Liver, Pancreas, Gallbladder, and Biliary Board Review Elizabeth Paine, MD July 18, 2015 ** I have...

Liver, Pancreas, Gallbladder, and Biliary Board Review

Elizabeth Paine, MDJuly 18, 2015

** I have no financial interests regarding the content of my presentation **

Liver enzyme elevationsHepatocellular diseases (predominant ALT/AST elevations)NAFLDChronic viral hepatitisAutoimmune hepatitisWilson’s diseaseHereditary hemochromatosisAlcoholic liver diseaseDrug toxicityAlpha 1 antitrypsin deficiency

Cholestatic diseases (predominant Alkaline phosphatase/GGT elevations)

Gallstones with biliary obstructionPrimary biliary cirrhosisCancerDrug toxicityPrimary sclerosing cholangitisSarcoidosisAutoimmune cholangiopathy

Adapted from Aragon and Younossi. CCJM 2010 March;77(3):195-204.

Elevated ALT/AST workup

Aragon and Younossi. CCJM 2010;77:195-204

Elevated Alkaline Phosphatase

Aragon and Younossi. CCJM 2010;77:195-204

A. Give albumin now and wait to start antibiotics until cultures return

QuestionA 56 year old man with diabetes, hypertension and obesity (BMI 31) is found to have an ALT 67 and AST 40 with a normal albumin, total bilirubin, and alkaline phosphatase. He states that he has never been a drinker and has no family history of liver diseases. What is the most likely etiology of his abnormal liver enzymes from the choices below?

A. Autoimmune hepatitisB. Non-alcoholic fatty liver diseaseC. Wilson diseaseD. Hereditary hemochromatosis

Nonalcoholic fatty liver disease (NAFLD)

• Broad term (steatosis cirrhosis)

• Associated with metabolic syndrome and obesity

• Diagnosis inferred by absence of other etiologies of liver disease

• TreatmentChalasani et al. Hepatology 2012;55(6): 2005-2023 http://liverbasics.com/hepatic-

steatosis.html

Autoimmune Hepatitis

• Range of presentations• Fatigue, jaundice,

malaise• Types 1 and 2• Autoantibodies seen:

ANA, ASMA, IgG, LKM1 • Treatments

Manns MP, Lohse AW, Vergani D. Autoimmune hepatitis – Update 2015. J. Hepatol. 2015 Apr;62(1S):S100-S111

Wilson’s disease

• Rare, autosomal recessive disorder

• Usually a young patient with neuropsychiatric symptoms

• Very low alkaline phosphatase• Low ceruloplasmin• Kayser-Fleischer rings• Can present in acute liver failure

http://www.wilsonsdisease.org/wilson-disease/kayserfleischerrings.php

Iron overload syndromes

• Hereditary hemochromatosis• Iron loading anemias (chronic hemolytic

anemias, sideroblastic anemia, thal major)• Chronic liver disease (alcoholic, viral hepatitis,

NAFLD)• Parenteral iron overload (RBC transfusions,

long standing HD)

Hereditary Hemochromatosis

• Most common genetic disease in Caucasians

• Iron saturation >45%• HFE genes C282Y and

H63D• Clinical features• Treatment:

phlebotomy with goal ferritin <50

https://cornellbiochem.wikispaces.com/Hereditary+Hemochromatosis

Viral Hepatitis

• Transmission- Fecal-oral: Hep A an E- Sexual: Hep B and D, also C

• Clinical features• Typical course

Question

Mr. Smith presents to your clinic and reports a 2 weeks history of fatigue and feeling “sick to my stomach.” He also reported that he saw another provider 1 week ago who mentioned something was abnormal with his liver. You order a CBC, CMP, and Hepatitis panel and find that he has positive IgM anti-HAV, positive Hepatitis B surface antibody, and elevated ALT/AST. What is the most likely etiology of his clinical picture?

A. Hepatitis BB. Hepatitis CC. Hepatitis AD. Hepatitis D

QuestionMr. Smith presents to your clinic and reports a 2 weeks history of fatigue and feeling “sick to my stomach.” He also reported that he saw another provider 1 week ago who mentioned something was abnormal with his liver. You order a CBC, CMP, and Hepatitis panel and find that he has positive IgM anti-HAV, negative IgG anti-HAV, positive Hepatitis B surface antibody, and elevated ALT/AST. What is the most likely etiology of his current clinical picture?

A. Hepatitis BB. Hepatitis CC. Hepatitis AD. Hepatitis D

Hepatitis B

• Incubation period• Multiple modes of

transmission• Can present with serum

sickness• Extraintestinal

manifestations: remember association with PAN

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.zwallpix.com/polyarteritis-nodosa-string-of-pearls.html&ei=zFtaVfXxAcLBtQWT-oCoBg&psig=AFQjCNEZZpTXSSNERPtdFYvcyEQLa4KnSQ&ust=1432071479708556

Hepatitis B

http://www.bio-rad.com/en-us/product/hepatitis-b/monolisa-anti-hbc-igm-eia

Hepatitis B serologiesHBsAg anti-HBs anti-HBc

IgManti-HBcIgG

HBeAg DX

+ - + - + Acute infection

+ - - + +/- Chronic infection

- + - - - Vaccinated

- + - + - Exposed immune

- - + - - Acute window

- - - + -Exposed, Ab lost

Hepatitis B treatment options

• Entecavir• Tenofovir• Adefovir• Lamivudine (if not resistant)• PEG IFN• Telbivudine

Hepatitis B treatmentHep B eAg HBV DNA ALT Treatment strategy

Positive >20K <2 x ULN Primarily observe until ALT elevated, can consider bx and tx if significant fibrosis

Positive >20K >2 x ULN Observe for 3-6 months and treat if no seroconversion

Negative >20K > 2x ULN Treat, endpoint not defined

Negative >2K 1-2 x ULN Treat if liver bx shows significant necroinflammation or fibrosis

Negative <2K < ULN Observe

Pos or Neg Detectable Cirrhosis If DNA > 2K, treat. If < 2K, consider tx if ALT elevated

Pos or Neg Undetectable Cirrhosis Compensated: observeDecompensated: refer for transplant

Adapted from Lok and McMahon. Chronic Hepatitis B: Update 2009. Hepatology September 2009.

Caveats with Hepatitis B

• If Hepatitis B eAg positive patient is treated, treat for 6 months after seroconversion to Hep B eAb positive

• Pregnancy and Hep B• HCC screening

Hepatitis C

• Risk factors• Genotypes – gt1 is most common in US• Screening: HCV Ab• Confirmation: PCR testing• CDC guidelines: Adults born 1945-1965

should be tested once (without prior ascertainment of HCV risk factors)

• Disease progression

Hepatitis C treatment

• Rapidly changing• Doubt this will be testable now since it is

changing by the month with new drugs

Hep C Extraintestinal manifestations

• Cryoglobulinemia• Porphyria cutanea tarda• Membranoproliferative

glomerulonephritis• Inflammatory arthritis• Sjogren’s syndrome

http://www.porphyria-professionals.uct.ac.za/ppb/professional/gallery/skindisease

Hepatitis D

• Requires co-existent Hepatitis B• Usually found in IVDA• Coinfection vs. superinfection• Diagnosis• Treatment

Alcoholic hepatitis

• Jaundice, fever, ascites, AST/ALT >2

• Path• Treatment• Reassess in 7 days

with Lille score

http://missinglink.ucsf.edu/lm/IDS_106_Liver_histo_path/Assets/Liver_path.htm

Primary biliary cirrhosis

• Usually middle aged female

• Itching and fatigue• Increased alkaline

phosphatase• Elevated AMA• Treat with ursodiol• Manage cirrhosis

https://www.pathology.med.umich.edu/greensonlab/pbc2.jpg

Primary Sclerosing Cholangitis

• Autoimmune• Fibrosis of large bile

ducts• RUQ pain, fatigue,

weight loss• 70% associated with UC• Increased risk of

cholangiocarcinoma• Diagnosed with MRCP

or ERCP

http://openi.nlm.nih.gov/detailedresult.php?img=2880347_ijgm-3-143f3&req=4

PSC Pathology

http://library.med.utah.edu/WebPath/LIVEHTML/LIVER054.html

Question

A 63 year old patient presents because of abnormal liver function tests including AST 123, ALT 143, alkaline phosphatase 143. He drinks 1 glass of wine daily. He takes amiodarone, losartan, and metformin. A liver biopsy is done and shows Mallory hyaline bodies consistent with fatty deposition. What is the most likely cause?

A. AlcoholB. MetforminC. AmiodaroneD. Losartan

DILI evaluation

Chalasani et al. Am J. Gastroenterol 2014/109:950-966

http://gi.org/wp-content/uploads/2014/06/DILI_fig1.jpg

Drugs Commonly Associated with DILI

Drug Pattern Features

Amiodarone Macrovesicular fat “Bright” on non-contrast CT

Acetaminophen Acute hepatitis ALT >5000, renal injury

Amoxicillin/clavulanateTMP/SMX

Cholestasis May occur after treatment finished

Valproate Microvesicular fat Encephalopathy

NitrofurantoinMinocycline

Mimics autoimmune hepatitis

Can occur after months on the drug; may require steroids

Methotrexate Fibrosis Probably rare

Phenytoin Mixed Hypersensitivity features

Adapted from Mayo Clinic Gastroenterology and Hepatology Board Review 2013

QuestionA 22 year old woman who is 23 weeks pregnant presents to clinic complaining of itching. This itching is primarily on her palms and soles and is worse at night. She denies any tylenol usage or usage of other OTC medications except a prenatal vitamin. Her abdominal ultrasound is normal. Which of the following is the most likely diagnosis?

A. Intrahepatic cholestasis of pregnancyB. HELLP (Hemolysis, Elevated Liver Enzymes, Low

Platelets) syndromeC. Acute fatty liver of pregnancyD. Acute Hepatitis A

Intrahepatic cholestasis of pregnancy

• Usually 3rd trimester, sometimes 2nd

• Pruritus - particularly palms and soles

• Less than ¼ develop jaundice• Treatment

Williamson and Geenes. Obstet Gynecol. 2014 July;124(1):120-33.

HELLP diagnosis

• Combination of clinical features• Abdominal imaging• Common lab features: H: LDH >600, abnormal smear EL: AST >70, AST/ALT elevation up to 10:10-20 fold LP: platelets <150,000

Acute Fatty Liver of Pregnancy

• Often presents as fulminant hepatic failure• Usually late 3rd trimester• Occurs in 1 in 6700 3rd trimester pregnancies• Associated factors• Treatment

Liver Diseases in Pregnancy

ICP HELLP AFLP

% Pregnancies 0.1% (USA) 0.2%–0.6% 0.005%–0.01%

Onset/trimester 25–32 weeks 3 or postpartum 3 or postpartum

Family history Often No Occasionally

Preeclampsia No Yes 50%

Typical clinical featuresPruritus, mild jaundice, increased bile acids, dec vit K

Hemolysis Thrombocytopenia

Liver failure with coagulopathy, HE hypoglycemia, DIC

Aminotransferases Mild to 10–20-fold ↑ Mild to 10–20-fold ↑ 300–500 but varies

Bilirubin <5 mg/dL <5 mg/dL unless massive necrosis

often <5 mg/dL, higher if severe

Hepatic imaging Normal Hepatic infarcts, hematomas, rupture Fatty infiltration

Histology Nl–mild cholestasis, no necrosis

Patchy/extensive necrosis, hemorrhage

Microvesicular fat in zone 3

Recurrence in subsequent pregnancies 45%–70% 4%–19% (LCHAD) defect—yes

Gilbert’s disease

• Unconjugated hyperbilirubinemia• Autosomal dominant• Jaundice worsens with stress and fasting• Usually not treated

Cirrhosis

Taylor CR. Cirrhosis Imaging. http://emedicine.medscape.com/article/366426-overview

Cirrhosis complications

• Ascites• Spontaneous bacterial peritonitis• Hepatic encephalopathy• Hepatorenal syndrome• Hepatocellular carcinoma

QuestionA 53 y/o man with DM2 and HTN presents to your clinic with a 2

month history of his pants becoming progressively tighter. He drinks a case of beer on the weekends but denies drug use. On exam, his BP is 99/55 with pulse of 75/minute and T 98.2°F. His abdomen is tense with no tenderness or rebound.

Labs: WBC 5, Hb 9.2, platelets 160,000, creatinine 2,albumin 3.4, AST 67, INR 1.4. Abdominal CT shows a large amount of ascites and some coarsening of the liver parenchyma. He underwent a 7L paracentesis with fluid studies as follows: fluid albumin 2, fluid total protein 1.5, fluid PMN’s 287.

Which of the following is the best next step?

A. Start Vancomycin 1g IV dailyB. Give albumin now and wait to start antibiotics until cultures returnC. Begin ciprofloxacin 250mg po weekly for SBPD. Start Cefotaxime and albumin

Ascites on CT

Poggi et al. International Journal of Case Reports and Images. 2013;4(1):32-36.

Serum-ascites albumin gradient (SAAG)

SAAG (g/dL)

≥ 1.1 < 1.1

Total protein (g/dL)

< 2.5 Cirrhosis Nephrotic syndrome

Acute liver failure

≥ 2.5 CHF Peritoneal carcinomatosis

Constrictive pericarditis

TB peritonitis

Budd-Chiari syndrome

Pancreatic ascites

Veno-occlusive disease

Chylous ascites

Ascites therapy: dietary and diuretics

• Sodium restriction < 2 grams/day• Spironolactone/furosemide in a ratio

of 100/40• Goal is weight loss of 0.5-1kg/day• Diuretics are titrated to achieve

weight loss without complications

Runyon and AASLD Practice Guideline Committee. Management of Adult Patients with Ascites Due to Cirrhosis. 2013.

Refractory ascites

• Definition• Reversible

factors• Treatment

options• TIPS

https://www.uic.edu/com/virtualpatient/part3/data/surgeryhtml/1310detail.htm

Runyon and AASLD Practice Guideline Committee. Management of Adult Patients with Ascites Due to Cirrhosis. 2013 .

Spontaneous bacterial peritonitis (SBP)

• Definition• Frequency• Clinical manifestations• Diagnosis: absolute

PMN > 250• Bacterial culture

Example ascitic fluid labs in patient with SBP:

WBC 5300/mm3

87% neutrophilsAlbumin <1


SBP treatment

• Need to control ascites• Cefotaxime 2g IV q8

hours• Uncomplicated SBP

outpatient can be treated with oral ofloxacin

• Albumin infusion

Runyon and AASLD Practice Guideline Committee. Management of Adult Patients with Ascites Due to Cirrhosis. 2013 .

Primary and secondary prophylaxis

• Primary prophylaxis: - IV cefotaxime or BID norfloxacin - Indicated for the following patients: cirrhotic with GI bleed (for 7 days) pts w ascitic fluid protein <1.5 and Cr≥1.2, BUN≥25, Na ≤130, CTP ≥9, bili≥3 (long term abx can be considered)

• Secondary prophylaxis: - Norfloxacin 400mg daily or bactrim/cipro daily. Daily dosing recommended over weekly dosing. - For patients who previously had SBP


Question

A 42 year old woman with cirrhosis presents to the ER with active hematemesis and an emesis basin full of bright red blood. What is the most likely etiology of her upper GI bleeding?

A. Dieulafoy lesionB. Portal hypertensive gastropathyC. Angioectasia/AVMD. Esophageal varices

Esophageal varices• ~1/4 to 1/3 of cirrhotics hemorrhage at least

once from varices• Have portal HTN with pressures > 12mmHg• Esophageal variceal hemorrhage• Management of bleeding esophageal varices

Garcia-Tsao et al. Hepatology 2007:46(3):922-934.

Esophageal varices

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/variceal-hemorrhage/

Question

A 65 year old man with cirrhosis is brought in to the clinic by his wife after he had several days of staying up all night and sleeping all day, along with intermittent periods of “not making sense.” He has asterixis on exam. What should be done for this patient?

A. Start lactulose and titrate for 3 loose stools dailyB. Restrict the protein in his dietC. Initiate metronidazoleD. Start furosemide

Hepatic encephalopathy

• Describes the spectrum of potentially reversible neuropsychiatric abnormalities in patients with liver dysfunction

• Presumed mechanism• Early feature is sleep disturbance• Later features are asterixis,

hyperactive DTRs, transient decerebrate positioning

Vistrup et al. Hepatology 2014 Aug;60(2):715-35.

Hepatic encephalopathy management

• Identification and avoidance of precipitants• Lactulose 30mL BID-TID, titrated for 2-4 BM daily

Rifaximin 550mg po BID• Protein restriction is no longer recommended for

most patients• Treatment of post-TIPs hepatic encephalopathy

Vistrup et al. Hepatology 2014 Aug;60(2):715-35.

QuestionA 55 year old man with history of cirrhosis and ascites undergoes his q6 month surveillance imaging. On ultrasound, he was found to have a new 2.6cm liver lesion. AFP was 532. Subsequent 3phase liver CT showed the same lesion with arterial enhancement and portal venous washout. What is the most likely diagnosis?

A. HemangiomaB. Hepatocellular carcinomaC. MetastasisD. Hepatic cyst

Hepatocellular carcinoma

• Cirrhotic patients have increased risk for HCC

• Hep B patients can develop HCC without cirrhosis

• Common signs/symptoms

• Diagnosis

Bruix and Sherman. Management of Hepatocellular Carcinoma. AASLD guideline 2011.

Barcelona criteria

Sherman M et al. Current Oncology 2011. 18(5):228-240.

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=wPr8c_qHSJiPlM&tbnid=A0ZO1odeLOPnLM:&ved=0CAcQjRw&url=http://www.current-oncology.com/index.php/oncology/article/view/952/762&ei=QRU8VPL0D-fC8AHrhIGwCA&bvm=bv.77161500,d.b2U&psig=AFQjCNHpmobd5PB9WriDHZBUrAUW5KVyfQ&ust=1413310136774658

QuestionA 65 year old man with alcoholic cirrhosis is admitted to House Medicine with spontaneous bacterial peritonitis. He has not been taking NSAIDs or diuretics. His initial serum creatinine is 1.1 but 4 days later, his creatinine has risen to 3.6 and he is anuric. His creatinine does not improve after receiving 2 days of albumin infusions. Which of the following statements is true?

A. He likely has type I hepatorenal syndromeB. He likely has type II hepatorenal syndrome and will improve

without treatmentC. He should be given vasodilators to improve renal perfusionD. He should be given furosemide and aldactone in a 40/100

ratio

Hepatorenal syndrome diagnosis

Salerno et al. Gut 2007;56:1310-1318.

Diagnostic criteria (Salerno et. al 2007)

• Cirrhosis with ascites• Serum Cr >1.5• No improvement after 2 days of diuretic withdrawal

and plasma volume expansion with albumin (100g/day)

• Absence of shock• No current or recent nephrotoxic drugs or

vasodilation• Absence of parenchymal kidney disease with

proteinuria <500, no US evidence of obstructive uropathy or microhematuria

Hepatorenal syndrome

• Types: - Type 1 HRS - Type 2 HRS• Treatment - Prevention - Therapy


Schistosomiasis – Hepatic involvement

• In adults with chronic infection – “pipestem fibrosis”

• Portal HTN & splenomegaly• GI varices• Often no abnormalities in LFTs• Gold standard for dx is

microscopy of stool or urine sample for schistosome eggs

• Treatment: praziquantel 40-60 mg/kg

http://www.microbiologybook.org/parasitology/sch3.jpg

Acute pancreatitis

• Acute onset persistent epigastric abdominal pain

• Usually with nausea/vomiting

• Elevated amylase, lipase

• ImagingMunoz and Katerndahl. Am Fam Physician 2000 July 1;62(1):164-174

Etiologies of acute pancreatitis

• Alcohol abuse• Gallstones• Hypertriglyceridemia• Post-ERCP• Pancreatic malignancy• Medications• Hypercalcemia

Medications:FurosemideThiazidesEstrogensAzathioprine5-ASATetracyclinesSulfonamidesAnti-HIV drugsValproic acidSome diabetes drugs

Poor prognostic indicators in acute pancreatitis

• SBP <90 with HR >130• PO2 < 60mmHg• Urine output <50mL/hr• Altered mental status• Pancreatic necrosis• Altered mental status• Low calcium (<8mg/dL) and albumin <3.2 g/dL• Hemoconcentration (Hct > 44%)• APACHE 2 score > 8

Complications of acute pancreatitis

• Necrosis• Pseudocyst• Abscess• Shock• Left sided pleural

effusion• Splenic vein

thrombus http://www.top5plus5.com/Pseudocyst%20of%20the%20Pancreas_files/Pseudocysts%20Images.html

Management of acute pancreatitis

• Supportive care• NPO initially but early enteral feeding as able• IVF • Systemic antibiotics if infected or severe• Pain control• ERCP for cholangitis or sepsis

Chronic pancreatitis

• Usually result of chronic ETOH

• Early sx: recurrent abdominal pain

• Late sx: steatorrhea and DM

• Imaginghttp://www.nytimes.com/imagepages/2007/08/01/health/adam/1157PancreatitischronicCTscan.html

Complications of chronic pancreatitis

• Pancreatic cancer (~ 4% of pts with chronic pancreatitis >20 years)

• Brittle DM, prone to hypoglycemia• Splenic vein thrombosis• B12 malabsorption

Management of chronic pancreatitis

• Pancreatic enzymes (start with 500 lipase units/kg/meal) with antacids

• Decrease fat in diet• Add medium-chain TG• Avoid ETOH• Stop smoking

Autoimmune pancreatitis

• Often have painless obstructive jaundice

• Can have elevated IgG4

• Imaging findings• Tx: steroids

Chruch et al. Am. J. Gastroenterol 2007(102):2417-2425.

Pancreatic cancer

• Jaundice, weight loss, abdominal pain

• If in pancreatic head: painless jaundice

• If in body/tail: pain, weight loss

• Diagnosis• Treatment

http://www.aboutcancer.com/pancreas1_images.htm

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.aboutcancer.com/pancreas1_images.htm&ei=qBRmVfeZHYmLsAWi2YGwBg&psig=AFQjCNEs-NtUUd8IKHP5xMDuAcWvEYjtBQ&ust=1432839609355182

Question

A 65 y/o veteran is found to have the following ultrasound but is asymptomatic with normal labs. What should be done next?

A. ObservationB. Referral to SurgeryC. Abdominal CTD. MRI

Cholelithiasis

• Very common• Association with obesity, OCP, ileal

disease/resection• Symptoms: post-prandial RUQ pain• US to diagnose• If asymptomatic, do nothing• If symptomatic refer to surgery

Choledocholithiasis

• Stones in CBD• Elevated AlkPhos and

bilirubin• Can also see CBD

dilation on US• Tx: ERCP with

sphincterotomy in most cases http://www.healthhype.com/gallbladder-tests-

ultrasound-ct-hida-scan-ercp.html

Acute Cholecystitis

• RUQ pain, fever, leukocytosis• Calculous vs. acalculous• Frequently have positive “Murphy’s sign”• Ultrasound• HIDA scan• Tx: cholecystectomy (if good surgical

candidate), percutaneous cholecystotomy with abx if very sick

Porcelain gallbladder

http://www.ultrasoundcases.info/files/Jpg/lbox_15380.jpg

Acute cholangitis

• Charcot’s triad• Complication of choledocholithiasis or cancer• Need antibiotics• Also need ERCP with endoscopic

sphincterotomy or surgery if ERCP isn’t available

Liver/Biliary history pearls

• Pruritus/cholestasisPBC/PSC

• Undercooked food, oysters, daycareHepatitis A

• ICU, hypotension, right sided CHFHepatic congestion

• Neuropsych findingsWilson’s disease


• Metabolic syndrome, mildly elevated ALT/ASTFatty liver

• HyperpigmentationHemochromatosis or PBC

• Kayser-Fleischer rings/sunflower cataractsWilson’s disease


• SplenomegalyPortal hypertension or infiltrative process

• Pulsatile liverTricuspid insufficiency

• Hepatic bruitsHepatocellular carcinoma

Questions?

Liver, Pancreas, Gallbladder, and Biliary Board Review Elizabeth Paine, MD July 18, 2015 ** I have...

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