5 and 10 year survival in a cohort of patients with HIV associated non-‐cirrhotic portal
hypertension (NCPH) Kate Childs, Corinna Pseusdomakis, Lauran Hookham, Kosh Agarwal, Mark Nelson, Chris Taylor, Abid Suddle.
Dr Kate Childs, King’s NHS Foundation Trust
Background
• In 2007 case reports of variceal bleeding and manifestations of portal hypertension in patients with HIV infection emerged. Clinical picture was of portal hypertension with histological finding of nodular regenerative hyperplasia (NRH) and portal obliterative venopathy (POV)
• In the vast majority of reports the patients had been exposed to didanosine (DDI) A case control study demonstrated that didanosine exposure was associated with non cirrhotic portal hypertension.
• Idiopathic non cirrhotic portal hypertension is well described in HIV negative patients.
Schiano TD, Kotler DP, Ferran E, Fiel MI. Hepatoportal sclerosis as a cause of noncirrhotic portal hypertension in patients with HIV. Am J Gastroenterol. 2007;102:2536–2540. Saifee S, Joelson D, Braude J, et al. Noncirrhotic portal hypertension in patients with human immunodeficiency virus-‐1 infection. Clin Gastroenterol Hepatol. 2008;6:1167–1169. Vispo E, Moreno A, Maida I, et al. Noncirrhotic portal hypertension in HIV-‐infected patients: unique clinical and pathological findings. AIDS. 2010;24:1171–1176.Mallet VO, Varthaman A, Lasne D, et al. Acquired protein S deficiency leads to obliterative portal venopathy and to compensatory nodular regenerative hyperplasia in HIV-‐infected patients. AIDS. 2009;23:1511–1518.Kovari H, Ledergerber B, Peter U, et al. Association of noncirrhotic portal hypertension in HIV-‐infected persons and antiretroviral therapy with didanosine: a nested case-‐control study. Clin Infect Dis. 2009;49:626–635.
Aim
• To describe the clinical findings, natural history and clinical outcome of patients with HIV and non-‐cirrhotic portal hypertension.
Method• Retrospective cohort study on all patients at 2 London centres • Definition of non-‐cirrhotic portal hypertension = evidence of portal hypertension (splenomegaly, varices, portal hypertensive gastropathy) and either a liver biopsy showing ≤F3 fibrosis or in the absence of a biopsy a Fibroscan <11kPa. • All patients meeting this definition and HBV SAg negative, HCV Ab negative were included.• Demographics, laboratory, radiological and histological data were gathered.• Kaplan-‐Meier survival analyses were performed.
Characteristic at time of NCPH presentation N = 41N(%)/Median (IQR)
Gender M 22 (53.7)F 19 (46.3%)
Ethnicity Caucasian (Cauc) 15 (37%)
Black African (BA) 25 (61%)
Age at presentation (years) 44.3(38, 49)History of DDI exposure 41/41 (100%)
Duration DDI exposure (months) 72 (54, 96)
Portal Vein Thrombosis 20/41 (48.7%)Time since HIV diagnosis (years) 12.5 (10.3, 18.9)
HIV viral load <50 copies/ml at presentation 38/41 (92.6%)CD4 cells/ml at presentation cells/ml 265 (162, 350)
Results: n=41
The majority presented with clinical symptoms
Lab parameters Symptomatic AST GGT/ALP Bilirubin Ascites UGI Bleed Imaging Other
41% 59%
Portal Vein Thrombosis and Haematological abnormalities were common
• 20/41 had PVT• 16/20 underwent full procoagulant profile, 5/16 had coagulation abnormalities
• low protein s + c,• low protein s plus lupus anticoag,• low protein s• MTHF heterozygote, • low protein c and ATIII
• 11 were anticoagulated (of those not anticoagulated, 6 no longer in care, 2 not yet, 1 high risk)• Median time of anticoagulation 4.1 years (2.5, 7.5).• No variceal bleeds occurred in anticoagulated patients• During follow up 29/41 experienced anaemia requiring treatment. Of these 8 were anticoagulated.
Why anticoagulate in portal vein thrombosis?
Biopsy findings n=31Histological feature Number of biopsies Histological feature Number of biopsies
Nodular regenerative hyperplasia
7 Steatosis (1-‐5%) 5
Venopathy 5 Non-‐specific mild inflammation/mild fibrosis
Only finding on 9 biopsies
Vascular abnormality
1 Bile ductular reaction
1
Hepatoportal sclerosis
2 Cholangiopathy 1
Clinical Outcome
• Median follow up duration per patient of 107 months (73, 129)• Total duration of follow up 286 patient years• 5 underwent liver transplantation (OLT), 2 listed for OLT• 3 died liver related death, 2 died non –liver related death
0 50 100 150 2000
50
100
Liver death and transplant free survival
Time months
Per
cent
sur
viva
l
5 year survival 92%, 10 year survival 72.6% 5 year survival 87%, 10 year survival 66%
Predictors Liver Death/transplantVariable P-‐value in univariate
Gender 0.63
Ethnicity 0.83
Duration DDI 0.64
Age 0.97
CD4 count 0.25
PVT 0.4
Clinical vs non clinical presentation
0.98
Anaemia 0.0560 50 100 150 200
0
50
100
Liver death and transplant free survival
Time months
Per
cent
sur
viva
l
Patients presenting with clinical symptoms (ascites/upper GI bleed) were more likely to have further episodes GI bleeding during follow up for
NCPHOutcome P-‐value
All cause death/transplant 0.49Liver death/transplant 0.98
New upper GI bleed (after diagnosis NCPH) 0.017
11/22 of those presenting with clinical symptoms experienced a bleed during follow up compared to 2/17 who presented based on lab parameters.
Age Gender (race)
CD4 (cells/ml)
Indication UKELD Warfarin pre-‐OLT
Years survivalpost OLT
Outcome
54 M (Cauc) 310 Encephalopathy 50 y 4.5 In Follow up
44 F (BA) 199 Diuretic resistant ascites 46 y 3 months RIP. Complicated post OLT with thrombosis/haemorrhage /ARFFinal event small and large bowel ischaemia secondary to SMV thrombus.
68 F (BA) 75 Encephalopathy plus diuretic resistant ascites
53 y 2.7 In Follow up
69 M (Cauc) 314 Encephalopathy post TIPSS
50 n 1.8 In Follow up
65 M (Cauc) 167 Synthetic failure 52 n 14 months In Follow up
5 patients underwent Liver Transplantation
Summary• HIV associated NCPH carries a significant morbidity and mortality. • Diagnosing patients before complications of PHT develop reduces risk of upper GI bleed but is not associated with overall outcome.• Although anticoagulation seems counterintuitive, it has not resulted in complications in our cohort.• NCPH in HIV positive patients can result in end stage liver disease. Liver transplantation is a treatment option.
Summary• A high index of suspicion is required as some patients only present with subtle derangements of liver function tests• More data is required to inform positive and negative prognostic factors and the benefit of therapeutic interventions such as anticoagulation • The HIV/liver clinic in King’s liver unit is happy to receive referrals of patients with NCPH.
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