCV/RBV flat dose, and SOF/DCV/ RBV weight-based dose, respectively. Treatment duration was 24 weeks. Sustained virological response (SVR) was evaluated at week 12 posttreatment (SVR12). Results: Overall, SVR12 was achieved in 220 out of 233 patients (94.4%). The SVR12 rate was lower in the DCV/SOF group than in the DCV/SOF/RBV flat-dose group and the DCV/ SOF/RBV weight-based group (87.1% vs 97.7% and 97.4%, respectively, p=0.007). A higher incidence of anemia occurred in the DCV/SOF/RBV weight-based group compared to those in the other two groups (p<0.007). Conclusions: We found that the DCV/SOF/RBV flat-dose regimen is an effective treatment in terms of efficacy and safety in patients with G3-HCV compensated or decompensated cirrhosis. Therefore, antiviral regimens without RBV should be restricted only to naïve patients with G3-HCV compensated cirrhosis who have a clear contraindication for RBV. [ABSTRACT FROM AUTHOR]

Compared with the general population, incarcerated people have a higher prevalence of several communicable diseases, including viral hepatitis. Nevertheless, there is still a lack of literature in field. Our review aims to shed the actual knowledge on viral hepatitis among incarcerated people in Italy. We performed a comprehensive literature search, through key electronic databases (Scopus, Pubmed–MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles and reviews), grey literature on viral hepatitis prevalence, and models proposed for active case finding and control strategies in prison settings. We found that viral hepatitis epidemiology drastically changed in the last five years, particularly on hepatitis C virus (HCV), reporting an HCV antibody (HCV-Ab) prevalence decrease from up to 38% to ˂20% in penitentiary institutes, as well as an even more important reduction in active infections. Probably, the availability of direct-acting antivirals is contributing to this scenario. However, there is a lack of data available regarding incarcerated women. For this reason, more tailored interventions are needed for this sub-population. Judiciary and regulatory bodies should be prompted to discuss and define specific regulations to optimize case active finding strategies, guarantee wide access to effective preventive and treatment options for viral hepatitis and enhance treatment management. [ABSTRACT FROM AUTHOR]

A correction is presented of the article "Management of HCV infection in the penitentiary setting in the direct‑acting antivirals era: practical recommendations from an expert panel" is presented.