L12: Alcoholic liver disease

Question 1

Blood flow in the liver

Answer 1

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

Question 2

Stages of Alcoholic liver disease

Answer 2

Not distinct stages, multiple stages may be present at once

1. Fatty Liver (Simple Steatosis) (present in most drinkers >60g/day)
2. Alcoholic Hepatitis
3. Chronic Hepatitis with fibrosis or cirrhosis

Question 3

Risk factors for Alcoholic liver disease

Answer 3

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

Question 4

Progression of cirrhosis/fibrosis/HCC

Answer 4

Normal liver + chronic alcohol use 
Steatosis
Steatohepatitis
Fibrosis
Cirrhosis
Hepatocellular Carcinoma

Question 5

How much do you have to drink to get alcoholic liver disease?

Answer 5

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

Question 6

Fatty liver pathophysiology

Answer 6

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

Question 7

Fatty liver presentation

Answer 7

Asymptomatic +/- hepatomegaly

Question 8

Fatty liver management

Answer 8

Often completely reversible with 4-6 weeks of abstinence

May progress to fibrosis or cirrhosis, especially with continued drinking

Question 9

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%

Answer 9

Alcoholic hepatitis

Question 10

Alcoholic hepatitis presentation

Answer 10

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

Question 11

Alcoholic hepatitis labs

Answer 11

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

Question 12

Alcoholic hepatitis histology

Answer 12

Clumps of intracellular material→ Alcoholic hyaline (Mallory bodies)

Fatty infiltration

• Neutrophil infiltration* around clusters of necrotic hepatocytes
• Fibrosis* around hepatic venules→ precursor to cirrhosis

Question 13

Alcoholic hepatitis diagnosis

Answer 13

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

Question 14

Alcoholic hepatitis management

Answer 14

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

Question 15

Mallory bodies

Answer 15

Seen on histology of alcoholic hepatitis:

Clumps of intracellular material→ Alcoholic hyaline

Question 16

Folate deficiency + elevated LFTs

Answer 16

Alcoholic hepatitis

Question 17

Discontinuing all alcohol in alcoholic hepatitis

Answer 17

Improve outcome
Improve histological features
Reduce portal pressure/complications (ascites, variceal bleeding)
Decrease progression to cirrhosis
Improve survival

Question 18

Severe alcoholic hepatitis is defined as

Answer 18

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

Question 19

Risk assessment calculators

Answer 19

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?)

Question 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

Answer 20

Hepatic encephalopathy

Question 21

Hepatic encephalopathy presentation

Answer 21

EEG changes

Asterixis: flapping tremor

Question 22

Grading of hepatic encephalopathy

Answer 22

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

Question 23

Stroop test

Answer 23

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)

Question 24

Hepatic encephalopathy treatment

Answer 24

Treat any precipitating factors: GI bleeding, infection, sedating
medications, electrolyte abnormalities, constipation, renal failure

Lactulose, Rifaximin

Question 25

Lactulose

Answer 25

ammonia reducer acute overt hepatic encephalopathy and secondary prophylactic therapy for an indefinite period of time

Question 26

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

Answer 26

Chronic Hepatitis with Fibrosis or Cirrhosis

Question 27

Compensated Chronic Hepatitis with Fibrosis or Cirrhosis

Answer 27

Portal Pressure is <10. Median Survival ~ 12 years Splenomegaly→ thrombocytopenia, leukopenia, anemia, AST elevation

Question 28

Decompensated Chronic Hepatitis with Fibrosis or Cirrhosis

Answer 28

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

Question 29

Complications of Chronic Hepatitis with Fibrosis or Cirrhosis

Answer 29

Portal hypertension Spontaneous bacterial peritonitis Hepatic encephalopathy Hepatorenal syndrome

Question 30

Chronic Hepatitis presentation

Answer 30

``` 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) ```

Question 31

Chronic hepatitis labs

Answer 31

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

Question 32

Portal hypertension

Answer 32

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

Question 33

Pathophysiology of portal htn in chronic hepatitis

Answer 33

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

Question 34

How to get a liver transplant if you have chronic hepatitis

Answer 34

Refer decompensated cirrhosis + MELD >15 | Requires 6 months abstinence before can consider for transplant→ AA/Abstinence Program

Question 35

Ascites treatment

Answer 35

<2g/d sodium Lasix, Spironolactone Fluid restriction ONLY if sodium is <125 mmol/L

Question 36

Refractory ascites treatment

Answer 36

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

Question 37

Prophylaxis for variceal bleeding

Answer 37

Non-selective beta blocker | HR 55-60 and SBP <90 is goal→ no EGD for surveillance needed

Question 38

How to monitor or band varices

Answer 38

EGD

Question 39

Hepatocellular carcinoma surveillance for chronic hepatitis

Answer 39

US q 6 months +/- AFP

Question 40

Is (acute) Alcoholic hepatitis reversible?

Answer 40

Mild cases with abstinence are reversible. Recurrent episodes→ irreversible, progressive liver disease, decompensated cirrhosis.

Question 41

Prognosis for alcoholic cirrhosis

Answer 41

poor Continued ETOH→ 4 year survival with a major complication (Refractory Ascites, HRS*) < 20%

Question 42

Hepatorenal syndrome

Answer 42

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

Question 43

Hepatorenal syndrome diagnsosi

Answer 43

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

Question 44

Hepatorenal syndrome presentation

Answer 44

Ascites Serum creatinine level >1.5 mg/dL Azotemia → increased BUN Oliguria→ < 500 ml/d Hyponatremia (<130) Hypotension

Question 45

Hepatorenal syndrome prevention

Answer 45

Albumin IV if large volume (>5L) paracentesis Protect against GI bleeding→ EGD Surveillance or beta blocker use

Question 46

Don't give _____ to prevent Hepatorenal syndrome

Answer 46

NSAIDs or Supplements

Question 47

Spontaneous bacterial peritonitis prophylaxis

Answer 47

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

Question 48

Benign Lesions usually requiring no further intervention if definitely identified on imaging

Answer 48

Cavernous Hemangioma < 4 cm Focal nodular hyperplasia Simple cyst < 4 cm and asymptomatic Focal fatty change/sparing

Question 49

Malignant Lesions requiring appropriate management

Answer 49

Metastases Lymphoma “The Great Masquerader” Primary Liver neoplasm: 1. Hepatocellular carcinoma 2. Cholangiocarcinoma 3. Rare tumors→ cystadenocarcinoma, angiosarcoma

Question 50

Benign Lesions requiring further investigation and therapy→ refer to GI/hepatology

Answer 50

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

Question 51

Hepatocellular cancer

Answer 51

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

Question 52

Risk for hepatocellular cancer

Answer 52

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

Question 53

Hepatocellular cancer presentation

Answer 53

Cachexia Weakness Weight loss Sudden appearance of ascites

Question 54

Hepatocellular cancer diagnosis

Answer 54

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

Question 55

Hepatocellular cancer management

Answer 55

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

Question 56

Hepatocellular carcinoma arises from

Answer 56

Parenchymal cells

Question 57

Radiofrequency Ablation (RFA)

Answer 57

for small tumors ( ~ 3cm) if non-operative

Question 58

Transarterial Chemoembolization (TACE)

Answer 58

large tumors if sufficient hepatic reserve

Question 59

Transarterial Radioembolization (TARE)

Answer 59

large tumors if sufficient hepatic reserve

Question 60

Radiation/ Radiotherapy (XRT)

Answer 60

large tumors if sufficient hepatic reserve