Liver Proliferation Is an Essential Driver of Fibrosis in Mouse Models of Nonalcoholic Fatty Liver Disease

Ashley Cast, Meenasri Kumbaji, Amber D'Souza, Katherine Rodriguez, Anita Gupta, Rebekah Karns, Lubov Timchenko, Nikolai Timchenko – 17 July 2019 – Nonalcoholic fatty liver disease (NAFLD) involves development of hepatic steatosis, fibrosis, and steatohepatitis. Because hepatic steatosis appears first in NAFLD animal models, the current therapy development focuses on inhibition of hepatic steatosis, suggesting that further steps of NAFLD will be also inhibited. In this report, we show that the first event of NAFLD is liver proliferation, which drives fibrosis in NAFLD.

Incidence, Risk Factors, and Outcomes of Transition of Acute Kidney Injury to Chronic Kidney Disease in Cirrhosis: A Prospective Cohort Study

Rakhi Maiwall, Samba Siva Rao Pasupuleti, Chhagan Bihari, Archana Rastogi, Pawan Kumar Singh, Vini Naik, Akanksha Singh, Priyanka Jain, Awinash Kumar, Amar Mukund, R.P. Mathur, Guresh Kumar, Shiv Kumar Sarin – 16 July 2019 – Transition to chronic kidney disease (CKD) after an episode of acute kidney injury (AKI) is known in patients without cirrhosis. We studied the incidence and risk factors for development of CKD in patients with cirrhosis. Competing risk analysis was performed to identify risk factors for CKD development.

Acetaminophen Intoxication Rapidly Induces Apoptosis of Intestinal Crypt Stem Cells and Enhances Intestinal Permeability

Daniel M. Chopyk, Johnasha D. Stuart, Matthew G. Zimmerman, Jing Wen, Sanjeev Gumber, Mehul S. Suthar, Manoj Thapa, Mark J. Czaja, Arash Grakoui – 15 July 2019 – Acetaminophen (APAP)‐induced liver injury is the most common cause of acute liver failure (ALF) in the Western world. APAP toxicity progresses to multiorgan dysfunction and thus has broader whole‐body implications. Importantly, greater 30‐day mortality has been observed in liver transplant recipients following ALF due to APAP‐related versus non‐APAP‐related causes. Reasons for this discrepancy have yet to be determined.

PNPLA3 I148M Variant Impairs Liver X Receptor Signaling and Cholesterol Homeostasis in Human Hepatic Stellate Cells

Francesca Virginia Bruschi, Thierry Claudel, Matteo Tardelli, Patrick Starlinger, Fabio Marra, Michael Trauner – 15 July 2019 – The patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) I148M variant predisposes to hepatic steatosis and progression to advanced liver injury with development of fibrosis, cirrhosis, and cancer. Hepatic stellate cells (HSCs) drive the wound healing response to chronic injury, and lack of liver X receptor (LXR) signaling exacerbates liver fibrogenesis by impairing HSC cholesterol homeostasis.

A National Hospital‐Based Study of Hospitalized Patients With Primary Biliary Cholangitis

Valerio Manno, Alessio Gerussi, Marco Carbone, Giada Minelli, Domenica Taruscio, Susanna Conti, Pietro Invernizzi – 15 July 2019 – Epidemiological studies on primary biliary cholangitis (PBC) have been based primarily on tertiary referral case series. We aimed to estimate the incidence and prevalence and describe comorbidities in hospitalized patients with PBC in Italy using a national hospital‐based data source. Data were extracted from the National Hospital Discharge Database, which includes all Italian individuals discharged from any hospital in the country.

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