Transcript Liver diseases

Liver diseases
Review Outline
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Hepatology
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Abnormal LFTs
Viral hepatitis (A, B, C)
PSC
PBC
AIH
NASH/NAFLD
Drugs (Tylenol)
Cirrhosis
Ascites
Metabolic liver diseases (A1AT, HH, Wilsons)
Gilbert’s Disease
Liver masses
Pregnancy
Pancreatiobiliary
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Pancreatitis – acute and chronic
Pancreatitis complications
Pancreatic cancer
Billiary disease
Hepatology Pearls
Hepatitis: AST and ALT
Cholestasis:  TB and ALP
ALT more specific than AST
Measures of function: ALB, Coags,
Bili
• Alcoholic hepatitis AST>ALT 2-3:1
(NASH with cirrhosis also)
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Abnormal LFT’s
• 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
Abnormal LFT’s
• ALT >10 fold (>400)
– Acute viral
– Drug/toxin
– Ischemic/Budd Chiari
– Autoimmune hepatitis
– Wilson’s disease
Abnormal LFT’s
• Modest ALT (<300) has a wide differential
• Usually EtOH or chronic viral hepatitis
• Remember AST:ALT > 2:1 highly
suggestive of EtOH
• AIH, NASH/NAFLD, Wilson’s,
Hemochromatosis,
infiltrative/granulomatous dz
Abnormal LFT’s
• 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
Abnormal ALP
• Hepatic
– PBC (middle aged women)
– PSC (IBD history)
– Gallbladder/stone disease
– Meds (tetracyclines, OCP’s, ceftriaxone)
– Infiltrative liver dz (sarcoid, TB, CA)
• Pregnancy
• Bone (Mets or Paget’s disease)
Hepatitis A
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Fecal-oral transmission
Symptoms: Adult > 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
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)
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
Hep B Serology
• Anti-HBc: first Ab to appear, 1°IgM
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
HBV Window Period
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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
HBV Scenarios
HBsAg
anti-HBs
anti-HBc
IgM
anti-HBc
IgG
HBeAg
DX
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Acute
infection
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Carrier
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Vaccinated
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Exposed
Immune
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Acute
Window
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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
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
Treatment of Chronic Hep B
• Interferon:
– 4-6 months
– 30% long term remission
• Lamivudine:
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6 months
Decreases HBV-DNA (does not eradicate)
Reduces ALT levels
15-20% seroconvert
• HBeAg + to - with new anti-HBe
• Adefovir (Hepsera)
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
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25% carriers
50% abnl LFT’s but asymp
25% with chronic active/sx
25% cirrhosis post 20-25 years of infection
• 5% sexual transmission over 10-20 yrs
• <5% transplacental transmission
Serological Tests
• Third generation anti-HCV+ >95%
sensitive
• If high pre-test probability and antiHCV negative can do PCR testing
(more often in renal failure or
transplant)
• Genotype testing required for
treatment candidates only
Hepatitis C Therapy
• Interferon Alone < 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
HB<12 female, <13 male
WBC<1500
Plt<100,000
Severe psych dz (depression)
Pregnancy
Decompensated Cirrhosis
CAD
Autoimmune diseases
Extrahepatic Manifestations
of Hepatitis C:
Extrahepatic
Manifestations:
Extrahepatic Manifestations
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Glomerulonephritis/MPGN
Cryoglobulins
Porphyria cutanea tarda (PCT)
Thrombocytopenia
– Autoantibody
– ITP
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Neuropathy
Thyroiditis
Sjogren’s Syndrome
Inflammatory arthritis
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
Hepatitis E
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Monsoon flooding
Fecal-oral route
No chronic forms
Fulminant hepatitis in 3rd trimester
of pregnancy
Chronic Hepatitis
• By definition, active hepatitis for 6
months or longer
• Usually viral but also metabolic and
autoimmune
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:
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
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:
Primary Sclerosing Cholangitis
(PSC)
• Male: female 2:1
• 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
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
NASH/NAFLD
• Risk Factors:
– Obesity or gastric bypass
– DM
– Hyperlipidemia
– TPN, amiodarone
• Histology: Steatosis, PMN’s,
Necrosis
• Tx: Wt Loss (>15%), Exercise,
Control of DM, Lipid Lowering
Agents
Drugs and chronic hepatitis
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Methyldopa
Acetaminophen
Trazodone
Nitrofurantoin
Phenytoin
INH-1% severe
hepatitis,
correlates with age
• OCP’s-cholestasis,
benign adenomas,
FNH
• Erythromycin
• Valproic Acid
• Methotrexateindolent cirrhosis
Acetaminophen
• Pt who drinks EtOH and ingests an “overthe-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 Tylenoleven therapeutic doses
• Tx: N-acetylcysteine
• Beware of the “normal” acetaminophen
level
Fulminant Hepatic Failure
• Acetaminophen, viral, AIH, Wilson’s
disease, Budd-Chiari syndrome
• Tylenol survival >50%, viral 30-50%
• Remember Kings College Criteria
– Mainly encephalopathy (III or IV)
– pH < 7.3, PT > 100, Cr > 3.4
• Main cause of death: cerebral edema,
sepsis
• Transfer these patients to a transplant
center
Hepatic Masses
• HCC > 75% in setting of cirrhosis
– Esp. chronic Hepatitis B, Hep C,
hemochromatosis, EtOH
– Aflatoxin (raw peanuts, raw peanut
butter)
–  alpha-fetoprotein (>100), tender
hepatomegaly
• Adenomas: on OCP’s. Need resection
because of bleeding risk and progression
to cancer
• Hemangiomas rarely need resection
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
Cirrhosis
• Encephalopathy
– Hyperreflexia and Asterixis
– Usually precipitated by infection, bleed,
drugs
– Tx: Lactulose (acidifies the colonic
contents)
• Hepatorenal Syndrome
– Urinary Na+ < 10, no urine protein
– Oliguric Renal Failure
– Usually iatrogenic with diuretics/Abxesp Aminoglycosides
Ascites
• Cause: requires peritoneal tap-send for
cell count, protein, albumin, cytology
• SAAG: Serum albumin-ascitic albumin
– >1.1 Portal Hypertension
• Budd-Chiari, RHF, Cirrhosis
– <1.1 Non Portal Hypertensive causes
• TB, Nephrotic syndrome, Pancreatitis
and Peritoneal carcinomatosis
• Chylous Ascites (lymph blockage)
– Trauma, Lymphoma, TB and Filiarisis
Ascites
• If protein < 1.0 in cirrhotic ascites then
patient is at increased risk for SBP
– SBP:
• Cloudy fluid, some with fever, abd pain
• > 250 PMN’s or >400 total WBC’s
• 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
Gilbert’s Syndrome
• Benign, chronic disorder 
glucuronyl transferase
• Autosomal dominant with variable
penetrance
• 7% of the population
• Mild Unconjugated
hyperbilirubinemia (indirect
bilirubin), <5.0 TB.
•  Bili induced by exercise, EtOH,
surgery, infection and fasting
• No treatment needed
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
• Question:
49 yo wm with h/o of emphysema
presents with elevated AST and ALT.
(ALT>AST ) 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?
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
Hemochromatosis
• Autosomal Recessive
• Presents in the 50’s with cirrhosis or CHF
• Iron deposition in liver, heart, pancreas,
and pituitary
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Hepatomegaly (95%)
Hyperpigmentation (90%)
Diabetes (65%)
Arthropathy (40%) / CPPD
Cardiac involvement (15%)
Hemochromatosis
• 25-30% risk for hepatocellular carcinoma
• Diagnosis:
–  Serum Iron, ferritin (1000’s) and transferrin
percent sat > 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
Wilson’s 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
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
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
HELLP Syndrome
• Hemolysis, Elevated LFT’s, Low
Platelets
• Third trimester
• Difficult to distinguish from AFLP
with DIC clinically
• Severe abdominal pain and
hypotension may be hepatic
hematoma
• Delivery
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 <2.5
• 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