Bile acids (BA) as important signaling molecules are considered crucial in development of cholestatic liver injury, but there is limited understanding on the involved cell types and signaling pathways. The aim of this study was to evaluate the inflammatory and fibrotic potential of key BA and the role of distinct liver cell subsets focusing on the NLRP3 inflammasome. C57BL/6 wild-type (WT) and Nlrp3^−/− mice were fed with a diet supplemented with cholic (CA), deoxycholic (DCA) or lithocholic acid (LCA) for 7 days. Additionally, primary hepatocytes, Kupffer cells (KC) and hepatic stellate cells (HSC) from WT and Nlrp3^−/− mice were stimulated with aforementioned BA ex vivo. LCA feeding led to strong liver damage and activation of NLRP3 inflammasome. Ex vivo KC were the most affected cells by LCA, resulting in a pro-inflammatory phenotype. Liver damage and primary KC activation was both ameliorated in Nlrp3-deficient mice or cells. DCA feeding induced fibrotic alterations. Primary HSC upregulated the NLRP3 inflammasome and early fibrotic markers when stimulated with DCA, but not LCA. Pro-fibrogenic signals in liver and primary HSC were attenuated in Nlrp3^−/− mice or cells. The data shows that distinct BA induce NLRP3 inflammasome activation in HSC or KC, promoting fibrosis or inflammation.

Shear wave elastography and shear wave dispersion imaging in primary biliary cholangitis—a pilot study Marten Schulz, Anne-Christin B. Wilde, Münevver Demir, Tobias Müller, Frank Tacke, Alexander Wree

Steatosis is a condition of hepatic fat overload that is associated with overweight and the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease with a global impact on healthcare. A proportion of NAFLD patients develops nonalcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis or hepatocellular carcinoma (HCC). Identifying patients at risk for potentially life-threatening complications is crucial in their prevention, surveillance and treatment. In addition to hepatic disease progression (cirrhosis, portal hypertension, HCC), NAFLD patients are also at risk of cardiovascular and metabolic diseases as well as extrahepatic malignancies. Liver fibrosis is related to morbidity and mortality in NASH patients, and biomarkers, imaging techniques (ultrasound, elastography, MRI) as well as liver biopsy help in diagnosing fibrosis. In this review, we discuss the tools for identifying patients at risk and their reasonable application in clinical routine in order to stratify prevention and treatment of this emerging disease.

Hepatic sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD) can be a life-threatening complication after hematopoietic stem cell transplantation (HSCT). Diagnosis is often difficult and traditionally based on clinical parameters. Shear wave elastography (SWE) is a modern non-invasive liver stiffness measurement technique using ultrasound. In this monocentric study, we evaluated the role of SWE in diagnosing SOS/VOD in 63 adult patients undergoing HSCT from February 2020 to August 2020 in real world settings. Three patients developed SOS/VOD. This was accompanied by an increase in shear wave velocity in all three patients, indicating that this method may contribute to establishing the diagnosis SOS/VOD after HSCT.

Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries which is usually characterized by a self-limited course. However, there is an increased risk of HEV persistence in immunocompromised risk populations, comprising patients following solid organ transplantation or hematological malignancies. Recently, chronic HEV infection following rituximab-containing treatment regimens has been described. Here we report five patients with chronic hepatitis E after prior rituximab therapy for various indications. We determined the immunological characteristics of these patients and analyzed the development of ribavirin (RBV) treatment failure-associated mutations in the HEV genome. One patient became chronically HEV-infected 110 months after administration of rituximab (RTX). Immunological characterization revealed that all patients exhibited significant hypogammaglobulinemia and CD4+ T cell lymphopenia. One patient permanently cleared HEV following weight-based ribavirin treatment while three patients failed to reach a sustained virological response. In depth mutational analysis confirmed the presence of specific mutations associated with RBV treatment failure in these patients. Our cases indicate that rituximab-containing treatment regimens might imply a relevant risk for persistent HEV infection even years after the last rituximab application. Moreover, we provide further evidence to prior observations suggesting that chronically HEV infected patients following RTX-containing treatment regimens might be difficult to treat.