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Objective: To evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19. Design: This interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death. Results: 152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F40 U/L (P60 years) patients with comorbidities are characterized by worse outcome.

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.

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&nbsp

We read with great interest the letter by Kawada in which the studies assessing colchicine as a treatment for COVID-19 were reviewed.1 Given its known inhibitory effect on NACHT-LRRPYD-containing protein 3 inflammasome2 and its possible antiviral properties,2 colchicine was hypothesised as a candidate therapy for COVID-19 since the very beginning of the pandemic.3 4 To the best of our knowledge, our observational retrospective study5 reported on the largest number of patients with COVID-19 treated with colchicine (122 consecutive patients), and they were compared with a control group treated with the Standard of Care (SoC, 140 consecutive patients).5 Kawada underlined the effectiveness of colchicine in reducing mortality and the need for non-invasive ventilation, as shown by different studies.5–7 After the hospital discharge, we observed additional deaths in patients treated with colchicine and in those treated with SoC (p=0.25). The long-term analysis of our cohort confirmed the original description of improved survival for patients treated with colchicine (mortality rate at 270 days: colchicine 20% vs SoC 44%; p=0.0001). We would like to point out the statement by Kawada reporting that ferritin and arterial oxygen tension (or pressure) (PaO2 …

ObjectivesThe 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).MethodsIn 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).ResultsPatients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%)vs63.6% (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), pConclusionThis 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.

Background: HIV positive patients may be affected by hypertransaminasemia notwithstanding they are not co- infected with HCV and HBV. Aims: To understand the causes of this abnormality and what correlates are in terms of ultrasonic transient elastography (UTE) and ultrasonography (U) features and fibrosis scores. Methods: HIV positive patients with hypertransaminasemia have been studied. They underwent UTE and U. Non-invasive fibrosis scores (APRI and FIB-4) were calculated. Moreover, they underwent immunological and virological tests to exclude known causes of liver damage (including alcohol abuse). Results: Among 24 patients, 3 presented a progressive fibrosis at UTE. 3/3 with progressive fibrosis and further 14 patients among the entire sample had steatosis at U. Using non-invasive fibrosis scores, no patients had significant fibrosis, while 5 patients had mild fibrosis. 14 patients had hepatomegaly independently from steatosis. One patient has progressive fibrosis at UTE and mild fibrosis at both APRI and FIB-4, while 2 patients had fibrosis only at UTE, 2 only at APRI and 1 at both APRI and FIB-4, but not at UTE. Alcoholaemia was negative in all patients, confirming anamnestic information. No other causes of liver disease were found. Conclusions: In this series, more than 50% of patients had steatosis at U. Discordance between the non-invasive methods to estimate liver fibrosis were found. Further prospective studies are necessary to assess concordance between these methods and liver biopsy and assess the prognostic value of UTE, APRI and FIB-4 for liver complications in HIV mono- infected patients so as to improve diagnostic algorithms.

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.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.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-43.25 was 0.013 per PYFU (95% CI, 0.010-0.017) and 0.018 per PYFU (95% CI, 0.014-0.022) for APRI1.5. In multivariate analyses, for transition to higher classes, HIV RNA level500 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-43.25 and APR I1.5 as study outcomes.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.

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.

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.

Measures of glomerular filtration rate (GFR) showed discordant results. CKD-EPI creatinine formula resulted more accurate than other equations in subjects with normal or mildly decreased renal function in the general population and cystatin C could be even a more sensitive measure. As for lipids, lipoprotein subfractions were suggested to be more informative on the cardiovascular risk than the commonly used cholesterol subfractions, with protection conferred especially by HDLp-small (Baker et al. JID 2010). Prospective evaluation of all these markers upon initiation of standard HAART regimens is lacking. We conducted a small, intensive, randomized study in naive HIV-infected patients comparing TDF/FTC+ATV/r versus TDF/FTC+EFV as first-line therapy for these novel markers. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P85 Cite this article as: Izzo et al.: A magnifying glass onto renal function and serum lipid evolutions after tenofovir (TDF) and emtricitabine (FTC) in combination with atazanavir/ritonavir (ATV/r) versus efavirenz (EFV) as first-line HAART (the INCA trial). Journal of the International AIDS Society 2010 13(Suppl 4):P85. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113092/

Introduction Chronic GVHD (cGVHD) is the most common non-relapse problem in long-term survivors after allogeneic stem cell transplantation (SCT). Liver is a commonly target-organ, being often refractory to immunosuppressive therapy. Hepatic cGVHD develops generally as an indolent cholestatic disease or as an autoimmune hepatitis. Both primary biliary cirrhosis and cGVHD show some analogies in the damage of bile ducts. Liver biopsy specimens show degeneration of the small bile ducts, portal fibrosis and are helpful to confirm the diagnosis and the prognosis of hepatic cGVHD. However, liver biopsy is not always feasible, because it may generate clinical complications such as bleeding and infections. Transient hepatic elastography (FibroScan) is a new, fast and non-invasive technique to measure liver stiffness. FibroScan has been validated to detect significant positive relationship between liver stiffness values and histological fibrosis in chronic liver diseases such as chronic hepatitis B and C, cirrhosis and, primary biliary cirrhosis. Being fibrosis a hallmark of cGVHD, we prospectively evaluated the usefulness of FibroScan as non-invasive tool to make diagnosis of liver cGVHD. Patients and methods Liver stiffness measurements were performed on 10 healthy subjects and on 18 patients undergoing allogeneic SCT (15 with related and 3 with unrelated donor) before transplantation, then every 3 months and at the diagnosis of cGVHD. Median age was 42 years (range, 22–62); 61% of patients were male. 72% received a reduced intensity conditioning and stem cells source was mainly peripheral blood (83%). Cyclosporine A and short course of methotrexate were used for GVHD prophylaxis. One patient was HCV RNA-positive. No patients had any sign of liver disease at transplantation. In transient elastography (TE), only procedures with at least ten successful acquisitions and a success rate of at least 60% were considered reliable. The median value of successful measurements was considered representative of the liver stiffness in a given patient, only if the interquartile range (IQR) of all validated measurements was less than 30% of the median value. Results were expressed in kilopascals (kPa). Wilcoxon test was used for statistical analysis of the data. Results Eight patients (44%) developed cGVHD at a median time of 5 months (range, 4–6). cGVHD was extensive in 6 patients (75%) with a median onset time of 6 months (range, 4–10). Liver was involved in 6 patients (75%). Liver stiffness values did not differ significantly in healthy subjects, patients before allo-SCT and patients after allo-SCT without cGVHD. Patients with hepatic cGVHD had higher stiffness values than healthy subjects (7,7 ± 4,6 vs 4,6 ± 1,5 kPa, p=0,03) and than patients without cGVHD (7,7 ± 4,6 vs 4,6 ± 1,9 kPa, p=0,03). Furthermore, liver stiffness values were higher in all patients with cGVHD than in healthy subjects (7 ± 3,9 vs 4,6 ± 1,5 kPa, p=0,04) and patients without cGVHD (7 ± 3,9 vs 4,6 ± 1,9 kPa, p=0,04). A trend to higher liver stiffness in patients with cGVHD was observed at 3rd month as well (6,4 ± 2,5 vs 4,6 ± 1,5 kPa, p=0,05). Discussion Our prospective study suggests that FibroScan could be a reliable non-invasive technique for the early diagnosis of hepatic cGVHD, which could replace liver biopsy in the future. In addition, TE could be an effective procedure to assess disease progression or response to therapy. However, it was not possible to demonstrate significantly different stiffness values in the setting of cGVHD between patients with and without liver involvement. The small number of patients included in the survey or a clinically silent involvement of liver in all cases of cGVHD may account for this observation. Further studies could support these preliminary results and answer to other interesting open questions.

Purpose of the study: Liver fibrosis (LF) progression is fated to become one of the major long-term complications in HIV patients, even in those without HCV or HBV co-infections (HIV-mono-infected). The aim of this study was to assess LF progression in HIV-mono-infected patients and associated risk factors. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P92 Cite this article as: Mendeni et al.: Liver fibrosis: concordance analysis between APRI and FIB-4 scores, evolution and predictors in a cohort of HIV patients without HCV and HBV infection. Journal of the International AIDS Society 2010 13(Suppl 4):P92. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113100/