Background and Aim: Severe alcoholic hepatitis (SAH) is an inflammatory response with multiple morbidity factors like leucocytosis, hepatomegaly, renal failure, hepatic encephalopathy, endotoxemia, ...and a high mortality rate. Identifying therapeutic interventions that can improve prognosis is the goal of research.
Methods: Questionnaires were sent to 1234 medical institutions asking for information on patients with SAH during 2004 to 2008, including patients' demography, disease profile and the therapeutic interventions patients had received during hospitalization.
Results: Forty‐five hospitals had treated SAH patients, and provided full demographic data on 98 patients. Forty‐eight patients had received no treatment, 12 patients had received granulocytes/monocytes apheresis (GMA) to deplete elevated myeloid lineage leucocytes, the rest had received one or more of the following treatments, corticosteroids, plasma exchange (PE) and hemodialysis (HD). Further, 38 patients had died and 60 had survived within 100 days of hospitalization. Serum creatinine (Cr) was higher in patients who had died versus patients who had survived (P = 0.001). Likewise, patients with white blood cells (WBC) ≥ 104/µL had higher mortality rate versus patients with WBC < 104/µL (P = 0.018). GMA in patients with WBC ≥ 104/µL showed improved prognosis versus in patients with WBC ≥ 104/µL who did not receive GMA (P = 0.0006). Corticosteroids, plasma exchange and HD did not significantly impact prognosis of SAH patients.
Conclusions: Our perception is that, patients with elevated myeloid leucocytes benefit most from GMA, while plasma exchange appears to support patients with coagulation deficiency or high plasma bilirubin and HD has indication in patients with high Cr.
Purpose
To clarify the etiology of hepatocellular carcinoma (HCC) in Japanese patients with non-viral liver disease, we performed a nationwide survey. The influence of obesity, lifestyle-related ...diseases, and alcohol consumption was focused on.
Methods
A nationwide survey of 14,530 HCC patients was conducted in 2009. Clinical features were studied for HCC patients with nonalcoholic fatty liver disease (NAFLD-HCC;
n
= 292), alcoholic liver disease (ALC-HCC;
n
= 991), and chronic liver disease of unknown etiology (unknown HCC;
n
= 614). The unknown HCC was divided into two subgroups, a no alcohol intake group and a modest alcohol intake group.
Results
ALC-HCC accounted for 7.2% of all HCC, followed by unknown HCC (5.1%) and NAFLD-HCC (2.0%). The characteristics of these three groups were clearly different (median age was 72 years for NAFLD-HCC, 68 years for ALC-HCC, and 73 years for unknown HCC,
p
< 0.01; female gender was 38, 4, and 37%, respectively,
p
< 0.01). Obesity and lifestyle-related diseases were significantly more frequent in NAFLD-HCC than in ALC-HCC and unknown HCC. The no alcohol intake subgroup of unknown HCC showed female predominance (58%) and was older, without a high prevalence of obesity and lifestyle-related diseases. In contrast, the modest alcohol intake subgroup showed the same trends regarding gender, body mass index, prevalence of lifestyle-related diseases, and liver function as the ALC-HCC group.
Conclusions
The clinical features of ALC-HCC, NAFLD-HCC, and unknown HCC were clearly different. Modest intake of alcohol might have a more significant role in hepatic carcinogenesis than is presently thought.
Ischemia and reperfusion (I/R) exerts multiple insults in microcirculation, frequently accompanied by endothelial cell injury, enhanced adhesion of leukocytes, macromolecular efflux, production of ...oxygen free radicals, and mast cell degranulation. Since the microcirculatory disturbance results in injury of organ involved, protection of organ after I/R is of great importance in clinic. Salvia miltiorrhiza root has long been used in Asian countries for clinical treatment of various microcirculatory disturbance-related diseases. This herbal drug contains many active water-soluble compounds, including protocatechuic aldehyde (PAl), 3,4-dihydroxyphenyl lactic acid (DLA) and salvianolic acid B (SalB). These compounds, as well as water-soluble fraction of S. miltiorrhiza root extract (SMRE), have an ability to scavenge peroxides and are able to inhibit the expression of adhesion molecules in vascular endothelium and leukocytes. Moreover, lipophilic compounds of SMRE also prevent the development of vascular damage; NADPH oxidase and platelet aggregation are inhibited by tanshinone IIA and tanshinone IIB, respectively, and the mast cell degranulation is blunted by cryptotanshinone and 15,16-dihydrotanshinone I. Thus, the water-soluble and lipophilic compounds of SMRE appear to improve the I/R-induced vascular damage multifactorially and synergically. This review will summarize the ameliorating effect of compounds derived from SMRE on microcirculatory disturbance and target organ injury after I/R and will provide a new perspective on remedy with multiple drugs.
Nationwide surveys to clarify the characteristics and trends of the drinking behavior of Japanese adults were carried out in 2003, 2008, and 2013.
These were periodical cross-sectional surveys. ...Subjects were chosen through a stratified two-stage random sampling method. The surveys included drinking frequency and amount, ICD-10 alcoholism diagnostic standards, questionnaire for the determination of harmful alcohol use (
Alcohol Use Disorders Identification Test). In 2003, the surveys obtained responses from 2547 people (73% response rate); in 2008, 4123 people (55% response rate); and in 2013, 4153 people (59% response rate).
The proportion of lifetime experience of alcohol dependence diagnosed by ICD-10 was 1.9% for male and 0.2% for female, and the estimated number of patients was 1.07 million. The declining trends were observed in the percentage of daily drinkers and the amount of alcohol consumed per week for male. The lowering of the age for consuming their first alcoholic drink and their first drunken experience was observed among female. The gender difference of prevalence of problem drinking is getting smaller. The binge drinking and heavy episodic drinking were observed especially younger generation. The only small proportion of patients with alcohol dependence had received specialized medical care, whereas the many of these visited medical institutions and health screening.
The survey observed many hidden alcoholic patients, and showed the possibility that the healthcare facilities and health screening became the place of screening and intervention for alcohol dependence.
Lower educational background for both men and women was associated with a higher risk for heavy episodic drinking, while higher household income for men was associated with a higher risk for ...hazardous drinking in Japan.
Figure Legend: OR, odds ratio; HED, heavy episodic drinking; HD, hazardous drinking.
Drinkers who had neither HED nor HD were adopted as the reference group in order to calculate the OR.
Display omitted
•The risk for hazardous drinking (HD) was higher in persons of less education for both genders.•Unlike most countries, women with lower education showed higher risk of HD in Japan.•Heavy Episodic Drinking (HED) risk was high among men with higher SES and among working women in Japan.•HED and HD may vary with SES characteristics in the Japanese population.
Hazardous drinking (HD) and heavy episodic drinking (HED) constitute different types of alcohol-related harm. The socioeconomic status (SES) background of various alcohol consumption behaviors is not clear. The purpose of this study was to clarify existing SES differences between HD and HED.
The 2013 national survey regarding alcohol use among Japanese adults was utilized. The results from 1193 men and 1503 women aged 20–64 years were included in the analysis. Education attainment, household income, marital status, working status, and occupation were adopted as SES determinants. Binomial logistic regression analysis was conducted to estimate the odds ratios (ORs) of HD and HED for each SES group.
ORs (95% confidence intervals) of HD were higher among persons with less education among both men 1.61 (1.18–2.20) and women 1.78 (1.19–2.67). The OR of HED in men was significantly higher among those who belonged to high household income, were married, and managers or professionals. The OR of HED among women was higher in persons who were employed, as compared with those who engaged in housework. There were no correlations between HED and educational background.
This study showed that in Japan, a lower educational background for both men and women was associated with a higher risk for HD, while higher current SES for men and working women were associated with a higher risk for HED. It is necessary to recognize the SES differences between HD and HED to achieve a policy to reduce alcohol-related harm.
Aim
To clarify the clinical features of patients with hepatocellular carcinoma (HCC) with cryptogenic liver diseases, we analyzed the data from a nationwide survey in Japan.
Methods
The survey was ...conducted in 2009. The factors examined included age and underlying liver diseases: alcoholic liver disease (ALD; n = 991), non‐alcoholic fatty liver disease (n = 292), modest alcohol intake (intake between 20 and 70 g/day, n = 214) and cryptogenic liver diseases (n = 316). We compared the clinical features of cryptogenic HCC among patient‐age subgroups.
Results
HCC with ALD etiology was most common among the non‐viral HCC patients under 80 years old; for those aged 80 years or older, cryptogenic HCC was the most common etiology. Among the cryptogenic HCC patients, the body mass index values and the prevalences of liver cirrhosis (LC) and diabetes mellitus (DM) were significantly lower in the 80 years or older group versus the 50–79 years group. In the 80 years or older group, 28% of the patients developed HCC without cirrhosis, obesity and DM.
Conclusion
In the HCC patients aged 80 years and over, the etiology of most of the non‐viral HCC cases was classified as cryptogenic. In light of our finding that the prevalences of obesity, DM and LC in the 80 years or older group of cryptogenic HCC patients were significantly lower those in the younger patients, it is apparent that analyses of HCC cases must take age differences into account.
Background/Aims King's College Hospital (KCH) criteria and the model for end-stage liver disease (MELD) score are useful and widely-employed prognostic markers for acute liver failure (ALF). We ...previously reported that liver atrophy is an important prognostic factor for ALF. The aim of the present study was to assess the value of liver volumetry and to generate a new prognostic formula. Methods Computed tomography-derived liver volume (CTLV) and standardized liver volume (SLV) of 30 adult ALF patients were calculated at the time of diagnosis. Patients were assigned to one of two groups: group A consisted of 13 patients who recovered without surgical intervention, and group B consisted of 17 patients who died due to liver failure or who underwent living donor liver transplantation (LDLT). Results The median CTLV/SLV ratios of groups A and B were 1.019 and 0.757, respectively (P = 0.0009). The difference was most significant (P = 0.0002) at the probability cutoff point of 0.80 for CTLV/SLV ratio; the sensitivity and specificity were 76.5% and 92.3%, respectively. Serum total bilirubin (TB) levels and CTLV/SLV ratio were selected as independent prognostic factors by multivariate analysis. A prognostic formula including volumetric analysis was established: Z = -2.3813 - 0.15234 x TB (mg/dl) + 4.5734 x CTLV/SLV (AUC = 0.87783, P = 0.0002). Conclusions The CTLV/SLV ratio is a very useful marker for predicting the prognosis of adult ALF. Our prognostic formula including only the CTLV/SLV ratio and TB is simple and useful and awaits validation in a future larger-scale prospective study.
A 3-month alcoholism rehabilitation program at psychiatric hospitals is common in Japan for patients with alcohol use disorder (AUD). However, many AUD patients are often hospitalized for the ...treatment of digestive disorders due to alcohol-related liver diseases and pancreatitis. In this sense, AUD patients need to be better supported by professionals and departments in general hospitals. Here we analyzed the problems in alcohol-related medical care in Japan and examined the measures to be taken at general hospitals.
Recent epidemiological studies showed that alcoholic liver cirrhosis (ALC) and alcohol-related hepatocellular carcinoma (HCC) continue to increase despite a gradual decrease in alcohol intake, ...indicating that there are other risk factors for the development of ALC and alcohol-related HCC. A nationwide survey of liver cirrhosis (LC) was undertaken by asking major hospitals in Japan to provide information on the number of patients with LC admitted in 2012 along with information related to etiology including alcohol history and other relevant demographics. Among the 1,478 ALC patients, total alcohol intake was lower in women than in men, and mean age was also lower in women. Mean age was older in the present study in 2012 compared with the data in 2008. Compared to patients without diabetes mellitus (DM), patients with DM had lower daily alcohol intake and higher mean age. The prevalence of HCC was much higher in male elderly ALC patients and also in DM patients among the younger ALC patients (65 years). DM, female sex, and age were identified as risk factors for development of ALC, and DM, male sex, and age were identified as significant risk factors for HCC in ALC.
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.
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