Macrophages M1 polarization Hepatocytes Lipid accummulation inflammatory response p38α Steatohepatitis TNFα CXCL10 IL-6 Highlights p38a expression is increased in livers of human patients with non-alcoholic fatty liver diseases. Macrophage p38a induces experimental steatohepatitis. Macrophage p38a causes M1 macrophage polarization. p38a deleted macrophages attenuate steatohepatitic changes in hepatocytes. Pharmacological p38 inhibitors prevent steatohepatitis in mice.

Prognostication of patients with cirrhosis is complex, depending on more than just the severity of liver disease. Scores such as the model for end-stage liver disease (MELD) and Child Pugh can assist with prognostication, yet by focusing on physiological parameters they fail to completely capture the elements contributing to a patient's clinical status. Evidence is increasing to support an important role for physical functioning in patient outcomes. Frailty has been increasingly recognised in medical literature over recent years, including in hepatology where it is identified in nearly half of cirrhosis patients. It is a complex construct consisting of multisystemic physiological decline and increased vulnerability to stressors. Diagnosis is complicated by lack of a consensus definition and measurement tool for frailty in cirrhosis. Frailty heralds a poor prognosis, predicting increased morbidity and mortality both pre- and postliver transplant, independent of MELD score. It is thought to be reversible, with promising data supporting prehabilitation and lifestyle intervention programs. In the future, assessment of patients with cirrhosis is likely to incorporate a measure of frailty, however, further research is required.