Hepatic Disorders

Question 1

Acute Viral Hepatitis (Overview)

Answer 1

• Phases:
  
  • prodromal phase:
    
    • malaise, arthralgia, fatigue, URI sxs, N/V, abd pain, loss of appetite, decreased desire to smoke
  • Icteric Phase:
    
    • Jaundice, (most don’t progress past this phase)
  • Fulminant:
    
    • encephalopathy, coagulopathy, hepatomegaly, jaundice, edema, ascites
• Dx:
  
  • Elevated ALT & AST (>500)
  • hyperbili
• outcomes:
  
  • acute: clinical recovery within 3-16 weeks
  • chronic: disease > 6 months duration, only HBV, HCV, HDV
    
    • may lead to ESLD or HCC
  • Fulminant: see other flashcard

Question 2

Fulminant Hepatitis

Answer 2

• Definition:
  
  • acute hepatic failure in patients with hepatitis
• etiology:
  
  • acetaminophen toxicity = most common
  • viral hepatitis, autoimmune hepatitis
  • reyes syndrome: aspirin after viral infx
• S/sxs:
  
  • encephalopathy:
    
    • vomiting, coma, AMS, seizures, asterixis (flapping tremor), hyperreflexia, cerebra edema
  • coagulopathy:
    
    • increased PT/INR & PTT
• PE:
  
  • Hepatomegaly
  • Jaundice
  • Reyes syndrome: (aspirin after viral infx)
    
    • → rash, intractable vomiting, liver damage, dilated pupils
• Dx:
  
  • combo of symptoms
  • Abnormal LFTs
  • increased INR (>1.5)
  • hypoglycemia
  • increased ammonia (encephalopathy)
• Tx:
  
  • Supportive: IV fluids, PPI for stress ulcer prophylaxis, mannitol
  • Definitive = Liver transplant

Question 3

Asterixis

Answer 3

flapping tremor

Question 4

Reyes Syndrome

Answer 4

rash, intractable vomiting, liver damage, dilated pupils

caused by taking aspirin after a viral illness or by kids <18 taking aspirin

Question 5

Hepatitis A

Answer 5

• Definition: acute viral infection of the liver due to HAV infx
• Transmission:
  
  • fecal-oral, early fecal shedding
• Virus:
  
  • ssRNA, heat/acid stable
• s/sxs:
  
  • Most pts are asymptomatic or mild
  • SPIKING FEVER
  • malaise, anorexia, N/V, abd pain
• PE:
  
  • Hepatomegaly
  • Jaundice
• Dx:
  
  • elevated ALT, AST, bili
• Serology:
  
  • acute: anti-HAV IgM
  • past exposure: HAV IgG (lifelong), negative IgM
• Tx:
  
  • no treatment needed → self-limiting
  • Post-exposure prophylaxis;
    
    • healthy 1-40 yo: HAV Iz
    • healthy > 40 yo: HAV iz + immunoglobulin (IG)
    • immunocompromised: HAV iz + IG

Question 6

Hepatitis B

Answer 6

• Definition: acute viral infection of the liver due to HBV infection
• Transmission:
  
  • percutaneous (contaminated syringe), sexual (body fluids), parenteral,perinatal
• Virus:
  
  • Dane particle, many antigens (HBsurfaceAg = HBsAg, HBcoreAg= HBcAg, & HBeAG)
• S/sxs:
  
  • mostly asymptomatic
  • Acute, icteric, fulminant stages
  • Chronic stages:
    
    • persistent sxs, elevated LFTS, increased viral load
• Dx:
  
  • LFTs:
    
    • acute: AST/ALT in thousands range
    • chronic: AST/ALT in hundreds
    • increased bilirubin
  • Serology Variations**:
    
    • -window period: positive IgM
    • -vaccination: positive surface antibody (anti-HBs)
    • -Acute hepatitis: positive surface antigen & IgM
    • -chronic hepatitis: positive surface antigen & IgG
    • -recovery: positive surface antibody & IgG
• Tx:
  
  • Life threatening
  • Management = supportive
  • Acute Management:
    
    • pegylated interferon alpha-2a
    • antivirals: entecavir, tenofovir
    • stop tx after confirmation that the pt has cleared HBsAg
    • ***Not expensive like Hep C tx***

Question 7

Hepatitis C

Answer 7

• Definition: acute viral infx of the liver due to HCV infx. Most common cause of chronic liver disease, cirrhosis, & liver transplantation in the U.S.
• Transmission:
  
  • percutaneous (IV drug use), sexual (not common), parenteral
• S/sxs:
  
  • most pts are asymptomatic
  • fatigue, myalgias, nausea, RUQ pain
• PE;
  
  • jaundice, dark urine, clay-colored stool
• Dx:
  
  • HCV serology:
    
    • incubation (4-7 weeks): HCV RNA
    • Acute (4-12 weeks): HCV ag
    • Cure (years): anti-HCV ab
• Tx:
  
  • Life threatening
  • progression: exposure (acute)→ chronic → cirrhosis → HCC (transplant, death)
  • 85% of patients with HCV develop a chronic infection
  • Management:
    
    • (95% cure rate within 12 weeks)
    • New regiments: ledipasvir/sofosbuvir + more
    • old regimen: interferon alpha-2b + ribavirin

Question 8

Hepatitis D

Answer 8

• Definition: defective virus that requires Hepatitis B Virus to cause co- or superimposed infection
• Pathophys:
  
  • HDV uses HBsAG as its envelope protein
• Transmission:
  
  • parenteral (exposure to blood), sexual.
• Preventable with HBV iz
• S/sxs:
  
  • most patients are asymptomatic
  • fatigue, malaise, nausea, RUQ pain
• PE:
  
  • jaundice, dark urine, clay-colored stool
• Dx:
  
  • Serology:
    
    • -Cure: anti-HDV, anti-HBs
    • -confirm with liver biopsy for HDag or PCR assays for HDV RNA in serum
• Tx:
  
  • Life threatening
  • Management:
    
    • -no FDA approved management
    • -interferon alpha
    • -definitive: liver transplant

Question 9

Hepatitis E

Answer 9

• Definition: acute viral infx of the liver due to HEV infx
• Transmission:
  
  • fecal-oral route, unhealthy lifestyle, alcoholism
• S/sxs:
  
  • pts are mostly asymptomatic
  • malaise, anorexia, fever, N/V, abd pain
• PE:
  
  • Hepatomegaly
  • Jaundice
• Dx:
  
  • LFTs: elevated ALT, AST, bilirubin
  • serology: Acute: anti-HEV IgM
• Tx:
  
  • No tx needed
  • *HIGHESTmortality due to fulminant hepatitis duringpregnancy(esp 3rd trimester)*

Question 10

Autoimmune Hepatitis

Answer 10

• Definition: idiopathic chronic inflammation of the liver due to circulating autoantibodies
• Epidemiology:
  
  • young women
• S/sxs:
  
  • Most patients are asymptomatic or have non-specific symptoms
• PE;
  
  • may be normal
  • Hepatomegaly
  • Jaundice
  • splenomegaly
• Dx:
  
  • Autoantibodies:
    
    • Type I: Positive ANA, smooth muscle antibodies
    • Type II: anti-liver/kidney microsomal antibodies
  • LFTs: hepatocellular pattern (elevated ALT, AST, bili)
  • granulomatous hepatitis:
    
    • granulomas on liver biopsy
• Tx:
  
  • corticosteroids
  • complications:
    
    • cirrhosis
    • pericarditis
    • myocarditis
    • uveitis
    • glomerulonephritis

Question 11

Drug Induced Liver Disease: Epidem, types, risks, S/sxs

Answer 11

• Epidemiology:
  
  • ⅓ of fulminant hepatic failure (20% acetaminophen, 15% other drugs), 20% of jaundice in geriatric patients
• Types:
  
  • hepatocellular injury:
    
    • anesthetics, antimicrobials, anticonvulsants, NSAIDs, analgesics, labetalol, nicotinic acid
  • cholestatic injury:
    
    • contraceptives, steroids, abx, psychotropics
  • Granulomatous:
    
    • quinidine, allopurinol
  • vascular injury:
    
    • plant alkaloids, bone marrow transplant, azathioprine
  • neoplastic lesions:
    
    • contraceptive steroids, anabolic steroids
• Risks:
  
  • depends on the drug
• S/sxs:
  
  • *Diverse clinical presentation → may present with asymptomatic elevation of hepatic enzymes
  • Cholestatic injury → jaundice, pruritus
  • Vascular injury:
    
    • mild viral-like illness → hepatic failure
    • rapid weight gain
    • jaundice
    • ascites
    • portal HTN
  • granulomatous:
    
    • fever
    • diaphoresis
    • malaise
    • anorexia
    • jaundice
    • RUQ pain
  • Chronic (2-24 months)
    
    • fatigue, anorexia, weight loss, jaundice, ascites, hepatosplenomegaly, portal HTN
  • Hypersensitivity:
    
    • fever, rash, arthralgias, eosinophilia

Question 12

Drug Induced Liver Disease: Dx & Tx

Answer 12

• Dx:
  
  • drug history!
    
    • dose, duration, time between initiation & sxs
    • jaundice
    • abnormalities of hepatic enzymes (ALT, AST, bili)
    • hepatitis-like symptoms
    • exclusion of other causes of liver disease
  • granulomatous hepatitis:
    
    • granulomas on liver biopsy
• Tx:
  
  • 10% mortality for agents causing fulminant hepatitis or toxic steatosis. Jaundice = worse prognosis
  • Progression:
    
    • no progression despite continued use of medication (drug tolerance) → common with INH & phenytoin
    • progression to hepatic injury with continued use of medication → hepatic failure
  • Management:
    
    • d/c the offending drug
    • hepatocellular recovery within 4 weeks
    • cholestatic has a prolonged recovery

Question 13

Alcoholic Liver disease: types, risks, co-morbidities, s/sxs

Answer 13

• Types:
  
  • alcoholic fatty liver (80%)
  • alcoholic hepatitis (50%)
  • alcoholic cirrhosis (15%)
• Risks
  
  • alcohol quantity:
    
    • in men: 40-80g/d → fatty liver, 160 g/d x 10 years → hepatitis/cirrhosis
    • women: 20g/d → liver dx
    • concurrent HCV infx, genetics (PNPLA 3), fatty liver
• Comorbidities:
  
  • pancreatitis, cardiomyopathy, skeletal myopathy, neuro deficits, osteoporosis, bone marrow suppression, cancer, psychiatric
• S/sxs:
  
  • fatty liver → asymptomatic & reversible
  • Alcoholic hepatitis:
    
    • jaundice, anorexia, weight loss, N/V, fever, hepatomegaly, abd pain

Question 14

Alcoholic Liver Disease Histology

Answer 14

Question 15

Alcoholic Liver Disease: Dx & Tx

Answer 15

• Dx: History of excessive alcohol intake (CAGE questions)
  
  • Labs: AST > ALT (2:1)
    
    • AST < 300, ALT < 100 (*not as high as viral hepatitis)
    • increased MCV
    • increased uric acid
  • Histology:
    
    • *Liver biopsy not indicated in majority of cases (use in atypical to determine severity, alcohol vs viral)
    • fatty liver: microvesicular, steatosis
    • hepatitis: steatosis, heaptocyte ballooning +/- mallory bodies, neutrophil-rich inflammation
    • cirrhosis: steatofibrosis starts in space of Disse & extends outward, do trichrome stain
• tx:
  
  • alcoholic hepatitis has poor 30-day mortality rate of >50%
  • management:
    
    • lifestyle changes: alcohol abstinence, quit tobacco, weight loss
    • steroids: use when DF > 32 or MELD > 20, prednisone 40mg/day x 4 weeks with steroid taper
    • TNFa inhibitor or S-adenosylmethionine (SAMe)
    • vitamin B1, B6, B12, &folic acid
    • liver transplant after a defined period of sobriety
  • MELD SCORE:
    
    • predictor of 90-day mortality in pts with ESLD & shows how much you need a liver transplant
    • HIGHER number = more urgent case
    • -uses dialysis, creatinine, bilirubin, INR, & sodium

Question 16

MELD Score

Answer 16

used in Alcoholic Liver Disease

• predictor of 90-day mortality in pts with ESLD & shows how much you need a liver transplant
• HIGHER number = more urgent case
• -uses dialysis, creatinine, bilirubin, INR, & sodium
• > 20 : use steroids

Question 17

Non-Alcoholic Fatty Liver Disease

Answer 17

• Definition:
  
  • fatty liver disease in the absence of alcohol
  • extremely common cause of mildly abnormal LFTs
• Types:
  
  • non-alcoholic fatty liver: relatively benign
  • non-alcoholic steatohepatitis (NASH): inflammation & fibrosis with potential to progress to cirrhosis, RARE
• Risks:
  
  • obesity, DM II, dyslipidemia, HTN, metabolic syndrome
• S/sxs:
  
  • may be asymptomatic
  • fatigue, malaise, RUQ pain
  • hepatomegaly, splenomegaly (if advanced fibrosis)
• Dx:
  
  • presence of risk factors & absence of alcohol
  • ALT > AST
  • Ultrasound of liver for all patients - findings steatohepatitis (increased echogenicity and coarsened echotexture of the liver)
  • Biopsy → microvesicular fatty deposits, used to distinguish fatty liver vs NASH & to grade disease
  • serologic tests to r/o hep B/C
• Tx:
  
  • lifestyle modification - weight loss, alcohol cessation, diabetes control, low-fat diet
  • correct the underlying cause:
    
    • weight loss: lose 7-10% of BW over 6-12 months
    • insulin sensitizers: metformin, pioglitazone (can be used even in non-diabetic patients)
    • bariatric surgery

Question 18

Cirrhosis (End-Stage Liver Disease): Def, pathophys, Etiology, Progression, & Stages

Answer 18

• Definition:
  
  • mostly irreversible liver fibrosis with nodular regeneration secondary to chronic liver disease
• Pathophys:
  
  • nodules & fibrosis → heaptic venous outflow block → portal HTN (HVPG > 10 mmHg) → bypass routes to heart (esophagus, paraumbilical area, anal canal, retroperitoneal, base area of liver); macronodules associated with higher risk of hepatocellular carcinoma (HCC)
• Etiology:
  
  • Chronic HCV = most common, HBV, HDV, alcohol, non-alcoholic fatty liver disease, hemochromatosis, autoimmune hepatitis, primary biliary cirrhosis, drug toxicity
• Progression:
  
  • chronic liver disease → compensated cirrhosis → decompensated cirrhosis (symptomatic) → death
• Stages:
  
  • stage 0: no fibrosis
  • Stage 1: portal fibrosis, no septa
  • Stage 2: few septa
  • stage 3: numerous septa
  • stage 4: cirrhosis

Question 19

Cirrhosis (End-Stage Liver Disease): S/sxs, PE, Dx, & Tx

Answer 19

• S/sxs:
  
  • *may be asymptomatic for a very long time with ⅓ of patients never developing symptoms
  • fatigue, weakness, weight loss, malaise, anorexia
• PE:
  
  • Ascites (shifting dullness, flank dullness, puddle sign)
    
    • → d/t portal HTN, low albumin & RAAS pathway
  • Variceal hemorrhage (esophagus most common)
  • Caput medusae = paraumbilical varices
  • Red Whale → longitudinal red streaks on varices = recent bleed
  • splenomegaly, hard/nodular liver
  • gynecomastia
  • spider angioma, telangiectasia, muscle wasting, bleeding, palmar erythema, jaundice
• Dx:
  
  • CBC
  • coag test
  • LFTs
  • Biopsy
  • paracentesis: cell count, cx, ascites, albumin
  • serum-ascites gradient = serum alb - ascites alb
    
    • if > 1.1 it is portal HTN
    • if < 1.1 it is cancer, TB, pancreatitis
• Tx:
  
  • avoid alcohol, hepatotoxic meds, weight reduction, vaccination
  • tx the underlying cause
  • definitive = liver transplant
  • pruritus: cholestyramine
  • surveillance: US q 6 months
  • Management of ascites:
    
    • diuretics, sodium restriction (<2g/day), fluid restriction
    • paracentesis
    • transjugular intrahepatic portosystemic shunts (TIPS): if extremely frequent/complicated paracentesis
    • transplant

Question 20

Spontaneous Bacterial Peritonitis

Answer 20

• Definition: infection of ascitic fluid without perforation of the bowel. Complication of cirrhosis (increases space between tight junctions of epithelial cells)
• Etiology:
  
  • E.coli = #1 cause, pneumococcus, klebsiella
• S/sxs:
  
  • *often subtle signs d/t large amounts of fluid
  • fever, chills
  • abd pain, increasing girth
  • diarrhea
• PE:
  
  • ascites → shifting dullness, fluid wave
  • abd tenderness
• Dx:
  
  • paracentesis = test of choice
    
    • absolute PMN > 250 cells/mm3
    • gram stain, cx (often negative)
• Tx:
  
  • Antibiotics: cefotaxime, ceftriaxone
  • Prophylaxis: lifelong prophylaxis with trimethoprim-sulfamethoxazole (Bactrim) or Norfloxacin

Question 21

Hepatorenal Syndrome

Answer 21

• definition: renal failure in the setting of cirrhosis
• Dx:
  
  • Criteria:
    
    • creatinine > 1.5 or CrCl < 40
    • no improvement of renal function after volume expansion
    • no proteinuria
    • absence of shock/infection
• Tx:
  
  • definitive = liver transplant
  • dialysis, midodrine, octreotide

Question 22

Hepatic Encephalopathy

Answer 22

• Definition: neuropsychiatric abnormalities in pts with portal HTN d/t ammonia release (has neurotoxic effects)
• Grades:
  
  • 0: no clinical signs
  • 1: sleep-wake reversal
  • 2: lethargy, slurred speech
  • 3: stupor
  • 4: coma
• PE:
  
  • Asterixis
• Dx:
  
  • r/o other causes: infx, bleed
  • identify precipitating factor (like worsening liver function)
• Tx:
  
  • dietary protein restriction (ammonia comes from protein)
  • -Catharsis: lactulose (increases fecal nitrogen excretion)
  • -Abx: neomycin, metronidazole, rifaximin

Question 23

Hepatocellular Carcinoma

Answer 23

• Definition: primary neoplasm of the liver
  
  • tumor in on part of the liver (vs. cirrhosis which is the entire liver)
• Risks:
  
  • chronic liver disease (chronic HBV, HCV, HDV, cirrhosis)
• s/sxs:
  
  • *many are asymptomatifc
  • weight loss, malaise, jaundice, abd pain
  • hepatomegaly, splenomegaly
• Dx:
  
  • CT scan or MRI
  • US guided liver biopsy
  • increased serum Alpha-fetoprotein level
• Tx:
  
  • surgical resection if confined to one lobe & not associated with cirrhosis
  • Surveillance: US q 6. months in high-risk patients

Question 24

Hepatic Vein Obstruction

Answer 24

• Aka Budd Chiari Syndrome
• Definition: hepatic venous outflow obstruction leading to decreased liver drainage with subsequent portal HTN & cirrhosis
• Most common cause of portal HTN in children
• Types:
  
  • primary: hepatic vein thrombosis
  • Secondary: hepatic vein or IVC occlusions
• Risks:
  
  • malignancy, polycythemia, pregnancy, clotting disorders
• S/sxs:
  
  • TRIAD: ascites, hepatomegaly RUQ abd pain
  • *rapid development of liver disease
• Dx:
  
  • US = initial screening
  • Venography = Gold standard
  • liver biopsy: usually not needed but “nutmeg liver”
• tx:
  
  • shunt decompression of the liver or decompression with stenting
  • anticoag if thrombotic
  • ascites: diuretics, low sodium diet, paracentesis (if large volume)

Question 25

Primary Biliary Cholangitis (Cirrhosis)

Answer 25

• Definition: idiopathic autoimmune disorder of intrahepaticsmall bile ducts → decreased bile salt excretion, cirrhosis, & ESLD
• Epidemiology:
  
  • middle-age women (30-60)
• S/sxs:
  
  • *most are asymptomatic
  • fatigue = 1st sx
  • pruritus, jaundice
  • RUQ pain
• PE:
  
  • hepatomegaly, jaundice, xanthelasma, osteoporosis
• Dx:
  
  • Increased alkaline phosphatase & GGT
  • antimitochondrial antibody (hallmark)
  • U/S
  • liver biopsy = definitive
• Tx;
  
  • Ursodeoxycholic acid = first line
  • Pruritus: Cholestyramine (Bile acid sequestrant) & UV light
  • Definitive = liver transplant

Question 26

Primary Sclerosing Cholangitis

Answer 26

• Definition:
  
  • autoimmune progressive cholestasis → diffuse fibrosis of intra- and extrahepatic biliary ducts
• Risks:
  
  • Ulcerative colitis, men 20-40yo
• S/sxs:
  
  • Jaundice, Pruritus, Fatigue
  • RUQ pain
  • hepatomegaly, splenomegaly
• Dx:
  
  • Increased alkaline phosphatase & GGT
  • positive P-ANCA (hallmark)
  • ERCP: beaded appearance of the biliary ducts
  • liver biopsy: rarely used
• Tx:
  
  • stricture dilation for symptom relief
  • Pruritus: Cholestyramine (binds to bile acids which are the cause of itchiness)
  • Definitive = liver transplant

Question 27

Coagulopathy of Liver Disease

Answer 27

• definition:
  
  • decreased production of coagulation factor proteins associated with advanced liver disease
• S/sxs:
  
  • bruising, GI bleeding
• Dx:
  
  • increased PT/INR
  • low albumin
  • increased PTT (advanced)
• Tx:
  
  • correct the underlying cause
  • cryoprecipitate: if actively bleeding

Question 28

PT/INR measures which factors:

Answer 28

I, II, V, VII, & X

Question 29

PTT measures which factors?

Answer 29

VIII, IX, XI, & XII

Question 30

Tx of Acetaminophen overdose

Answer 30

N-acetylcysteine