Alcoholic Liver Disease (알코올성 간질환)
만성적이고 지속적인 음주 3 Main lesions :
1) fatty liver, (2) alcoholic hepatitis, and (3) cirrhosis 알코올 : 직접 간독성
지방간-거의 모든 음주자
단지10 - 20% of alcoholics 만 alcoholic hepatitis 경험 지속 음주시에는 지방간 환자의 30% 가량이 간경화로 진행.
Factor : quantity and duration, gender, heredity, and immunity.
beverage types ?
우리나라 과다 음주자(남성 40g/day, 여성 20g/day Risk Factors for Alcoholic Liver Disease Quantity: men, 10-20 years
40–80 g/d -> fatty liver 160 g/d->hepatitis or cirrhosis.
Gender : women half quantity
Hepatitis C: younger age for severity, more advanced histology, decreased survival.
Genetics : Gene polymorphisms Malnutrition
Table 301-1 Risk Factors for Alcoholic Liver Disease
Risk Factor
Comment
Quantity In men, 40–80 g/d of ethanol produces fatty liver; 160 g/d for 10–20 years causes hepatitis or cirrhosis. Only 15% of alcoholics develop alcoholic liver disease.
Gender Women exhibit increased susceptibility to alcoholic liver disease at amounts >20 g/d; two drinks per day probably safe.
Hepatitis HCV infection concurrent with alcoholic liver disease is
Risk Factor
Comment
C associated with younger age for severity, more advanced histology, decreased survival.
Genetics Gene polymorphisms may include alcohol
dehydrogenase, cytochrome P4502E1, and those associated with alcoholism (twin studies).
Malnutritio n
Alcohol injury does not require malnutrition, but obesity and fatty liver from the effect of carbohydrate on the transcriptional control of lipid synthesis and transport may be factors. Patients should receive vigorous attention to nutritional support.
Pathogenesis
완전한 기전은 밝혀지지 않음
Alcohol : direct hepatotoxin, metabolic responses 유발 initial concept of malnutrition
->현재의 이해 :hepatic metabolism of alcohol 이 pathogenic process.
Production of toxic protein-aldehyde adducts, endotoxins, oxidative stress, immunologic activity, and pro-inflammatory cytokine release (Fig. 301-1).
Complex interaction of intestinal and hepatic cells is crucial to alcohol- mediated liver injury.
Tumor necrosis factor α(TNF-α) and intestine-derived endotoxemia : hepatocyte apoptosis and necrosis.
Stellate cell activation and collagen production : hepatic fibrogenesis.
Alcoholic hepatitis
Fatty liver : initial and most common histologic response
Extensive fatty change and distortion of the hepatocytes with macrovesicular fat
금주시는 회복됨
Steatohepatitis + giant mitochondria, perivenular fibrosis, and macrovesicular fat
progressive liver injury
Alcoholic hepatitis
The transition between fatty liver and the development of alcoholic hepatitis 모호
- Hallmark of alcoholic hepatitis : 중심부 소엽에 심한 병변 : ballooning degeneration
: spotty necrosis
: PMN (polymorphonuclear) infiltration
: perivenular & perisinusoidal space of Disse fibrosis
- Mallory body (70-75%) inclusion found in the cytoplasm of liver cells : not specific & not diagnostic
Micrograph showing a Mallory body with the characteristic twisted-rope appearance (centre of image - within a ballooning hepatocyte). H&E stain.
Clinical Features
우연히 무증상 발견 다수
hepatomegaly 정도만 관찰가능
alcoholic fatty liver, non alcoholic fatty liver : drinking history 외 구분 어렵다 Alcoholic hepatitis : 광범위한 clinical features.
Cytokine production 이 systemic manifestations of alcoholic hepatitis 관련.
Fever, spider nevi, jaundice, and abdominal pain simulating an acute abdomen represent 가 나타날 수 있으나 대개 무증상
Portal hypertension, ascites, or variceal bleeding : cirrhosis 없이도 가능.
Laboratory Features
fatty liver nonspecific 하나 AST, ALT, GGTP 와 더불어 hypertriglyceridemia, hypercholesterolemia, hyperbilirubinemia 도 종종
In alcoholic hepatitis and in contrast to other causes of fatty liver, the AST and ALT are usually elevated two- to sevenfold. They are rarely >400 IU, and the AST/ALT ratio >1 (Table 301-2).
Table 301-2 Laboratory Diagnosis of Alcoholic Fatty Liver and Alcoholic Hepatitis
Test Comment
AST Increased two- to sevenfold, <400 U/L, greater than ALT ALT Increased two- to sevenfold, <400 U/L
AST/ALT Usually >1
GGTP Not specific to alcohol, easily inducible, elevated in all forms of fatty liver
Bilirubin May be markedly increased in alcoholic hepatitis despite modest elevation in alkaline phosphatase
PMN If >5500/㎕predicts severe alcoholic hepatitis when discriminant function > 32
Note: AST, aspartate aminotransferase; ALT, alanine
aminotransferase; GGTP, gamma-glutamyl transpeptidase; PMN, polymorphonuclear cells.
Derangement in hepatocyte synthetic function: more serious disease.
Hypoalbuminemia and coagulopathy are common in advanced liver injury.
- anemia 유발기전
: acute & chronic GI blood loss : nutritional deficiency : hypersplenism : hemolytic anemia : direct toxic effect on BM
* Prognosis
- 과량의 음주시 10-15% 만이 alcoholic hepatitis 와 LC 로 진행한다.
- ALD mortality 예측인자 : PT, bilirubin
- Severe alcoholic hepatitis 기준 -bil>8mg/dL, PT 5 초 이상 연장, Alb<2.5mg/dL,
anemia, ascites, renal failure - Alcoholic hepatits (구판)
: precursor of the LC, 금주시 potentially reversible
: but 이미 발생한 fibrosis 는 금주해도 LC 로 진행(50%), liver Bx. 꼭 실시 - Critically ill with alcoholic hepatits : short-term mortality rates = 70%
- Severe alcoholic hepatitis 로 입원시 5 년 안에 LC 로 갈 확률 = 50%
- Alcoholic LC +금주시 mortality,morbidity 감소, but major Cx.이 있으면서 계속 음주시 5 yrs < 50%
- significant differences in 4-year survival rates among the 4 groups
Critically ill patients with alcoholic hepatitis : short-term (30 day) mortality rates
>50%.
Discriminant function :
4.6 x [prothrombin time control (seconds)] + serum bilirubin (mg/dL) poor prognosis (discriminant function > 32).
The presence of ascites, variceal hemorrhage, deep encephalopathy, or hepatorenal syndrome predicts a dismal prognosis.
* Treatment ① 금주
② Multi vitamin
Thiamine (Wernicke-Korsakoff disease)
③ Nutritional support
④ Severe alcoholic hepatitis
Pathogenic mechanisms in alcoholic hepatitis involve
cytokine release and the perpetuation of injury by immunologic processes.
Glucocorticoids have been extensively evaluated in the treatment of alcoholic hepatitis.
Discriminant function > 32
prednisone, 40 mg/d, or prednisolone, 32 mg/d, for 4 weeks followed by a steroid taper (Fig. 301-2).
Exclusion criteria: active gastrointestinal bleeding, sepsis, renal failure, or pancreatitis. Women with encephalopathy from severe alcoholic hepatitis :particularly good candidates
Steroid contraindication : pentoxyfylline(경구 phosphodiesterase 억제제로 TNFa 생성억 제)- 신부전이나 출혈시 사용가능, 오심과 구토는 스테로이드보다 흔해
