Transcript PBC PSC & Abnormal LFT’s

Pancreatic and biliary
disease
Intrahepatic cholestasis of
pregnancy
• Presents with sometimes intense
pruritis
• Functional disorder of bile secretion
• ALP mod high, Bili high,
Transaminases <200, NORMAL
FUNCTIONAL TESTS, NORMAL
PLTS, NORMAL COAGS
• Watch for fat malabsorbtion, vitamin
deficiencies (decreased bile salts)
Acute Pancreatitis
• Causes:
– EtOH and Gallstones
• 75% of people with negative RUQ u/s have sludge or
micoliths
– Drugs: Lasix, thiazides, estrogen, azathioprine,
tetracycline, sulfa drugs, ddI, ddC, valproic
acid, 6-MP, L-asparginase
– Hypertriglyceridemia >1000mg/dl
– Cystic fibrosis
– Hypercalcemia
– Trauma
– ERCP
Acute Pancreatitis (continued)
• Physical exam signs and symptoms:
• Pain radiating from epigastrium
“boring through” to the back
• Cullen’s sign
– blue around the umbilicus
• Turner’s Sign
– purple or green discoloration of
the flanks.
Acute Pancreatitis (continued)
• Dx:
– Elevated amylase and lipase, when
amy >900 U/L and lipase >6000
U/L--97% specific
– Both elevated also in biliary dz,
perforation, renal insufficiency
– Amylase also high in parotitis,
macroamylasemia, chronic EtOH
Acute Pancreatitis (continued)
• Initial Eval: RUQ U/S of biliary tree,
CT after 48 hours if not improved or
complication suspected
– Don’t worry about MRCP vs ERCP
• Prognosis
– APACHE II, Ranson’s, and
Balthazar have been validated for
mortality
– Failure of one or more organ
system is more clinically useful
57 yo woman s/p traumatic pancreatitis 8
mos ago presents in F/U. She is
asymptomatic. No meds. No EtOH. PE:
epigastric fullness, no pain. Amylase 180
U/L. Serial CT Scans reveal an 8 cm cystic
lesion with a well-defined capsule in the
pancreatic body. No  in 6 mos. Best
Management?
A. Conservative
B. Percutaneous drainage
C. ERCP with internal drainage
D. Surgical drainage
Fluid Collections and
Pancreatitis
• Pancreatitic fluid collection high in
amylase may appear in 48 hours, usually
resolves
• Left pleural effusion common
• Fluid collection with clinical signs of
infection should be aspirated to r/o
infection
• Necrosis, within 2 weeks, if infected-surgical debridement
• Severe pancreatitis with suspected
infection: empiric coverage with imipenem
Fluid collections
• Pseudocyst develops in 10-15% of pts,
requires 1-4 weeks to develop
– Complications of hemorrhage, rupture, fistula
formation
– Drainage rec’d only if symptomatic or infected
• Abscess develops 4-6 weeks post acute
attack
– CT guided aspiration 90% accurate
– Surgical debridement
Pancreatic Pearls
• Abdominal Pain and  amylase don’t
always equal acute pancreatitis:
– Acute cholecystitis
– Intestinal infarction
– DKA
– Perforated Ulcer
– Salpingitis
– Ectopic pregnancy
– Perforated Diverticulum
– Macroamylasemia
Chronic Pancreatitis
• 60-70% due to EtOH, usu >10 years.
• Other causes CF, pancreas divisum, tumor,
hyperparathyroidism
• Loss 80-90% of endocrine/exocrine function
develop DM and steatorrhea
• Increased risk for pancreatic cancer
• Dx:
– 1) Ca+ on AXR
– 2) CT or MRI or EUS or secretin test (bicarb<80
mEq/L)
– 3) ERCP
Complications of Chronic
Pancreatitis
• Gastric varices due to splenic vein
thrombosis
• B12 malabsorption
• Brittle DM, prone to hypoglycemia
secondary to loss of pancreatic glucagon
– No retinopathy or nephropathy
• Jaundice due to obstruction of CBD as it
runs through the pancreatic head
Chronic Pancreatitis
Treatment
• Low fat diet, less than 25 g/d
• Pancreatic enzyme replacement has little
or no effect on pain but can help with
steatorrhea
• Must be enteric coated or given with PPI
because gastric acid inactivates them
• If pancreatic duct is dilated, ERCP or
surgery have shown improvement in pain
Pancreatitis Pearls
• Microlithiasis may cause recurrent
pancreatitis in setting of no EtOH
and no gallstones on U/S
• Splenic vein thrombosis in severe
acute pancreatitis causes gastric not
esophageal varices
• ERCP
– cholangitis/sepsis
– TB > 2.5 or dilated CBD on imaging
Pancreatic Neoplasms
• Pancreatic Adenocarcinoma:
– Classic presentation is painless
jaundice
– Risk Factors: chronic pancreatitis,
diabetes mellitus, smokers (2x),
perhaps heavy EtOH users
– >80% present with advanced disease
– CT is first test, Double duct sign on
ERCP, EUS good for staging
– If no mets then Whipple procedure,
rarely curative
Cystic Neoplasms of the
Pancreas
• They happen and need biopsy to r/o
cystadenocarcinoma
• All have malignant potential and
need resection
Other Pancreatic Neoplasia
• Glucagonoma
– Plasma glucagon usually >
1000pg/dl
– Scaly necrotizing dermatitis
• Necrolytic migratory erythema (NME)
– Wt loss
– Anemia
– Hyperglycemia
Other Pancreatic Neoplasia
• Insulinoma
• VIPoma
–“pancreatic cholera”, profuse
watery diarrhea
• Gastrinoma
–ZE syndrome, elevated gastrin
level (off PPI), think about MEN
I
Biliary Disease
• Cholelithiasis
– 20% females, 8% of males
– Obesity, Pregnancy
– Native American (Pima Indian), Hispanic
– Oral contraceptive use, Clofibrate tx,
TPN
– Ileal disease (Crohn’s) or resection
– 80% of stones are radioluscentcholesterol
• good case-pt s/p gastric bypass,
rapid wt loss--cholesterol stones
Cholelithiasis
• Pigment stones: Clonorchis, Sickle cell dz
(i.e., hemolysis)
• Dx: U/S 90% sensitive; HIDA best for
determining cystic duct obstruction
• Tx:
– Symptomatic-Elective cholecystectomy
– If not surgical candidate: Actigall-cholesterol stones only
– Low suspicion for CBD stone: MRCP or
EUS
– High suspicion CBD stone: ERCP
70 yo asymptomatic woman undergoes
abd U/S after a pulsatile mass is
found on physical exam. A 3 cm
aortic aneurysm and multiple
gallstones are found. The next step
in management is:
A.
B.
C.
D.
E.
ERCP with sphincterotomy
Lithotripsy
Elective cholecystectomy
Ursodeoxycholic Acid
Observation/No treatment
• Asymptomatic: Observation!!!
• Cholangitis
– Charcot’s Triad:
• Fever
• Biliary colic
• Jaundice
– Tx:
• Abx
• ERCP for sphincterotomy
Other Diseases of the GB
• Calcifications of GB wall on X-Ray
highly suggestive of canceropen
cholecystectomy
• Emphysematous
cholecystitisemergent laparotomy
– Abx-Gram- and anaerobes, no
ceftriaxone (biliary concretions)!
Primary Biliary Cirrhosis
• EPIDEMIOLOGY
– 95% women
– onset 30-65
– incidence 2.7 per 100,000 person years
Primary Biliary Cirrhosis
• EPIDEMIOLOGY
– clustering in geographic areas
– prevalence 1000x greater in families of a
patient than general population
• no obvious inheritance pattern
Primary Biliary Cirrhosis
• SYMPTOMS / PRESENTATION
– abnormal LFT’s
– fatigue
– pruritus
– decompensated cirrhosis
Primary Biliary Cirrhosis
• SYMPTOMS / PRESENTATION
– osteoporosis
– osteomalacia
– steatorrhea
– xanthomata
– hyperlipidemia
Primary Biliary Cirrhosis
• ASSOCIATED CONDITIONS
– rheumatoid arthritis 5-10%
– Sjogren’s 40-65%
– scleroderma 5-10%
– hypothyroidism 20%
Primary Biliary Cirrhosis
• PHYSICAL EXAM
– Skin hyperpigmentation
– Xanthomas
– Hepatomegaly
– Kayser-Fleischer rings (rare)
• not just Wilson’s
– Splenomegaly, ascites, etc
Primary Biliary Cirrhosis
• LABORATORY
– Alk phos - may be only abnormality
– AST/ALT - normal or mild elevation
– bilirubin - normal early, elevated later
Primary Biliary Cirrhosis
• LABORATORY
– Antimitochondrial antibody
• sensitivity 95%
• specificity 98%
– IgM - elevated
– Eosinophilia
Primary Biliary Cirrhosis
• LABORATORY
– Hyperlipidemia
• elevated in > 50%
• mild LDL and VLDL elevations
• significantly elevated HDL
• no known increased risk of CAD
Primary Biliary Cirrhosis
• LIVER BIOPSY
– Diagnosis often made prior to liver
biopsy
– Biopsy may stage the degree of fibrosis
(0-4)
Primary Biliary Cirrhosis
• NATURAL HISTORY
– Mahl et al., Yale, Hepatology 1994
– 250 patients, up to 24 years follow-up
– Median survival
• symptomatic - 7.5 years
• asymptomatic - 16 years
Primary Biliary Cirrhosis
• TREATMENT
– Malabsorption
• Vitamin D
• Vitamin A
• Vitamin E - in advanced disease
• Vitamin K - in advanced disease
Primary Biliary Cirrhosis
• TREATMENT
– Drugs that didn’t work
• steroids
• azathioprine
• penicillamine
• silymarin (milk thistle)
• cyclosporine - effective but toxicities
Primary Biliary Cirrhosis
• TREATMENT
– Ursodeoxycholic acid
• UDCA decreases plasma and biliary
endogenous bile acid concentrations
• UDCA may decrease immune-mediated
destruction of hepatocytes by decreasing
the expression of HLA class I and II
antigens on hepatocytes, which may
diminish recognition by the immune system
Primary Biliary Cirrhosis
• TREATMENT
– Ursodeoxycholic acid
• 13-15 mg/day
• Moderate to severe disease
– decreased likelihood of transplantation or death
– 47% versus 66% at 4 years
– meta-analysis showed no benefit but many
studies short-term
Primary Biliary Cirrhosis
• TREATMENT
– Ursodeoxycholic acid
• Mild to moderate disease
– improvement in LFT’s
– improved histology
Primary Biliary Cirrhosis
• TREATMENT
– Colchicine
• mechanism unclear
• dose 1 mg/day
• well-tolerated in studies
• less effective than ursodiol
• no clear benefit to combination therapy
Primary Biliary Cirrhosis
• TREATMENT
– Methotrexate
• Dose 0.25 mg/kg PO qweek
• Conflicting results
• No long-term efficacy, safety data
Primary Biliary Cirrhosis
• TREATMENT
– Liver Transplantation
• survival similar to other etiologies of liver
disease
• recurrence after liver transplant uncommon
– similar appearance to chronic rejection
Primary Sclerosing Cholangitis
• Characterized by progressive
inflammation, fibrosis, and
stricturing of the intrahepatic and
extrahepatic bile ducts
Primary Sclerosing Cholangitis
• “Secondary” sclerosing cholangitis
– prior biliary surgery
– choledocholithiasis
– intra-arterial chemo (floxuridine)
– bacterial cholangitis
– AIDS cholangiopathy
Primary Sclerosing Cholangitis
• EPIDEMIOLOGY
– Prevalence 1- 6 per 100,000 in US
– 70% men
– mean age at diagnosis 40 years
Primary Sclerosing Cholangitis
• ASSOCIATION WITH IBD
– Among patients with PSC, ulcerative
colitis present in 25-90% (likely 90%)
– Among patients with ulcerative colitis,
PSC present in 5%
– Less common but seen in Crohn’s
Primary Sclerosing Cholangitis
• PATHOGENESIS
– Unknown but proposed
• autoimmune (given association with UC),
common ANA, ASMA, ANCA
• inflammatory reaction in the liver and bile
ducts induced by chronic or recurrent entry
of bacteria into the portal circulation
• ischemic damage to bile ducts
Primary Sclerosing Cholangitis
• DIAGNOSIS
– Gold standard - ERCP
• MRCP also
– most patients asymptomatic with
abnormal LFT’s
– consider if IBD and elevated alk phos
Primary Sclerosing Cholangitis
• LABORATORY
– alk phos & bili fluctuate
– AST/ALT normal or up to 200
Primary Sclerosing Cholangitis
• LABORATORY
– elevated IgG 30%
– elevated IgM 40-50%
– p-ANCA 30-80%
– HLA DRw52a 0-100%
Primary Sclerosing Cholangitis
• LIVER BIOPSY
– sampling likely so not a good
diagnostic tool
– may stage disease
Primary Sclerosing Cholangitis
• LOCATION
– Intra- & extrahepatic bile ducts: 87%
– Intrahepatic bile ducts alone: 11%
– Extrahepatic bile ducts alone: 2%
Kaplan, NEJM 1995
Primary Sclerosing Cholangitis
• PRESENTATIONS
– Ascending cholangitis
– Abnormal LFT’s
– Pruritus
Primary Sclerosing Cholangitis
• NATURAL HISTORY
– complications vary
• biliary - ascending cholangitis
• liver failure - portal hypertension, etc
• cholangiocarcinoma
Primary Sclerosing Cholangitis
• NATURAL HISTORY
– mean survival 12 years after diagnosis
• worse if symptomatic at diagnosis
Primary Sclerosing Cholangitis
• TREATMENT
– No proven medical therapy
•
•
•
•
•
•
D-penicillamine
Steroids
Cyclosporine, Tacrolimus
Methotrexate
Azathioprine, 6-MP
Ursodeoxycholic acid (small study, benefit
to  dose)
Primary Sclerosing Cholangitis
• TREATMENT
– Relieve biliary obstruction
• risk of infection
– Dominant stricture
• r/o cholangiocarcinoma
• dilate or stent
Primary Sclerosing Cholangitis
• TREATMENT
– Liver Transplantation
• survival similar to other etiologies of liver
disease
• disadvantage if symptoms due to
cholangitis and not liver failure in MELD
–
living donor?
Primary Sclerosing Cholangitis
• CHOLANGIOCARCINOMA
– 10-15% lifetime risk
– increased if IBD or cirrhosis
– contraindication to liver transplant
• protocol for aggressive chemotherapy
Primary Sclerosing Cholangitis
• CHOLANGIOCARCINOMA
– Diagnosis difficult
– CT/MRI - low sensitivity
– CA 19-9 - low sensitivity
Autoimmune Hepatitis
• EPIDEMIOLOGY
– Female > Male 4:1
– Two peaks
• 20’s and Middle age
• also seen in children
– 50-200 cases/million
Autoimmune Hepatitis
• SYMPTOMS/PRESENTATION
– Abdominal pain
– fever
– anorexia
– malaise
Autoimmune Hepatitis
• SYMPTOMS/PRESENTATION
– Acute or chronic disease
– 30 - 80 % cirrhotic at presentation
Autoimmune Hepatitis
• ASSOCIATED CONDITIONS
– Arthropathy
– Ulcerative colitis
– Sjogren’s syndrome
– Autoimmune thyroiditis
– Fibrosing Alveolitis
– Glomerulonephritis
Autoimmune Hepatitis
• DIAGNOSIS
• PATHOLOGY
– Interface hepatitis
– Lymphocytes and plasma cells
– Bridging necrosis
– Cirrhosis
Autoimmune Hepatitis
• CLASSIFICATION
• Type 1
– ANA, anti-smooth muscle antibody
• Type 2
– anti-LKM, liver cytosol antigen
– girls, young women
Autoimmune Hepatitis
• CLASSIFICATION
• Overlap Syndrome
– path  autoimmune hepatitis
– serology  PBC (+AMA)
• Autoimmune cholangiopathy
– path  PBC
– serology  ANA, asma
Autoimmune Hepatitis
• TREATMENT
– Corticosteroids
• acute management
– Azathioprine
• goal - maintain remission
• 2 mg/kg per day
• goal to d/c Prednisone
NASH
• Nonalcoholic steatohepatitis
• Nonalcoholic fatty liver disease
(NAFLD)
NASH
• DEFINITION
– liver biopsy with macrovesicular
steatosis & inflammation
– minimal or no EtOH
– negative serologic work-up
NASH
• EPIDEMIOLOGY
– #1 cause of liver disease?
– Women > men
– Most 40-60
• reported in children
NASH
• ASSOCIATED CONDITIONS
– obesity
– type 2 diabetes mellitus
– hyperlipidemia
– medications
– obesity bypass procedures
– TPN
NASH
• DIAGNOSIS
– liver biopsy
• confirms or excludes dx
• negative serologic work-up
NASH
• TREATMENT
– treat underlying condition
• obesity, DM, lipids
– stay tuned...
Alcoholic Hepatitis
• EPIDEMIOLOGY
– alcohol
• cirrhosis  80 gm/d EtOH for 10-20 years
– other factors
• female gender
– reduced gastric ADH activity
– size
• co-existing HBV, HCV
Alcoholic Hepatitis
• SYMPTOMS
– fever
– hepatomegaly
– jaundice
– anorexia
Alcoholic Hepatitis
• DIAGNOSIS
– liver biopsy
• steatosis, inflammation
– AST > 2x ALT
Alcoholic Hepatitis
• PROGNOSIS
– liver failure
• coagulopathy
• encephalopathy
– Discriminant function =
(4.6 x [PT - control PT]) + (serum bili, mg/dl)
– DF > 32: mortality 35-45%
Alcoholic Hepatitis
• TREATMENT
– Supportive care
– Who gets steroids?
• DF > 32
• Encephalopathy
• No infection, no GI bleeding
Abnormal Liver Tests
• Hepatocellular - AST, ALT 
• Cholestatic - alkaline phosphatase 
– bilirubin can be elevated in both
Abnormal Liver Tests
• AST 124 U/L
• ALT 157 U/L
• Alk phos 149 U/L
• T. bili 1.6 mg/dl
Abnormal Liver Tests
• AST/ALT mildly elevated (<250 U/L)
– chronic viral hepatitis
• HCV Ab, HBV surface antigen
– alcoholic hepatitis (AST > ALT)
• drug reaction - consider d/c
• NSAIDs, statins, antibiotics (INH)
– hemochromatosis (Fe/TIBC > 45%)
– steatosis, steatohepatitis
Abnormal Liver Tests
• AST/ALT mildly elevated (<250 U/L)
– less common causes
– autoimmune hepatitis
• ANA, ASMA, a-LKM
– Wilson’s disease
• age < 40; check ceruloplasmin, K-F rings
– Alpha-1-antitrypsin deficiency
• emphysema; alpha-1-antitrypsin level
Abnormal Liver Tests
• AST/ALT mildly elevated (<250 U/L)
– non-hepatic causes
– muscle source
– hypothyroidism
– celiac disease
• diarrhea, Fe deficiency; anti-endomysial IgA
– adrenal insufficiency
Abnormal Liver Tests
• AST/ALT mildly elevated (<250 U/L)
– negative serologic work-up
– consider liver biopsy if persistently
abnormal
Abnormal Liver Tests
• AST 1480 U/L
• ALT 1704 U/L
• Alk phos 229 U/L
• T. bili 4.8 mg/dl
Abnormal Liver Tests
• AST/ALT  > 10x ULN
– acute viral hepatitis
• hep A IgM
• hep B core IgM
• hep D
– autoimmune hepatitis
– shock liver (ischemic hepatitis)
– drug or toxin (acetaminophen)
Abnormal Liver Tests
• AST/ALT  > 10x ULN
– Rarer forms
– acute Budd-Chiari syndrome
– veno-occlusive disease
– HELLP syndrome
– acute fatty liver of pregnancy
Abnormal Liver Tests
• AST/ALT  > 10x ULN
– Acute Liver Failure
– Elevated PT
•  factor V
– Encephalopathy
• If discharge patient, clarify supervision
– Transfer to Transplant Center
Abnormal Liver Tests
• Bilirubin
– unconjugated
• Overproduction of bilirubin or impaired
uptake, conjugation
• tightly bound to albumin so not filtered and
not present in urine
– conjugated
• impaired excretion into bile ductules
• present in the urine
Abnormal Liver Tests
• Unconjugated bilirubin
– hemolysis
– impaired bilirubin uptake
• CHF
• Portosystemic shunts
• Certain drugs - rifampin, probenecid
Abnormal Liver Tests
• Unconjugated bilirubin
– hemolysis
– impaired bilirubin uptake
– impaired bilirubin conjugation
• Gilbert’s
• Crigler-Najjar
• hyperthyroidism
• cirrhosis
• Wilson’s disease
Abnormal Liver Tests
• Unconjugated bilirubin
– Gilbert’s Syndrome
• Uridinediphosphoglucuronate
glucuronosyltransferases (UGTs) mediate
glucuronidation
• Mutation of UGT1A
• 9% western world homozygous
• 30% heterozygous
–
Slightly higher bili
Abnormal Liver Tests
• Unconjugated bilirubin
– Gilbert’s Syndrome
• Bilirubin
–
Usually < 3 mg/dl, rarely > 6
• Factors
–
Fasting
–
Stress (surgery, etc)
–
Infection
Abnormal Liver Tests
• Unconjugated bilirubin
– Gilbert’s Syndrome
• Diagnosis
– rise in bilirubin concentration following a
low lipid, 400 kcal diet
– administration of IV nicotine
– seldom necessary in clinical practice
Abnormal Liver Tests
• Conjugated bilirubin
– Extrahepatic cholestasis
• PSC
• intrinsic & extrinsic tumors
• AIDS cholangiopathy
• cholelithiasis
• parasites - ascaris lumbricoides, liver flukes
Abnormal Liver Tests
• Conjugated bilirubin
– Intrahepatic cholestasis
• Viral hepatitis
• Alcoholic hepatitis
• Nonalcoholic fatty liver disease
• PBC
• Drugs, toxins
• Sepsis
Abnormal Liver Tests
• Conjugated bilirubin
– Intrahepatic cholestasis
• Infiltrative diseases - sarcoidosis, amyloid,
lymphoma
• TPN
• Pregnancy
• Cirrhosis
• Dubin Johnson, Rotor syndrome
Abnormal Liver Tests
• AST 32 U/L
• ALT 29 U/L
• Alk phos 472 U/L
• T. bili 1.0 mg/dl
• (5’-nucleotidase )
Abnormal Liver Tests
• Elevated alkaline phosphatase
– primary biliary cirrhosis
– primary sclerosing cholangitis
– partial bile duct obstruction
– drugs (androgenic steroids, phenytoin)
– sarcoidosis
– metastatic cancer