Masahiro Kikuchi

Aim of the study: Non-alcoholic fatty liver disease (NAFLD) is a pathological condition associated with inflammation owing to fat deposition in the liver. Managing hypertriglyceridemia is essential for patients with NAFLD, including treatment with pemafibrate. However, whether pemafibrate...

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.

当院のアルコール診療では、精神科がアルコールや薬物依存のプログラムを持ちあせてないこともあり、純粋の依存症による精神症状で精神科が加療するケースは少なく、アルコールに起因した消化器症状が前面にたち、消化器内科に入院するケースが多い。消化器内科全体でも、リピーターを含めアルコール関連疾患が多く、アルコール診療の重要性を示唆する。一方で臨床的に問題になるのは、レジデントを含め、アルコール飲酒の問診が不十分な点にある。離脱症状の管理やアルコール依存症自己診断（CAGE）テストでさえ理解せずに診療しているケースが多い。コメディカルにおいてはさらに深刻で、以前のトラウマからかアルコール患者に対して敬遠する傾向もあり、アルコール診療に対する固定観念の変革が不可欠である。困難を極めるのは患者背景を加味した上で、いかに今後断酒できる環境整備が出来るかという点にある。当院の取り組みとして、内科・精神科間の連携を強化し、内科入院早期の段階で、精神科にコンサルトしメンタルケアの介入を行っている（アルコール多飲歴入院患者の約20％で実施）。医師、ケースワーカー、精神看護専門の看護師などで構成されたリエゾンチームにより回診が行われ、症例によっては内科加療に目途がついた時点で精神科に転科し2週間程の教育入院を引き続いて行う場合もある。その後精神科医の判断で、アルコール症センターに教育入院を依頼するケース、近医のアルコール診療クリニックに依頼するケース、当院で消化器内科外来と並行して精神科フォローするケースなどがある。このようにアルコール診療においては、1内科診療医の裁量では限界があり、精神科との強い連携をとり、看護師、保健師を含めた包括的な診療体制の構築が必要であると考えられた。

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.

Along with the development of interferon and therapeutic medication, the incidence of viral hepatitis constituting the largest part of liver disease decreased, and the main target in the field of liver disease is now shifting from viral hepatitis to alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) as metabolic liver disease. Although these diseases tend.to. be gathered as non-viral liver disease because the similar specific liver tissue, the natural history and etiology are considerably different between them. We need to distinguish both of them to do appropriate treatment intervention. Questioning of amount of drinking is needed, but we experience some difficult cases to understand drinking history because of a too little declaration of amount of drinking. A new ultrasonic image analyses using propagation speed in the organization of the pulse vibration wave was developed as Fibroscan by Echosens company in recent years. Fibroscan is a non-invasive test to quantify liver fibrosis as Liver Stiffness Measurement (LSM). It also detects and quantifies steatosis simultaneously using the Controlled Attenuation Parameter (CAP). CAP is a measurement of the ultrasound attenuation. We measured liver steatosis of patients using Fibroscan, and other blood tests. 63 cases of ALD, 177 cases of NAFLD, 57 cases of Virus and 271 cases of Normal were enrolled. CAP value were significantly lower in the ALD group compared with NAFLD group. (P < 0.0053, ALD 268 dB/m : NAFLD 290 dB/m) We elucidate the diagnostic accuracy of CAP using Fibroscan for ALD patients, comparing the results of them to those of virus patients and NAFLD patients.

The objective of this study was to determine whether Cardiotopic Pills (CP) affects fatty liver in rats fed ethanol chronically. Male Wistar rats were treated with liquid diet that contained ethanol (36% of total calories) or an isocaloric carbohydrate instead of ethanol for 6 weeks. CP, an oral herbal medicine including Danshen (Salviae Miltiorrhiza), Panax notoginseny and Dyroblanops aromatica gaertn, have been clinically used for vascular diseases such as coronary diseases and cerebral infarction. CP was administered orally with the liquid diets for 2 weeks 0.4 mg/kg body weight/day with the liquid diet thereafter. Serum triglyceride and total cholesterol levels, total protein, albumin, and AST and ALT activities are measured. Histological examination was also carried out. In another set of experiments, autofluorescence of NAD(P)H, an indicator of mitochondrial O2 consumption and redox status, was measured by an intravital microscopy, and peroxisome proliferators-activated receptor-(PPAR)-alpha and gamma mRNA levels were evaluated by real time quantitative PCR methods. Chronic ethanol consumption elevated serum triglyceride level, and caused fatty degeneration of liver. After administration of CP, fatty degeneration was not observed in rats fed ethanol chronically. Elevation of serum triglyceride level was not noted after treatment with CP (Ethanol: 79.4 +/- 9.3 mg/dl, Ethanol+CP: 48.0 +/- 4.4, respectively, p<0.05). CP did not affect any other laboratory data or NAD(P)H levels. Chronic ethanol consumption did not affect PPAR-gamma mRNA levels, while it decreased PPAR-alpha mRNA levels in the liver. CP prevented the ethanol-induced decrease in PPAR-alpha mRNA levels. CP and its components could enhance expression of PPAR-alpha mRNA levels. These results suggest that CP may be useful to prevent alcoholic fatty liver via enhanced expression of PPAR-alpha.

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. 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). 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 × TB (mg/dl)] + [4.5734 × CTLV/SLV] (AUC = 0.87783, P = 0.0002). 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.

Recently prevalence of alcoholic liver disease has been increasing in Japan associated with an increase in alcoholic beverage consumption. In the present study, we addressed the recent trend in the etiology of liver cirrhosis (LC) in Japan, and investigated the influence of habitual drinking and viral hepatitis type C in the progression of LC. We carried out nation-wide survey by asking for the hospitals that are approved by the Japanese Society of Gastroenterology for the etiology of in-patients with LC, and compared to that in our hospital. Regarding the cases in nation-wide survey, 1274 cases (14%) of 9126 patients with LC were pure (without any markers of hepatitis virus) heavy drinkers, and 580 cases (6%) were heavy drinkers with any markers of hepatitis virus. However, in our general hospital, 24 cases of 101 patients with LC (24%) were pure heavy drinker, and 31 cases (30%) were heavy drinkers with any markers of hepatitis virus. In conclusion, although influence of hepatitis virus infection in alcoholic LC has been decreasing, it still plays an important role in the progression of alcoholic LC, especially in the general hospitals. Education of abstinence or low risk drinking is important not only heavy drinkers but also habitual drinkers with hepatitis virus infection.