1. Non Cirrhotic Portal Hypertension: A Serious Hepatic Complication in HIV and the Use of Transient Elastography for Diagnosis Dronamraju D,Vachon ML, and Dieterich DT Division of Liver Disease, Mount Sinai School of Medicine International Conference on Viral Hepatitis April 11-12, 2011, Baltimore

2. Background Liver disease is a major cause of morbidity and mortality among patients with HIVmainly secondary to co-infection with HCV Insulin resistance and dyslipidemia also contribute to increased rates of steatosis/steatohepatitis in this group Portal hypertension is a known consequence of advanced liver disease and is usually secondary to liver cirrhosis Recently, non-cirrhotic portal hypertension (NCPH) and its associated clinical manifestations have been described in HIV- infected patients without viral hepatitis In most case series, it is found to be associated with didanosine (ddI) use

3. Non-cirrhotic Portal Hypertension (NCPH) Maida et al. (2006) described a cohort of 17 HIV-infected patients with symptoms of portal hypertension in setting of didanosine (ddI) use Saifee et al. (2008) described a cohort of 11 HIV-infected patients with NCPH and correlated it to either ddI use and/or to a predisposing hypercoaguable state Kovari et al. (2009) conducted a nested case control study of 15 HIV-infected patients showing strong association between prolonged ddI exposure and NCPH Mendizabal et al. (2009) described 6 HIV-infected patients with NCPH in the setting of ddI use

4. Histopathologic Findings of NCPH

5. Nodular Regenerative Hyperplasia (NRH) On microscopic examination, clustered nodules surround portal triads Central portion of nodules are made up of hypertrophied hepatocytes arranged in multilayer plates Cells in periphery are atrophic and arranged in parallel sheets Characteristically no fibrosis is seen between nodules These findings are easily missed with routine staining and reticulin staining is needed Courtesy of MI Fiel

6. Hepatoportal Sclerosis (HPS) Characterized by various degrees of fibrosis and sclerosis of portal vein branches May also see marked dilatation of sinusoids- Megasinusoids May see herniation of portal veins Courtesy of MI Fiel

7. Objectives 1) To describe the clinical characteristics of a series of HIV patients with portal hypertension in a liver clinic in New-York City 2) To measure liver stiffness in these patients using transient elastography, a non-invasive diagnostic tool to measure liver stiffness, and evaluate its role in evaluating such patients

8. Methods Design: Observational Retrospective Case Series Patients: HIV-infected patients who attended Mount Sinai liver clinic between 2/2008-9/2010 o with clinical evidence of portal hypertension (ascites, splenomegaly, esophageal varices, encephalopathy, and/or thrombocytopenia) and o without HBV or HCV co-infection

9. Results Patient Characteristics (n = 16)

10. Results Clinical Manifestations of Portal Hypertension Thrombocytopenia, n (%) (platelets < 120,000) 12 (75%) Splenomegaly, n (%) 13 (81%) Esophageal Varices, n (%) 13 (81%) Ascites, n (%) 5 (31%) Portal Vein Thrombosis, n (%) 5 (31%)

11. Results Transient Elastography (n=16) and Biopsy (n=9) Median Transient Elastography Score (KPa) (Range) 8.4* ( 4.7-27.7 ) Hepatoportal Sclerosis (HPS), n (%) 3 (33%) Nodular Regenerative Hyperplasia (NRH) 1 (11%) Hepatoportal Sclerosis & Nodular Regenerative Hyperplasia 2 (22%) Cirrhosis Suggested at CT Scan n (%) Found at Liver Biopsy n (%) 10 (66%) 2 (22%) * 8.4 KPa is consistent with fibrosis METAVIR stage F2

12. Summary NCPH is a new entity in HIV-infected patients Patients usually present with splenomegaly and esophageal varices The typical liver biopsy can show either nodular regenerative hyperplasia or hepatoportal sclerosis The low (but not normal) transient elastography score (not compatible with cirrhosis) we found in these patients suggests this may be a useful test in initial evaluation of HIV-infected patients with evidence of portal hypertension

13. Summary Based on these data, we are developing a clinical algorithm using transient elastography to evaluate HIV patients with significant thrombocytopenia (< 120,000) and clinical signs of portal hypertension, like varices or splenomegaly. We invite interested groups with a fibroscan to contact us directly to collaborate on a larger study validating a new algorithm using fibroscan, clinical and laboratory markers to define NCPH

14. References: Kovari et al. Association of Non Cirrhotic Portal Hypertension in HIV- Infected Persons and Antiretroviral Therapy with Didanosine: A Nested Case Control Study. Clin. Infect. Dis 49 (4) 626-635. 2009. Maida et al. Severe Liver Disease Associated with Prolonged Exposure to Antiretroviral Drugs. JAIDS 42(2) 177-182 2006. Mendizabal et al. Non Cirrhotic Portal Hypertension: Another Cause of Liver Disease in HIV patients. Ann. Hept. 8(4) 390-395 2009. Saifee et al. Non Cirrhotic Portal Hypertension in Patients with HIV-1. Clin Gastro and Hept. 6(10) 1167-1169 2008,