Current Status of Alcoholic Liver Disease in Japan and Therapeutic Strategy

Alcoholism results in an estimated 3.3 million deaths annually worldwide, accounting for 5.9% of all mortality. Although per capita alcohol consumption in Japan, had been gradually decreasing since 1999, it has plateaued in the past 5 years. Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease, and includes alcoholic fatty liver, alcoholic hepatitis (AH), alcoholic fibrosis, alcoholic liver cirrhosis (ALC), and alcoholic hepatocellular carcinoma (HCQ. Although alcohol consumption is the predominant etiological factor in the pathogenesis of ALD, there is marked variation in liver mortality rates among. different countries and over time within countries. Six national surveys of ALD in Japan were carried out by the Japanese ALD study groups. The first three studies reported that the prevalence of ALD increased in parallel with an increase in alcoholic beverage -intake and that the rise in ALD was one major- factor contributing to the increased prevalence of liver cirrhosis. However; recent epidemiological studies- showed that ALC continues to rise despite a gradual decrease in alcohol intake, indicating that there are other risk factors for the development of ALC. Our recent survey revealed that the prevalence of ALC has been rapidly increasing in Japan and that the prevalence of alcoholic HCC in ALC was higher in elderly male patients and younger patients with diabetes mellitus (DM). DM, female sex, and age were identified as risk factors for the development of ALC, while DM, male sex, and age were identified as significant risk factors for HCC in ALC. Severe alcoholic hepatitis (SAH) is an inflammatory response with multiple morbidity factors like leucocytosis, hepatomegay, and renal failure, and has a high mortality rate. We have created a new scoring system for AH (Japan Alcoholic Hepatitis Score [JAS]). Its ability to predict outcome was confirmed by examining the data of 59 patients with AH in 2011: 26 had moderate AH of whom 22 were alive and were dead, while 33 had SAH of whom 16 were alive and 17 were dead. There was no report of death in patients with mild AH (JAS was ≤ 7). The prevalence of renal failure, DIC and gastrointestinal bleeding was higher in patients who had died, while Cr and PT (INR) were higher in SAH patients who had died. These results suggest that JAS allows stratification of the risk of death and can help manage patients with AH. Our belief is that patients with elevated myeloid leucocytes benefit most from granulocytes/monocytes apheresis, while exchange appears to support patients with coagulation deficiency of high plasma bilirubin and hemodialysis is indicated for hit Cr. Liver transplantation is the ultimate therapy for ALD, but it has always been controversial. In Japan, most cases are living donor liver transplantations because the number of brain-dead donors are low. Although 6 months of abstinence is required for brain-dead donor liver transplantation in most countries, 18 months of proven abstinence is required in Japan.