This review describes the influence of ethanol consumption on hepatic lipophagy, a selective form of autophagy during which fat-storing organelles known as lipid droplets (LDs) are degraded in lysosomes. During classical autophagy, also known as macroautophagy, all forms of macromolecules and organelles are sequestered in autophagosomes, which, with their cargo, fuse with lysosomes, forming autolysosomes in which the cargo is degraded. It is well established that excessive drinking accelerates intrahepatic lipid biosynthesis, enhances uptake of fatty acids by the liver from the plasma and impairs hepatic secretion of lipoproteins. All the latter contribute to alcohol-induced fatty liver (steatosis). Here, our principal focus is on lipid catabolism, specifically the impact of excessive ethanol consumption on lipophagy, which significantly influences the pathogenesis alcohol-induced steatosis. We review findings, which demonstrate that chronic ethanol consumption retards lipophagy, thereby exacerbating steatosis. This is important for two reasons: (1) Unlike adipose tissue, the liver is considered a fat-burning, not a fat-storing organ. Thus, under normal conditions, lipophagy in hepatocytes actively prevents lipid droplet accumulation, thereby maintaining lipostasis; (2) Chronic alcohol consumption subverts this fat-burning function by slowing lipophagy while accelerating lipogenesis, both contributing to fatty liver. Steatosis was formerly regarded as a benign consequence of heavy drinking. It is now recognized as the “first hit” in the spectrum of alcohol-induced pathologies that, with continued drinking, progresses to more advanced liver disease, liver failure, and/or liver cancer. Complete lipid droplet breakdown requires that LDs be digested to release their high-energy cargo, consisting principally of cholesteryl esters and triacylglycerols (triglycerides). These subsequently undergo lipolysis, yielding free fatty acids that are oxidized in mitochondria to generate energy. Our review will describe recent findings on the role of lipophagy in LD catabolism, how continuous heavy alcohol consumption affects this process, and the putative mechanism(s) by which this occurs.

Background: Portal vein thrombosis (PVT) would exert a further increase in resistance to portal blood flow, resulting in worsening portal hypertension and poor outcome. This study aimed to identify risk factors and develop an clinically applicable dynamic nomogram predicting the occurrence of PVT in cirrhotic patients during primary prophylaxis for variveal hemorrhage (VH).Methods: The multi-center retrospective study enrolled cirrhotic patients with high-risk varices, which were further divided into training and validation cohorts for 3 years follow-up. A dynamic nomogram based on the Cox proportional hazard regression model was developed with the cutoff value calculated by X-title analysis. The performance of the nomogram was evaluated with Harrell’s concordance index (C-index), calibration curve and decision curve analysis.Results: 91 (34.0%) of the whole cohort were diagnosed with PVT during 3-year follow-up. Variables including carvedilol (P < 0.001), low portal vein velocity (P < 0.001), increased size of esophageal varices (P = 0.005), and high HbA1c (P < 0.001) and procalcitonin (P = 0.015) were identified to be independently associated with PVT, which were further incorporated into the dynamic nomogram with optimal cutoff (8.8 and 14.6) for risk-stratification. The C-indexes (0.894 of internal validation and 0.892 of external validation) and calibration curves demonstrated ideal discrimination and calibration. The thresholds for more reasonable application of the nomogram were 0–0.27, 0–0.66, and 0.04–1.00 at 1, 2, and 3-year, respectively.Conclusion: The dynamic nomogram could be accurately and reliably used for clinical risk-stratification of PVT in cirrhotic patients during primary prophylaxis for VH.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease, affecting 25% of world population. Hepatic steatosis has 60–90% prevalence among obese patients. It is also associated with multitude of detrimental effects and increased mortality. This narrative chapter investigates hepatic lipid homeostasis in NAFLD, focusing on the four molecular pathways of hepatic steatosis to lipid homeostasis in the liver. Hepatic steatosis is a consequence of lipid acquisition pathways exceeding lipid disposal pathways. In NAFLD, hepatic uptake of fatty acids and de novo lipogenesis surpass fatty acid oxidation and lipid export. The imbalance of the hepatic lipid may promote cellular damage by inducing oxidative stress in peroxisomes and cytochromes, especially with compromised mitochondrial function. Lipid export may even decrease with disease progression, sustaining the accumulation of lipids. NAFLD has a complex molecular mechanism regulating hepatic lipid homeostasis. Thus, as well as inter-individual differences, any intervention targeting one or more pathway is likely to have consequences on multiple cellular signaling pathways. We should be taken into careful consideration when developing future treatment options for NAFLD.