PANCREATIC & BILIARY DISORDERS IN HIV Dr.BujjiBabu ,M.D Consultant HIV Physician Dr.Bujjibabu HIV Clinic

Pancreatic Disorders Acute Pancreatitis Chronic Pancreatitis(On Autopsy usually) Pancreatic Neoplasm – Lymphoma Kaposi’s Sarcoma

Acute Pancreatitis Hyperamylasemia in ~40% of all AIDS Clinical pancreatitis < 10% of all Even lesser in those not on drugs Usually mild unless due to drug Drugs account for 40-50% cases Hyperamylesemia(<3ULN) can occur without pancreatitis

Mechanism HIV itself Opportunistic Infections CMV,HSV,MAC,Crypaococcus, Toxoplasma, Myco.tuberculosis, Candida Usually involves other organs also Pancreatic neoplasms:Lymphoma, Kaposi Sarcoma 5% of AIDS; Pancreatitis rare Usually in setting of wide spread disease DRUGS

Drugs causing Acute Pancreatitis in HIV Co-trimaxozole Pentamidine (I.V. or Inhalational) Dideoxylnosine (ddl) Clinical course mild,severe or fatal ddl : >40% develop asymptomatic hyperamylasemia > 20% Clinical Pancreatitis (Usually after several months Advanced AIDS & Previous H/o Pancreatitis – high risk Dose reduction decreases the risk Careful monitoring of glucose

CECT : Acute pancreatitis in HIV

Diagnosis Clinical features Elevated amylase & lipase Imaging (USG & or CT) Occasionally FNAC for etiology

Acute pancreatitis in HIV Cappell et al Gut,1995 Ac.Panc+HIV(44) Ac. Pancreatitis(44) Clinical Features Similar Anemia More Less hypoalbuminemia Leucopenia Fever,Diarrhoea, hepatomegaly More incidence Drug Induced 18 2 Gall stone 22 Severe course (Prolong stay & death) 12 Ranson & Glasgow Poor Good APACHE II

Acute Pancreatitis in 939 HIV cases Conclusion Incidence 4.7% in HIV +ve patients Clinical features similar in 2 groups High frequency of drug induced and low frequency of gall stones High frequency of HIV related etiology AIDS and Leukopenia – Severe hospital course APACHE II –Good for predicting severity, prognosis & death Cappell et al GUT; 1995

Acute pancreatitis in HIV: Total No: 73 Drug Induce – 46% Idiopathic 26% 25% had severe pancreatitis by Atlanta 15% Severe hospital course & death APACHE –II – Best (Accuracy 75%) Glasgow & Ranson – Poor Conclusion: AP in HIV Pts. had similar outcome as general population & APACHE-II is useful and applicable in this group. Gan et al Am J Gastro 2003

Biliary Disorders in HIV Patients Non HIV associated : Stones, benign strictures, ascariasis ,neoplasms etc Acalculus cholecystitis AIDS cholangiopathy

CBD Stone in an AIDS Patient

Periampullary Ca

Acalculus cholecystitis in AIDS Uncommon – Few case reports only CMV & cryptosporidum usually Young & ambulatory patients with RUQ pain and abnormal LFT USG or scintigraphy for diagnosis Cholecystectomy is therapeutic

AIDS Cholangiopathy Classification (Cello JP et al 1987) Papillary stenosis Sclerosing cholangitis Pap. stenosis with extra and Intrahepatic sclerosing cholangitis:most common Long extrahepatic bile duct stricture (>1-2cms)

AIDS Cholangiopathy : Clinical Features Mean age 36-37 years AIDS usually labeled 1-2 years before RUQ & /or epigastric pain : 64-88% Fever : 20-65% Cholestasis : 75 – 80% ALP(>2ULN) : Almost all S.bilirubin usually normal or mild increase USG/CT – Dilated ducts(Intra &/or extra hepatic) ERCP : Gold standard

ERCP confirmed cholangiopathy USG Normal in 10/38 CT Normal in 5/17 ERCP Normal USG Abnormal - 1/10 CT Abnormal - 0/9

CECT : AIDS Cholangiopathy

Pathogenesis Possibly multifactorial Infections – CMV, cryptosporidium, microsporidium & HIV Immunosuppression HIV itself Genetic predisposition Not clear 50% have no identifiable pathogen Neoplasms – Lymphoma & Kaposi’s sarcoma

CMV & AIDS >50% AIDS have CMV viremia > 90% AIDS have e/o CMV(Autopsy) >50% AIDS have CMV viremia 5-44% AIDS +extrahepatic CMV Also have hepatic CMV inclusions 33% of CMV Viremia have abnormal LFT 33% of abnormal LFT will have abnormal bile ducts

Cryptosporidium & AIDS Cholangiopathy 82 HIV patients acquired cryptosporidiosis in an outbreak in Milwaukee ’93 29% developed biliary symptoms 10 had ERCP – All had AIDS cholangiopathy Suggest biliary cryptosporidiosis CD4 < 50 high risk and all died within 1 year Vakil et al;NEJM:1996

ERCP in AIDS cholangiopathy Papillary stenosis & dilated CBD & IHD Beaded appearance (Intramural/Submucosal edema or Infiltrates) Left hepatic duct more often involved Irregular sacculations containing debris & mucosal sloughs Markedly irregular ducts and pruning of smaller intrahepatic ducts CBD Irregularly strictured and rarely > 4-5 mm diameter >50% have pap.stenosis plus sclerosing cholangitis

ERCP : Papillary stenosis in HIV

AIDS Cholangiopathy

TREATMENT Papillary Stenosis Endoscopic sphincterotomy Balloon sphincteroplasty CBD stenting Lymphoma or Kaposi Sarcoma -Chemotherapy Acalculus cholecystitis - Cholecystectomy Antiviral drugs if CMV or HSV

AIDS cholangiopathy : Natural history Forbes et al Gut 1993 ERCP proven AIDS cholangiopathy : 20 cases Median age 33.5 yrs (range 27-50 yrs) Abd.pain 100%,Wt. Loss 90%,Diarrhea 55%,Skin KS 20%, Hepatomegaly 25%,Abn.LFT 80%,Liver Bx. Scl. Cholangitis 50%, Abn.USG50%(CBD dilated40%,thick25%),CD4 median24/cmm Cryptosporidium: 13(Stools12, Ampulla Bx.2,Intestinal Bx.5) CMV at some site:6(Ampulla Bx.3,Intestine Bx.5,Retina 1) Cryptosporidium + CMV : 4 ERCP : Extrahepatic 2,Intrahep 3,Wide spread 15, Cystic lesion 2 Panc duct : Marked dialation 3,Minor changes 4 17/20 Died(median 7month), 3Alive at 10,11 & 21 months Poor correlation with CD4 counts & Increased age protective

Data on HIV patients n=227 HIV related symptoms : 75% GIT symptoms : 56% Abdominal pain : 08% Jaundice/Icterus : 2.2% Hepatomegaly : 9.2% Spleenomegaly : 1.3% Hepatospleenomegaly : 6.2% Abnormal LFT : 6.2% Acute pancreatitis : 2 cases HIV cholangiopathy : 2 cases Pancreatic pseudocyst : 1 case

Diagnosis of AIDS Cholangiopathy CLINICAL FEATURES LFT Normal Abnormal Look for other causes USG &/or CT If no other cause Dilated ducts ERCP with histology & bile c/s Endoscopic TT

Conclusions Pancreatitis in HIV is no different than in non-HIV patients & should be treated in the same way Careful monitoring & selection of drug reduces incidence AIDS cholangiopathy is a grave situation with a very high mortality Maintenance of CD4 counts with HAART therapy appears to have reduced the incidence

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