Drug-induced liver injury associated to red yeast rice.

Hepatotoxicity is defined as a liver injury induced by a drug or a non-pharmacological agent like herbal medications or dietary supplements. Red yeast rice is rich in monacolin K, which has the same chemical structure as lovastatin, reason why it has been used for the management of hiperlipidemia. A 62 years old woman presented to the emergency service with 38.5ºC fever, coluric orine and loss of weight in the previous 3 weeks. The patient was taking RYR since the week before to the initial symptoms. Mixed hepatocellular and cholestatic acute hepatitis was diagnosed. Autoimmune liver serology resulted positive. Total DILI RECAM Score was 8 (highly probable DILI). Conservative treatment with exclusion of RYR was decided and during follow-up bilirubin and transaminases gradually dropped off. It has been reported a few cases of hepatitis associated to the use of RYR, promoted by a toxic or immunogenic metabolite. Cross-reactions may justify positive autoantibodies so hepatotoxicity should not be discard as a diagnose.

Dynamic Changes in Non-Invasive Markers of Liver Fibrosis Are Predictors of Liver Events after SVR in HCV Patients.

Objectives: The course of progressive liver damage after achieving sustained virological response (SVR) with direct-acting antivirals (DAAs) remains undetermined. We aimed to determine risk factors associated with the development of liver-related events (LREs) after SVR, focusing on the utility of non-invasive markers. Methods: An observational, retrospective study that included patients with advanced chronic liver disease (ACLD) caused by hepatitis C virus (HCV), who achieved SVR with DAAs between 2014 and 2017. Patients were followed-up until December 2020. LREs were defined as the development of portal hypertension decompensation and the occurrence of hepatocellular carcinoma (HCC). Serological markers of fibrosis were calculated before treatment and one and two years after SVR. Results: The study included 321 patients, with a median follow-up of 48 months. LREs occurred in 13.7% of patients (10% portal hypertension decompensation and 3.7% HCC). Child-Pugh [HR 4.13 (CI 95% 1.74; 9.81)], baseline FIB-4 [HR 1.12 (CI 95% 1.03; 1.21)], FIB-4 one year post-SVR [HR 1.31 (CI 95% 1.15; 1.48)] and FIB-4 two years post-SVR [HR 1.42 (CI 95% 1.23; 1.64)] were associated with portal hypertension decompensation. Older age, genotype 3, diabetes mellitus and FIB-4 before and after SVR were associated with the development of HCC. FIB-4 cut-off values one and two years post-SVR to predict portal hypertension decompensation were 2.03 and 2.21, respectively, and to predict HCC were 2.42 and 2.70, respectively. Conclusions: HCV patients with ACLD remain at risk of developing liver complications after having achieved SVR. FIB-4 evaluation before and after SVR may help to predict this risk, selecting patients who will benefit from surveillance.

HCV microelimination strategies: An interventional study in diagnosed patients without access to the system.

Hepatitis C virus (HCV) one-step diagnosis improves recovery in patients with active infection. However, patients with previous anti-HCV+ may be excluded. We aimed to identify and retrieve non-referred or lost-to-follow-up HCV-infected patients. All anti-HCV+ patients seen in our hospital between 2013 and 2018 were included. In the first phase, we identified anti-HCV+ patients who were not referred to the Gastroenterology Unit (GU) or lost-to-follow-up. In the second phase, recovered patients were invited for a one-step visit for liver evaluation. A total of 1330 anti-HCV+ patients were included: 21.7% had not been referred to GU, and 23.1% were lost-to-follow-up. In the second phase, 49.6% of patients were contacted, and 92.8% attended a medical consultation: 62.7% had active infection, 92.2% were treated, and 86.5% achieved SVR (ITT). We concluded that screening microbiological data and referring unidentified patients with active HCV infection directly to specialists is an effective tool in achieving HCV microelimination.

Liver manifestations in COVID-19 and the influence of pre-existing liver disease in the course of the infection.

INTRODUCTION: patients with advanced chronic liver disease (CLD) may be at an increased risk of a severe course due to cirrhosis-associated immune dysfunction. The aim of this study was to determine the prevalence of CLD in COVID-19 patients and to analyze the course of the infection, compared with patients with non-liver disease. MATERIALS AND METHODS: this was a retrospective single center study of all patients with a positive SARS-CoV-2 polymerase chain reaction (PCR) test from March 23rd to April 30th, 2020. Clinical and biochemical data of patients with and without CLD and COVID-19 were collected from the medical records. RESULT: four hundred and forty-seven patients with a SARS-CoV-2 positive PCR were included, 6.3 % had CLD; 69.7 % of patients with CLD were male, with a median age of 65.5 years and active alcohol consumption and smoking; 75 % had non-advanced liver fibrosis and most had non-alcoholic fatty liver disease (NAFLD). The hospital admission rate (92.9 % vs 47.7 %, p < 0.001), concomitant comorbidities (diabetes 38.5 vs 16.5 %, p = 0.011; obesity 30.8 vs 8.5 %, p = 0.033; cancer 23.1 vs 5 %, p = 0.027; and chronic obstructive pulmonary disease (COPD) 19.2 vs 9 %, p = 0.009) and concomitant antibiotics treatment (19.3 vs 5 %, p = 0.018) were higher in patients with CLD than in those without CLD. In-patient hospital mortality rates were similar in both groups (30.8 vs 19.6 %, p = 0.289). The presence of CLD was not associated with mortality (OR = 1.06; 95 % CI = 0.35-3.18; p = 0.924). However, patients with CLD and COVID-19 who were male, obese or under concomitant antibiotic treatment had the highest risk of mortality according to the univariate analysis. CONCLUSION: patients with CLD had a higher risk of hospital admission, with worse outcomes during the COVID-19 infection associated to other concomitant comorbidities and a suspicion of bacterial co-infection.

Chronic hepatitis C patients lost in the system: predictive factors of non-referral or loss of follow-up in Hepatology units.

INTRODUCTION: several barriers remain in the hepatitis C care cascade, which need to be removed in order to eliminate chronic hepatitis C. These barriers include deficiencies in screening and confirmatory diagnosis as well as difficulties in accessing treatment. AIMS: to identify factors associated with the non-referral of patients with positive hepatitis C virus (HCV) antibodies and to identify factors associated with loss of follow-up or non-attendance of these patients to specialist consultation after referral. METHODS: observational and retrospective single-center-study, including all positive HCV serology tests performed between January 2013 and May 2018, in the Virgen Macarena health area (Seville, Spain) before implementing the one-step diagnosis. Non-referred patients and patients who were lost to follow-up after being referred were identified. RESULTS: a total of 54 (77.4 %) patients diagnosed in Primary Care (PC) and 54 (22.2 %) from hospital specialists were not referred (p < 0.001). Predictors for non-referral were: stay in prison/institutionalization (p = 0.04), suffering chronic obstructive pulmonary disease (COPD) (p = 0.07), a normal AST value (p = 0.034) or test requested by Primary Care physician (PCP) (p = 0.004). Patients referred from PC were more likely to be lost to follow-up than those referred from hospital specialists (p < 0.001). Predictors of follow-up loss included: opioid replacement therapy (p = 0.034), absence of high blood pressure (p = 0.039) and test requested by PCP (p = 0.049). CONCLUSIONS: a high percentage of patients with positive HCV serology were not referred or were lost to follow-up, mainly those belonging to high risk social groups or those with associated comorbidities. Patients with average values of transaminases or those diagnosed in PC were also less frequently referred.

Long-term follow-up of patients with chronic hepatitis C treated with α-interferon and ribavirin antiviral therapy: clinical and fibrosis impact of treatment response.

BACKGROUND AND GOALS: The slow progression of chronic hepatitis C (CHC) infection requires long observation periods to detect clinical changes. We compare the incidence of clinical events, hepatocellular carcinoma (HCC), overall mortality, liver-related mortality, and fibrosis progression between patients with a sustained virological response (SVR) and nonresponders (NR) after a 13-year follow-up period. STUDY: One hundred and eighty-two CHC patients, who received interferon and ribavirin treatment between 1996 and 2000, were included. Clinical events were evaluated during follow-up. At the end of follow-up, transient elastography was used to assess fibrosis progression. RESULTS: Of the 182 patients, 46.7% (n=85) achieved an SVR. Twenty-seven patients developed hepatic decompensation (one SVR) and 15 developed HCC (three SVR). Twenty-nine patients died (eight SVR). Twelve of the 29 deaths were liver related (two SVR). Independent factors associated with hepatic decompensation were NR to treatment [hazard ratio (HR)=23.35; 95% confidence interval (CI): 2.90-189.25; P=0.003], advanced fibrosis at baseline (HR=9.11; 95% CI: 4.13-20.09), and treatment delay after diagnosis (HR=1.02; 95% CI: 1.00-1.03; P=0.012). Only the latter two were associated with HCC development and liver-related mortality. An assessment of liver fibrosis was performed on 125 patients (66 SVR). Fibrosis values were significantly lower in SVR patients, showing less progression to advanced stages of fibrosis [SVR: 6.6 (2.8); 95% CI: 5.8-7.3] than NR [NR: 14.0 (11.1); 95% CI: 11.1-16.9; P<0.001]. CONCLUSION: In patients with CHC, SVR is durable and reduces clinical events. The risk of HCC development is lower, but not eliminated. Sustained responders showed fibrosis stabilization or improved fibrosis values.

Is safety infliximb during pregnancy in patients with inflammatory bowel disease?

BACKGROUND: in most cases, inflammatory bowel disease (IBD) debuts at reproductive age. The data available in the literature show infliximab (IFX) to be a safe drug during pregnancy but there is very little evidence about the activity of the disease following drug withdrawal during pregnancy. AIMS: determine the drug's safety in pregnant women in our setting and assess its effect on the foetus, drawing on the experience of several hospitals. Secondly, observe the effect of treatment withdrawal on disease activity during pregnancy. MATERIAL AND METHODS: a retrospective study was conducted of women with IBD who had received IFX treatment during pregnancy in five hospitals in Spain. Disease activity was assessed using Crohn's Disease Activity Index, while UC was assessed using the Truelove-Witts Index in each trimester of pregnancy. Gestational age, weight and diseases in the foetus were determined at birth. RESULTS: the study included 12 women with a mean age of 29 years; 4 had ulcerative colitis and 8 Crohn's disease, with mean disease duration of 7 years. All but one, who was diagnosed during pregnancy, was receiving IFX treatment at conception. Six patients received uninterrupted treatment throughout the pregnancy, 2 requested voluntary interruption and in 3 cases treatment was interrupted in the third trimester as a precaution. They received a mean IFX dose of 400 mg every 8 weeks. Of the 6 patients who received continuous treatment, in 50% disease was held in remission. The 6 remaining patients suspended treatment for different reasons, presenting disease recurrence in all but one case (83.3%). Eight deliveries were vaginal and 4 by caesarean section. Newborns presented no congenital anomalies, intrauterine growth retardation or low birth weight and there was only one premature delivery. CONCLUSIONS: although cases included in the study are not significant, in our experience, IFX during pregnancy is a safe treatment for the mother and the foetus. In fact, in our study and in some cases, its withdrawal may lead to a worsening of the disease. However, further control studies are required with larger samples to obtain more representative findings.