Dysmetabolism, Diabetes and Clinical Outcomes in Patients Cured of Chronic Hepatitis C: A Real-Life Cohort Study.

The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE-Lombardia registry). In a subset (n = 748), liver stiffness measurement (LSM) was available at baseline and follow-up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2 , 1.03-1.09) and diabetes (OR 2.01 [1.65-2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35-0.60]; P < 0.0001 for all). The impact of BMI was greater in those without diabetes (P = 0.003). Diabetes was independently associated with less pronounced LSM improvement after viral eradication (P = 0.001) and in patients with advanced fibrosis was an independent predictor of the most frequent clinical events, namely de novo hepatocellular carcinoma (HCC; hazard ratio [HR] 2.09 [1.20-3.63]; P = 0.009) and cardiovascular events (HR 2.73 [1.16-6.43]; P = 0.021). Metformin showed a protective association against HCC (HR 0.32 [0.11-0.96]; P = 0.043), which was confirmed after adjustment for propensity score (P = 0.038). Diabetes diagnosis further refined HCC prediction in patients with compensated advanced chronic liver disease at high baseline risk (P = 0.024). Conclusion: Metabolic comorbidities were associated with advanced liver fibrosis at baseline, whereas statins were protective. In patients with advanced fibrosis, diabetes increased the risk of de novo HCC and of cardiovascular events. Optimization of metabolic comorbidities treatment by a multi-disciplinary management approach may improve cardiovascular and possibly liver-related outcomes.

Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome.

OBJECTIVES: The outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with 'standard-of-care' (SoC). METHODS: In the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5-19 March 2020, were treated with 'SoC' (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction). RESULTS: Patients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%) vs 63.6% (SE=4.1%), p=0.001). Cox proportional hazards regression survival analysis showed that a lower risk of death was independently associated with colchicine treatment (HR=0.151 (95% CI 0.062 to 0.368), p<0.0001), whereas older age, worse PaO2/FiO2, and higher serum levels of ferritin at entry were associated with a higher risk. CONCLUSION: This proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.

Renal safety in 3264 HCV patients treated with DAA-based regimens: Results from a large Italian real-life study.

BACKGROUND: Sofosbuvir (SOF)-based regimens have been associated with renal function worsening in HCV patients with estimated glomerular filtration rate (eGFR) ≤ 45 ml/min, but further investigations are lacking. AIM: To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD). METHODS: All HCV patients treated with DAA in Lombardy (December 2014-November 2017) with available kidney function tests during and off-treatment were included. RESULTS: Among 3264 patients [65% males, 67% cirrhotics, eGFR 88 (9-264) ml/min], CKD stage was 3 in 9.5% and 4/5 in 0.7%. 79% and 73% patients received SOF and RBV, respectively. During DAA, eGFR declined in CKD-1 (p < 0.0001) and CKD-2 (p = 0.0002) patients, with corresponding rates of CKD stage reduction of 25% and 8%. Conversely, eGFR improved in lower CKD stages (p < 0.0001 in CKD-3a, p = 0.0007 in CKD-3b, p = 0.024 in CKD-4/5), with 33-45% rates of CKD improvement. Changes in eGFR and CKD distribution persisted at SVR. Baseline independent predictors of CKD worsening at EOT and SVR were age (p < 0.0001), higher baseline CKD stages (p < 0.0001) and AH (p = 0.010 and p < 0.0001, respectively). CONCLUSIONS: During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.

Evaluation of liver fibrosis: concordance analysis between noninvasive scores (APRI and FIB-4) evolution and predictors in a cohort of HIV-infected patients without hepatitis C and B infection.

BACKGROUND: There is lack of data on the incidence of liver fibrosis (LF) progression in patients with human immunodeficiency virus (HIV) monoinfection and risk factors for LF. METHODS: We performed an observational prospective study in a cohort of HIV-infected patients who had initiated highly active antiretroviral therapy (HAART). FIB-4 and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) were assessed. The concordance between the 2 scores was assessed by weighted kappa coefficient. Kaplan-Meier analysis was used to estimate the incidence of LF. Cox regression analysis was used to assess the predictors of transition. RESULTS: A total of 1112 patients were observed for a mean of 2249 days of follow-up. The concordance between FIB-4 and APRI was moderate (kappa = .573). The incidence of transition to higher FIB-4 classes was 0.064 (95% confidence interval [CI], 0.056-0.072) per person-year of follow-up (PYFU), whereas the incidence of transition to higher APRI classes was 0.099 (95% CI, 0.089-0.110) per PYFU. The incidence of transition to FIB-4 >3.25 was 0.013 per PYFU (95% CI, 0.010-0.017) and 0.018 per PYFU (95% CI, 0.014-0.022) for APRI >1.5. In multivariate analyses, for transition to higher classes, HIV RNA level <500 copies/mL was found to be protective for both scores, and higher CD4+ T cell count was found to be protective for FIB-4. Additional risk factors were age ≥ 40 years, male sex, intravenous drug use as an HIV infection risk factor, higher degree of LF, higher gamma-glutamyl transpeptidase (γGT) at baseline, and use of dideoxynucleoside-analogue drugs (DDX). Consistent results for the main study outcomes were obtained for confirmed LF transition and transition to FIB-4 > 3.25 and APR I> 1.5 as study outcomes. CONCLUSIONS: Overall, our results suggest a possible benefit associated with earlier HAART initiation, provided that the effectiveness of HAART is sustained and treatment with DDX is avoided.

Cryptogenic liver diseases: sailing by sight from HIV co-infection with hepatitis viruses to HIV mono-infection through the Pillars of Hercules.

Liver injury in the HIV-positive population has been classically associated with hepatitis B or C viruses (HBV and HCV). While HBV or HCV co-infections have represented "Pillars of Hercules" for hepatic disease (not further beyond), it is now time to move forward and shed light on liver disease in HIV-infected patients without HBV or HCV co-infections. Indeed, over the last years, liver disease in HIV-mono-infected patients has emerged and fated to become one of the main non AIDS-related complications. Although several cases have specific etiologies (e.g., alcohol abuse), other cases are most challenging for the clinicians because the actual causes are only hypothesized, such as it is difficult to treat them appropriately. This new clinical entity has been named "cryptogenic" liver disease; it is polymorphic (e.g., hepatic steatosis, nodular regenerative hyperplasia or noncirrhotic portal hypertension) and multifactorial in nature, but HIV per se may play a key role. In this paper, we present a critical review of the relevant literature data, focusing on practical implications (including diagnostic tools and differential diagnosis), and delineate priorities for future research on this important topic.

Treating hepatitis C virus in HIV patients: are side effects a real obstacle?

Hepatitis C virus-related long-term complications are nowadays a leading cause of morbidity and mortality in HIV-infected persons. According to international guidelines, all HIV/HCV-coinfected patients should be evaluated and, if eligible, treated with pegylated interferon plus ribavirin. The management of anti-HCV treatment side effects, which may be even more serious in HIV patients, is very important to minimize treatment early discontinuations. The purpose of this review is to supply clinicians with an update, provided by the most recent and relevant literature, of underlying mechanisms, incidence, and advice about the management of pegylated interferon and ribavirin side effects in HCV/HIV-coinfected patients.