pancreatic and biliary disease

Post on 02-Feb-2016

100 Views

Category:

Documents

4 Downloads

Preview:

Click to see full reader

DESCRIPTION

Pancreatic and biliary disease. Intrahepatic cholestasis of pregnancy. Presents with sometimes intense pruritis Functional disorder of bile secretion ALP mod high, Bili high, Transaminases

TRANSCRIPT

Pancreatic and biliary Pancreatic and biliary diseasedisease

Intrahepatic cholestasis of Intrahepatic cholestasis of pregnancypregnancy

• Presents with sometimes intense Presents with sometimes intense pruritispruritis

• Functional disorder of bile secretionFunctional disorder of bile secretion• ALP mod high, Bili high, ALP mod high, Bili high,

Transaminases <200, NORMAL Transaminases <200, NORMAL FUNCTIONAL TESTS, NORMAL PLTS, FUNCTIONAL TESTS, NORMAL PLTS, NORMAL COAGSNORMAL COAGS

• Watch for fat malabsorbtion, vitamin Watch for fat malabsorbtion, vitamin deficiencies (decreased bile salts)deficiencies (decreased bile salts)

Acute PancreatitisAcute Pancreatitis• Causes:Causes:

– EtOH and GallstonesEtOH and Gallstones• 75% of people with negative RUQ u/s have sludge or 75% of people with negative RUQ u/s have sludge or

micolithsmicoliths

– DrugsDrugs: Lasix, thiazides, estrogen, azathioprine, : Lasix, thiazides, estrogen, azathioprine, tetracycline, sulfa drugs, ddI, ddC, valproic tetracycline, sulfa drugs, ddI, ddC, valproic acid, 6-MP, L-asparginaseacid, 6-MP, L-asparginase

– HypertriglyceridemiaHypertriglyceridemia >1000mg/dl >1000mg/dl– Cystic fibrosisCystic fibrosis– HypercalcemiaHypercalcemia– TraumaTrauma– ERCPERCP

• Physical exam signs and symptoms: Physical exam signs and symptoms:

• Pain radiating from epigastrium Pain radiating from epigastrium “boring through” to the back“boring through” to the back

• Cullen’s signCullen’s sign

– blue around the umbilicusblue around the umbilicus

• Turner’s SignTurner’s Sign– purple or green discoloration of purple or green discoloration of

the flanks.the flanks.

Acute Pancreatitis (continued)

• Dx:Dx: – Elevated amylase and lipase, when Elevated amylase and lipase, when

amy >900 U/L and lipase >6000 amy >900 U/L and lipase >6000 U/L--97% specific U/L--97% specific

– Both elevated also in biliary dz, Both elevated also in biliary dz, perforation, renal insufficiencyperforation, renal insufficiency

– Amylase also high in parotitis, Amylase also high in parotitis, macroamylasemia, chronic EtOHmacroamylasemia, chronic EtOH

Acute Pancreatitis (continued)

• Initial Eval: RUQ U/S of biliary tree, CT Initial Eval: RUQ U/S of biliary tree, CT after 48 hours if not improved or after 48 hours if not improved or complication suspectedcomplication suspected– Don’t worry about MRCP vs ERCPDon’t worry about MRCP vs ERCP

• PrognosisPrognosis– APACHE II, Ranson’s, and Balthazar APACHE II, Ranson’s, and Balthazar

have been validated for mortalityhave been validated for mortality– Failure of one or more organ Failure of one or more organ

system is more clinically usefulsystem is more clinically useful

Acute Pancreatitis (continued)

57 yo woman s/p traumatic pancreatitis 8 mos 57 yo woman s/p traumatic pancreatitis 8 mos ago presents in F/U. She is asymptomatic. ago presents in F/U. She is asymptomatic. No meds. No EtOH. PE: epigastric fullness, No meds. No EtOH. PE: epigastric fullness, no pain. Amylase 180 U/L. Serial CT Scans no pain. Amylase 180 U/L. Serial CT Scans reveal an 8 cm cystic lesion with a well-reveal an 8 cm cystic lesion with a well-defined capsule in the pancreatic body. No defined capsule in the pancreatic body. No in 6 mos. Best Management? in 6 mos. Best Management?

A. ConservativeA. Conservative

B. Percutaneous drainageB. Percutaneous drainage

C. ERCP with internal drainageC. ERCP with internal drainage

D. Surgical drainageD. Surgical drainage

E. TPNE. TPN

Fluid Collections and Fluid Collections and PancreatitisPancreatitis

• Pancreatitic fluid collection high in amylase Pancreatitic fluid collection high in amylase may appear in 48 hours, usually resolvesmay appear in 48 hours, usually resolves

• LeftLeft pleural effusion common pleural effusion common• Fluid collection with clinical signs of Fluid collection with clinical signs of

infection should be aspirated to r/o infection should be aspirated to r/o infectioninfection

• Necrosis, within 2 weeks, if infected--Necrosis, within 2 weeks, if infected--surgical debridementsurgical debridement

• Severe pancreatitis with suspected Severe pancreatitis with suspected infection: empiric coverage with imipenem infection: empiric coverage with imipenem or cefuroximeor cefuroxime

Fluid collectionsFluid collections• PseudocystPseudocyst develops in 10-15% of pts, develops in 10-15% of pts,

requires 1-4 weeks to developrequires 1-4 weeks to develop– Complications of hemorrhage, rupture, fistula Complications of hemorrhage, rupture, fistula

formationformation– Drainage rec’d only if Drainage rec’d only if symptomaticsymptomatic or or infectedinfected

• AbscessAbscess develops 4-6 weeks post acute develops 4-6 weeks post acute attackattack– CT guided aspiration 90% accurateCT guided aspiration 90% accurate– Surgical debridementSurgical debridement

• Abdominal Pain and Abdominal Pain and amylase don’t amylase don’t always equal acute pancreatitis:always equal acute pancreatitis:– Acute cholecystitisAcute cholecystitis– Intestinal infarctionIntestinal infarction– DKADKA– Perforated UlcerPerforated Ulcer– SalpingitisSalpingitis– Ectopic pregnancyEctopic pregnancy– Perforated DiverticulumPerforated Diverticulum– MacroamylasemiaMacroamylasemia

Pancreatic Pearls

Chronic PancreatitisChronic Pancreatitis• 60-70% due to EtOH, usu >10 years.60-70% due to EtOH, usu >10 years.• Other causes CF, pancreas divisum, tumor, Other causes CF, pancreas divisum, tumor,

hyperparathyroidismhyperparathyroidism• Loss 80-90% of endocrine/exocrine function Loss 80-90% of endocrine/exocrine function

develop DM and steatorrheadevelop DM and steatorrhea• Increased risk for pancreatic cancerIncreased risk for pancreatic cancer• Dx:Dx:

– 1) Ca+ on AXR1) Ca+ on AXR– 2) CT or MRI or EUS or secretin test (bicarb<80 2) CT or MRI or EUS or secretin test (bicarb<80

mEq/L) mEq/L) – 3) ERCP3) ERCP

Complications of Chronic Complications of Chronic PancreatitisPancreatitis

• Gastric varicesGastric varices due to splenic vein due to splenic vein thrombosisthrombosis

• B12 malabsorptionB12 malabsorption• Brittle DMBrittle DM, prone to hypoglycemia , prone to hypoglycemia

secondary to loss of pancreatic glucagonsecondary to loss of pancreatic glucagon– No retinopathy or nephropathyNo retinopathy or nephropathy

• JaundiceJaundice due to obstruction of CBD as it due to obstruction of CBD as it runs through the pancreatic headruns through the pancreatic head

Chronic Pancreatitis Chronic Pancreatitis TreatmentTreatment

• Low fat diet, less than 25 g/dLow fat diet, less than 25 g/d• Pancreatic enzyme replacement has little Pancreatic enzyme replacement has little

or no effect on pain but can help with or no effect on pain but can help with steatorrheasteatorrhea

• Must be enteric coated or given with PPI Must be enteric coated or given with PPI because gastric acid inactivates thembecause gastric acid inactivates them

• If pancreatic duct is dilated, ERCP or If pancreatic duct is dilated, ERCP or surgery have shown improvement in painsurgery have shown improvement in pain

Pancreatitis PearlsPancreatitis Pearls• Microlithiasis Microlithiasis may cause recurrent may cause recurrent

pancreatitis in setting of no EtOH pancreatitis in setting of no EtOH and no gallstones on U/Sand no gallstones on U/S

• Splenic vein thrombosis in severe Splenic vein thrombosis in severe acute pancreatitis causes acute pancreatitis causes gastricgastric not not esophageal varicesesophageal varices

• ERCP ERCP – cholangitis/sepsischolangitis/sepsis– TB > 2.5 or dilated CBD on imagingTB > 2.5 or dilated CBD on imaging

Pancreatic NeoplasmsPancreatic Neoplasms

• Pancreatic AdenocarcinomaPancreatic Adenocarcinoma: :

– Classic presentation is painless Classic presentation is painless jaundicejaundice

– Risk Factors: chronic pancreatitis, Risk Factors: chronic pancreatitis, diabetes mellitus, smokers (2x), diabetes mellitus, smokers (2x), perhaps heavy EtOH usersperhaps heavy EtOH users

– >80% present with advanced disease>80% present with advanced disease– CT is first test, Double duct sign on CT is first test, Double duct sign on

ERCP, EUS good for stagingERCP, EUS good for staging– If no mets then Whipple procedure, If no mets then Whipple procedure,

rarely curativerarely curative

Cystic Neoplasms of the Cystic Neoplasms of the PancreasPancreas

• They happen and need biopsy to r/o They happen and need biopsy to r/o cystadenocarcinomacystadenocarcinoma

• All have malignant potential and All have malignant potential and need resectionneed resection

Other Pancreatic NeoplasiaOther Pancreatic Neoplasia

• GlucagonomaGlucagonoma– Plasma glucagon usually > Plasma glucagon usually >

1000pg/dl1000pg/dl– Scaly necrotizing dermatitis Scaly necrotizing dermatitis

• Necrolytic migratory erythema (NME)Necrolytic migratory erythema (NME)

– Wt lossWt loss– Anemia Anemia – HyperglycemiaHyperglycemia

• InsulinomaInsulinoma• VIPomaVIPoma

–““pancreatic cholera”, profuse pancreatic cholera”, profuse watery diarrheawatery diarrhea

• GastrinomaGastrinoma–ZE syndrome, elevated gastrin ZE syndrome, elevated gastrin

level (off PPI), think about MEN Ilevel (off PPI), think about MEN I

Other Pancreatic Neoplasia

Biliary DiseaseBiliary Disease• CholelithiasisCholelithiasis

– 20% females, 8% of males20% females, 8% of males– Obesity, PregnancyObesity, Pregnancy– Native American (Pima Indian), HispanicNative American (Pima Indian), Hispanic– Oral contraceptive use, Clofibrate tx, TPNOral contraceptive use, Clofibrate tx, TPN– Ileal disease (Crohn’s) or resectionIleal disease (Crohn’s) or resection– 80% of stones are radioluscent-cholesterol80% of stones are radioluscent-cholesterol

• good case-pt s/p gastric bypass, rapid good case-pt s/p gastric bypass, rapid wt loss--cholesterol stoneswt loss--cholesterol stones

CholelithiasisCholelithiasis• Pigment stones: Clonorchis, Sickle cell dz Pigment stones: Clonorchis, Sickle cell dz

(i.e., hemolysis)(i.e., hemolysis)• Dx: U/S 90% sensitive; HIDA best for Dx: U/S 90% sensitive; HIDA best for

determining cystic duct obstructiondetermining cystic duct obstruction• Tx:Tx:

– Symptomatic-Elective cholecystectomySymptomatic-Elective cholecystectomy– If not surgical candidate: Actigall--If not surgical candidate: Actigall--

cholesterol stones onlycholesterol stones only– Low suspicion for CBD stone: MRCP or Low suspicion for CBD stone: MRCP or

EUSEUS– High suspicion CBD stone: ERCPHigh suspicion CBD stone: ERCP

70 yo asymptomatic woman undergoes 70 yo asymptomatic woman undergoes abd U/S after a pulsatile mass is abd U/S after a pulsatile mass is found on physical exam. A 3 cm found on physical exam. A 3 cm aortic aneurysm and multiple aortic aneurysm and multiple gallstones are found. The next step gallstones are found. The next step in management is:in management is:

A.A. ERCP with sphincterotomyERCP with sphincterotomy

B.B. LithotripsyLithotripsy

C.C. Elective cholecystectomyElective cholecystectomy

D.D. Ursodeoxycholic AcidUrsodeoxycholic Acid

E.E. Observation/No treatmentObservation/No treatment

• Asymptomatic: Observation!!!Asymptomatic: Observation!!!

• CholangitisCholangitis

– Charcot’s Triad: Charcot’s Triad:

• Fever Fever

• Biliary colicBiliary colic

• JaundiceJaundice

– Tx:Tx:

• AbxAbx

• ERCP for sphincterotomyERCP for sphincterotomy

Other Diseases of the GBOther Diseases of the GB

• Calcifications of GB wall on X-RayCalcifications of GB wall on X-Ray highly suggestive of highly suggestive of cancercanceropen open cholecystectomycholecystectomy

• Emphysematous Emphysematous cholecystitischolecystitisemergent laparotomyemergent laparotomy– Abx-Gram- and anaerobes, no Abx-Gram- and anaerobes, no

ceftriaxone (biliary concretions)!ceftriaxone (biliary concretions)!

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• EPIDEMIOLOGYEPIDEMIOLOGY– 95% women95% women

– onset 30-65onset 30-65

– incidence 2.7 per 100,000 person yearsincidence 2.7 per 100,000 person years

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• EPIDEMIOLOGYEPIDEMIOLOGY– clustering in geographic areasclustering in geographic areas

– prevalence 1000x greater in families of a prevalence 1000x greater in families of a patient than general populationpatient than general population• no obvious inheritance patternno obvious inheritance pattern

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• SYMPTOMS / PRESENTATIONSYMPTOMS / PRESENTATION– abnormal LFT’sabnormal LFT’s

– fatiguefatigue

– prurituspruritus

– decompensated cirrhosisdecompensated cirrhosis

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• SYMPTOMS / PRESENTATIONSYMPTOMS / PRESENTATION– osteoporosisosteoporosis

– osteomalaciaosteomalacia

– steatorrheasteatorrhea

– xanthomataxanthomata

– hyperlipidemiahyperlipidemia

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• ASSOCIATED CONDITIONSASSOCIATED CONDITIONS– rheumatoid arthritis 5-10%rheumatoid arthritis 5-10%

– Sjogren’s 40-65%Sjogren’s 40-65%

– scleroderma 5-10%scleroderma 5-10%

– hypothyroidism 20%hypothyroidism 20%

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• PHYSICAL EXAMPHYSICAL EXAM– Skin hyperpigmentationSkin hyperpigmentation

– XanthomasXanthomas

– HepatomegalyHepatomegaly

– Kayser-Fleischer rings (rare)Kayser-Fleischer rings (rare)• not just Wilson’snot just Wilson’s

– Splenomegaly, ascites, etcSplenomegaly, ascites, etc

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• LABORATORY LABORATORY – Alk phos - may be only abnormalityAlk phos - may be only abnormality

– AST/ALT - normal or mild elevationAST/ALT - normal or mild elevation

– bilirubin - normal early, elevated laterbilirubin - normal early, elevated later

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• LABORATORY LABORATORY – Antimitochondrial antibodyAntimitochondrial antibody

• sensitivity 95%sensitivity 95%

• specificity 98%specificity 98%

– IgM - elevatedIgM - elevated

– EosinophiliaEosinophilia

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• LABORATORY LABORATORY – HyperlipidemiaHyperlipidemia

• elevated in > 50%elevated in > 50%

• mild LDL and VLDL elevationsmild LDL and VLDL elevations

• significantly elevated HDLsignificantly elevated HDL

• no known increased risk of CADno known increased risk of CAD

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• LIVER BIOPSYLIVER BIOPSY– Diagnosis often made prior to liver Diagnosis often made prior to liver

biopsybiopsy

– Biopsy may stage the degree of fibrosis Biopsy may stage the degree of fibrosis (0-4)(0-4)

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• NATURAL HISTORYNATURAL HISTORY– Mahl et al., Yale, Hepatology 1994Mahl et al., Yale, Hepatology 1994

– 250 patients, up to 24 years follow-up250 patients, up to 24 years follow-up

– Median survivalMedian survival• symptomatic - 7.5 yearssymptomatic - 7.5 years

• asymptomatic - 16 yearsasymptomatic - 16 years

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• TREATMENTTREATMENT– MalabsorptionMalabsorption

• Vitamin DVitamin D

• Vitamin AVitamin A

• Vitamin E - in advanced disease Vitamin E - in advanced disease

• Vitamin K - in advanced diseaseVitamin K - in advanced disease

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• TREATMENTTREATMENT– Drugs that didn’t workDrugs that didn’t work

• steroidssteroids

• azathioprineazathioprine

• penicillaminepenicillamine

• silymarin (milk thistle)silymarin (milk thistle)

• cyclosporine - effective but toxicitiescyclosporine - effective but toxicities

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• TREATMENTTREATMENT– Ursodeoxycholic acidUrsodeoxycholic acid

• UDCA decreases plasma and biliary UDCA decreases plasma and biliary endogenous bile acid concentrations endogenous bile acid concentrations

• UDCA may decrease immune-mediated UDCA may decrease immune-mediated destruction of hepatocytes by decreasing destruction of hepatocytes by decreasing the expression of HLA class I and II the expression of HLA class I and II antigens on hepatocytes, which may antigens on hepatocytes, which may diminish recognition by the immune systemdiminish recognition by the immune system

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• TREATMENTTREATMENT– Ursodeoxycholic acidUrsodeoxycholic acid

• 13-15 mg/day13-15 mg/day

• Moderate to severe diseaseModerate to severe disease

– decreased likelihood of transplantation or deathdecreased likelihood of transplantation or death

– 47% versus 66% at 4 years47% versus 66% at 4 years

– meta-analysis showed no benefit but many meta-analysis showed no benefit but many studies short-termstudies short-term

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• TREATMENTTREATMENT– Ursodeoxycholic acidUrsodeoxycholic acid

• Mild to moderate diseaseMild to moderate disease

– improvement in LFT’simprovement in LFT’s

– improved histologyimproved histology

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• TREATMENTTREATMENT– ColchicineColchicine

• mechanism unclearmechanism unclear

• dose 1 mg/daydose 1 mg/day

• well-tolerated in studieswell-tolerated in studies

• less effective than ursodiolless effective than ursodiol

• no clear benefit to combination therapyno clear benefit to combination therapy

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• TREATMENTTREATMENT– MethotrexateMethotrexate

• Dose 0.25 mg/kg PO qweekDose 0.25 mg/kg PO qweek

• Conflicting resultsConflicting results

• No long-term efficacy, safety dataNo long-term efficacy, safety data

Primary Biliary CirrhosisPrimary Biliary Cirrhosis

• TREATMENTTREATMENT– Liver TransplantationLiver Transplantation

• survival similar to other etiologies of liver survival similar to other etiologies of liver diseasedisease

• recurrence after liver transplant uncommonrecurrence after liver transplant uncommon

– similar appearance to chronic rejectionsimilar appearance to chronic rejection

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• Characterized by progressive Characterized by progressive inflammation, fibrosis, and inflammation, fibrosis, and stricturing of the intrahepatic and stricturing of the intrahepatic and extrahepatic bile ductsextrahepatic bile ducts

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• ““Secondary” sclerosing cholangitisSecondary” sclerosing cholangitis– prior biliary surgery prior biliary surgery

– choledocholithiasischoledocholithiasis

– intra-arterial chemo (floxuridine)intra-arterial chemo (floxuridine)

– bacterial cholangitis bacterial cholangitis

– AIDS cholangiopathyAIDS cholangiopathy

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• EPIDEMIOLOGYEPIDEMIOLOGY

– Prevalence 1- 6 per 100,000 in USPrevalence 1- 6 per 100,000 in US– 70% men70% men– mean age at diagnosis 40 yearsmean age at diagnosis 40 years

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• ASSOCIATION WITH IBDASSOCIATION WITH IBD– Among patients with PSC, ulcerative Among patients with PSC, ulcerative

colitis present in 25-90% (likely colitis present in 25-90% (likely 90%)90%)

– Among patients with ulcerative colitis, Among patients with ulcerative colitis, PSC present in 5%PSC present in 5%

– Less common but seen in Crohn’sLess common but seen in Crohn’s

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• PATHOGENESISPATHOGENESIS– Unknown but proposedUnknown but proposed

• autoimmune (given association with UC), autoimmune (given association with UC), common ANA, ASMA, ANCAcommon ANA, ASMA, ANCA

• inflammatory reaction in the liver and bile inflammatory reaction in the liver and bile ducts induced by chronic or recurrent entry ducts induced by chronic or recurrent entry of bacteria into the portal circulationof bacteria into the portal circulation

• ischemic damage to bile ductsischemic damage to bile ducts

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• DIAGNOSISDIAGNOSIS– Gold standard - ERCPGold standard - ERCP

• MRCP alsoMRCP also

– most patients asymptomatic with most patients asymptomatic with abnormal LFT’sabnormal LFT’s

– consider if IBD and elevated alk phosconsider if IBD and elevated alk phos

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• LABORATORYLABORATORY– alk phos & bili fluctuatealk phos & bili fluctuate

– AST/ALT normal or up to 200AST/ALT normal or up to 200

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• LABORATORYLABORATORY– elevated IgG 30%elevated IgG 30%

– elevated IgM 40-50%elevated IgM 40-50%

– p-ANCA 30-80%p-ANCA 30-80%

– HLA DRw52a 0-100%HLA DRw52a 0-100%

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• LIVER BIOPSYLIVER BIOPSY– sampling likely so not a good sampling likely so not a good

diagnostic tooldiagnostic tool

– may stage diseasemay stage disease

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• LOCATIONLOCATION– Intra- & extrahepatic bile ducts: 87%Intra- & extrahepatic bile ducts: 87%

– Intrahepatic bile ducts alone: 11%Intrahepatic bile ducts alone: 11%

– Extrahepatic bile ducts alone: 2%Extrahepatic bile ducts alone: 2%

Kaplan, NEJM 1995Kaplan, NEJM 1995

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• PRESENTATIONSPRESENTATIONS– Ascending cholangitisAscending cholangitis

– Abnormal LFT’sAbnormal LFT’s

– PruritusPruritus

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• NATURAL HISTORYNATURAL HISTORY– complications varycomplications vary

• biliary - ascending cholangitisbiliary - ascending cholangitis

• liver failure - portal hypertension, etcliver failure - portal hypertension, etc

• cholangiocarcinomacholangiocarcinoma

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• NATURAL HISTORYNATURAL HISTORY– mean survival 12 years after diagnosismean survival 12 years after diagnosis

• worse if symptomatic at diagnosisworse if symptomatic at diagnosis

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• TREATMENTTREATMENT– No proven medical therapyNo proven medical therapy

• D-penicillamine D-penicillamine • Steroids Steroids • Cyclosporine, Tacrolimus Cyclosporine, Tacrolimus • Methotrexate Methotrexate • Azathioprine, 6-MP Azathioprine, 6-MP • Ursodeoxycholic acid (small study, benefit Ursodeoxycholic acid (small study, benefit

to to dose) dose)

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• TREATMENTTREATMENT– Relieve biliary obstructionRelieve biliary obstruction

• risk of infectionrisk of infection

– Dominant strictureDominant stricture• r/o cholangiocarcinomar/o cholangiocarcinoma

• dilate or stentdilate or stent

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• TREATMENTTREATMENT– Liver TransplantationLiver Transplantation

• survival similar to other etiologies of liver survival similar to other etiologies of liver diseasedisease

• disadvantage if symptoms due to disadvantage if symptoms due to cholangitis and not liver failure in MELDcholangitis and not liver failure in MELD

– living donor?living donor?

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• CHOLANGIOCARCINOMACHOLANGIOCARCINOMA– 10-15% lifetime risk10-15% lifetime risk

– increased if IBD or cirrhosisincreased if IBD or cirrhosis

– contraindication to liver transplantcontraindication to liver transplant• protocol for aggressive chemotherapyprotocol for aggressive chemotherapy

Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

• CHOLANGIOCARCINOMACHOLANGIOCARCINOMA– Diagnosis difficultDiagnosis difficult

– CT/MRI - low sensitivityCT/MRI - low sensitivity

– CA 19-9 - low sensitivityCA 19-9 - low sensitivity

Autoimmune HepatitisAutoimmune Hepatitis

• EPIDEMIOLOGYEPIDEMIOLOGY– Female > Male 4:1Female > Male 4:1– Two peaksTwo peaks

• 20’s and Middle age20’s and Middle age• also seen in childrenalso seen in children

– 50-200 cases/million50-200 cases/million

Autoimmune HepatitisAutoimmune Hepatitis

• SYMPTOMS/PRESENTATIONSYMPTOMS/PRESENTATION– Abdominal painAbdominal pain– feverfever– anorexiaanorexia– malaisemalaise

Autoimmune HepatitisAutoimmune Hepatitis

• SYMPTOMS/PRESENTATIONSYMPTOMS/PRESENTATION– Acute or chronic diseaseAcute or chronic disease– 30 - 80 % cirrhotic at presentation30 - 80 % cirrhotic at presentation

Autoimmune HepatitisAutoimmune Hepatitis

• ASSOCIATED CONDITIONSASSOCIATED CONDITIONS– Arthropathy Arthropathy – Ulcerative colitisUlcerative colitis– Sjogren’s syndromeSjogren’s syndrome– Autoimmune thyroiditisAutoimmune thyroiditis– Fibrosing AlveolitisFibrosing Alveolitis– GlomerulonephritisGlomerulonephritis

Autoimmune HepatitisAutoimmune Hepatitis

• DIAGNOSISDIAGNOSIS

• PATHOLOGYPATHOLOGY– Interface hepatitisInterface hepatitis– Lymphocytes and Lymphocytes and plasma cellsplasma cells– Bridging necrosisBridging necrosis– CirrhosisCirrhosis

Autoimmune HepatitisAutoimmune Hepatitis

• CLASSIFICATIONCLASSIFICATION

• Type 1Type 1– ANA, anti-smooth muscle antibodyANA, anti-smooth muscle antibody

• Type 2Type 2– anti-LKM, liver cytosol antigenanti-LKM, liver cytosol antigen– girls, young womengirls, young women

Autoimmune HepatitisAutoimmune Hepatitis

• CLASSIFICATIONCLASSIFICATION

• Overlap SyndromeOverlap Syndrome– path path autoimmune hepatitis autoimmune hepatitis– serology serology PBC (+AMA) PBC (+AMA)

• Autoimmune cholangiopathyAutoimmune cholangiopathy– path path PBC PBC– serology serology ANA, asma ANA, asma

Autoimmune HepatitisAutoimmune Hepatitis

• TREATMENTTREATMENT– CorticosteroidsCorticosteroids

• acute managementacute management

– AzathioprineAzathioprine• goal - maintain remissiongoal - maintain remission• 2 mg/kg per day2 mg/kg per day• goal to d/c Prednisonegoal to d/c Prednisone

NASHNASH

• Nonalcoholic steatohepatitisNonalcoholic steatohepatitis

• Nonalcoholic fatty liver disease Nonalcoholic fatty liver disease (NAFLD) (NAFLD)

NASHNASH

• DEFINITIONDEFINITION– liver biopsy with macrovesicular liver biopsy with macrovesicular

steatosis & inflammation steatosis & inflammation

– minimal or no EtOHminimal or no EtOH

– negative serologic work-upnegative serologic work-up

NASHNASH

• EPIDEMIOLOGYEPIDEMIOLOGY– #1 cause of liver disease?#1 cause of liver disease?

– Women > menWomen > men

– Most 40-60Most 40-60

• reported in childrenreported in children

NASHNASH

• ASSOCIATED CONDITIONSASSOCIATED CONDITIONS– obesityobesity

– type 2 diabetes mellitustype 2 diabetes mellitus

– hyperlipidemiahyperlipidemia

– medicationsmedications

– obesity bypass proceduresobesity bypass procedures

– TPNTPN

NASHNASH

• DIAGNOSISDIAGNOSIS– liver biopsy liver biopsy

• confirms or excludes dxconfirms or excludes dx

• negative serologic work-upnegative serologic work-up

NASHNASH

• TREATMENTTREATMENT– treat underlying conditiontreat underlying condition

• obesity, DM, lipidsobesity, DM, lipids

– stay tuned...stay tuned...

Alcoholic HepatitisAlcoholic Hepatitis

• EPIDEMIOLOGYEPIDEMIOLOGY– alcoholalcohol

• cirrhosis cirrhosis 80 gm/d EtOH for 10-20 years 80 gm/d EtOH for 10-20 years

– other factorsother factors• female genderfemale gender

– reduced gastric ADH activityreduced gastric ADH activity

– sizesize

• co-existing HBV, HCVco-existing HBV, HCV

Alcoholic HepatitisAlcoholic Hepatitis

• SYMPTOMSSYMPTOMS– feverfever

– hepatomegalyhepatomegaly

– jaundicejaundice

– anorexiaanorexia

Alcoholic HepatitisAlcoholic Hepatitis

• DIAGNOSISDIAGNOSIS– liver biopsyliver biopsy

• steatosis, inflammationsteatosis, inflammation

– AST > 2x ALTAST > 2x ALT

Alcoholic HepatitisAlcoholic Hepatitis

• PROGNOSISPROGNOSIS– liver failureliver failure

• coagulopathycoagulopathy

• encephalopathyencephalopathy

– Discriminant function = Discriminant function =

(4.6 x [PT - control PT]) + (serum bili, mg/dl)(4.6 x [PT - control PT]) + (serum bili, mg/dl)

– DF > 32: mortality 35-45%DF > 32: mortality 35-45%

Alcoholic HepatitisAlcoholic Hepatitis

• TREATMENTTREATMENT– Supportive careSupportive care

– Who gets steroids?Who gets steroids?

• DF > 32DF > 32

• EncephalopathyEncephalopathy

• No infection, no GI bleedingNo infection, no GI bleeding

Abnormal Liver TestsAbnormal Liver Tests

• Hepatocellular - AST, ALT Hepatocellular - AST, ALT • Cholestatic - alkaline phosphatase Cholestatic - alkaline phosphatase

– bilirubin can be elevated in bothbilirubin can be elevated in both

Abnormal Liver TestsAbnormal Liver Tests

• AST 124 U/LAST 124 U/L

• ALT 157 U/LALT 157 U/L

• Alk phos 149 U/LAlk phos 149 U/L

• T. bili 1.6 mg/dlT. bili 1.6 mg/dl

Abnormal Liver TestsAbnormal Liver Tests

• AST/ALT mildly elevated (<250 U/L)AST/ALT mildly elevated (<250 U/L)– chronic viral hepatitischronic viral hepatitis

• HCV Ab, HBV surface antigenHCV Ab, HBV surface antigen

– alcoholic hepatitis (AST > ALT)alcoholic hepatitis (AST > ALT)• drug reaction - consider d/cdrug reaction - consider d/c

• NSAIDs, statins, antibiotics (INH)NSAIDs, statins, antibiotics (INH)

– hemochromatosis (Fe/TIBC > 45%)hemochromatosis (Fe/TIBC > 45%)

– steatosis, steatohepatitissteatosis, steatohepatitis

Abnormal Liver TestsAbnormal Liver Tests

• AST/ALT mildly elevated (<250 U/L)AST/ALT mildly elevated (<250 U/L)– less common causesless common causes– autoimmune hepatitis autoimmune hepatitis

• ANA, ASMA, a-LKMANA, ASMA, a-LKM

– Wilson’s diseaseWilson’s disease• age < 40; check ceruloplasmin, K-F ringsage < 40; check ceruloplasmin, K-F rings

– Alpha-1-antitrypsin deficiencyAlpha-1-antitrypsin deficiency• emphysema; alpha-1-antitrypsin levelemphysema; alpha-1-antitrypsin level

Abnormal Liver TestsAbnormal Liver Tests

• AST/ALT mildly elevated (<250 U/L)AST/ALT mildly elevated (<250 U/L)– non-hepatic causesnon-hepatic causes

– muscle sourcemuscle source

– hypothyroidismhypothyroidism

– celiac diseaseceliac disease• diarrhea, Fe deficiency; anti-endomysial IgAdiarrhea, Fe deficiency; anti-endomysial IgA

– adrenal insufficiencyadrenal insufficiency

Abnormal Liver TestsAbnormal Liver Tests

• AST/ALT mildly elevated (<250 U/L)AST/ALT mildly elevated (<250 U/L)– negative serologic work-upnegative serologic work-up

– consider liver biopsy if persistently consider liver biopsy if persistently abnormalabnormal

Abnormal Liver TestsAbnormal Liver Tests

• AST 1480 U/LAST 1480 U/L

• ALT 1704 U/LALT 1704 U/L

• Alk phos 229 U/LAlk phos 229 U/L

• T. bili 4.8 mg/dlT. bili 4.8 mg/dl

Abnormal Liver TestsAbnormal Liver Tests

• AST/ALT AST/ALT > 10x ULN > 10x ULN– acute viral hepatitisacute viral hepatitis

• hep A IgMhep A IgM

• hep B core IgMhep B core IgM

• hep Dhep D

– autoimmune hepatitisautoimmune hepatitis– shock liver (ischemic hepatitis)shock liver (ischemic hepatitis)– drug or toxin (drug or toxin (acetaminophenacetaminophen))

Abnormal Liver TestsAbnormal Liver Tests

• AST/ALT AST/ALT > 10x ULN > 10x ULN– Rarer formsRarer forms

– acute Budd-Chiari syndromeacute Budd-Chiari syndrome

– veno-occlusive diseaseveno-occlusive disease

– HELLP syndromeHELLP syndrome

– acute fatty liver of pregnancyacute fatty liver of pregnancy

Abnormal Liver TestsAbnormal Liver Tests

• AST/ALT AST/ALT > 10x ULN > 10x ULN– Acute Liver FailureAcute Liver Failure

– Elevated PTElevated PT factor Vfactor V

– EncephalopathyEncephalopathy• If discharge patient, clarify supervisionIf discharge patient, clarify supervision

– Transfer to Transplant CenterTransfer to Transplant Center

Abnormal Liver TestsAbnormal Liver Tests

• BilirubinBilirubin– unconjugatedunconjugated

• Overproduction of bilirubin or impaired Overproduction of bilirubin or impaired uptake, conjugationuptake, conjugation

• tightly bound to albumin so not filtered and tightly bound to albumin so not filtered and not present in urine not present in urine

– conjugatedconjugated• impaired excretion into bile ductulesimpaired excretion into bile ductules

• present in the urinepresent in the urine

Abnormal Liver TestsAbnormal Liver Tests

• Unconjugated bilirubinUnconjugated bilirubin– hemolysishemolysis

– impaired bilirubin uptakeimpaired bilirubin uptake• CHFCHF

• Portosystemic shuntsPortosystemic shunts

• Certain drugs - rifampin, probenecidCertain drugs - rifampin, probenecid

Abnormal Liver TestsAbnormal Liver Tests

• Unconjugated bilirubinUnconjugated bilirubin– hemolysishemolysis

– impaired bilirubin uptakeimpaired bilirubin uptake

– impaired bilirubin conjugationimpaired bilirubin conjugation• Gilbert’sGilbert’s

• Crigler-Najjar Crigler-Najjar

• hyperthyroidismhyperthyroidism

• cirrhosiscirrhosis

• Wilson’s diseaseWilson’s disease

Abnormal Liver TestsAbnormal Liver Tests

• Unconjugated bilirubinUnconjugated bilirubin– Gilbert’s SyndromeGilbert’s Syndrome

• Uridinediphosphoglucuronate Uridinediphosphoglucuronate glucuronosyltransferases (UGTs) mediate glucuronosyltransferases (UGTs) mediate glucuronidation glucuronidation

• Mutation of UGT1AMutation of UGT1A

• 9% western world homozygous9% western world homozygous

• 30% heterozygous30% heterozygous

– Slightly higher biliSlightly higher bili

Abnormal Liver TestsAbnormal Liver Tests

• Unconjugated bilirubinUnconjugated bilirubin– Gilbert’s SyndromeGilbert’s Syndrome

• BilirubinBilirubin

– Usually < 3 mg/dl, rarely > 6Usually < 3 mg/dl, rarely > 6

• FactorsFactors

– FastingFasting

– Stress (surgery, etc)Stress (surgery, etc)

– InfectionInfection

Abnormal Liver TestsAbnormal Liver Tests

• Unconjugated bilirubinUnconjugated bilirubin– Gilbert’s SyndromeGilbert’s Syndrome

• DiagnosisDiagnosis

– rise in bilirubin concentration following a rise in bilirubin concentration following a low lipid, 400 kcal diet low lipid, 400 kcal diet

– administration of IV nicotine administration of IV nicotine

– seldom necessary in clinical practiceseldom necessary in clinical practice

Abnormal Liver TestsAbnormal Liver Tests

• Conjugated bilirubinConjugated bilirubin– Extrahepatic cholestasisExtrahepatic cholestasis

• PSCPSC

• intrinsic & extrinsic tumorsintrinsic & extrinsic tumors

• AIDS cholangiopathyAIDS cholangiopathy

• cholelithiasischolelithiasis

• parasites - ascaris lumbricoides, liver flukesparasites - ascaris lumbricoides, liver flukes

Abnormal Liver TestsAbnormal Liver Tests

• Conjugated bilirubinConjugated bilirubin– Intrahepatic cholestasisIntrahepatic cholestasis

• Viral hepatitisViral hepatitis

• Alcoholic hepatitisAlcoholic hepatitis

• Nonalcoholic fatty liver diseaseNonalcoholic fatty liver disease

• PBCPBC

• Drugs, toxinsDrugs, toxins

• SepsisSepsis

Abnormal Liver TestsAbnormal Liver Tests

• Conjugated bilirubinConjugated bilirubin– Intrahepatic cholestasisIntrahepatic cholestasis

• Infiltrative diseases - sarcoidosis, amyloid, Infiltrative diseases - sarcoidosis, amyloid, lymphomalymphoma

• TPNTPN

• PregnancyPregnancy

• CirrhosisCirrhosis

• Dubin Johnson, Rotor syndromeDubin Johnson, Rotor syndrome

Abnormal Liver TestsAbnormal Liver Tests

• AST 32 U/LAST 32 U/L

• ALT 29 U/LALT 29 U/L

• Alk phos 472 U/LAlk phos 472 U/L

• T. bili 1.0 mg/dlT. bili 1.0 mg/dl

• (5’-nucleotidase (5’-nucleotidase ))

Abnormal Liver TestsAbnormal Liver Tests

• Elevated alkaline phosphataseElevated alkaline phosphatase– primary biliary cirrhosisprimary biliary cirrhosis

– primary sclerosing cholangitisprimary sclerosing cholangitis

– partial bile duct obstructionpartial bile duct obstruction

– drugs (androgenic steroids, phenytoin)drugs (androgenic steroids, phenytoin)

– sarcoidosissarcoidosis

– metastatic cancermetastatic cancer

top related