L12: Alcoholic liver disease Flashcards
Blood flow in the liver
Hepatic artery→ oxygenated blood to liver→ hepatic veins→ inferior vena cava
GI tract and spleen→ Portal vein→ products of digestion to liver→ processes nutrients and filters toxins→ hepatic veins→ inferior vena cava
Stages of Alcoholic liver disease
Not distinct stages, multiple stages may be present at once
- Fatty Liver (Simple Steatosis) (present in most drinkers >60g/day)
- Alcoholic Hepatitis
- Chronic Hepatitis with fibrosis or cirrhosis
Risk factors for Alcoholic liver disease
Women→ 2x as sensitive to ETOH hepatotoxicity & develop more severe ALD at lower doses with shorter duration
African American>Hispanic> Caucasian males
Obesity→ limit to 1 drink a day
Genetic Factors→ alcoholism & ALD
Hepatitis C+ alcohol→ more rapid progression→ limit to 1 drink a day
ALD + smoking→ increased risk of hepatocellular cancer
Progression of cirrhosis/fibrosis/HCC
Normal liver + chronic alcohol use Steatosis Steatohepatitis Fibrosis Cirrhosis Hepatocellular Carcinoma
How much do you have to drink to get alcoholic liver disease?
Risk of developing cirrhosis increases with daily consumption:
Men >3 drinks/day for >5 years
Women >2 drinks/day for >5 years
Risk increased with >30 g/day
Amount of alcohol ingested→ most important risk factor
+/- Type of alcohol→ Beer or spirits > wine
Pattern of Drinking→ drinking outside meal times increases risk
Relationship to quantity is not completely linear
Fatty liver pathophysiology
Increased mobilization of free fatty acid from peripheral stores
Increased triglyceride formation
Decreased fatty acid oxidation
Reduced lipoprotein release by liver
Accumulation of fat (small or large droplets) in the cytoplasm of liver cells
Fatty liver presentation
Asymptomatic +/- hepatomegaly
Fatty liver management
Often completely reversible with 4-6 weeks of abstinence
May progress to fibrosis or cirrhosis, especially with continued drinking
Inflammation of liver characterized by necrosis (death) and fibrotic scarring
Mild (few symptoms) to severe presentation with advanced liver disease (cirrhosis in 50%)
High risk of progressive liver injury with cirrhosis developing in 50%
Alcoholic hepatitis
Alcoholic hepatitis presentation
Asymptomatic to mild to severe Severe→ marked impairment of liver function: Fever Leukocytosis Hepatic encephalopathy Spider angiomas *Jaundice* Hepatosplenomegaly with liver tenderness Edema (scrotal or LE) *Ascites* *Variceal bleeding* Oliguria
Alcoholic hepatitis labs
CBC – leukocytosis with left shift, Macrocytosis (MCV elevated), Thrombocytopenia AST/ALT ratio >2→ classic AST <500 IU/L. (2-6X ULN) ALT < 200 IU/L ALP→ mildly elevated Bilirubin→ Elevated, Direct>Indirect PT/ INR→ Elevated Albumin→ low Hyponatremia Hypokalemia GTP→ Elevated secondary to ETOH use Folate→ Low
Alcoholic hepatitis histology
Clumps of intracellular material→ Alcoholic hyaline (Mallory bodies)
Fatty infiltration
- Neutrophil infiltration* around clusters of necrotic hepatocytes
- Fibrosis* around hepatic venules→ precursor to cirrhosis
Alcoholic hepatitis diagnosis
Liver biopsy is required for diagnosis
* When there is an unclear history of alcohol use and elevated liver tests
* Confounded by other risk factors for liver disease and considering
pharmacotherapy with steroids
Alcoholic hepatitis management
Nutritional Assessment + therapy
Do not limit protein intake
Sodium restricted diet (<2000 mg/day)
Address vitamin deficiencies/malnutrition
Discontinue non-selective beta blockers (increase risk of AKI)
Treatment of Alcohol Withdrawal
Infection Surveillance
Fluid overload management→ Diuretics→ Lasix, Spironolactone
Mallory bodies
Seen on histology of alcoholic hepatitis:
Clumps of intracellular material→ Alcoholic hyaline
Folate deficiency + elevated LFTs
Alcoholic hepatitis
Discontinuing all alcohol in alcoholic hepatitis
Improve outcome Improve histological features Reduce portal pressure/complications (ascites, variceal bleeding) Decrease progression to cirrhosis Improve survival
Severe alcoholic hepatitis is defined as
MDF >32 or MELD >20
These people get a 7 day trial of steroids using MDF for starting steroids, Lillie score for discontinuing steroids
They can get a liver transplant if they meet specific criteria
Risk assessment calculators
Risk assessment calculators:
Model of End Stage Liver Disease (MELD score) → bilirubin, creatinine, INR→
> 20→ Severe, poor prognosis
Maddery (Modified) Discriminant Factor (MDF) → Protein, Protein control, bilirubin→ > 32→ Severe, Poor Prognosis (50% mortality 1 month) → steroids beneficial
Lillie Score → bilirubin, albumin, creatinine, protime at day 0→ bilirubin day 7→ Determine if steroids should be continue
If a patient is has a high mortality risk, they are hospitalized (MELD >20?)
Hepatocellular dysfunction + portosystemic shunting→ Failure of the liver to detoxify noxious agents of gut origin→ impaired brain function
Ammonia is the best known neurotoxin
Hepatic encephalopathy
Hepatic encephalopathy presentation
EEG changes
Asterixis: flapping tremor
Grading of hepatic encephalopathy
Grade I→ Subclinical or Covert Encephalopathy→ Changes in behavior, mild confusion, slurred speech,
disordered sleep pattern
Grade II→ Lethargy, moderate confusion
Grade III→ Marked confusion (stupor), incoherent speech, sleeping but can arouse.
Grade IV→ Coma, unresponsive to pain
Stroop test
Brief cognitive screening tools, which do not require psychological expertise in administration interpretation
Evaluate psychomotor speed and cognitive flexibility→ diagnose minimal hepatic encephalopathy (very sensitive + specific)
Hepatic encephalopathy treatment
Treat any precipitating factors: GI bleeding, infection, sedating
medications, electrolyte abnormalities, constipation, renal failure
Lactulose, Rifaximin
Lactulose
ammonia reducer
acute overt hepatic encephalopathy and secondary
prophylactic therapy for an indefinite period of time
Widespread destruction and regeneration of liver tissue→ marked increase in fibrotic connective tissue, scarring→ impairment of liver function
Regenerated liver tissue forms nodules→ permanent alters the structure
Continued necrosis & fibrosis→ progressive deterioration
Inflammatory cell infiltration common
Chronic Hepatitis with Fibrosis or Cirrhosis
Compensated Chronic Hepatitis with Fibrosis or Cirrhosis
Portal Pressure is <10.
Median Survival ~ 12 years
Splenomegaly→ thrombocytopenia, leukopenia, anemia, AST elevation
Decompensated Chronic Hepatitis with Fibrosis or Cirrhosis
Increased Portal Pressure. Decreased
Liver Function.
Median Survival <2 years
Microvasculature severely distorted→ hepatic blood flow bypasses vascular scars→ portal hypertension, portosystemic shunting, impaired liver function
Complications of Chronic Hepatitis with Fibrosis or Cirrhosis
Portal hypertension
Spontaneous bacterial peritonitis
Hepatic encephalopathy
Hepatorenal syndrome
Chronic Hepatitis presentation
Cirrhosis with increased portal hypertension (decompensated) Ascites Esophageal and rectal varices Splenomegaly→ leukopenia, thrombocytopenia Dilated abdominal veins Fatigue, anorexia Weakness Palmar erythema Parotid enlargement Dupuytren’s contracture Palmar erythema Jaundice Gynecomastia Testicular atrophy Spider nevi Muscle wasting anemia (chronic disease or IDA). Hepatic encephalopathy (asterixis)
Chronic hepatitis labs
Similar to Alcoholic hepatitis
AST elevation
Normal in compensated cirrhosis
Anemia→ Anemia of chronic disease, folate deficiency, suppression of hematopoiesis from ETOH, hemolysis, GI blood loss, or splenomegaly
Coagulation abnormalities→ reduced synthesis of clotting factors
Splenomegaly→ leukopenia, thrombocytopenia
Portal hypertension
Increased pressure within the portal venous system
+/- 3 sites of obstruction:
1. Prehepatic: portal vein thrombosis (cirrhosis or other)
2. Intrahepatic: cirrhosis
3. Posthepatic: CHF, constrictive pericarditis
Pathophysiology of portal htn in chronic hepatitis
Increase hydrostatic pressure in peritoneal capillaries→ ascites
Splenomegaly→ anemia, leukopenia, thrombocytopenia→ bleeding
Collateral channels→ caput medusae, esophageal/rectal varices, hemorrhoids
Shunting of ammonia/toxins from intestine to general circulation→ hepatic encephalopathy
How to get a liver transplant if you have chronic hepatitis
Refer decompensated cirrhosis + MELD >15
Requires 6 months abstinence before can consider for transplant→ AA/Abstinence Program
Ascites treatment
<2g/d sodium
Lasix, Spironolactone
Fluid restriction ONLY if sodium is <125 mmol/L
Refractory ascites treatment
Stop beta blocker
Therapeutic Paracentesis→ with 6-8 Albumin per liter drained if > 5-6L (prevent kidney injury)
TIPS→ Transjugular intrahepatic Portosystemic Shunt→ reduces ascites, variceal hemorrhage, quality of life→ no increased survival rate
Prophylaxis for variceal bleeding
Non-selective beta blocker
HR 55-60 and SBP <90 is goal→ no EGD for surveillance needed
How to monitor or band varices
EGD
Hepatocellular carcinoma surveillance for chronic hepatitis
US q 6 months +/- AFP
Is (acute) Alcoholic hepatitis reversible?
Mild cases with abstinence are reversible.
Recurrent episodes→ irreversible, progressive liver disease, decompensated cirrhosis.
Prognosis for alcoholic cirrhosis
poor
Continued ETOH→ 4 year survival with a major complication (Refractory Ascites, HRS*) < 20%
Hepatorenal syndrome
Functional renal failure in setting of decompensated cirrhosis
Type 1→ Rapidly + progressive renal failure with severe multi-organ failure
Median survival < 4 weeks
Type 2→ associated with refractory ascites
Median survival ~ 6 months
Hepatorenal syndrome diagnsosi
Cirrhosis with Ascites
Absence of shock
Renal Impairment
Rise in Cr of 0.3+ mg/dL in 48 hours
50% increase from baseline in 1 week
No improvement with correction of volume status + albumin* x 2 days
Withdrawal of diuretics
Volume expansion with albumin*
Absence of other causes of AKI
Exclude shock, infection, bleeding, sepsis, fluid losses, use of nephrotoxic drugs, intrinsic renal pathology
Hepatorenal syndrome presentation
Ascites
Serum creatinine level >1.5 mg/dL
Azotemia → increased BUN
Oliguria→ < 500 ml/d
Hyponatremia (<130)
Hypotension
Hepatorenal syndrome prevention
Albumin IV if large volume (>5L) paracentesis
Protect against GI bleeding→ EGD
Surveillance or beta blocker use
Don’t give _____ to prevent Hepatorenal syndrome
NSAIDs or Supplements
Spontaneous bacterial peritonitis prophylaxis
Previous dx → DS Bactrim daily or Ciprofloxacin 500 mg daily
Variceal bleed x 3-7 days → 3-7 days IV ceftriaxone
Ascetic protein < 1.5 g/dl
Benign Lesions usually requiring no further intervention if definitely identified on imaging
Cavernous Hemangioma < 4 cm
Focal nodular hyperplasia
Simple cyst < 4 cm and asymptomatic
Focal fatty change/sparing
Malignant Lesions requiring appropriate management
Metastases
Lymphoma “The Great Masquerader”
Primary Liver neoplasm:
- Hepatocellular carcinoma
- Cholangiocarcinoma
- Rare tumors→ cystadenocarcinoma, angiosarcoma
Benign Lesions requiring further investigation and therapy→ refer to GI/hepatology
Adenoma→ malignant potential (5%) and increase risk of bleeding
Associated with use of oral contraceptives pills (OCP)
Liver Abscess→ pyogenic, amebic
Inflammatory pseudotumor
Atypical/complex cysts and large symptomatic simple cysts
Hepatocellular cancer
Third leading cause of cancer
More common→ Africa, China, Japan, SE Asia
High index of suspicion: Cirrhotic patients or patients with
non-cirrhotic Hepatitis B with liver lesion on imaging
M>F
Risk for hepatocellular cancer
All suspected cirrhotic patients from any liver disease
Platelet count <150, 000
US Elastography w/ kPA > 20
Chronic Hepatitis B (non-cirrhotic)
Asian females >50
Asian males > 40
FH + Hep B infection
African descent >20
Screen with US q 6 months +/- AFP
Hepatocellular cancer presentation
Cachexia
Weakness
Weight loss
Sudden appearance of ascites
Hepatocellular cancer diagnosis
Elevated Alkaline Phosphatase
Elevated Alpha-fetoprotein
Triphasic CT scan → non-diagnostic→ Triphasic MRI with gadolinium
Liver Biopsy is DIAGNOSTIC→ risk of tumor seeding→ not needed if imaging + elevated AFP
Hepatocellular cancer management
Resection rarely feasible due to background cirrhosis
Non-cirrhotic HBV often resectable even if large tumor
Cirrhotic HCC when bilirubin is normal and no portal HTN
Liver Transplant→ early stage cancer
• 1 lesion up to 5 cm or 3 lesions up to 3 cm AND no vascular invasion or distant spread
RFA for small tumors ( ~ 3cm) if non-operative
TACE/TARE or XRT→ large tumors if sufficient hepatic reserve
Advanced stage→ Systemic Therapy for distant spread
End Stage→ Symptomatic
Hepatocellular carcinoma arises from
Parenchymal cells
Radiofrequency Ablation (RFA)
for small tumors ( ~ 3cm) if non-operative
Transarterial Chemoembolization (TACE)
large tumors if sufficient hepatic reserve
Transarterial Radioembolization (TARE)
large tumors if sufficient hepatic reserve
Radiation/ Radiotherapy (XRT)
large tumors if sufficient hepatic reserve
