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The Liver and Biliary System 10 cases to guide you

Chapy Venkatesan, MDDepartment of MedicineVCU School of Medicine Inova Campus

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OverviewTo be familiar with the approach to differential diagnosis and management hepatobiliary disease– will not be all-encompassing

Case and image basedInteractiveHope for you to get three learning points out of thisWill review what we covered at the end– motivate/challenge you to read on your own

Show you that medicine is FUN!

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Background/PatternsHepatocellular - ALT, AST > 3x uln; AP < 2x ulnCholestatic/Obstructive - AP > 3x uln; AST, ALT < 2x ulnMixed - ALT and AP > 2-3x ulnBili variable in allAlcohol - AST>ALT in 2-3:1, AST < 300, ALT < 100– ratios outside of these ranges in someone who

drinks EtOH suggests a concomitant disorder

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Liver Function

PT/INRAlbuminGlucose

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Case #142 year old male with recent onset jaundiceVague epigastric/RUQ discomfortNo IVDU, transfusions, unprotected sexRecently taking acetaminophen 3g/day for a viral URIBP - normalAlert and oriented, jaundicedINR - 4.2; Cr - 3.0; AST - 14,380; ALT -6,740; Alk Phos - 70; tb - 11.2

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7www.edu.rcsed.ac.uk/ photoalbum/ph93.htm

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QuestionsWhat is the most likely underlying risk factor for the patient’s acute liver disease?– alcoholic cirrhosis

What is the most likely diagnosis for the acute liver disease?– acetaminophen hepatotoxicity

What is the therapy/antidote?– N-acetylcysteine

What are other causes of transaminases in the 1,000’s– acute viral hepatitis (risk factors), ischemic

hepatitis/shock liver (hypotension, diminished cardiac output)

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Induced by alcohol

No synthesis due to liver dz

TOXIC

Current Diagnosis & Treatment in Gastroenterology - 2nd Ed. (2003)

N-acetylcysteineis a substitute

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Rumack BH, Matthew H: Acetaminophen poisoning and toxicity. Pediatrics 1975;55:871

14Lee 333 (17): 1118, Table 2 October 26, 1995 - NEJM

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Case #224 y.o. female prostitute, IV drug user presents with headache, malaise, fever, arthralgias, and nausea followed by jaundice Hepatomegaly and jaundice on examAST - 850, ALT - 1,250; bili - 4.0; AP -normalAnti-HAV IgM, Anti-HCV, HBsAg, HBsAb all negative

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QuestionsWhat is the best serologic test to make the diagnosis?– HBcAb IgM

What is the pattern of vaccination versus hepatitis B; remote hepatitis B?– + HBsAb, neg HBcAb; +HBsAb, +HBcAb

The patient’s liver enzymes fall and then peak 4 weeks later, what is the best way to make the diagnosis?– Anti HDV or HDV RNA

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Questions

Twenty years later, the HBsAg is positive. There is no evidence of cirrhosis. The alkphos and AFP are elevated and the pt has fever and polycythemia. What is the most likely diagnosis?– hepatocellular carcinoma

What are other risk factors for hepatoma?

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Risk factors for hepatoma

Cirrhosis of any etiologyAlcoholHepatitis B (does not have to progress through cirrhosis)Hepatitis CHemochromatosis

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Case #3

20 y.o. female with jaundice for one weekHad nausea and abdominal pain for three weeksFriends brought her in d/t hallucinationsYou note a tremor on examALT - 170, AST - 95; AP - 120; bili - 8.0Retic - 10.5%; LDH - 1000, Hct - 33, Coombs negative

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QuestionsWhat are blood and urine tests that support this diagnosis?– Wilson’s disease - low ceruloplasmin, high

24 hr urine copperWhat is the medical therapy?– penicillamine– may need liver transplant - especially if

presenting with fulminant hepatic failure (acute liver failure with hepatic encephalopathy)

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Case #452 y.o. white female (nondrinker, diabetic w/ A1C - 9.2%)with incidentally noted ALT - 75, AST - 52, AP - 65, bili normalBMI - 36LDL - 245, TG - 380U/S demonstrates a hyperechoic liverhep B, C, iron studies, ceruloplasmin, alpha one antitrypsin level, anti-mitochondrial antibody, anti-smooth muscle antibodies negative

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Questions

What is the best treatment?– pt has NASH / NAFLD– gradual weight loss and treatment of DM,

hyperlipid / triglyceridemiaWhat are other causes of chronically elevated liver enzymes?

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HistorySerology

Obesity, DM, hyperlipidemia;

exclusion of other causes

Polyclonal gammopathy,Anti Sm m Ab, Anti LKM Ab

Hypogonadism,Arthritis,DM, CHF

Fe studies, geneticstudies

KF rings; neuro,Psyc, Hepatic,

Heme; ceruloplasmin,urine Cu

Emphysema, FmHxliver dz, panniculitis,

level, genotype

Malabsorption, Fe def,osteoporosis, misdx with IBS

CK, aldolase,TSH

Causes of Chronically Elevated Aminotransferase Levels

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AssociationsChronic hepatitis B– polyarteritis nodosa (intestinal ischemia, renal

failure, vasculitis)– membranous GN, MPGN

Chronic hepatitis C– DM– porphyria cutanea tarda– lichen planus– cryoglobulinemia, MPGN, membranous GN

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Case #5

43 y.o. female with fatigue and pruritis at all timesHad a recent pathologic fracture and Z score on DEXA was - 2.9ALT - 70, Alk Phos - 600

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Questions

What is the most likely diagnosis?– primary biliary cirrhosis

What are sources of alk phos?– placenta, bile duct epithelium, and bone

• Paget’s disease of bone, bone metastases, primary hyperparathyroidism, Vitamin D deficiency

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Case #6

25 y.o. male returned from a trip to India three months agoDevelops two weeks of fever and RUQ pain without diarrheaWBC 14K

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QuestionsWhat is the next diagnostic test to order?– amebic liver abscess

• E. Histolytica serology• no aspiration

– risk of amebic peritonitis, inadvertent puncture of an echinococcal cyst,

– can use if no better on therapy, or to exclude other diagnoses

Next therapy?– metronidazole

When would you suspect a pyogenic liver abscess and aspirate the abscess?– jaundiced, septic, h/o abd surgery or biliary

disease, picture not typical of amebic

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Case #763 y.o. female with acute onset of fever, chills, n/vT - 103 F, P - 120, RR - 28, BP - 80/50Pt is jaundiced with scleral icterus on examAST and ALT - 125, Alk Phos - 800, bili -12.5, dbili - 11.6U/S shows gallstones and CBD dilatationHypotension persists despite 4L of NS

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QuestionsWhat is the next step in addition to supportive care and broad spectrum antibiotics?– ERCP for drainage and relief of the

obstruction– can do abx only with ERCP electively

unless:• no better over 1st 24 hours, fever > 103,

persistent pain, hypotension despite resuscitation

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Case #8

22 y.o. with ulcerative colitis presents with jaundice, alk phos of 500, ALT of 75

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Questions

What is the diagnosis?– Primary sclerosing cholangitis– most have UC, most of UC do not have

PSCWhat is the concern if the patient develops a dominant biliarystricture?– Cholangiocarcinoma

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Case #9

45 y.o. male admitted with an acute MIFound to have a total bili of 6.0, dbili -0.3One year later, the bili decreases to 2.5, dbili - 0.3The remainder of the liver panel is normal, as is the CBC, retic count and peripheral smear

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Questions

What is the next diagnostic test?– NONE

What is the therapy?– NONE

Gilbert’s syndromeIndirect hyperbilirubinemia– hemolysis, ineffective erythropoiesis

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Case #10A

27 y.o. female, G1P0; at 38 weeksPresents with acute onset N/V, jaundice, encephalopathyAST and ALT ~ 700; Alk Phos - nl; NH3 - 95; Plt - 45K; PT/PTT -elevated; d-dimer - elevated; fibrinogen - low

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Questions

What is the diagnosis?– acute fatty liver of pregnancy– can recur with subsequent pregnancies– stabilize the mother and deliver the fetus

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Case #10B

26 y.o. female, G4P3, 34 wksRUQ pain, N/VBP - 145/90; 2+ edemaHct - 24; Plt - 75K; bili - 5.0 (dbili -0.5); ALT - 300; LDH - 1000; 4+ urine protein; Uric acid - 7.0

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Diagnosis?

HELLP Syndrome

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Case #10C

28 y.o. G1P0 living in PakistanThe pt and her husband develop an illness characterized by jaundice, N/V, malaise, anorexiaHer husband’s illness is self-limitedShe develops encephalopathy, ALT -1200, and dies

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Diagnosis?

Hepatitis E - increased mortality and FHF in pregnancy

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Other pregnancy tidbits

Hyperemesis gravidarum causes elevations in the transaminases -usually below 300Benign Recurrent IntrahepaticCholestasis of Pregnancy -intractable pruritis, elevated alkphos, can recur with subsequent pregnancies

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What did we cover?Patterns of liver panelPhysical findings of cirrhosisAcetaminophen hepatotoxicity and other forms of drug-induced liver diseaseCauses of AST and ALT > 1000Drug induced liver diseaseHepatitis B serologiesHepatocellular carcinoma RF’s

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What did we cover?Wilson’s diseaseNASH/NAFLDChronically elevated aminotransferasesAssociations of hepatitis B and CPBCAmebic liver abscessCholangitis

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What did we cover?

PSCCholangiocarcinomaGilbert’s syndromePregnancy and liver disease