Transcript Liver and Pancreas

Liver and Pancreas
ABNORMAL LIVER TESTS
AST/ALT
• > 300
– Viral, toxin-induced, ischemia, meds
• < 300
– EtOH Hepatitis, cholestasis
• AST/ALT ratio
– > 2 = EtOH
– < 1 = Viral or obstructive
Alcoholic Hepatitis
• Jaundice, fever, ascites, HE, AST/ALT > 2 with
AST/ALT < 300-400.Increased WBC
• PATH: Steatosis, Fibrosis,Mallory bodies
• Treatment:
• If MDF > 32 start prednisone 40 mg X 4 wks
• After 7 days on steroids if no improvement and
Lillie score >.45 Stop Steroids.
• If steroids are C/I add pentoxifiline to prevent
HRS
DILI
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Acetaminophen
Antibiotics: Bactrim, Augmentin, E-cin
Phenytoin
Valproic acid
Immunomodulators
INH
Viral Hepatitis: Transmission
• Fecal-Oral: Hepatitis A and E
• Sexual: Hepatitis B and D; also C (to a lesser
extent)
• Note: Hepatitis D requires coexisting Hep. B
infection
Viral Hepatitis: Clinical
• Symptoms include fatigue, anorexia nausea
and vomiting
• Lab shows elevated AST/ALT and bili
• May resolve, turn fulminant, or become
chronic
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
• HAV Vaccination 2 doses 6-12 months apart.
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)
Extra intestinal Manifestations of Hep B
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Polyarteritis Nodosa
Arthritis
Glomerulonephritis
Urticaria
Mixed Cryoglobulinemia
Polyneuropathy
Hepatitis B Serology
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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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 CHB
• HBeAg + HBV DNA > 20000, ALT > 2 x ULN
• Observe for 6 months and treat if no
spontaneous conversion.
• Consider Liver Bx
• Rx: Peg IFN o
• Entecavir, tenofovir, telbivudine
• Continue Rx for 6 months after seroconversion
Treatment of CHB
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HbeAG –
HBV DNA > 20000 , ALT > 2 x ULN
RX
Continue till HBsAG loss
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
• 85 % of Hep C infected become chronic
– 25% cirrhosis post 20-25 years of infection
– 5 %/yr risk to develop HCC in those with cirrhosis
• 5% sexual transmission over 10-20 yrs
• <5% trans placental transmission. HIV co-infection
increases transmission rate.
Serological Tests
• Third generation anti-HCV+ >95% 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
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
Recommended regimen for treatment-naive
patients with HCV genotype 1 who are
eligible to receive IFN.
Daily sofosbuvir
RBV
plus weekly PEG for 12 weeks is
recommended for IFN-eligible persons with
HCV genotype 1 infection, regardless of
subtype.
Recommended regimen for treatment-naive
patients with HCV genotype 1 who are not
eligible to receive IFN.
Daily sofosbuvir
RBV for 12 weeks is recommended for IFNineligible patients with HCV genotype 1
infection, regardless of subtype.
Recommended regimen for treatment-naive
patients with HCV genotype 2, regardless of
eligibility for IFN therapy:
Daily sofosbuvir
RBV for 12 weeks is recommended for
treatment-naive patients with HCV genotype
2 infection.
Recommended regimen for treatment-naive
patients with HCV genotype 3, regardless of
eligibility for IFN therapy:
Daily sofosbuvir
RBV for 24 weeks is recommended for
treatment-naive patients with HCV genotype
3 infection.
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
• A 30 y/o female presents with c/o
fatigue,arthralgias,weight loss, amenorrhea. PE
reveals Icterus and HSM. No h/o alcohol or drug
abuse. No FH of Liver disease.Labs: T.Bili 6mg/dl,
AST 300 U/L,ALT350 U/L, ALP 100 U/ml, Albumin
2.9 g/dl. Iron studies are normal. Hepatitis profile
and HIV is negative.
Which of the following are correct:
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1. ANA and ASMA are likely to be positive
2. Liver Biopsy should be done to confirm Dx
3. She will likely respond to steroid therapy
4. All of the above are correct.
Autoimmune Hepatitis
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AIH: Asymptomatic mild disease to Fulminant
Liver failure.
Fatigue, Jaundice, Maliase
Type I:ANA +, ASMA +, Increased IG,SLA/LP Ab
Common in USA
Type II: LKM1
Common in Europe, poor prognosis, Rx failures
RX:
Steroids
Immunomodulators.
Primary Biliary Cirrhosis
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Usually middle aged women
Pruritis, fatigue
Increased alk phos
The clue:
elevated Antimitochondrial Antibodies (AMA)
– Anticentromere antibodies
– Associated with sicca syndrome and scleroderma
• Treat with ursodiol
Primary Sclerosing Cholangitis
• An autoimmune fibrosis
of large bile ducts
• Clinical: RUQ pain, fatigue,
weight loss
• 70% of cases associated
with ulcerative colitis
• Increased risk of
cholangiocarcinoma
• Diagnose with ERCP
– Beading of the bile ducts on
ERCP/MRCP
– 10-15% get bile duct
carcinoma
NAFLD
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NAFLD: Steatosis
NASH: Steatohepatitis
Characteristics:
Metabolic Syndrome
Elevated AST/ALT
Liver Biopsy
Dx of exclusion:
RX:
RF Modification
Antioxidants
Oral hypoglycemics
ABNORMAL LIVER TESTS
Other liver tests
• Autoimmune hepatitis (ANA, ASMA, Antiliver/kidney microsomal, anti-SLA)
• PBC (AMA)
• PSC (p-ANCA 70%)
• Hemochromatosis Iron Saturation >45%
• Wilsons Disease (low ceruloplasmin,
incresed serum and urine Cu)
• Alfa 1 antitrypsin def
Hemochromatosis
• Most common genetic disease in Caucasians
• Iron deposits in liver, heart, pancreas, pituitary, Joints
• Bronze pigmentation, new onset
DM,arthritis,hypogonadism.
• Can lead to cirrhosis and HCC
• Iron Sat > 45%
• Increased Ferritin
• Abnormal Lft’s
• HFE gene mutation C282Y and H63D
• RX: Phlebotomy
• Goal ferritin < 50
Wilson’s Disease
• Rare Autosomal Recessive d/o 1:30000
• Increased cooper uptake and decreased biliary
excretion.
• May present as fulminant liver failure
• Neuropsychiatry symptoms
• Increased AST/ALT
• Low ALP
• Low Cerruloplasmin
• Increased urinary copper excretion
• KF rings on slit lamp
Liver Diseases in Pregnancy
1st Trimester
2nd Trimester
3rd Trimester
Acute viral hepatitis
A-E
Acute viral hepatitis
A-E
Acute viral hepatitis
A-E
Hyperemesis GV
Gallstones
Gallstones
Gallstones
Herpes Hepatitis
Herpes Hepatitis
ICP
ICP
AFLP
Pre-eclampsia
HELLP
Portal HTN
• Increased portal blood flow:
Increased cardiac index
Splanchnic vasodilation
Hypervolemia
• Increased resistance to portal blood flow:
Fixed resistance from fibrosis
Dynamic resistance
• RX:
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NSBB
Octreotide
Diuretics
TIPS
Portal HTN
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Most common cause is cirrhosis
Manifestations:
Hepatic Encephalopathy
Gastro-esophageal Varices
Ascites
Approach to the Patient with Ascites
ASCITES
Workup
• Need to know if ascites is CHF, cirrhosis or
malignancy (exudate)
• Serum-ascites albumin gradient > 1.1 = transudate
(Portal HTN)
• If ascites protein > 2.5, then CHF
• If ascites protein < 2.5, then cirrhosis
• <1.1 = ascites is NOT from portal hypertension
– “Higher SAAG = higher pressure”
ASCITES
Workup
Tap all new ascites
• Tap all ascites in cirrhotics with clinical
change
• Labs
– < 250 cells/μl
– 1 neutrophil/250 RBC
– 2 lymphocyte/750 RBC
– Innoculate cultures at the bedside
– Gram stain
• If TB is suspected, you need a peritonal bx
ASCITES
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Treatment
2g Na restriction/day
No benefit in restricting fluids
Spironolactone 100mg/day + Lasix 40mg/day
Large volume paracentesis
TIPS for paracentesis-resistant ascites
SBP
• Translocation of bacteria across they bowel wall into
susceptible ascites.
• Subclinical
• Fever, Abd pain,encepahlopathy
• DX:
• PMN > 250
• GN organisms E.coli most common
• Treat SBP with 3rd generation cephalosporin IV for 5
day and then PO Abx
• Pplx with oral quinolones after SBP
• IV Albumin to prevent HRS.
Hepatic Encephalopathy
• Ppting Factors:
• GI bleed, SBP, Sepsis, sedatives, constipation,
electrolyte abnormalities, acute liver injury, HCC,
surgery.
• RX:
• Recognize and Correcting ppting factors
• Correct electrolytes.
• Lactulose
• Rifaximin.
Hepatorenal syndrome (HRS)
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HRS Type I: Rapid decline in renal function
HRS Type II: Chronic usually due to refractory ascites.
DDX: ATN, Pre-renal
DX:
Sr Creatinine > 1.5
No improvement after holding diuretics and volume
expansion with IV Albumin
• Absence of shock,
hypotension,proteinuria,nephrotoxics
• Low urine sodium.
HRS
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Rx:
Avoiding and holding all nephrotoxics.
Hold diuretics
IV Albumin
Midodrine and octreotide
OLT is the definitive treatment
Fulminant Hepatic Failure
• Jaundice and hepatic encephalopathy in the
absence of chronic liver disease.
• Acetaminophen is the most common cause in US
( worsened by alcohol, malnutrition and fasting
state)
• Acute viral hepatitis is the most common cause
world wide.
• Other meds: INH, NSAIDS, herbal meds
• Other causes: AIH, BCS, AFLP, HELLP, Amanita
Phalloids
Fulminant Hepatic Failure
• Complications: Hypoglycemia, Cerebral
edema,coagulopathy,infection
• RX;
• Supportive care in ICU
• Early recognition and transfer to the transplant
center.
• NAC for acetaminophen toxicity
• Acyclovir for HSV hepatitis.
• Pen G for mushroom toxicity
• Antiviral for acute hepatitis B
Disease
Liver Biochemistry Pattern
AP
TBili
Primary biliary
cirrhosis
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Primary
sclerosing
cholangitis
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Large bile duct
obstruction
Drug-induced
cholestasis
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Infiltrative liver
disease
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Historical
Features
More common in
women, fatigue,
pruritus
Diagnostic
Evaluation
Antimitochondria
l antibodies
present in 95%,
liver biopsy
More common in Cholangiography
men, history of
inflammatory
bowel disease
Pain and fever
Cholangiography
History of
Improvement
drug/medication with cessation
use within 3
months, often of
a drug previously
associated with
liver injury
CT, MRI, liver
biopsy
Liver Enzyme Pattern
Disease
Viral hepatitis A
ALT
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AST
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Viral hepatitis B
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Viral hepatitis C
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Alcoholic hepatitis
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Drug-induced hepatitis ↑↑↑↑
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Fatty liver, nonalcohol ↑↑
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Ischemic
hepatitis
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Acute liver failure
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History
Fecal oral
exposure
Blood/body fluid
exposure
Recent
intravenous drug
use
DX
(IgM anti-HAV)
(IgM anti-HBc) and
+ (HBsAg)
(HCV RNA);
variable presence
of (anti-HCV)
Heavy alcohol use, AST:ALT >2, AST
either binge or chr usually <500
H/of drug/med
Absence of other
use within 3 mo liver disease
Late pregnancy,
amiodarone
History of
medication use,
absence of other
liver disease
Severe
rapid
hypotension
improvement with
resolution of
hypotension
Ingestion of an
Signs of impaired
associated agent; hepatic synthetic
rapid progression function
Disease
Liver Enzyme
Pattern
ALT
AST
Viral hepatitis B
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Viral hepatitis C
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Fatty liver,
nonalcohol
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Alcoholic liver
disease
Autoimmune
hepatitis
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Hemochromatosi ↑
s
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Wilson disease
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α1-Antitrypsin
deficiency
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Historical Features
Diagnostic Findings
Fecal oral exposure, endemic HBsAg; may have
area
hepatitis B DNA (HBV
DNA)
IVDA, blood tx prior to 1992, Anti-HCV, HCV RNA
Vert Tx , parenteral expos
Presence of metabolic
syndrome (obesity, insulin
resistance, hypertriglycer)
Remote history of heavy
alcohol use
More common in women
Arthritis, diabetes, family
history
Absence of other liver dz
imaging shows fat
Absence of other liver
disease
Positive , ANA and anti–
SMA
Ferritin (>1000) and iron
sat (>55%), HFE gene
mutations
Young, movement disorders, Hemolysis, low ALP, low
psychiatric disease, KF rings ceruloplasmin
Lung disease
Low serum A1AT, liver
biopsy
ABNORMAL LIVER TESTS
History Pearls
• Pruritus/Cholestasis
• PBC, PSC
• Undercooked food, oysters, daycare
– Hep A
• ICU, hypotension, Rt. Sided heart failure
– Hepatic congestion
• Chronic pancreatitis
– Stenosis of CBD
ABNORMAL LIVER TESTS
History Pearls
• Neurological/Psych findings
– Wilson’s disease
• Metabolic syndrome
– Fatty liver
• Hyperpigmentation
– Hemochromatosis or PBC
• Kayser-Fleischer rings and sunflower
cataracts
– Wilson’s disease
ABNORMAL LIVER TESTS
History Pearls
• Splenomegaly
– Portal HTN or infiltrative process
• Pulsatile liver
– Tricuspid insufficieny
• Hepatic bruits
– HCC
Acute Pancreatitis
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Alcohol
Biliary Tract Disease
Trauma
Post ERCP
Hyperlipidemia
Pancreatic Malignancy
Causes of Acute Pancreatitis
Obstructive
Toxins/Drugs
Metabolic
Infectious
Vascular
Gallstones (45%)
Pancreas divisum
Malignancy
Choledochocele
Parasites (Ascaris lumbricoides)
Alcohol (35%)
Azathioprine
Sulfa drugs
Aminosalicylates
Metronidazole
Pentamidine
Didanosine
Hyperlipidemia
Hypercalcemia
Viral (Cytomegalovirus, Epstein-Barr virus)
Parasites (Toxoplasma, Cryptosporidium)
Ischemia
Vasculitis
Poor Prognostic Indicators In
Pancreatitis
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SBP < 90 , HR > 130
PO2 < 60 mmHg
Urine out put < 50ml/hr or BUN/Cr Elevation
GI Bleeding
Pancreatic necrosis
HCT > 44
CRP > 150
Apache score > 8
Ranson score > 3
Complications of Pancreatitis
• Sepsis;
Necrosis, infected pseudocyst,Abscess
• Early:
Shock, ARDS, GIB, DIC, Uremia,hypocalcemia
Splenic infarction & rupture, Pl Effusion.
Late:
Phlegmon, Pseudocyst, abscess
Ascites, Pleural Effusion
Splenic Vein thrombosis– GV--GIB
Ranson Criteria
Admission
• Age > 55
• WBC > 15K
• Glucose > 200
• AST > 250
• LDH > 350
During 48 hrs
• PO2 < 60 mmHg
• Drop in HCT > 10 %
• BUN increases > 5mg/dl
• Calcium < 8 mg/dl
• Fluid sequestration
Pearls
• Acute Pancreatitis is a clinical and lab Dx and
not imaging
• Alcohol and Gall Stones most important
causes
• Prophylactic Abx (Imipenum) in necrotising
pancreatitis
• Early enteral Feeding is preferred.
Pancreatic Adenocarcinoma
• Risk Factors:
Age, Smoking, Chronic pancreatitis,Hereditary
pancreatitis, Obesity, Fatty diet
• Manifestation:
Pain radiating to back, Wt Loss, jaundice,
Painless jaundice due obstruction of CBD by
pancreatic head mass
Diagnosis:
CT-Scan pancreas protocol, EUS, MRI, ERCP
GOOD LUCK !