363: Alcoholic Liver Disease Flashcards
Pathology of alcoholic liver disease consists of 3 major lesions
- Fatty liver (present in 90% of daily and binge drinkers)
- Alcoholic hepatitis
- Cirrhosis
T or F: Alcohol is an indirect hepatotoxin.
False.
Direct hepatotoxin
World’s 3rd largest risk factor for disease burden
Alcohol
Most important risk factors in development of alcoholic liver disease
QUANTITY and DURATION of alcohol intake
Strong determinant for alcoholic liver disease
Gender
Women>Men
T or F: Time it takes to develop liver disease IS DIRECTLY RELATED to the amount of alcohol consumed
True
Equivalent of 12g of alcohol
- One beer
- Four ounces of wine
- One ounce of 80% spirits
Factors for gender-dependent differences in development of alcoholic liver disease
- Effects of estrogen
- Proportion of body fat
- Gastric metabolism of alcohol
Important comorbidity in progression of alcoholic liver disease to cirrhosis in chronic and excessive drinkers
Chronic Hepatitis C infection
Risk factor for alcoholic liver disease:
QUANTITY and GENDER
QUANTITY:
Men: 40-80g/d of etOH produces fatty liver; 160g/d for 10-20 yrs cause hepatitis or cirrhosis; 15% develop ALD
Gender: Women with increased susceptibility at amounts >20g/d; two drinks per day is probably safe
Risk factor for alcoholic liver disease:
HEPATITIS C, GENETICS, FATTY LIVER
Hepa C: HCV with ALD associated with younger age for severity, more advanced histology, decreased survival
Genetics: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) associated with alcoholic cirrhosis
Fatty liver: Obesity and nonalcoholic fatty liver are risk factors. Emphasis on nutritional support
Intestinal derived endotoxins that initiates pathogenic process that facilitates hepatocyte apoptosis and necrosis
Toll-like receptor 4
Tumor necrosis factor alpha (TNF-a)
Initial and most common histologic response to hepatotoxic stimuli, including excessive alcohol ingestion
Fatty liver
Major enzyme responsible for alcohol metabolism
Alcohol dehydrogenase
T or F: Cessation of drinking results in normalization of hepatic architecture and fat content in ALD (Reversible)
True
Hallmark of alcoholic hepatitis
Hepatocyte injury
Ballooning degeneration, spotty necrosis, polymorphonuclear infiltrate, fibrosis of perivenular and perisinusoidal space of Disse
T or F: Portal hypertension, ascites and variceal bleeding can occur in the absence of cirrhosis.
True
Laboratory features of alcoholic liver disease
- Elevated AST, ALT two to sevenfold. Rarely >400IU, and AST/ALT is >1
- Hyperbilirubinemia
- Modest increase in alkaline phosphatase level
Short-term (30-day) mortality rates is observed in what percentatge of critically ill patients with alcoholic hepatitis
> 50%
Features of severe alcoholic hepatitis
- Coagulopathy (Prothrombin time increased >5s)
- Anemia
- Serum albumin concentration <25g/L (2..5mg/dL)
- Serum bilirubin levels >137 umol/L (8 mg/dL)
- Renal failure
- Ascites
MELD score that is associated with significant mortality in alcoholic hepatitis
> /= 21
Cornerstone of treatment of alcoholic liver disease
Complete abstinence from alcohol
T or F: Referral of patients to experienced alcohol counselors and/or alcohol treatment programs should be routine in management of alcoholic liver disease
True
Severe alcoholic hepatitis in discriminant function and MELD
Discriminant function >32
MELD >20
Preferred treatment for severe alcoholic hepatitis
Prednisone 40 mg/d OR
Prednisolone 32 mg/d
For 4 weeks followed by steroid taper
Exclusion: Active GI bleeding, renal failure, pancreatitis
*Women are good candidates
Scoring system that uses pretreatment variables plus the change in total bilirubin at day 7 of glucocorticoids to identify patients unresponsive to therapy
Lille score >0.45
A nonspecific TNF inhibitor that demonstrated improved survival in the therapy of severe alcoholic hepatitis, primarily due to decrease in hepatorenal syndrome; Alternative treatment
Pentoxifylline 400mg PO TID x 4 weeks
An accepted indication for treatment in selected and motivated patients with end-stage cirrhosis
Liver transplantation
