ABIM Board Review: Hepatology

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ABIM Board ReviewHepatology
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Hepatocellular liver disease

• Transaminase elevation
• AST, ALT
• Two categories
• Acute
• Chronic

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Acute hepatitis

• Symptoms
• Fatigue, nausea, abdominal pain, jaundice
• Fevers, diarrhea, vomiting
• Labs
• AST/ALT gt 500, sometimes gt 1000 or 5000
• Usual etiology
• viral (HAV, HBV, HSV)
• medication (acetaminophen, antiepileptic, CAM)
• ischemia

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Chronic hepatitis

• Usually asymptomatic
• Labs
• AST/ALT lt 500 (usually lt 150), sometimes normal
• Usual etiology
• viral (HBV, HCV)
• NASH
• Autoimmune
• Metabolic

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Cholestatic liver disease

• Two types
• Intrahepatic
• PBC, PSC, drug-induced, infiltrative (cancer,
  sarcoid, amyloid)
• Extrahepatic
• Gallstones, pancreatic cancer

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Categories

• Viral
• Toxin-mediated
• Autoimmune
• Metabolic

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Viral hepatitis

• HAV
• HBV
• HCV
• HDV
• HEV

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HAV

• Half of all causes of viral hepatitis in US
• Fecal-oral transmission
• Day care, travel, raw shellfish, MSM
• Jaundice, abdominal pain, nausea, diarrhea
• Think Young medical student with one week of
  malaise, anorexia, nausea/vomiting, jaundice
  after eating raw oysters in Guatemala during a
  mission trip

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HAV

• Diagnosis
• Anti-HAV IgM
• Treatment
• Supportive (self-limited infection)
• Prophylaxis
• Immune globulin (HBIg) to close contacts within 2
  weeks
• Vaccinate travelers, high risk, or concominant
  liver disease

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HBV

• Represents 20-30 of acute viral hepatitis and
  15 of chronic viral hepatitis in US
• Much more common in Asia and Africa
• Risks
• Sexual, needles
• Vertical
• Can be fulminant presentation
• Vaccine available

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HBV serologies

• HBsAg
• Active viral replication
• Anti-HBs (IgG)
• Exposure to virus
• Vaccination
• Anti-HBcore (IgM, IgG)
• Exposure to virus
• False positive
• HBV DNA
• Confirm infection
• Treatment

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HBV

• Course
• Perinatal ? almost always chronic
• Adult ? almost always clear it
• CHB with normal LFTs, low HBV DNA, normal biopsy
  ? good prognosis
• CHB with abnormal LFTs, active replication,
  abnormal biopsy ? worse prognosis
• High risk of cirrhosis, HCC

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HBV

• Treatment
• Indications
• Abnormal LFTs
• HBV DNA gt 105
• Abnormal liver biopsy
• Agents
• Lamivudine
• Adefovir
• Entecavir
• IFN

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HBV

• HCC surveillance
• Ultrasound and AFP every 6-12 months
• Who
• HBV cirrhotics
• No cirrhosis but early age of infection and Asian
  pt with family history of HCC, Asian men gt 40,
  Asian women gt 50, Africans gt 20
• Think Asian IVDU patient with multiple sexual
  partners with abnormal LFTs, family history of
  liver problems/cancer

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HCV

• Most common bloodborne infection in US
• Usually asymptomatic
• Associated with leukocytoclastic vasculitis
• Chronic infection
• Only about 15-20 of patients clear the initial
  infection
• Variable duration to cirrhosis
• Transaminase levels do not accurately predict
  severity of disease

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HCV

• Risks
• IVDU, blood transfusion (before 1990s), tattoos
• Diagnosis
• Anti-HCV
• HCV RNA
• Treatment
• IFN, ribavirin
• No vaccine

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HCV

• Assessing pt
• Determining possible time of infection
• AST/ALT
• Genotype
• HCV RNA quant
• Liver biopsy
• Who to treat
• Genotype 2 or 3
• Those at risk of cirrhosis
• Long duration of HCV, alcohol use, stage 2-3
  fibrosis
• Extrahepatic manifestations of HCV

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HCV

• If no treatment is indicated, need yearly
  evaluation with labs, etc.
• Consider repeat biopsy in 3-5 years
• If cirrhotic
• Highest risk of morbidity and mortality
• Ultrasound and AFP every 6-12 months
• Transplant evaluation
• VACCINATE against HAV and HBV

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HDV

• Requires HBV to infect a liver
• Coinfection
• Superinfection
• Risk in US IVDU with HBV
• Think IVDU pt with HBV gets a flare of disease

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HEV

• Self-limited, tropics
• PREGNANCY
• may develop fulminant failure

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Toxin-related liver disease

• Alcohol
• Drug-induced

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Alcoholic liver disease

• Along with HCV, top cause of chronic liver
  disease in US
• Frequently accompanies HCV due to risky lifestyle
• Adds risk to pt with pre-existing liver disease
• Amounts
• Men gt60-80g (6-8 drinks) daily x 5 years
• Women gt30-40g (3-4 drinks) daily x 5 years

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Alcoholic liver disease

• Alcoholic hepatitis
• Fevers, jaundice, signs of portal HTN
• AST/ALT gt 2/1 (and usually lt 300)
• Elevated WBC common
• Discriminant function (PT and TB)
• gt32 50 30-day mortality
• May require steroids

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Alcoholic liver disease

• Treatment
• Abstinence
• Supportive
• Early identification of complications from portal
  HTN (encephalopathy, thrombocytopenia, etc)
• Steroids if DF gt 32
• Pentoxifylline
• If bad enough and has underlying cirrhosis, refer
  to transplant center

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Drug-induced liver disease

• Most common cause of fulminant liver failure in
  US
• Acetaminophen is overwhelming cause of majority
• Antibiotics also a common cause
• Two main types
• Acute hepatitis
• Acetaminophen, NSAIDs, antidepressants
• Cholestatic
• Antibiotics

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DILI

• Treatment
• If LFTs mildly elevated and no symptoms ? observe
• If LFTs high and pt with symptoms ? discontinue
  drug, evaluate for complications
• Always look for concominant liver disease
• Remember CAM

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Autoimmune disorders

• Autoimmune hepatitis
• Primary biliary cirrhosis
• Primary sclerosing cholangitis

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Autoimmune hepatitis

• Inflammatory condition with no known cause
• Risk group
• Females 3-4x that of males
• Ages 20-40
• Other autoimmune disorders (30-50)
• Can be acute/fulminant or chronic

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AIH

• Symptoms
• Fatigue
• Jaundice, anorexia, myalgias, diarrhea
• Exam
• Hepatomegaly, signs of advanced liver disease
• Labs
• AST/ALT usually lt 500 but can be gt 1000
• Elevated ANA (gt180), ASMA, pANCA
• Elevated IgG

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AIH

• Treatment
• Prednisone
• 80 remission at 3 years
• Relapse common
• 50-85 within 6 months
• Azathioprine
• Multiple relapses
• Transplant
• Refracory disease or cirrhosis
• Overall prognosis is excellent if successfully
  treated
• Think young woman with fatigue for a few
  months and abnormal LFTs, h/o thyroid disease

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PBC

• Chronic, progressive, autoimmune disorder of
  biliary system
• Risks
• Women between 40-60 years old
• Other autoimmune disease
• Symptoms
• Fatigue, pruritis (perineal or palmar/plantar),
  jaundice
• Asymptomatic in 50

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PBC

• Labs
• Elevated AP/GGT (gt10xULN)
• AMA (gt140)
• Biopsy with aseptic cholangitis
• Treatment
• UDCA
• Improves labs and itching, slows cirrhosis,
  delays transplant
• Transplant
• Intractable pruritis, cirrhosis
• Think middle age women with itching, abnormal
  LFTs

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PSC

• Progressive bile duct destruction
• Risks
• Men (3x)
• 20-30 years old
• Ulcerative colitis (80)
• UC ? PSC lt 5
• Symptoms
• Usually asymptomatic
• Pruritis, jaundice, pain, fatigue

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PSC

• Labs
• AP gt5xULN
• TB slightly elevated
• Diagnosis
• ERCP with strictures and dilations
• Biopsy with periductal (onionskin) fibrosis

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PSC

• Complications
• Metabolic bone disease
• Steatorrhea
• Cholangiocarcinoma (10-30 lifetime risk)
• Increased risk with UC
• Hepatocellular carcinoma with advanced disease
• Treatment
• Transplant
• Think 40 y/o male with UC x 20 years now with
  jaundice and pruritis, elevated AP

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PBC vs PSC important differences
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Metabolic liver disease

• NAFLD
• Hemochromatosis
• Wilsons disease

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NAFLD

• Broad spectrum disorder
• Simple steatosis (NAFLD) to necroinflammatory
  steatosis with cirrhosis (NASH)
• Prevalence in US
• NAFLD 15-40
• NASH 1-10
• AND CLIMBING

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NAFLD

• Risks
• Obesity, dyslipidemia, DM2/IFG
• Small bowel resection or bypass
• Medications
• Tamoxifen, corticosteroids, amiodarone
• Symptoms
• Usually none
• RUQ pain, fatigue

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NAFLD

• Labs
• AST and ALT gt 3-5xULN
• ALTgtAST
• Imaging
• US ? hyperechoic liver parenchyma
• CT ? low-density liver parenchyma
• Biopsy
• Indicated for those thought to have advanced
  disease
• Steatosis, inflammation, fibrosis

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NAFLD

• Treatment
• Weight loss
• Control of DM2, lipids
• Removal of offending agent
• Medication
• TZDs in patients with metabolic syndrome
• Statins
• Think obese pt with metabolic syndrome and
  asymptomatic elevated ALT/AST

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Hereditary hemochromatosis

• Autosomal recessive disorder characterized by
  increased intestinal iron absorption and
  deposition in target tissues
• Most common single-gene inherited disorder among
  whites
• Heterozygote 110
• Homozygote 1200
• Two genes
• C282Y and H63D

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HH

• Presentation
• Age 40-50 (men earlier than women)
• Abnormal LFTs, bronze diabetes
• Fatigue, impotence
• destructive arthropathy
• 2nd and 3rd MCPs
• Screening
• Family history of HH
• Signs of iron overload

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HH

• Labs
• Iron studies
• sat gt 50
• Ferritin gt 1000
• LFTs
• AST/ALT elevated
• Treatment
• Phlebotomy
• Weekly until ferritin lt 50

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HH

• Complications
• Cirrhosis
• 30 of these get HCC
• Cardiac arrhythmia/failure
• DM
• Thyroid disorders
• Arthropathy
• Think 50 y/o male with elevated AST/ALT, high
  iron studies, DM2, CHF, arthritis of the 2nd/3rd
  MCPs and family history of liver problems (may
  also drink alcohol)

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Wilsons disease

• Autosomal recessive disorder of copper metabolism
  (low excretion in bile)
• ATP7B gene on chr13
• Affected organs
• Liver, brain, corneas, kidneys
• Nearly 50 of patients present with liver disease
• Asymptomatic elevated AST/ALT, cirrhosis, active
  hepatitis, fulminant failure (adolescents)

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Wilsons disease

• Presentation
• Neurologic findings
• Parkinsonian, extrapyramidal
• Mental status changes
• Personality changes, psychosis
• Abnormal AST/ALT
• Hemolytic anemia
• Exam
• Kayser-Fleischer rings

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Wilsons disease

• Labs
• LFTs range
• Mild elevations to fulminant labs
• AP usually can be very low
• Low ceruloplasmin (lt30)
• High 24-hr urinary copper
• Treatment
• Penicillamine
• Transplant
• Think young male recently doing poorly in
  school now with mental status changes and
  hemolytic anemia

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Complications of Chronic Liver Disease

• Portal hypertension
• Ascites
• Spontaneous bacterial peritonitis
• Hepatorenal syndrome
• Hepatic encephalopathy
• Hepatocellular carcinoma

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Portal hypertension

• Leads to bleeding from esophageal varices,
  gastric varices, and portal hypertensive
  gastropathy
• EV most clinically important
• Both mechanical and vascular factors
• Treatment
• EV banding
• Nonselective beta blockers
• TIPS

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Ascites

• Stimulation of RAA system ? renal sodium and
  water retention ? increased pressure in hepatic
  sinusoids and splanchnic vessels ? third space
  fluid
• Paracentesis
• SAAG calculation
• gt1.1 cirrhosis, heart failure
• lt1.1 nephrotic syndrome, malignancy, TB
• Treatment
• Diuretics
• TIPS
• LVP

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SBP

• Bacterial infection of ascites without an
  intraabominal source
• Common cause of decompensation
• Diagnosis PMNs gt 250
• Treatment
• 3rd gen cephalosporin
• fluoroquinolone

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Hepatorenal syndrome

• Development of renal failure in patients with
  portal hypertension and normal renal tubular
  function
• Neurohormonal mediators ? renal vasoconstriction
• Severe liver dysfunction with infection,
  overdiuresis/volume depletion, pre-existing CRI
• Diagnosis
• Treatment

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Hepatic encephalopathy

• Reversible decrease in level of consciousness in
  patients with severe liver disease
• Diagnosis
• Evaluation of cause
• GI bleed, infection (SBP), electrolyte disorders,
  noncompliance
• Treatment
• Lactulose, antibiotics (neomycin, rifaximin)

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Hepatocellular carcinoma

• Occurs almost exclusively in cirrhosis
• Exception HBV
• Risk greater in viral causes of cirrhosis
• Diagnosis
• Cirrhosis with characteristic mass and AFP gt 400
• Treatment
• Transplantation, TACE, sorafenib
• Ablation, resection
• Screening
• Ultrasound every 6-12 months, /- AFP

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Other liver issues

• Fulminant hepatic failure
• Liver transplantation
• Tumors, cysts, abscesses
• HELLP syndrome