Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic liver disease characterized by progressive cholangiocyte and bile duct destruction leading to fibrosis and finally to liver cirrhosis. The presence of disease-specific serological antimitochondrial antibody (AMA) together with elevated alkaline phosphatase (ALP) as a biomarker of cholestasis is sufficient for diagnosis. Ursodeoxycholic acid (UDCA) is the first treatment option for PBC. Up to 40% of patients have an incomplete response to therapy, and over time disease progresses to liver cirrhosis. Several risk scores are proposed for better evaluation of patients before and during treatment to stratify patients at increased risk of disease progression. GLOBE score and UK PBC risk score are used for the evaluation of UDCA treatment and Mayo risk score for transplant-free survival. Liver transplantation (LT) is the only treatment option for end-stage liver disease. More than 10 years after LT, 40% of patients experience recurrence of the disease. A liver biopsy is required to establish rPBC (recurrent primary biliary cholangitis). The only treatment option for rPBC is UDCA, and data show biochemical and clinical improvement, plus potential beneficial effects for use after transplantation for the prevention of rPBC development. Additional studies are required to assess the full impact of rPBC on graft and recipient survival and for treatment options for rPBC.

The liver is the primary site of synthesis for most coagulation factors and the central organ responsible for maintaining hemostatic equilibrium. In individuals with advanced liver disease, significant disruptions in coagulation homeostasis occur and consequently predispose patients to both thrombotic and bleeding complications. This review summarizes the pathophysiologic basics of liver cirrhosis-associated coagulopathies and discusses the diagnosis and treatment of common procoagulant conditions such as portal vein thrombosis and post-transplant hepatic artery thrombosis. The review also systematically addresses the most common bleeding complications, including spontaneous, portal hypertension-related, and periprocedural bleeding. The proper pre-procedural assessment of the bleeding risk is often required due to the great number of invasive procedures to which these patients are frequently subjected. The viscoelastic testing (thromboelastogram and thromboelastometry) seems to emerge as the most appropriate diagnostic method. Specific treatment recommendations for the correction of coagulation abnormalities and the management of severe thrombocytopenia are hereby presented.

Background: Hepatitis C virus (HCV) infection is still one of the leading causes of chronic liver disease with chronically infected making up approximately 1% of the global population. Of those infected, 70% (55-85%) will develop chronic HCV infection. Chronic HCV infection causes substantial morbidity and mortality, with complications including cirrhosis, end-stage liver disease, hepatocellular carcinoma, and eventually death. Objective: Therapeutic options for chronic HCV infection have evolved dramatically since 2014, with a translation from pegylated interferon and ribavirin (associated with suboptimal cure and high treatment-related toxicity) to oral direct-acting antiviral treatment. There are four classes of direct-acting antivirals which differ by their mechanism of action and therapeutic target. They are all pointed to proteins that form the cytoplasmic viral replication complex. Multiple studies have demonstrated that direct-acting antiviral therapy is extremely well tolerated, highly efficacious, with few side effects. Methods: We performed an indexed MEDLINE search with keywords regarding specific direct-acting antiviral regimes and their pharmacokinetics, drug drug interactions, and metabolism in specific settings of pregnancy, lactation, liver cirrhosis, liver transplantation and HCC risk, kidney failure and kidney transplantation. Results: We present a comprehensive overview of specific direct-acting antivirals metabolism and drug drug interaction issues in different settings. Conclusion: Despite its complex pharmacokinetics and possibility of drug drug interactions, direct-acting antivirals extremely high efficacy in providing viral clearance is an obvious advantage compared to possible interactions or side effects. They should be administered cautiously in patients with other comorbidities, and with a tight control of immunosuppressive therapy.

Parallel to the increased use of immune checkpoint inhibitors (ICIs), the incidence of immune-related adverse events (irAEs) is also increasing. Almost all organs can be affected by the immune-mediated response, including the liver, pancreas and biliary tract. Immune-Mediated Hepatitis is a common complication of ICI therapy, while cholangitis, cholecystitis and pancreatic involvement are less frequent. Emerging evidence from clinical trials and real-world data series helps us better understand the risk factors, diagnostic challenges and management strategies for these irAEs. With wider use of ICIs, more data are also available on the management of special populations with comorbidities and patients with difficult-to-treat or treatment-resistant adverse events, but larger prospective studies and more robust evidence are required for further recommendations on their management and ICI reintroduction. In clinical practice, a multidisciplinary approach to the management of ICI-mediated complications is advised, with close collaboration among specialties such as oncologists, gastroenterologists or hepatologists, pathologists, radiologists and others. While Immune-Mediated Hepatitis is a common irAE of ICI therapy, pancreato-biliary involvement is often overlooked and underdiagnosed. These irAEs require multimodal management, development of new biomarkers and prediction models to facilitate decision-making and improve patient outcomes.