Liver diseases

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Liver diseases
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Review Outline

• Hepatology
• Abnormal LFTs
• Viral hepatitis (A, B, C)
• PSC
• PBC
• AIH
• NASH/NAFLD
• Drugs (Tylenol)
• Cirrhosis
• Ascites
• Metabolic liver diseases (A1AT, HH, Wilsons)
• Gilberts Disease
• Liver masses
• Pregnancy
• Pancreatiobiliary
• Pancreatitis acute and chronic
• Pancreatitis complications
• Pancreatic cancer
• Billiary disease

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Hepatology Pearls

• Hepatitis ?AST and ALT
• Cholestasis ? TB and ALP
• ALT more specific than AST
• Measures of function ALB, Coags, Bili
• Alcoholic hepatitis ASTgtALT 2-31 (NASH with
  cirrhosis also)

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Abnormal LFTs

• Asymptomatic elevation of ALT is most common
  problem
• If isolated and less than 3-fold elevation then
  stop alcohol or drug and recheck in 2-3 months
• If persistent then further workup is needed

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Abnormal LFTs

• ALT gt10 fold (gt400)
• Acute viral
• Drug/toxin
• Ischemic/Budd Chiari
• Autoimmune hepatitis
• Wilsons disease

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Abnormal LFTs

• Modest ALT (lt300) has a wide differential
• Usually EtOH or chronic viral hepatitis
• Remember ASTALT gt 21 highly suggestive of EtOH
• AIH, NASH/NAFLD, Wilsons, Hemochromatosis,
  infiltrative/granulomatous dz

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Abnormal LFTs

• Mildly high ALP or TB without evidence of biliary
  dz, think infiltrative (TB, sarcoid, fungal) or
  metastatic disease
• Workup mainly by history and risk factors
• Image or biopsy for diagnostic purposes is not
  always needed

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Abnormal ALP

• Hepatic
• PBC (middle aged women)
• PSC (IBD history)
• Gallbladder/stone disease
• Meds (tetracyclines, OCPs, ceftriaxone)
• Infiltrative liver dz (sarcoid, TB, CA)
• Pregnancy
• Bone (Mets or Pagets disease)

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Hepatitis A

• Fecal-oral transmission
• Symptoms Adult gt children
• Transplacental transmission occurs
• No carrier states, rarely fulminant
• Can have cholestasis for up to 6 mos
• Vaccine Patients with liver dz/risks/ travelers
• Acute infection IgM anti-HAV, Vaccination
  IgG anti-HAV
• IG prophylactic for Hep A

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Hepatitis B

• Incubation 1-6 months
• Transmitted sexually, parenterally, mucous
  membrane exposure
• Can present with serum sickness (fever,
  arthritis, urticaria, angioedema)
• Associated with polyarteritis nodosa (PAN)

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Hepatitis B Serology

• HBsAg - first marker present in pts with active
  Hep B infection
• HBcAg - core inner shell of virion, not seen in
  serum, does not circulate
• HBeAg - soluble protein secreted from
  hepatocytes, correlates with with both quantity
  of intact virus, infectivity and liver
  inflammation

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Hep B Serology

• Anti-HBc first Ab to appear, 1IgM then IgG,
  persists for life, best marker for previous
  exposure
• Anti-HBe appears several wks post illness
• Anti-HBs indicates previous exposure to Hep B or
  the vaccine

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HBV Window Period

• HBsAg is not detectable
• Anti-HBs not yet present
• Anti-HBc appears
• May be several weeks
• Check Anti-HBc IgM to confirm acute infection,
  otherwise looks like previous exposure

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HBV Scenarios
HBsAg anti-HBs anti-HBc IgM anti-HBc IgG HBeAg DX
-
- -
- - - -
- - -
- - - -
- - - -
Acute infection
Carrier
Vaccinated
Exposed Immune
Acute Window
Exposed Ab lost
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Course of Hep B

• 90 self limited, 1-2 fulminant
• 5-7 chronic carrier states
• Asymptomatic
• chronic persistent hepatitis
• chronic hepatitis B - ? risk of hepatocellular
  CA, cirrhosis
• Inverse relationship between age and development
  of carrier state, 95 of infants-chronic
• 5-10 transplacental transmission

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HepB vaccine/prophylaxis

• 95 of immunocompetent pts develop antibody
  (anti-HBs)
• Only 50 of HD pts develop antibody
• May be given to pregnant pts
• 3 doses at 1, 2 and 6 months
• HBIG Alone
• sexual contacts of carriers and household members
  of acute Hep B
• HBIG vaccine (exposed is HBsAg negative)
• blood exposure to pt w/acute Hep B
• newborns of Hep B mothers

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Treatment of Chronic Hep B

• Interferon
• 4-6 months
• 30 long term remission
• Lamivudine
• 6 months
• Decreases HBV-DNA (does not eradicate)
• Reduces ALT levels
• 15-20 seroconvert
• HBeAg to - with new anti-HBe
• Adefovir (Hepsera)

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Hepatitis C

• Most common liver disease in the US
• IVDU, cocaine use, prisons, blood products prior
  to 1990, tattoo
• Genotype 1 most common in the US
• 70-80 of Hep C infected become chronic
• 25 carriers
• 50 abnl LFTs but asymp
• 25 with chronic active/sx
• 25 cirrhosis post 20-25 years of infection
• 5 sexual transmission over 10-20 yrs
• lt5 transplacental transmission

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Serological Tests

• Third generation anti-HCV gt95 sensitive
• If high pre-test probability and anti-HCV
  negative can do PCR testing (more often in renal
  failure or transplant)
• Genotype testing required for treatment
  candidates only

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Hepatitis C Therapy

• Interferon Alone lt 15
• Interferon/Ribavirin
• 12 months Genotype 1
• 6 months Genotype 2 and 3
• Sustained response (Hep C PCR- 6 mos post
  therapy)
• 5-15 monotherapy
• 35-40 combo therapy
• 45-70 PEG combo therapy
• Must use birth control--teratogenic

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Contraindications for Therapy

• HBlt12 female, lt13 male
• WBClt1500
• Pltlt100,000
• Severe psych dz (depression)
• Pregnancy
• Decompensated Cirrhosis
• CAD
• Autoimmune diseases

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Extrahepatic Manifestations of Hepatitis C
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Extrahepatic Manifestations
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Extrahepatic Manifestations

• Glomerulonephritis/MPGN
• Cryoglobulins
• Porphyria cutanea tarda (PCT)
• Thrombocytopenia
• Autoantibody
• ITP
• Neuropathy
• Thyroiditis
• Sjogrens Syndrome
• Inflammatory arthritis

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Hepatitis D

• Requires coexistent B
• Usually found in IVDA
• Coinfection does not worsen acute Hep B or ?
  risk for chronic state
• Superinfection frequently severe/fulminant
• Dx Anti-HDV IgM

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Hepatitis E

• Monsoon flooding
• Fecal-oral route
• No chronic forms
• Fulminant hepatitis in 3rd trimester of pregnancy

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Chronic Hepatitis

• By definition, active hepatitis for 6 months or
  longer
• Usually viral but also metabolic and autoimmune

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Case

• 38 yo woman presents to your office c/o fatigue
  and pruritis for 6 months. Routine bloodwork
  reveals normal CBC, TB, AST and ALT. ALP is
  elevated at 260.
• Skin exam shows this

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Primary Biliary Cirrhosis (PBC)

• Middle-aged woman
• Elevated alkaline phosphatase
• Symptom itching!
• Later jaundice, osteomalacia, osteoporosis
• Xanthomas/xanthalasmas
• hypercholesterolemia with low risk CAD
• Diagnosis
• antimitochondrial antibody (AMA)
• liver bx with granulomas
• Tx Ursodeoxycholic acid (Actigall) improves
  survival late-liver transplant
  

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Case

• 38 yo gentleman with h/o chronic diarrhea and
  occasional BRBPR who presents to your office with
  new onset jaundice and fever.
• ERCP shows

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Primary Sclerosing Cholangitis (PSC)

• Male female 21
• Intra and Extrahepatic inflammation and sclerosis
  of the biliary tree
• Strong Association (75) with IBD (Ulcerative
  colitis)
• Cholestatic enzyme pattern (TB and ALP)
• Dx ERCP or cholangiogram
• 15 develop cholangiocarcinoma
• Tx Stenting of dominant strictures, Liver
  Transplant

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Autoimmune Hepatitis

• Young women
• insidious hepatitis, elevated AST/ALT
• assoc with other autoimmune dz
• hypothyroid, ITP, Coombs anemia
• Dx
• Serology ANA, Anti-smooth muscle Ab (most
  specific), Elevated quant IgG, Anti-LKM
• Histology Plasma cells, interface hepatitis
• Tx Prednisone-rapidly reverses sx and improves
  survival, add azathioprine for steroid sparing

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NASH/NAFLD

• Risk Factors
• Obesity or gastric bypass
• DM
• Hyperlipidemia
• TPN, amiodarone
• Histology Steatosis, PMNs, Necrosis
• Tx Wt Loss (gt15), Exercise, Control of DM,
  Lipid Lowering Agents

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Drugs and chronic hepatitis

• Methyldopa
• Acetaminophen
• Trazodone
• Nitrofurantoin
• Phenytoin
• INH-1 severe hepatitis, correlates with age

• OCPs-cholestasis, benign adenomas, FNH
• Erythromycin
• Valproic Acid
• Methotrexate-indolent cirrhosis

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Acetaminophen

• Pt who drinks EtOH and ingests an
  over-the-counter pain medicine develops
  fulminant hepatitis (??AST/ALT/PT)
• Toxicity secondary to the depletion of
  glutathione, which reduces the metabolites.
• Malnutrition and EtOH deplete glutathione and
  therefore lead to ? toxicity of Tylenol-even
  therapeutic doses
• Tx N-acetylcysteine
• Beware of the normal acetaminophen level

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Fulminant Hepatic Failure

• Acetaminophen, viral, AIH, Wilsons disease,
  Budd-Chiari syndrome
• Tylenol survival gt50, viral 30-50
• Remember Kings College Criteria
• Mainly encephalopathy (III or IV)
• pH lt 7.3, PT gt 100, Cr gt 3.4
• Main cause of death cerebral edema, sepsis
• Transfer these patients to a transplant center

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Hepatic Masses

• HCC gt 75 in setting of cirrhosis
• Esp. chronic Hepatitis B, Hep C, hemochromatosis,
  EtOH
• Aflatoxin (raw peanuts, raw peanut butter)
• ? alpha-fetoprotein (gt100), tender hepatomegaly
• Adenomas on OCPs. Need resection because of
  bleeding risk and progression to cancer
• Hemangiomas rarely need resection

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Cirrhosis

• EtOH - most common cause in the U.S.
• Esophageal Varices
• 1/3 bleed 1/3 die with bleed
• Larger, distal varices bleed
• Propranolol ? rebleeds and may prevent the first
  bleed
• Tx
• Octreotide
• Banding or Sclerotherapy
• Transjugular intrahepatic portosystemic shunt
  (TIPS)

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Cirrhosis

• Encephalopathy
• Hyperreflexia and Asterixis
• Usually precipitated by infection, bleed, drugs
• Tx Lactulose (acidifies the colonic contents)
• Hepatorenal Syndrome
• Urinary Na lt 10, no urine protein
• Oliguric Renal Failure
• Usually iatrogenic with diuretics/Abx-esp
  Aminoglycosides

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Ascites

• Cause requires peritoneal tap-send for cell
  count, protein, albumin, cytology
• SAAG Serum albumin-ascitic albumin
• gt1.1 Portal Hypertension
• Budd-Chiari, RHF, Cirrhosis
• lt1.1 Non Portal Hypertensive causes
• TB, Nephrotic syndrome, Pancreatitis and
  Peritoneal carcinomatosis
• Chylous Ascites (lymph blockage)
• Trauma, Lymphoma, TB and Filiarisis

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Ascites

• If protein lt 1.0 in cirrhotic ascites then
  patient is at increased risk for SBP
• SBP
• Cloudy fluid, some with fever, abd pain
• gt 250 PMNs or gt400 total WBCs
• E. coli, Strep, Klebsiella
• Treat with cefotaxime
• Albumin (1.5 g/kg, then1.0 g/kg on day 3)
• Tx Na( 2 gm) and water restriction (2 L)
• Spironolactone loop diuretic
• Refractory TIPS

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Gilberts Syndrome

• Benign, chronic disorder ? glucuronyl transferase
• Autosomal dominant with variable penetrance
• 7 of the population
• Mild Unconjugated hyperbilirubinemia (indirect
  bilirubin), lt5.0 TB.
• ? Bili induced by exercise, EtOH, surgery,
  infection and fasting
• No treatment needed

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Hereditary Bilirubin Disorders

• Crigler-Najjar Syndrome
• moderate to severe unconjugated
  hyperbilirubinemia
• Usually presents in childhood
• Dubin-Johnson Syndrome
• Low level conjugated hyperbilirubinemia
• Pigmented granules in hepatocytes

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• Question
• 49 yo wm with h/o of emphysema presents with
  elevated AST and ALT. (ALTgtAST ) Previous CT Scan
  of the Chest revealed bulla at bilateral bases.
  Family history significant for brother with
  chronic liver disease and social history
  significant for 1-2 drinks/night.
• Suspected Diagnosis for LFT abnormalities?

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Alpha-1 Antitrypsin Deficiency

• Autosomal recessive
• Pt with lung disease and hepatitis
• Dx Alpha1-antitrypsin phenotype
• Pi ZZ
• Tx Liver transplant if lung disease does not
  preclude pt from this. Does not recur in
  transplanted liver

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Hemochromatosis

• Autosomal Recessive
• Presents in the 50s with cirrhosis or CHF
• Iron deposition in liver, heart, pancreas, and
  pituitary
• Clinical Signs
• Hepatomegaly (95)
• Hyperpigmentation (90)
• Diabetes (65)
• Arthropathy (40) / CPPD
• Cardiac involvement (15)

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Hemochromatosis

• 25-30 risk for hepatocellular carcinoma
• Diagnosis
• ? Serum Iron, ferritin (1000s) and transferrin
  percent sat gt 50, C282Y homozygotes
• Liver biopsy with Iron staining (hepatic iron
  index)
• Treatment Weekly phlebotomies (Hct 32),
  decreased ferritin
• prolongs life and improves color/cardiac fx
• Men 10x more symptomatic than women

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Wilsons Disease

• Autosomal recessive
• Liver dz or neuro/psych d/o in young adults
  (usually 15-25)
• Excess copper in body tissues
• Serum ceruloplasmin low
• Urinary copper high
• Kayser-Fleischer rings pathognomonic (almost)
• Hemolysis common
• Liver biopsy confirms dx
• Tx Chelation tx with Penicillamine, zinc,
  transplant

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Liver Disease and Pregnancy

• ALP slightly elevated during later half of
  pregnancy (placental source)
• Bili and other liver enzymes normal
• Most common cause of jaundice in pregnancy is
  acute viral hepatitis during 1st and 2nd
  trimesters
• Third trimester need to think of other things

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Acute Fatty Liver of Pregnancy

• Very serious, present with fulminant failure
• Microvesicular fat deposition
• Third trimester
• RUQ U/S shows fatty liver
• Encephalopathy, hypoglycemia, preeclampsia, DIC
  and renal failure
• Delivery

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HELLP Syndrome

• Hemolysis, Elevated LFTs, Low Platelets
• Third trimester
• Difficult to distinguish from AFLP with DIC
  clinically
• Severe abdominal pain and hypotension may be
  hepatic hematoma
• Delivery

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Liver transplant

• Treatment for most end-stage liver disease,
  confined liver cancer, and fulminant failure not
  responding to supportive measures
• Need to consider in all decompensated
  cirrhotics--encephalopathy, ascites, SBP,
  variceal bleeding, albumin lt2.5
• Also indicated for intractable pruritis, such as
  in PBC
• Contraindicated in Active EtOH or drug use,
  Metastatic CA, severe lung or cardiac disease
  /- HIV infection