CHAPTER 1. Alcoholic Liver Disease

Transcription

1 CHAPTER 1 Alcoholic Liver Disease

2 Major Lesions of Alcoholic Liver Disease Alcoholic fatty liver - >90% of binge and chronic drinkers Alcoholic hepatitis precursor of cirrhosis Alcoholic cirrhosis end result of chronic heavy drinking

3 Incidence of Alcoholic Hepatitis Develops in only 10 to 20% of chronic drinkers Risk factors include female gender, heredity and immunity

4 Etiology and Pathogenesis Quantity and duration of alcohol intake are most important Type of drink and pattern of drinking are less important Thresholds - Males g/day for 10 years - Females g/day for 10 years

5 Etiology and Pathogenesis Contributing factors include; - chronic viral hepatitis hepatitis C more than hepatitis B - non-alcoholic steatohepatitis (NASH) with or without obesity Alcohol a direct hepatotoxin involves release of pro-inflammatory cytokines and TNFα

6 Pathology Alcoholic fatty liver - macrovesicular steatosis starts with the perivenular hepatocytes - accumulation of fat due to inability of the hepatocyte to process and transport fat - benign and reversible

7 Pathology Alcoholic hepatitis - characterized by ballooning degeneration, hepatocyte necrosis, polymorphonuclear infiltration and fibrosis - Mallory bodies may be seen but is not specific - reversible unless with cirrhosis

8 Clinical Features Alcoholic fatty liver - most often asymptomatic except for hepatomegaly Alcoholic hepatitis - may present with fever and abdominal pain but may also be asymptomatic - may also present with hepatic parenchymal dysfunction (e.g. spider angiomas, jaundice) or portal hypertension (e.g. ascites, variceal bleeding) in the absence of cirrhosis

9 Laboratory Findings Elevated AST and ALT (<400 IU/L) AST/ALT ratio usually of > 2 Elevated gamma glutamyl transpeptidase (GGTP) sensitive but not specific to alcoholic liver disease Ultrasound detects hepatic enlargement and change in echogenicity Hepatic synthetic functional derangements (e.g. decreased albumin and prolonged protime) seen in cirrhosis

10 Prognosis in Alcoholic Hepatitis Discriminant function 4.6 x protime prolongation (sec) + serum bilirubin (mg%) - poor prognosis if > 32

11 Treatment of Alcoholic Hepatitis Alcohol abstinence include nutritional and psychological counseling Pharmacologic - prednisone 40 mg/day or prednisolone 32 mg/day for 4 weeks then taper for 4 weeks -TNFα inhibitor pentoxifylline 400 PO TID for 4 weeks

12 What is cirrhosis? A chronic or prolonged liver inflammation of various causes, characterized by: fibrosis (scar tissue) with architectural distortion disordered blood flow regenerative nodules alcoholic cirrhosis is usually micronodular unlike in posthepatitis cirrhosis

13 Cirrhosis Has always been thought to be irreversible but recent evidence state that early cirrhosis is reversible when the underlying insult is removed

14 What causes cirrhosis? viral hepatitis B and C alcohol biliary cirrhosis NASH cardiac cirrhosis inherited metabolic (hemochromatosis, Wilson s disease, α1 anti-trypsin deficiency)

15 Pathological and Clinical Features of Cirrhosis hepatic dysfunction jaundice, spider angioma, palmar erythema, testicular atrophy,sparse axillary hair edema, ascites, hepatic encephalopathy portal hypertension esophageal varices portal hypertensive gastropathy hypersplenism

16 Child- Pugh Classification Score bilirubin (micromol/l) < > 50 albumin (g/l) > < 28 PT (sec prolonged) < > 6 encephalopathy none mild marked ascites none mild marked The individual scores are summed and then grouped as: <7 = A 7-9 = B >9 = C

17 Prevention of Acute Complications Upper GI bleeding Hepatic Encephalopathy Subacute bacterial peritonitis Hepato-renal syndrome Infections

18 Hepatic Encephalopathy A syndrome observed in patients with cirrhosis characterized by personality changes, intellectual impairment and a decreased level of consciousness.

19 Pathogenesis of HE Several theories had been proposed for the development of Hepatic Encephalopathy Ammonia Hypothesis False Neurotransmitter Hypothesis GABA Hypothesis

20 Grading of the Symptoms of Hepatic Encephalopathy Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Clinically normal mental status but minimal changes in memory, concentration, intellectual function, and coordination Mild confusion, euphoria, or depression; decreased attention; slowing of ability to perform mental tasks; irritability; and disordered sleep pattern, such as inverted sleep cycle Drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behavior, and intermittent disorientation, usually about time Somnolent but can be aroused, unable to perform mental tasks, disorientation about time and place, marked confusion, amnesia, occasional fits of rage, present but incomprehensible speech Coma with or without response to painful stimuli.

21 Prevention of Decompensation Prevent ongoing liver damage - nucleoside analoques (lamivudine, entecavir,adefovir) - alcohol abstinence - avoidance of certain drugs - bile duct decompresssion -steroids - prophylactic band ligation Prevent deterioration of nutritional status