Alcoholic liver disease (ALD) continues to be a major metabolic liver disease in the world and is responsible for at least one third of 1.8 million annual deaths caused by cirrhosis and liver cancer. It is a disease caused by alcohol addiction but its initiation and progression are also predicated by secondary genetic and environmental factors. Its pathologic spectra are manifested by diverse and complex layers of cellular perturbation caused by metabolism of a simple molecule, ethyl alcohol. Alcoholic hepatitis defined as acute on chronic liver failure, is a very unique entity with high short-term mortality and limited therapeutic options. However, last three decades have witnessed remarkable advancements in our understanding of molecular mechanisms underlying the disease which even shaped basic science at the most fundamental level. Indeed, the ALD field has always been a forefront of research on oxidant stress, organelle stress, gut dysbiosis, endotoxin, inflammasome, macrophage and hepatic stellate cell biology, tumorigenesis, and metabolic reprogramming. Based on these new findings and better stratification of patients, novel therapeutic approaches have emerged and are being tested. This article will review the current understanding of molecular mechanisms of ALD and important challenges our society faces with the disease.

Chronic alcohol abuse elicits a wide spectrum of liver diseases ranging from fatty liver to cirrhosis. The initial, modest form of alcoholic liver disease (ALD) is fatty liver, which is reversible upon abstinence, whereas alcoholic hepatitis results in advanced fibrosis and hepatocarcinogenesis. Only a portion of heavy drinkers develop advanced liver diseases, which cannot be simply explained by the differences in genetic polymorphisms of alcohol metabolizing enzymes. Susceptibility to ALD varies among various ethnic groups and gender, and genetic factors such as patatin-like phospholipase encoding 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), and membrane bound O-acyltransferase domain containing 7 (MBOAT7) share a certain role as similar to nonalcoholic steatohepatitis (NASH). Emerging lines of evidence indicate that novel forms of cell death (necroptosis and pyloptosis), dysbiosis of gut microbiota, and altered innate immune responses profoundly contribute to the development of ALD, suggesting potential therapeutic targets.

Basic Act on Measures against Alcohol-related Harm gained approval in December 2013, and it came into force in June 2014. Basic principles of this Act is that preventive measures shall be implemented appropriately according to each stage of occurrence, progression and recurrence of Alcohol-related Harm, and support shall be provided so that a person who does or did suffer from Alcohol-related Harm and his/her family members can lead a normal life and a social life without difficulties. Basic Plan for Promotion of Measures against Alcohol-related Harm was approved in a Cabinet meeting in June 2016. The government put force national policy on the line with prior agendas.

The patient was an 84-year-old man. He had received repeated percutaneous local ablation or transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in the past. However, due to the worsening renal dysfunction, he was not able to receive TACE for intrahepatic recurrence. He was therefore administered Tegafur/uracil, resulting in an elevated tumor marker level and the growth of the primary tumor with multiple lung metastases. He was treated with the best supportive care and administered Juzentaihoto, a Japanese traditional herbal medicine. The tumor marker level subsequently decreased markedly, and the intrahepatic tumor shrank in size and the multiple lung metastases disappeared.

Juzentaihoto may be a promising treatment option for patients with advanced HCC refractory to recommended treatments or advanced HCC patients with a poor functional liver reserve.

There are many reports about liver damage with the overdosing of Calonal^®, an oral medicine of acetaminophen, but there are few reports with the overdosing of Aserio^® which is an intravenous formulation. We experienced a case of acute liver failure with hepatic coma after the administration of high-dose Aserio^® for pain control during the perioperative period. Severe liver damage was found three days after the administration of Aserio^®, and drug-induced toxic liver injury was suspected from the laboratory data and clinical course. We started N-acetylcystein and the drug adsorption therapy. Since we recognized grade III of hepatic encephalopathy, we started high-flow continuous hemodiafiltration. These therapies were able to improve the liver damage and disturbance of consciousness immediately. In general, acute liver failure with hepatic coma due to drug intoxication has a low survival rate, and we need to pay attention to dosage regimen when administering Aserio^®.

This study investigated the usefulness of shear wave (SW) speed (related to viscoelasticity), dispersion slope (related to viscosity), and attenuation value (related to steatosis) measurements obtained using a new ultrasound (US) elastography system in patients with nonalcoholic fatty liver disease (NAFLD). In multivariable analysis with histologic features as independent variables, the fibrosis stage was significantly related to SW speed (P=0.04) and the lobular inflammation grade was significantly related to dispersion slope (P=0.02). However, the steatosis grade was not significantly related to attenuation value (P=0.07). SW speed is more useful than dispersion slope for predicting the degree of fibrosis, and dispersion slope is more useful than SW speed for predicting the degree of necroinflammation. Dispersion slope, which reflects viscosity, may provide additional pathophysiological insight into NAFLD.