Alcoholic Liver Disease (ALD)/ Alcohol related liver disease

RF
 Drinking pattern
 Gender : F>M
 Obesity
 Hepatitis C: concurrent w ALD in younger age for severity

Pathophysiology
 Reach peak blood concentration after 20 min
 80% Metabolized to acetaldehyde by alcohol
dehydrogenase
 20% oxidize ethanol to acetate by CYP2E1  release free
radical  lipid peroxidation, mitochondrial damage
 Alcoholic hepatitis: lipogranuloma, neutrophil infiltration,
Mallory’s hyaline, pericellular fibrosis
 Macrovesicular steatosis
 Central hyaline sclerosis
 Fatty liver  alcohol hepatitis  cirrhosis

C/F Investigations
Fatty liver  FBC: macrocytosis w/t anemia – alcohol misuse,
 Asymptomatic abnormal liver biochemistry : high leucocytosis
transaminase  LFT: high ALT, AST, GGT (gamma-glutamyl transferase)-
 Normal/ large liver liver damage
 Right upper quadrant discomfort  Lipid profile: high TAG
Alcohol hepatitis  High bilirubin – high ALP
 Jaundice, fever, spider nevi  Hypoalbuminea, coagulopathy – severe case
 Malnutrition  Prothrombin time, bilirubin  calculate for discriminant
 Hepatomegaly function (DF)/ Maddrey score
 Portal hypertension: ascites, encephalopathy - DF = [4.6 x increase in PT (s)] + bilirubin (mg/dL)
Cirrhosis - >32: poor prognosis
 Stigmata of chronic liver disease
 Ascites/ varices/ encephalopathy
 Large liver
 Hepatocellular CA
Management
 Cessation of alcohol consumption – fatty liver disappear &
liver biochemistry return to normal

If Discriminant function >= 32/ MELD >= 21

 Prednisolone/ pentocifyllin (TNF inhibitor) – alcohol

hepatitis
 Ultrasound: fatty infiltration of liver, liver size, portal vein
flow reversal, ascites, intraabdominal venous collateral
(serious liver injury)
Non Alcoholic Fatty Liver Disease (NAFLD) : in absence of high alcohol consumption [<20g/day in women, <30g/day in men]
 Spectrum of progressive liver disease [fatty infiltration/ steatosis  fatty infiltration w inflammation/ non-alcoholic
steatohepatitis, NASH  cirrhosis, liver cancer]

RF
 Obesity
 Insulin resistance/ DM
 Dyslipidemia
 Lipodystrophy

Pathogenesis
 Obesity/ insulin resistance  increase hepatic free fatty
acid flex  imbalance btw synthesis & catabolism of
fatty acid in liver  steatosis  NASH  cellular
damage trigger cell death & inflammation  stellate cell
activation & fibrosis  cirrhosis

C/F Investigation
 Asymptomatic  High AST, ALT
 RUQ pain  High GGT
 Hepatomegaly  Low titre antinuclear Ab, ANA
 Stigmata of chronic liver disease: spider angiomata, palmar  High ferritin level
erythema, splenomegaly  NAFLD Fibrosis Score (NFS) , FIB -4  predictive for fibrosis
& cirrhosis
Complications  Ultrasound : hepatic fat content [bright/ increase
 End stage liver disease: jaundice, portal hypertension echogenicity]
 Liver biopsy – gold standard for assess degree
Management inflammation & extent of fibrosis
 Weight loss, physical exercise
 Treatment for HTN. Dyslipidemia
Cirrhosis: chronic diffuse liver disease, characterized by destruction of liver cell w fibrosis, distortion of normal architecture &
nodular degeneration (d/t proliferation of hepatocytes)

 Micronodular
 Macronodular

Causes: Stigmata of CLD/ Cirrhosis

 Chronic viral hepatitis (B, C, B&D)  Hand:
 Chronic alcoholism - Palmar erythema
 NAFLD - Dupuyten’s contracture , florid spider angioma– in
 Immunological : autoimmune liver disease, primary alcoholic cirrhosis
sclerosing cholangitis - Leukonychia
 Biliary PBC, secondary biliary cirrhosis - Clubbing – HF, RSP failure, IBD
 Genetic - Flapping tremor – liver failure
 Budd Chiari - Jaundice, xanthoma
 Drug: methotrexate - Tattoo, injection marks
- Bruising, ecchymose, petechiae
 Face
Portosystemic anastomosis (between portal & systemic vein)
- Xanthelasma
 Lower end of esophagus: left gastric vein (portal) –
- Spider angioma
hemiazygous vein (systemic)
- Bilateral carotid enlargement – alcoholic cirrhosis ,
 Lower end of anal canal & rectum: superior rectal vein –
sarcoidosis
rectal vein
- Pigmentation, jaundice
 Anterior abdominal wall (aound umbilicus): paraumbilical
- Hepatic facies : prominent of malar bone
 Bare area of liver : portal radicle of liver – diaphragmatic
- Black discoloration: Peutz Jeghers syndrome
vein
 Generalized pigmentation, purpura, ecchymosis
 Retroperitoneal site
 Chest
 Fissure of ligamentum venosum
- Gynaecomastia
- Spider naevie
Portal Hypertension (N; 2-5 mmHg)
- Loss of hair: chest, pubic hair
 Portal vein: fusion of superior mesenteric vein & splenic
vein
Abdomen
 A: liver cirrhosis (adult), extrahepatic portal vein Inspection
obstruction (children)
 Abdomen is distended, flanks are full
 Scaphoid abdomen: malignancy, malnutrition, prolong
Investigations
chronic disease
 LFT : total protein w albumin/ globulin ratio, prothrombin
 Umbilicus is everted [underlying ascites]
time, liver enzymes , serum bilirubin
 Visible superficial vein w normal flow (away from
 USG of abdomen: small liver ( in cirrhosis, exp alcoholic
umbilicus) – portal HTN
cirrhosis)
 Caput medusa
 Viral marker for HBV (HBsAg, HBeAg, anti HBC), HCV (anti-
Palpation
HCV)
 Liver x palpable , only palpable in alcoholic cirrhosis, viral
 Proctoscopy – hemorrhoid
hepatitis, malignancy
 Endoscopy – esophageal varices
 Spleen is palpable , 4cm from left costal margin in anterior
 CT scan axillary line towards RIF, smooth surface, firm in
 Liver biopsy consistency, non tender – portal hypertension
 Ascitec fluid test: cytology, SAAG  Small kidney in chronic kidney disease
 ERCP, MRCP – obstruction of bile duct  Testis – atrophy in alcoholic cirrhosis
 FBC, BUSE  Hernia orifice
Percussion
Complications – liver failure  Shifting dullness – ascites
 Rupture of Esophageal varices Auscultation
 Hepatoma  Hepatic bruit: hepatoma, hepatitis
 SBP, Hepato-pulmonary syndrome
Hereditary Hemochromatosis – body absorb too much iron Alpha 1 Anti-Trypsin Deficiency
from diet  Autosomal recessive disorder
 Autosomal recessive  Mutation of alpha 1 antitrypsin gene (chromosome 14) 
 Mutation in gene  impair control of intestine absorption misfolding of alpha 1 antitrypsin  inhibit protease
of iron from food & alter distribution of iron to other parts
of body  iron accumulate in tissue & organs: skin, heart,
liver pancreas, joint  body cannot excrete iron, excess
iron cause overload  damage tissue & organs

C/F
• Fatigue
• Joint pain, abdominal pain, weight loss
• Loss of sex drive
• Hepatomegaly
• Arthritis, liver cirrhosis, diabetes (destruction of pancreatic
islets), heart abnormalities (cardiac failure, dysrhythmia), C/F
skin discoloration (excess melanin)  Neonatal hepatitis w cholestatic jaundice – 10-20%
 Hepatitis
Investigations  Cirrhosis
 Serum iron, serum ferritin ↑
 TIBC ↓ Investigations
 Genotyping  Serum alpha-1 antitrypsin ↓
 Liver biopsy – fibrosis  Genotyping
 Hepatic iron index (HII) >1.9  Liver biopsy: acid Schiff +ve granule

Management
 IV augmentation therapy w plasma alpha 1 antitrypsin
Management  Cessation of smoking – if related to emphysema
  Weekly withdrawal of 500ml blood (250mg iron) – to
reduce ferritin <50 ug/L
 Screening for liver cirrhosis, DM, hepatocellular carcinoma
Primary Biliary Cirrhosis/ Cholangitis Wilson’s Disease
 Granulomatous inflammation of portal tract  progressive  Autosomal recessive
damage  progressive destruction of hepatic bile ducts   Copper (from diet)  portain vein  liver  mutation of
cholestasis (decrease bile flow) fibrosis, cirrhosis ATP 7B  accumulate in hepatocyte  production of free
 Common in cigarette smoker radical damage to hepatocyte  copper split into
interstitial space & b/supply  damage other tissues
C/F
 Lethargy, arthralgia
 Pruritus w or w/t jaundice
 Xanthelasma
 Bone pain/ fracture (osteomalacia – lack of bile salt – fat
soluble vitamin malabsorption)
 Hepato-splenomegaly

Investigations
 Liver function test: ↑ serum ALP
 Serum AMA, antinuclear antibody
 Liver biopsy: loss of bile ducts, granuloma formation,
fibrosis, cirrhosis
 Ultrasound: in jaundice, TRO biliary obstruction C/F
 Liver: Hepatitis, hepatic failure, cirrhosis
Management  Brain
 Hydrophilic bile acid – decrease production of bile, - Basal ganglia (Parkinson disease)
decrease sx - Cerebral cortex (dementia)
 Eye: Kayser-Fleischer rings (greening brown discoloration
Secondary Biliary Cirrhosis at junction of cornea)
 After prolonged large biliary duct obstruction [gallstone,  Kidney: Tubular damage
benign bile duct stricture, sclerosing cholangitis]
Investigations
C/F  24 hr urinary copper excretion, after given D-
 Liver abscess penicillamine - >25 umol/24hrs =diagnostic
 Ascites  Serum ceruloplasmin ↓ (less copper to be transported,
 Portal hypertension mainly as free copper d/t mutation)
 Free serum copper concentration ↑
Investigation  Urine copper excretion ↑ >0/6 umol/24 hrs
 MRCP – magnetic resonance cholangio-pancreatography  Genetic screening

Management
 Penicillamine : copper binding agent
- S/E: rash, lupus like syndrome, BM aspiration

Chronic Liver Disease: Liver disease >= 6 months

Chronic Liver Failure: functional capacity of liver cannot be maintain: encephalopathy, ascites = decompensated liver disease