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Background: Data from the first wave of the coronavirus disease 2019 (COVID-19) pandemic suggested that patients with inflammatory bowel disease (IBD) are not at higher risk of being infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and that a worse prognosis is not associated with immunomodulatory drugs, with the possible exception of systemic steroids., Methods: This retrospective, observational study included consecutive IBD patients from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) cohort who had a SARS-CoV-2 infection diagnosis (polymerase chain reaction-confirmed presence of the viral genome in a nasopharyngeal swab) during the second COVID-19 pandemic wave (September 2020 to December 2020). Data regarding demographics, IBD features and treatments, and comorbidities were analyzed in correlation with COVID-19 clinical outcomes., Results: Data on 122 patients (mean age, 43.9 ± 16.7 years; males, 50.0%; Crohn's disease, 62.3%; ulcerative colitis, 37.7%) were reported. Twelve patients developed COVID-19-related pneumonia (9.8%), 4 (3.3%) required respiratory assistance (nonmechanical ventilation or orotracheal intubation), and 4 died (case fatality rate, 3.3%). In a multivariable analysis, age (odds ratio [OR], 1.034; 95% CI, 1.006-1.147; P = .032) and severe IBD activity (OR, 13.465; 95% CI, 1.104-164.182; P = .042) were independent predictors of COVID-19-related pneumonia, while severe IBD activity (OR, 15.359; 95% CI, 1.320-178.677; P = .030) was the only independent predictor of severe COVID-19, a composite endpoint defined as the need for respiratory assistance or death. A trend towards a protective role of tumor necrosis factor α inhibitors on pneumonia development was reported (P = .076)., Conclusions: In this cohort of patients with IBD and SARS-CoV-2 infection, severe IBD activity was the only independent risk factor for severe COVID-19., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment. Methods: Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs). Results: In total, 34 studies of NAC usage in APAP-related DILI cases with 19,580 patients were identified, of which 2,376 patients developed hepatotoxicities. The mortality rate across different studies ranged from 0 to 52%. Large variability of NAC regimens was found, i.e., intravenous (I.V.) (100-150 mg/kg) and oral (70-140 mg/kg), and length of treatment varied-12, 24, or 48 h for I.V. regimen and 72 h for oral administration. The timing of initiation of NAC treatment showed different results in terms of occurrence of hepatotoxicity and mortality; if started within 8 h and no more than 24 h from APAP overdose, either intravenously or orally, NAC administration was efficacious in terms of mortality. The most frequent AEs reported were anaphylactic reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the oral one. Conclusion: NAC improves hepatotoxicity and reduces mortality. Timing of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the regimen or route of administration, is important to prevent or minimize liver damage, particularly in children and in elderly and obese patients., 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., (Copyright © 2022 Licata, Minissale, Stankevičiūtė, Sanabria-Cabrera, Lucena, Andrade and Almasio.)

Management for HCV has undergone a notable change using direct-acting antiviral drugs (DAAs), which are safe and effective even in elderly. Here, we define impact of comorbidities, concomitant medication and drug-drug interactions in elder patients with HCV related disease before starting DAAs regimen. We analyzed data of 814 patients prospectively enrolled at our Unit within the web based model HCV Sicily Network. Out of 814, 590 were treated with DAAs and 414 of them were older than 65 years. We divided those 414 in two groups, one including 215 patients, aged between 65 and 74 years, and another with 199 patients, aged of 75 years and over. Charlson Comorbidity Index (CCI) was assessed for each patient; drug-drug interactions (DDI) and de-prescribing process were carried out appropriately. Within 414 patients included, percentage rates of women treated was higher than males, BMI was lower and cirrhosis was frequently reported in patients older than 75 years. Hypertension, diabetes mellitus, dyslipidemia (p < 0.0001), prostatic pathologies, kidney disease, gastrointestinal disease (p < 0.0001), osteoporosis (p < 0.01) and depression were most common co-morbidities. CCI showed lower scores in the first group as compared with the second one (p < 0.0001). Among drugs, statins were frequently suspended and anti-hypertensive often replaced. DAAs are useful and effective regardless of disease severity, comorbidities, medications and age. De-prescribing allows a stable reduction of number of medications taken with real improvement of quality of life., (© 2021. The Author(s).)

Background & Aims: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), which in males, especially in advanced age, can sometimes evolve into acute respiratory distress syndrome. In addition, mild to moderate alterations in liver function tests (LFTs) have been reported in the worst affected patients. Our review aims to analyse data on the incidence and prognostic value of LFT alterations, the underlying mechanisms and the management of pre-existing liver disease in COVID-19 affected patients., Methods: We searched available literature through online PubMed database using terms as "SARS-CoV-2," "Liver damage," "Liver Function tests," "COVID-19," "pre-existing liver disease," "drug-induced liver injury.", Results: Available evidence suggest that there could be a relationship between SARS-CoV-2 infection and liver damage, although the underlying involved mechanism remains unclear. Cohort studies have shown that high ALT levels, low platelet counts and low albumin levels at admission and during hospitalisation are associated with a high mortality rate. Unfortunately, little is known about the impact of COVID-19 on pre-existing liver damage. While chronic viral infections or NAFLD are associated with an increased risk of COVID-19 progression, patients with cirrhosis may have increased susceptibility to SARS-CoV-2 infection due to their systemic immunocompromised status. DILI seems common among hospitalised patient with severe pneumonia., Conclusion: Mild to moderate liver impairment during Covid-19 is common, especially in patients with pre-existing liver disease. Further studies should be performed in order to understand how pre-existing liver conditions may influence and worsen progression of liver disease in COVID-19 patients., Competing Interests: None to declare., (© 2021 The Authors. GastroHep published by John Wiley & Sons Ltd.)

Aims: To analyze the main etiological factors and some clinical features of patients with hepatocellular carcinoma (HCC) at diagnosis and to compare them with those we described ten years ago. Materials and Methods . We compared two groups of patients with HCC, Group 1 consisting of 132 patients (82 M, 50 F) diagnosed in the 2003-2008 period and Group 2 including 119 patients (82 M, 37 F) diagnosed in the 2013-2018 period. For all patients, age, sex, viral markers, alcohol consumption, serum alpha-fetoprotein (AFP) levels, and the main liver function parameters were recorded. The diagnosis of HCC was based on AASLD, EASL guidelines. The staging was classified according to the "Barcelona Clinic Liver Cancer staging system" (BCLC)., Results: Mean age was 69.0 ± 8 years in Group 1 and 71.0 ± 9 in Group 2 ( P < 0.05). HCV subjects were significantly older in Group 2 ( P < 0.05). HCV subjects were significantly older in Group 2 ( P < 0.05). HCV subjects were significantly older in Group 2 ( P < 0.05). HCV subjects were significantly older in Group 2 ( P < 0.05). HCV subjects were significantly older in Group 2 ( P < 0.05). HCV subjects were significantly older in Group 2 ( P < 0.05). HCV subjects were significantly older in Group 2 ( P < 0.05). HCV subjects were significantly older in Group 2 (., Conclusions: This study shows that over the last decade a number of features of patients with HCC in our region have changed, particularly age at onset, etiological factors, and staging of HCC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Lydia Giannitrapani et al.)

Background: Cirrhosis is associated with morpho-functional cardiovascular alterations., Aims: To detect early features of cardiovascular damage in HCV-compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short-term behaviour after HCV eradication with direct antiviral agents (DAAs)., Methods: Thirty-nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain and ultrasound scan of carotid arteries. HCV-cirrhotics were reassessed by echocardiography and carotid ultrasound after obtaining sustained virological response (SVR) on DAAs., Results: HCV-cirrhotics showed at baseline a significantly reduced global longitudinal strain compared to controls -18.1 (16.3-20.5) vs -21.2 (20.4-22.3), P < 0.001. They also had a significantly higher pulse wave velocity 8.6 (7.7-9.1) m/s vs 6.6 (6.0-7.1) m/s, P = 0.0001, and β-stiffness index 12.4 (11.1-13.5) vs 8.6 (8.0-9.2) P = 0.0001. At multiple regression analysis, diabetes and HCV cirrhosis were independent predictors of global longitudinal strain. All HCV-cirrhotic patients had SVR on DAAs. Follow-up available in 32 of 39 (82%) at 9 (8-10) months showed a significant improvement of tricuspid annular plane systolic excursion (P = 0.01) and lateral E' velocity compared to baseline (P = 0.001)., Conclusions: HCV-cirrhotics show a significant rate of subclinical cardiac and vascular abnormalities. At a time when their survival is less linked to progression of liver disease, due to viral eradication on DAAs, cardiovascular morbidity and mortality may take a significant role., (© 2018 John Wiley & Sons Ltd.)

Aim/objective/background: Direct-acting oral anticoagulant drugs are marketed worldwide for the primary and secondary prevention and treatment of thromboembolic disorders. Rivaroxaban, an oral, direct factor Xa inhibitor, is one of the most used. Rivaroxaban-induced hepatotoxicity is unusual, although a number of adverse reports have recently been reported. Here, we report two new cases of rivaroxaban-induced hepatitis., Methods: A systematic search of case reports on the MEDLINE database encompassing the years 2008-2016 was carried out.Additional references were obtained following a manual search of the retrieved papers. We report two new cases of adverse events occurred in patients treated with rivaroxaban (20 mg/die) to prevent systemic embolism, who presented with hepatocellular liver injury with onset at 8 weeks after initiation of the drug intake., Results: Twenty-six cases were retrieved from MEDLINE (57.7% female, 42.3% male). Using the Roussel Uclaf Causality Assessment Method (RUCAM) scale, liver injury was classified as hepatocellular (42.3%), cholestatic (26.9%), or mixed (15.4%). Older age (≥65 years) was present as a risk factor in 57.7%. The time lapse between initiation of treatment and onset of hepatic injury ranged from 2 to 180 days (median: 15 days). Our two new patients were diagnosed with drug-induced liver injury (hepatocellular pattern) using the 'consensus criteria', for drug-induced liver injury. Their RUCAM scores were calculated and assessed as highly probable and probable, respectively. A clinical recovery after rivaroxaban withdrawal was observed., Conclusion: Direct-acting oral anticoagulants have been commonly prescribed, even if safety issues regarding the use of these drugs are still an ongoing concern, especially in patients experiencing chronic liver disease. Dedicated postauthorization safety studies should be undertaken to better define rivaroxaban-induced drug-induced liver injury.

Adverse drug reactions (ADRs) represent an important cause of morbidity and mortality worldwide. Statins are a class of drugs whose main adverse effects are drug-induced liver injury (DILI) and myopathy. Some of these may be predictable, due to their pharmacokinetic and pharmacodynamic properties, while others, unfortunately, are idiosyncratic. Genetic factors may also influence patient susceptibility to DILI and myopathy in the case of statins. This review will first discuss the role of statins in cardiovascular disease treatment and prevention and the underlying mechanisms of action. Furthermore, to explore the susceptibility of statin-induced adverse events such as myopathy and hepatotoxicity, it will then focus on the recent Genome-Wide Association Studies (GWAS) concerning the transporter genes, Cytochrome P450 (CYP), organic anion-transporting polypeptide (OATP) and ABCB1 and ABCC1, which seem to play a role in the development of clinically relevant adverse events. Finally, we appraise the evidence for and against the use of statins in metabolic syndrome and in HCV-infected patients, in terms of their safety and efficacy in cardiovascular events., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Drug-induced liver injury (DILI) is more often a challenge even for expert clinicians. Presently, there are limited data about the epidemiology, because the real incidence and prevalence of the disorder are underestimated, and further, sometimes the pharmacovigilance chain is unsuccessful as cases are largely underreported. We review available literature data and discuss our clinical experience regarding a prospective cohort of 185 patients with a diagnosis of DILI., Materials and Methods: Significant papers were identified by literature search, and selected based on content including the epidemiology of DILI. By analyzing our prospective cohort, consecutively collected since January 2000 to December 2016 at our tertiary referral center for liver disease, we report the frequency of different drug classes involved in DILI and their related clinical outcomes., Results: In our cohort of 185 patients, 56% were females and 44% males; the mean age was 53 years, even if about 70% of patients were 40 years old; only 2% had a previous chronic liver disease. At clinical presentation, 57.8% showed a hepatocellular pattern, whereas 18.3% a cholestatic and 23.2% a mixed one. Antibiotics were involved for 23.4%, NSAIDs for 35.5%, immunosuppressants for 10.9%, statins for 4.3%, anti-platelets and anti-psychiatric drugs for 7.6%, and other drugs for 9%. Regarding the evolution, antibiotics, NSAIDs, and immunosuppressant were frequently responsible for chronicity, whereas statins, anti-psychiatric and anti-platelets drugs were not., Conclusions: In this review, we discuss our clinical experience in the field of DILI, in which many efforts are required to reinforce the attention of a physician to the possibility that a patient with the acute liver disease could be diagnosed as a patient with DILI.

Background/aims: Low 25-hydroxyvitamin D serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC), and experimental evidence suggested a hepatoprotective role of vitamin D via interaction with hepatic vitamin D receptor (VDR). We assessed the hepatic expression of VDR protein and its association with liver disease severity., Methods: Ninety-one consecutive patients with biopsy-proven G1CHC and available frozen liver tissue were evaluated. Ten subjects without chronic liver diseases and nine patients with autoimmune hepatitis served as controls. The hepatic expression of VDR protein was assessed by Western blot for quantification and by immunohistochemistry for morphological distribution., Results: Liver VDR protein was mainly localized in hepatocytes and cholangiocytes, and its expression by a Western blot was similar in chronic hepatitis C (CHC) and controls (1.83 ± 0.97 vs 2.18 ± 0.62, P = .14) but was lower in autoimmune hepatitis (0.84 ± 0.14, P < .001). The expression was lower in CHC with severe necroinflammatory activity (1.44 ± 0.87) vs both controls and CHC with grade 1-2 inflammation (1.94 ± 0.97, P = .01 and P = .03, respectively) but higher compared with autoimmune hepatitis (P = .007). A similar difference was observed in CHC patients with F3-F4 fibrosis whose VDR expression (1.51 ± 1.07) was also lower compared with controls and CHC with F0-F2 fibrosis (1.98 ± 0.89, P = .02 and P = .04, respectively) but higher vs autoimmune hepatitis (P = .003). At multivariate logistic regression analysis, low VDR protein expression remained associated with severe necroinflammatory activity and severe fibrosis (odds ratio 0.543,95% confidence interval 0.288-0.989, P = .04; and odds ratio 0.484,95% confidence interval 0.268-0.877, P = .01, respectively) in CHC after correction for clinical, biochemical, and histological features., Conclusion: In a cohort of G1CHC patients, the hepatic expression of VDR protein is associated with the severity of both liver fibrosis and inflammation.

In the last years, several lines of evidence showed how metabolic factors may influence the natural history of patients with chronic hepatitis C. Chronic HCV infection is able to perturb the metabolic homeostasis of the host, in a context of complex interactions where pre-existent metabolic status and genetic background play an important role, allowing us to state that HCV infection is a systemic disease. In this review, we discuss the most recent lines of evidence on the main metabolic factors that are known to be associated with CHC, namely, insulin resistance/type 2 diabetes, steatosis, visceral obesity, atherosclerosis, vitamin D, menopause, fructose and coffee intake, lipoproteins, methylenetetrahydrofolate reductase status, and hyperuricaemia. In particular, we focus on the pathophysiological mechanisms underlying the correlation between HCV infection and metabolic disorders, the impact of metabolic factors on the progression of liver and non-liver-related diseases, and, on the contrary, the possible influence of chronic HCV infection on metabolic features. In this setting, the importance of a multifaceted evaluation of CHC patients and a prompt correction of modifiable metabolic risk factors should be emphasized.