Consensus Guidelines: Best Practices for Detection, Assessment and Management of Suspected Acute Drug-Induced Liver Injury During Clinical Trials in Adults with Chronic Viral Hepatitis and Adults with Cirrhosis Secondary to Hepatitis B, C and Nonalcoholic Steatohepatitis.

With the widespread development of new drugs to treat chronic liver diseases (CLDs), including viral hepatitis and nonalcoholic steatohepatitis (NASH), more patients are entering trials with abnormal baseline liver tests and with advanced liver injury, including cirrhosis. The current regulatory guidelines addressing the monitoring, diagnosis, and management of suspected drug-induced liver injury (DILI) during clinical trials primarily address individuals entering with normal baseline liver tests. Using the same laboratory criteria cited as signals of potential DILI in studies involving patients with no underlying liver disease and normal baseline liver tests may result in premature and unnecessary cessation of a study drug in a clinical trial population whose abnormal and fluctuating liver tests are actually due to their underlying CLD. This position paper focuses on defining best practices for the detection, monitoring, diagnosis, and management of suspected acute DILI during clinical trials in patients with CLD, including hepatitis C virus (HCV) and hepatitis B virus (HBV), both with and without cirrhosis and NASH with cirrhosis. This is one of several position papers developed by the IQ DILI Initiative, comprising members from 16 pharmaceutical companies in collaboration with DILI experts from academia and regulatory agencies. It is based on an extensive literature review and discussions between industry members and experts from outside industry to achieve consensus regarding the recommendations. Key conclusions and recommendations include (1) the importance of establishing laboratory criteria that signal potential DILI events and that fit the disease indication being studied in the clinical trial based on knowledge of the natural history of test fluctuations in that disease; (2) establishing a pretreatment value that is based on more than one screening determination, and revising that baseline during the trial if a new nadir is achieved during treatment; (3) basing rules for increased monitoring and for stopping drug for potential DILI on multiples of baseline liver test values and/or a threshold value rather than multiples of the upper limit of normal (ULN) for that test; (4) making use of more sensitive tests of liver function, including direct bilirubin (DB) or combined parameters such as aspartate transaminase:alanine transaminase (AST:ALT) ratio or model for end-stage liver disease (MELD) to signal potential DILI, especially in studies of patients with cirrhosis; and (5) being aware of potential confounders related to complications of the disease being studied that may masquerade as DILI events.

COVID-19 and liver disease: An update. / Actualización en COVID-19 y enfermedad hepática.

The SARS-CoV-2 pandemic has proven to be a serious challenge for the Spanish healthcare system. The impact of the virus on the liver is not well known, but in patients with chronic liver disease, mostly in advanced stages, it can critically compromise survival and trigger decompensation. Treatment in this subpopulation is complex due to the potential hepatotoxicity of some of the medicinal products used. Moreover, the pandemic has also negatively impacted patients with liver disease who have not contracted COVID-19, since the reallocation of human and material resources to the care of patients with the virus has resulted in a decrease in the treatment, diagnosis and follow-up of patients with liver disease, which will surely have negative consequences in the near future. Efficient reorganization of hepatology units is a priority to minimise the impact of the pandemic on a population as vulnerable as liver disease patients.

Assessment of depression and anxiety in patients with chronic liver disease.

BACKGROUND/AIM: In recent years mental health of patients including those with chronic liver disease (CLD), has become interesting because its disturbance leads to reduced quality of life, that is associated with worsening of clinical outcome, reduced compliance and increased mortality. The aim of the study was to determinate the frequency and severity of depression and frequency of anxiety in patients with CLD and to assess the contribution of selected socio-demographic, clinical and laboratory risk factors for depression and anxiety. METHODS: In this cross-sectional study, we used the Hamilton depression rating scale (HDRS) and Hamilton anxiety rating scale (HARS) in patients with CLD. RESULTS: The study included 54 male and 43 female patients. Depression was present in 62.9%, and anxiety in 13.4% of the patients. A higher HDRS was noted in the patients older than 50 years (p = 0.022) and unemployed patients (p = 0.043). The patients with at least one episode of gastrointestinal bleeding had a significantly higher frequency of anxiety than those without bleeding (p = 0.018). A higher HARS score was present in the women (p = 0.011), unemployed patients (p = 0.008) and those with non-alcoholic liver disease (p = 0.007). There was a significant correlation between the mean corpuscular volume (MCV) and the value of the HDRS score, and between serum potassium and sodium levels and HDRS score. CONCLUSION: Age and the mean corpuscular volume have significant influence on the HDRS score while unemployment, gastrointestinal bleeding, serum potassium and serum sodium have predictive value for HARS score.

Epidemiology and management of chronic hepatitis E infection in solid organ transplantation: a comprehensive literature review.

Hepatitis E virus (HEV) infection has emerged as a global public health issue. Although it often causes an acute and self-limiting infection with low mortality rates in the western world, it bears a high risk of developing chronic hepatitis in immunocompromised patients with substantial mortality rates. Organ transplant recipients who receive immunosuppressive medication to prevent rejection are thought to be the main population at risk for chronic hepatitis E. Therefore, there is an urgent need to properly evaluate the clinical impact of HEV in these patients. This article aims to review the prevalence, infection course, and management of HEV infection after solid organ transplantation by performing a comprehensive literature review. In addition, an in-depth emphasis of this clinical issue and a discussion of future development are also presented.

Assessment of sexual functions in patients with chronic liver disease.

We aimed to determine the sexual problems and the prevalence of erectile dysfunction (ED) in patients with chronic liver disease by means of International Index of Erectile Function (IIEF). A total of 81 patients with stable chronic liver disease were included in the study. Patients were grouped as mild to moderate (Child Pugh A and B) (n=10), chronic hepatitis (hepatitis B, C and D) (n=28) and carriers (n=43) according to the type of their chronic liver disease. All patients were asked to complete a questionnaire including IIEF and demographics. The IIEF domain scores were calculated and ED grading was determined on erectile function domain. IIEF domain scores were compared between these groups. The mean age was 54.8 +/- 10.8 y. Using the IIEF, the prevalence of any ED was 50.6% for all patients, and 50, 50, and 51.1% for cirrhosis, chronic hepatitis and carriers, respectively. The IIEF domain scores were not significantly different among the patient groups. Sexual functions did not appear to be affected by the stable chronic liver disease.