Alcoholic Liver Disease Flashcards
Most important risk factors involved in the devt of alcoholic liver disease
QUANTITY and DURATION of alcohol intake
MEN - quantity of ethanol that produces FATTY LIVER
40-80 g/day
MEN - quantity of ethanol that produces HEPATITIS or CIRRHOSIS for 10-20 yrs
160 g/day
Exhibit increased susceptibility to alcohol liver disease at amt > 20 g/day
WOMEN
safe - 2 drinks per day
Infection concurrent w/ alcoholic liver disease associated w/ younger age for severity, more advanced histology and decreased survival
Hepatitis C
Gene associated with ALCOHOLIC CIRRHOSIS
Patatin like phospholipase domain containing protein 3 (PNPLA3)
Important comorbidity in the progression of alcoholic liver disease to cirrhosis in chronic drinker
Chronic Infection with Hepatitis C virus
The Initial and MC histologic response to hepatotoxic stimuli
FATTY LIVER
Hallmark of Alcoholic Hepatitis
HEPATOCYTE INJURY
ballooning degeneration
spotty necrosis
polymorphonuclear infiltrate
fibrosis - perivenular and perisinusoidal space of Disse
Precursor to the devt of cirrhosis
ALCOHOLIC HEPATITIS
Often the only clinical finding in FATTY LIVER
HEPATOMEGALY
RUQ pain
nausea
jaundice (rare)
Clinical Manifestations Alcoholic Hepatitis
fever
spider nevi
jaundice
abdominal pain
Alcoholic cirrhosis clinical features
RUQ pain fever nausea and vomiting diarrhea anorexia malaise
MORE SPECIFIC COMPLICATIONS
ascites
edema
upper GI hemorrhage
PALMAR ERYTHEMA SPIDER ANGIOMAS DUPUYTREN CONTRACTURES DECREASED BODY HAIR TESTICULAR ATROPHY GYNECOMASTIA
AST (SGOT)
INC 2 to 7 fold, < 400 IU/L, GREATER than ALT
ALT (SGPT)
INC 2 to 7fold, < 400 IU/L
AST/ALT ratio
> 1
Common laboratory findings in ADVANCED LIVER INJURY
Hypoalbuminemia
Coagulopathy
Useful in detecting FATTY INFILTRATION of the liver and determining liver size
Ultrasonography
Heralds SEVERE ALCOHOLIC HEPATITIS
coagulopathy (PT > 5 s) anemia serum albumin < 25 g/L serum bilirubin > 137 mmol renal failure ascites
MELD score associated with significant mortality in alcoholic hepatitis
Model for End Stage Liver Disease (MELD > 21)
The cornerstone in the treatment of alcoholic liver disease
Complete abstinence from alcohol
FDA approved medications for alcohol dependence
Disulfiram
Acamprosate
Naltrexone
Glucocorticoids - extensively evaluated in the treatment of alcoholic hepatitis
PREDNISONE - 40 mg / day
PREDNISOLONE - 32 mg/ day
4 weeks followed by a steroid taper
Glucocorticoids - extensively evaluated in the treatment of alcoholic hepatitis
PREDNISONE - 40 mg / day
PREDNISOLONE - 32 mg/ day
4 weeks followed by a steroid taper
Nonspecific TNF inhibitor - for SEVERE alcoholic hepatitis
Pentoxifylline
Accepted indication for treatment in select patients with complications of cirrhosis secondary to alcohol abuse
Liver Transplantation
Can occur as a consequence of the overlapping injurious processes secondary to alcohol and HCV infection
Increased liver iron stores
Porphyria Cutanea Tarda
Secondary to effects on sterol regulatory transcription factor and peroxisome proliferator activated receptor a (PPAR- a)
steatosis from lipogenesis
fatty acid synthesis
depression of FA oxidation
Intestinal derived endotoxin initiates a pathogenic process through
toll like receptor 4
tumor necrosis factor a (TNF a)
– facilitates hepatocyte apoptosis and necrosis
Activate INNATE and ADAPTIVE immunity pathways releasing proinflammatory cytokines ( TNF a), chemokines, and proliferation of T and B cells
Ethanol and its metabolites
Pathologic features that may be associated with progressive liver injury
giant mitochondria
perivenular fibrosis
macrovesicular fat
Often present in florid cases but are NEITHER SPECIFIC NOR NECESSARY to establish the diagnosis
Mallory Denk Bodies
PRECURSOR to the devt of CIRRHOSIS
Alcoholic hepatitis
Present in up to 50% of patients with biopsy proven alcoholic hepatitis
Cirrhosis
Typical lab abnormalities (nonspecific) seen in FATTY LIVER
modest elevations of AST, ALT and gamma glutamyl transpeptidase (GGTP)
hypertriglyceridemia
hyperbilirubinemia
Findings that indicate SERIOUS LIVER INJURY with LESS POTENTIAL for complete reversal
ultrasound of portal vein flow reversal
ascites
intraabdominal venous collaterals
Severe alcoholic hepatitis defined as
discriminant function > 32
MELD > 20
EXCLUSION CRITERIA
active GI bleeding
renal failure
pancreatitis
Uses pretreatment variables plus the change in total bilirubin at day 7 of glucocorticoids to identify those patients unresponsive to therapy
LILLE SCORE > 0.45