Noncirrhotic Portal Hypertension in HIV-Infected Patients: A Case Control Evaluation and Review of the Literature

Abstract

Idiopathic noncirrhotic portal hypertension (NCPH) is an infrequent but possibly underestimated cryptogenetic liver disease recently described in small series of HIV-infected patients. The exposure to antiretroviral drugs, a direct role of HIV itself, microbial translocation from the gut, or a thrombophilic propensity have been suggested as possible pathogenic mechanisms. In this case control study, we describe 11 HIV-infected patients with idiopathic NCPH and compare the activity of protein C and S, and soluble CD14 levels (a surrogate marker of the translocation of intestinal bacterial products) with 10 age- and gender-matched HIV-infected controls with no liver disease. The clinical presentation of the 11 patients with NCPH was characterised by acute variceal bleeding (2/11), ascites (2/11), portal thrombosis (2/11), and ultrasonographic and endoscopic signs of portal hypertension (11/11), with slightly high alanine transaminase (ALT) and γglutamyl transpeptidase (γ-GT) levels. The FibroScan median liver stiffness was 8.1 kPa, which is inconsistent with significant fibrosis, and nodular regenerative hyperplasia was diagnosed in the 5 patients who underwent liver biopsy. The NCPH patients showed no impairment of hepatic synthesis, but had lower serum albumin levels and a higher international normalized ratio (INR) than the controls (p = 0.01), and lower protein C and S activity, although within the normal range (p = 0.02 and 0.3, respectively). No significant difference in soluble CD14 was seen between the two groups. In conclusion, the etiology of NCHP is not still established, but in order to prevent the dramatic complications of portal hypertension, all HIV-infected patients with unexplained liver enzyme abnormalities or thrombocytopenia should be considered for further investigations by means of thrombophilic screening, Doppler ultrasound evaluation, and in the presence of portal hypertension, endoscopy and liver biopsy.

Didanosine Exposure and Noncirrhotic Portal Hypertension in a HIV Clinic in North America: a Follow-up Study

“…Non-cirrhotic portal hypertension (NCPH) is a rare but increasingly recognized cause of liver morbidity and mortality among otherwise well controlled HIV patients (Maida et al, 2006, 2008; Mallet et al, 2007; Arey et al, 2007; Garvey et al, 2007; Sandrine et al, 2007; Saifee et al, 2008; Mendizabal et al, 2009; Cesari et al, 2010; Vispo et al, 2010). Its potential association with chronic antiretroviral use was first described in 2006 (Maida et al, 2006).…”

Noncirrhotic Portal Hypertension in Perinatally HIV-infected Adolescents Treated With Didanosine-containing Antiretroviral Regimens in Childhood

“…This may eventually lead to extrahepatic portal vein thrombosis. 6,12,15,24 In HIV-infected adults, possible causes of NCPH development might consist of the virus itself, a hypercoagulable state, exposure to thymidine analogues such as didanosine, Copyright © 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.…”

“…5,6,9,10,24 Whether the pathogenesis might be the same in perinatally infected children is not clear.…”

“…Although the liver histology was not uniform, common histological features in our case series consisted of the paucity of portal veins along with focal fibrous obliteration of small portal veins. 24 Due to these vascular changes hepatocyte regeneration could well have occurred, resulting in nodular remodeling of the parenchyma.…”

Human immunodeficiency virus and nodular regenerative hyperplasia of liver: A systematic review

“…Arey et al [21] Case report 1 Abdominal distention, abdominal, pain, EV Bihl et al [31] Case report 1 Abdominal pain, ALP, ascites, EV, GIB, splenomegaly Bissonnette et al [11] Case report 2 Ascites, EV, GIB Cachay et al [15] Case series 1 ALP Saifee et al [52] Case series 11 Ascites, EV, GIB Cesari et al [53] Case control 5 Ascites, EV, GIB, splenomegaly Cotte et al [12] Case control 13 Abdominal pain, ALP, ascites, EV, GIB, splenomegaly Alvarez Díaz et al [33] Case report 2 ALP, ascites, EV, GIB Ding et al [54] Case report 1 ALP, EV, GIB, ascites Dinh et al [55] Case control 3 Ascites, encephalopathy, EV Fernandez-Miranda et al [9] Case report 1 Unknown Garvey et al [19] Case report 2 EV, splenomegaly Hofmaenner et al [27] Case report 1 Epigastric pain, ALP Kochin et al [56] Case report 1 EV, GIB Kovari et al [23] Case control 1 EV Maida et al [8] Case series 2 Splenomegaly Mallet et al [4] Case control 13 ALP, EV, GIB Mallet et al [57] Case report 1 Portal hypertension Mallet et al [30] Case series 8 ALP, ascites, EV, splenomegaly Mendizabal et al [58] Case control 5 EV, GIB Podevin et al [59] Case report 1 Ascites, EV, splenomegaly Sandrine et al [20] Case report 1 ALP, ascites, EV, splenomegaly Santiago et al [28] Case report 1 Abdominal distention, splenomegaly Schiano et al [22] Case report 1 ALP, EV, splenomegaly Scourfield et al [60] Retrospective cohort 4 Unknown Schouten et al [61] Case report 3 EV, GIB Stebbing et al [62] Retrospective cohort 2 ALP Tateo et al [13] Case report 3 ALP, ascites, EV, GIB Vispo et al [29] Case report 3 ALP, ascites, EV, GIB ALP: Abnormal liver panel; EV: Esophageal varices; GIB: Gastrointestinal bleed. hypersplenism (Table 1).…”