When and how to treat acute hepatitis C?

Background: Appropriate treatment of acute hepatitis C is still a matter of controversy due to the lack of large controlled trials. Aim: To assess the effectiveness of interferon as treatment for acute hepatitis C by meta-analysis. Methods: MEDLINE search (1985-2002) was supplemented with manual searches of reference lists. Studies were included if they were controlled trials comparing interferon to no treatment and if they included patients with either post-transfusion or sporadic acute hepatitis C. Twelve trials were analyzed (414 patients). The outcome assessed was the sustained virological response (SVR) rate (undetectable hepatitis C virus RNA in serum at least 6 months after cessation of therapy). Results: Interferon significantly increased the SVR (risk difference 49%; 95% confidence interval 32.9-65%) in comparison to no treatment. The risk difference of SVR increased from 5 to 90% when trials were ordered by increasing interferon weekly dose. Delaying therapy by 8-12 weeks after the onset of disease does not compromise the SVR rate. Conclusions: Current evidence is sufficient to recommend interferon treatment of patients with acute hepatitis C. A later initiation of therapy yields the same likelihood of response as early treatment. A daily induction dose during the 1st month is the best option of treatment. © 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: The accuracy of noninvasive tools for the diagnosis of severe fibrosis in patients with nonalcoholic fatty liver disease(NAFLD) in clinical practice is still limited. We aimed at assessing the diagnostic performance of combined noninvasive tools in two independent cohorts of Italian NAFLD patients. METHODS: We analysed data from 321 Italian patients(179 Sicilian-training cohort, and 142 northern Italy-validation cohort) with an histological diagnosis of NAFLD. Severe fibrosis was defined as fibrosis ≥ F3 according to Kleiner classification. The APRI, AST/ALT, BARD, FIB-4, and NFS scores were calculated according to published algorithms. Liver stiffness measurement(LSM) was performed by FibroScan. Cut-off points of LSM, NFS and FIB-4 for rule-in or rule-out F3-F4 fibrosis were calculated by the reported formulas. RESULTS: In the Sicilian cohort AUCs of LSM, NFS, FIB-4, LSM plus NFS, LSM plus FIB-4, and NFS plus FIB-4 were 0.857, 0.803, 0.790, 0.878, 0.888 and 0.807, respectively, while in the northern Italy cohort the corresponding AUCs were 0.848, 0.730, 0.703, 0.844, 0.850, and 0.733 respectively. In the training cohort, the combination of LSM plus NFS was the best performing strategy, providing false positive, false negative and uncertainty area rates of 0%,1.1% and 48% respectively. Similar results were obtained in the validation cohort with false positive, false negative and uncertainty area rates of 0%,7.3% and 40.8%. CONCLUSIONS: The combination of LSM with NFS, two complementary, easy-to-perform, and widely available tools, is able to accurately diagnose or exclude the presence of severe liver fibrosis, also reducing of about 50-60% the number of needed diagnostic liver biopsies

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

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

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

Prioritization of high-cost new drugs for HCV: making sustainability ethical

Hepatitis C virus (HCV) infection is a major health problem worldwide. Chronic HCV infection may in the long run cause cirrhosis, hepatic decompensation and hepatocellular carcinoma, with an ultimate disease burden of at least 350,000 deaths per year worldwide. The new generation of highly effective direct acting antivirals (DAA) to treat HCV infection brings major promises to infected patients in terms of exceedingly high rates of sustained virological response (SVR) but also of tolerability, allowing even the sickest patients to be treated. Even in the face of the excellent safety and efficacy and wide theoretical applicability of these regimens, their introduction is currently facing cost and access issues denying their use to many patients in need. Health systems in all countries are facing a huge problem of distributive justice, since while they should guarantee individual rights, among which the right to health in its broader sense, therefore not limited to healing, but extended to quality of life, they must also grant equal access to the healthcare resources and keep the distribution system sustainable. In the face of a disease with a relatively unpredictable course, where many but not of all chronically infected will eventually die of liver disease, selective allocation of this costly resource is debatable. In most countries the favorite solution has been a stratification of patients for prioritization of treatment, which means allowing Interferon-free DAA treatment only in patients with advanced fibrosis or cirrhosis, while keeping on hold persons with lesser stages of liver disease. In this report, we will perform an ethical assessment addressing the issues linked to access to new therapies, prioritization and eligibility criteria, analyzing the meaning of the term “distributive justice” and the different approaches that can guide us (individualistic libertarianism, social utilitarianism and egalitarianism) on this specific matter. Even if over time the price of new DAA will be reduced through competition and eventual patent expiration, the phenomenon of high drug costs will go on in the next decades and we need adequate tools to face the problems of distributive justice that come with it

Coeliac disease: Oral ulcer prevalence, assessment of risk and association with gluten-free diet in children.

AIMS: Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. METHODS: A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. RESULTS: Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi-square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi-square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441). CONCLUSIONS: The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration

Alexithymia and personality traits of patients with inflammatory bowel disease

Psychological factors, specific lifestyles and environmental stressors may influence etiopathogenesis and evolution of chronic diseases. We investigate the association between Chronic Inflammatory Bowel Diseases (IBD) and psychological dimensions such as personality traits, defence mechanisms, and Alexithymia, i.e. deficits of emotional awareness with inability to give a name to emotional states. We analyzed a survey of 100 patients with IBD and a control group of 66 healthy individuals. The survey involved filling out clinical and anamnestic forms and administering five psychological tests. These were then analyzed by using a network representation of the system by considering it as a bipartite network in which elements of one set are the 166 individuals, while the elements of the other set are the outcome of the survey. We then run an unsupervised community detection algorithm providing a partition of the 166 participants into clusters. That allowed us to determine a statistically significant association between psychological factors and IBD. We find clusters of patients characterized by high neuroticism, alexithymia, impulsivity and severe physical conditions and being of female gender. We therefore hypothesize that in a population of alexithymic patients, females are inclined to develop psychosomatic diseases like IBD while males might eventually develop behavioral disorders