Abim hepatology Board Review 6-10-09 2009 abim exam

ABIM Hepatology Board Review

• 6-10-09

2009 ABIM exam

2008 UNC ITE

• Commonly missed Hepatology topics

• Diagnose and Manage Gilbert’s Syndrome
• Elevated indirect bilirubin, esp. during stress or other illness
• Genetic test now avail, no treatment needed
• Diagnose and treat AIP
• Acute intermittent visceral pain and neurologic sx
• Urine porphyrins (urine PBG – spot, followed by 24hr ALA PBG and porphyrin)
• Rx: avoid stressors that exacerbate dz, IV Hemin products
• Watch out for vampires
• Red urine, phosphorescent teeth, photosensitive skin

Roadmap

• Abnormal LFT’s

• NAFLD/NASH

• ETOH Liver Disease

• Viral Hepatitis

• AIH/PBC/PSC

• Cirrhosis and its complications

• ALF

• Transplant

• Liver disease in Pregnancy

• Genetic Liver disease

Abnormal LFT’s

• Asymptomatic patient

• History!

• Conceptualize if the pattern

• Hepatocellular injury (elevated AST, ALT)
• Cholestatic injury (elevated Tbili, AP, GGT)
• Assess synthetic function (Tbili, INR +/- Cr)

• Most common causes are NAFLD, chronic hepatitis and ETOH

NAFLD/NASH

• NAFLD encompasses simple steatosis to NASH to cirrhosis

• Highly prevalent ~30%
• Not all steatosis progresses
• NASH is high risk to progress

• Risk Factors

• DM, HTN, Hyperlipidemia,Central obesity

• Rx is to control risk factors

Steatohepatitis

• Histologic findings include

• Macrovesicular steatosis
• Cytologic ballooning
• Mallory bodies (eosinophilic concretions within ballooned hepatocytes)
• Scattered lobular inflammation
• Question #87

ETOH Liver Disease

• AST:ALT ratio 2:1 – 3:1

• AST rarely exceeds 300-400 unless another process is present

• Elevated GGT, AP may be normal

• AFLD

• ETOH hepatitis carries 50% mortality rate

• Rx Pentoxiphylline 400 TID or prednisilone 40 QD x 1 month
• Question #78
• Question #88

Viral Hepatitis

• Acute Viral Hepatitis

• Most commonly A & B, but all hepatotropic viruses can cause an acute illness

• Tests

• in general IgM for acute disease and IgG or total for chronic disease

• A : HAV IgM

• B : HBsAg, HBc IgM

• C : HCV Ab*, HCV RNA

• D : HBsAg*, HDV IgM

• E : HEV IgM – RNA test now avail

• Question #13
• Question # 33

Viral Hepatitis

• Chronic Viral Heptitis

• A & E do not have a chronic form
• D can only occur in setting of Chronic B

• HBV

• Only ~5% of adults get chronic HBV
• 90% of neonates get chronic HBV
• 20-30% progress to cirrhosis
• Rx: INF vs. oral nucleoside analogues
• Only treat those with active replication
• Usually long term – few seroconvert

Viral Hepatitis

• HCV

• 70-80% exposed develop chronic infection
• Current #1 indication for OLT in U.S.

• Current therapy is Peg-INF and ribavirin

• Genotype 1 most common in U.S. and most difficult to treat
• 48 weeks of weekly sq injections and BID ribavirin
• Monitor mental health (depression/suicide)
• Cytopenias
• Thyroid dysfunction
• Flu-like symptoms
• Fatigue
• Question #73

AIH/PBC/PSC

• AIH

• May present in asymptomatic patient or a life-threatening flare
• 30-50 y.o. WF, AST/ALT 400-500
• +ANA, elevated IG levels. Biopsy required for Dx
• Plasma cell infiltrate, “interface hepatitis”
• Treat with prednisone and long term AZA
• Recurs after OLT, but good survival

AIH/PBC/PSC

• PBC

• 90% cases are women
• Puritus and fatigue most common symptoms
• Disease of mostly intrahepatic bile ducts
• Elevated AP, GGT, +AMA, +ANA
• Some patients have clinically identical dz but AMA(-)
• “autoimmune cholangiopathy” or “seronegative PBC”
• Rx Urso 12-15mg/Kg/day

AIH/PBC/PSC

• PSC

• Cholestatic LFT’s, +pANCA, +ASMA, ERCP required for dx (MRCP?)
• Large duct disease
• Usually widespread but patients may have a “dominant stricture”
• “Beads on a string” found at ERCP
• 70-80% also have IBD (UC)
• 10-15% develop cholangiocarcinoma
• Rx Urso, treat dominant strictures, treat episodes of cholangitis, OLT
• Question #25

Etiologies of Cirrhosis

• Viral

• Hepatitis B
• Hepatitis C

• Toxic

• Alcohol, MTX

• Metabolic

• Non Alcoholic Fatty Liver disease (NAFLD)

• Biliary

• PSC
• PBC

Pathophysiologic Changes in Cirrhosis

• The liver is unable to process bile resulting in jaundice and scleral icterus

• Bile pigments deposit in the skin causing pruritus

• The liver cannot produce clotting factors resulting in coagulopathy

• The liver cannot make albumin contributing to ascites and edema

Assessing the Severity of Cirrhosis

• Liver biopsy can give grade of inflammation and stage of fibrosis

• Model for End-Stage Liver Disease (MELD) uses objective data to predict 3 month survival

• Used in transplant selection
• Bilirubin, INR, Creatinine

• Child-Pugh score

• Divides cirrhotics into class A,B,C to predict 1-2 year mortality
• Bilirubin, INR, Albumin, Ascites, Encephalopathy

Complications of Cirrhosis

• Once a patient develops complications of cirrhosis they have decompensated disease.

• Variceal hemorrhage
• Ascites
• Spontaneous bacterial peritonitis
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• Portopulmonary hypertension
• Hepatocellular carcinoma
• Hepatic encephalopathy

Variceal Hemorrhage

• Most devastating complication of cirrhosis and portal hypertension

• Occurs in 25-40% of cirrhotics
• Prior to current therapy, mortality 30% for a single episode and only 1/3 survived for one year afterwards
• Mortality remains high

Variceal Hemorrhage

• Therapy

• Prevention!
• All patients with cirrhosis need a screening EGD
• Non selective beta-blockers reduce portal hypertension
• Endoscopic variceal ligation now accepted as primary prophylaxis as well in new AASLD guidelines

Variceal Hemorrhage

• Acute bleeding

• Endoscopic variceal ligation “banding”
• Sclerotherapy
• Minnesota tube
• Transjugular Intrahepatic Portosystemic Shunt “TIPS”
• Question #4

Ascites

• Cirrhosis (75%)

• Most common cause of ascites
• Most common complication of cirrhosis
• Other causes occur more frequently in cirrhotics

• Malignancy (10%)

• Cardiac (3%)

• TB (2%)

• Pancreatic Ascites(1%)

• SAAG calculation

SAAG

Ascites

• Low Sodium Diet (<2g/d)

• Managed with Diuretics

• Furosemide for volume
• Spironolactone for renin-angitensin system and some diuresis

• Must watch renal function and sodium closely

• Diuretic dosing often limited by hyponatremia
• Diuretic induced acute or chronic renal failure is common

• Diuretic refractory/resistant ascites requires another intervention

• TIPS, Denver shunt, routine LVP

Spontaneous Bacterial Peritonitis

• Peritoneal fluid with >250 PMN

• Typically due to bacterial translocation from gut

• E. coli is the most common pathogen

• Treat with 3rd gen. cephalosporin or quinolone

• Secondary Prophalaxis

• Norfloxacin 400mg qd
• Ciprofloxacin 750mg q week
• SMZ-TMP never has been tested in a trial with mortality but used frequently

Hepatic Encephalopathy

• Reversible decrease in neurologic function

• May be subtle from sleep disturbance to outright coma with focal neurologic signs
• Often a precipitating factor
• Infection
• Volume depletion/dehydration
• Hyponatremia
• Acidosis
• drugs

Pathophysiology of Hepatic Encephalopathy

• Nitrogenous substances derived from the gut adversely affect brain function

• Ammonia is the best known metabolite associated with HE

• Compounds gain access to the systemic circulation via decreased metabolism in liver and/or portosystemic shunts

• Experimental models describe derangements in glutamine, serotonin, GABA, and catecholamine metabolism.

Encephalopathy

• First line therapy is lactulose/bowel catharsis

• Theoretically lactulose acidifies bowel and prevents NH3 absorption

• Non absorbable ABX

• Rifaximin
• Metronidazole
• Neomycin

• Misc

• Zinc
• Special diets (medium/branched chain FA)

Hepatorenal Syndrome

• Development of acute renal failure in a patient with cirrhosis or fulminant hepatic failure

• End stage of a sequence of events that reduces perfusion of kidneys

• Clinical presentation

• Oliguiria
• Low urine sodium (often undetectable)
• Bland urine sediment
• Systemic hypotension
• Absence of another cause of renal failure

Hepatorenal Syndrome

• Type I

• 50% reduction of plasma creatinine clearance to a level below 20ml/min or doubling of serum creatinine in less than 2 weeks. Rapidly fatal.

• Type II

• Less severe than type I, more indolent and primarily characterized by diuretic refractory ascities.

Hepatorenal Syndrome

• Treatment options

• Liver transplant. Renal dysfunction improves after transplant.
• Midodrine (alpha-1 agonist) and Octreotide (somatostatin analog)
• Midodrine promotes systemic vasoconstriction, octreotide inhibits vasodilitaion of splanchnic vasculature. End result is improved perfusion of kidneys.
• Norepinephrine
• Vasopressin analogs
• TIPS (controversial)
• Dialysis (only as a bridge to transplant)

Hepatorenal Syndrome

• Prevention is key in certain clinical situations

• SBP – administration of albumin
• Primary prophylaxis for SBP in patients with low albumin also reduces HRS
• Alcoholic Hepatitis – use of steroids or pentoxiphylline

Hepatopulmonary Syndrome

• HPS

• Liver disease
• Increased alveolar-arterial gradient on room air
• Evidence of intrapulmonary vascular dilitations (intrapulmonary shunting)

• Platypnea and orthodeoxia are the major symptom and sign

• No consistent correlation with severity of liver disease

• Presence of HPS independently worsens prognosis of liver disease
• Spider angiomata and hyperdynamic circulation associated with HPS

Hepatopulmonary Syndrome

• Etiology

• Nitric oxide plays a central role in animal models

• Diagnosis

• Impaired DLCO on PFT’s, evidence of intrapulmonary shunt on contrast enhanced echocardiography, technetium labeled macro-aggregated albumin scan, and pulmonary angiography

• Treatment

• Minimal role for medical therapy
• Supplemental oxygen
• Liver transplant best treatment, reversal of shunting in most patients post transplant.

Portopulmonary Hypertension

• 1998 WHO symposium defined pulmonary HTN as mean PAP >40mmHG (TR jet 3.0-3.5 m/s) and portopulmonary HTN as pulm HTN in association with portal HTN without other risk factors for secondary pulmonary HTN.

• Etiology unknown

• Presumed vasoactive substances like seratonin, IL-1, endothelin-1, glucagon, secretin, thromboxane B2 and VIP that are produced by splanchnic circulation and not metabolized by liver plus a genetic predisposition.

Portopulmonary Hypertension

• Diagnosis via echocardiography or right heart catheterization

• Treatment

• Similar to idiopathic pulm HTN: anticoagulants, vasodilators, prostacyclins (Flolan). No good data, many contraindications.

Hepatocellular Carcinoma

• 5th most common cancer worldwide

• nearly 1,000,000 new cases annually as of 2007
• increasing incidence

• HBV single most important etiologic factor worldwide

• Risk increased without cirrhosis

• HCV and ETOH main risk factors in West

Hepatocellular Carcinoma

• Diagnosis possible without biopsy

• AFP not sensitive or specific, levels over 200ng/dL highly suspicious for HCC
• characteristic appearance with contrasted imaging
• HCC has arterial blood supply that demonstrates uptake during early arterial phase and contrast washout in the delayed venous phase
• biopsy is warranted in a liver mass larger than 2 cm without typical radiographic findings and no elevation in AFP

Hepatocellular Carcinoma

• Early Arterial Phase CT

• heterogeneously enhancing mass 4-5 cm

• Portal Venous Phase CT

• Decreased enhancement, iso-enhancing with liver
• Question #37

TIPS

• Transjugular Intrahepatic Portosystemic Shunt

• Shunt placed between hepatic vein and portal vein with goal of reducing portal hypertension
• Utilized for varices and refractory ascites
• Controversial for HRS and HPS
• Lethal for PP-HTN
• Complications include hepatic encephalopathy and hepatic failure

ALF

• Encephalopathy that develops within 8 weeks of acute severe liver injury

• Definition has transplant implications
• Acetaminophen most common in U.S.
• Know the difference between labs showing liver injury and synthetic dysfunction
• e.g. decrease in transaminases after acute HBV infection, but INR drifting upwards…
• Rapid referral to transplant center
• Question #43

Transplant

• Status 1 : Acute liver failure

• Status 2 : MELD scoring system

• TB, Cr, INR.
• Score 6-40. Eval @12, transpalnt over 15.
• Most centers transplant in 22-26 range

• Status 7 : Inactive

• Question #5
• Question #43

Liver disease in Pregnancy

• HEV, VZV, HSV hepatitis may be more severe, but risk of acquisition unchanged

• Cholestatsis of pregnancy

• Puritus can be severe
• Check fasting bile acids
• Close monitoring (mom is ok, risk to fetus), urso, deliver baby

• HELLP

• Hemolysis, elevated LFTs, low platelets
• Deliver baby

• Acute fatty liver of pregnancy

• Large, acutely swollen liver on U/S
• Deliver baby
• Question #29

Genetic Liver disease

• Hemachromatosis

• C282Y homozygote or C282Y / H63D heterozygote
• Ferritin >1000, % sat >90%
• Rx phlebotomy or chelation

• Wilson’s Disease

• Ceruloplasm is LOW!
• KF rings, 24 hr urine copper confirm dx

• A1AT

• Homozygous ZZ most common genetic liver disease in kids
• Often emphysema develops later
• Question #19