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| Journal of the New Zealand Medical Association,
26-November-2010, Vol 123 No 1326
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A case of oesophageal varices and portal hypertension
in an HIV-positive patient with no evidence of cirrhosis
Sara Temelkovski, James Irwin, Jim Brooker
Non-cirrhotic portal hypertension (NCPH) is a condition of
elevated portal venous pressure in the absence of cirrhosis. NCPH was initially
described in the Indian subcontinent in association with anaemia and congestive
splenomegaly. It was initially referred to as ‘idiopathic portal
hypertension’ or ‘hepatoportal
sclerosis’.1 A mechanism of
thrombophlebitis as a result of recurrent gastrointestinal infection and
repeated embolisation into the intrahepatic and extrahepatic portal venous
circulation has been postulated to lead to increased portal venous
pressure.2
In the developed world, NCPH is much less common. It has
recently gained attention in the HIV-positive population following the
publication of a number of reports linking antiretroviral exposure to the
development of NCPH. It has not previously been described in NZ.
An estimated 1230 HIV-infected individuals were receiving
medical care in NZ in 2007,3 0.03% of the
general population. Exposure to patients with complications of HIV and treatment
is therefore low amongst non-specialist medical services.
Case reportA 49-year-old man was brought in by ambulance to this centre
following sudden onset nausea and multiple bouts of vomiting of fresh blood. He
had a 3-week history of intermittent abdominal pain prior to this event. He had
no previous gastric symptoms or NSAID use and drank alcohol occasionally. He had
no previous liver dysfunction or infection with hepatitis A, B or C.
He was diagnosed with HIV in 1996 at which time he was
asymptomatic with a CD4 count of less than
200×106/L. Antiretroviral
therapy (ART) was commenced in early 1999. He had been treated initially with 3
years of stavudine 40 mg bd, abacavir 300 mg bd and nelfinavir 1250 mg bd. This
was changed in 2002 to a regimen of didanosine 250 mg po od, efavirenz 600 mg od
and tenofovir 300 mg od. His disease at time of this presentation was stable
with an undetectable HIV viral load and a CD4 count of
290x106/L. He was believed to be adherent to
the antiretroviral regimen as detailed above.
On examination he was pale, thin and afebrile. He had mild
epigastric tenderness, but no peritonism. There was no ascites or
encephalopathy. Rectal examination revealed dark stools with no blood or
melaena.
The haemoglobin on admission was 115 g/L which dropped to 90
g/L the following day. Further blood tests revealed—bilirubin 9 umol/L
(2–22), ALP 71 g/L (40–110), ALT 26 U/L (0–45), GGT 135 U/L
(0–60), INR 1.1, and albumin 36 g/L (38–52). Blood tests excluded
the presence of hepatitis A, B, and C. Alpha-1-antitrypsin, iron studies, ANA
and smooth muscle antibodies, serum immunoglobulins and ceruloplasmin were all
normal.
At endoscopy, four large varices were noted protruding to
half of the lumen with a platelet plug visible at an obvious recent bleeding
site (Figure 1). A moderate amount of altered transported blood was found in the
stomach. Six variceal bands were applied. Prominent fundal folds were noted
raising the possibility of fundal varices. No obvious portal gastropathy was
seen.
Figure 1.
Endoscopic view of oesophagus with four large varices and a platelet plug
indicating the site of recent haemorrhage
 An ultrasound scan of the liver demonstrated slightly coarse
echotexture but no focal hepatic parenchymal pathology was seen. There was no
evidence of macronodular change and normal anterograde flow was seen in the
portal and hepatic veins. Portal venous flow was measured at 10 cm/second, which
is within the normal range. The spleen was slightly prominent at 14 cm in
length. No perisplenic varices were seen.
A Fibroscan showed a transient elasticity of 5.9 kPa (IQR
1.0 kPa, 10/10 recordings valid), consistent with minimal or no fibrosis. He
declined to have a liver biopsy.
The patient’s ART was changed to tenofovir 300 mg od,
efavirenz 600 mg od and abacavir 600 mg od, and propranolol 40 mg bd was
commenced as secondary prophylaxis of variceal haemorrhage. Elective oesophageal
banding was performed on a further three occasions during the subsequent 12
months with consequent reduction in varix size. He has not suffered any further
episodes of bleeding.
DiscussionIn patients who are HIV-positive, liver disease is usually
due to concurrent chronic viral hepatitis, alcohol abuse or non-alcoholic
steatohepatitis.
NCPH is a relatively newly described condition in patients
who are HIV-positive4 and has potentially
life-threatening sequelae, particularly variceal haemorrhage. The pathogenesis
of this condition is not well understood. In the HIV-positive population, an
increased incidence of NCPH has been found in those exposed through anal
intercourse.5
It has been hypothesised that transfer of microbes from the
gastrointestinal tract to the portal circulation and the resulting septic
microthrombophlebitis could account for the development of NCPH in this
group.4 In the Indian subcontinent,
‘noncirrhotic portal fibrosis’ (NCPF) has been described, and
accounts for approximately a quarter of all variceal bleeding seen within that
region. Similarly, the most widely proposed mechanism in the development of NCPF
is fibrosis due to recurrent microembolism in the portal circulation secondary
to abdominal sepsis.2
NCPH has been defined in a recent case-control study as the
presence of endoscopically documented oesophageal varices or an hepatic venous
pressure gradient >10 mmHg, no cirrhosis on liver biopsy, and the absence of
alternative aetiologies (hepatitis B, C, alcohol excess, haemochromatosis,
Wilson’s disease, alpha 1 antitrypsin deficiency, autoimmune hepatitis,
non alcoholic fatty liver disease or hepatotoxic
drugs).5
Liver biopsy in patients with NCPH may reveal a variety of
histologic lesions, though these are not consistently
present.6,7 They include periportal fibrosis,
perisinusoidal fibrosis, and nodular regenerative hyperplasia. These
histological features are consistent with a pathophysiological mechanism of
presinusoidal fibrosis leading to obstructive portal venopathy and intrahepatic
portal hypertension. By definition liver cirrhosis is absent on biopsy, and the
clinical sequelae of variceal haemorrhage and ascites are a consequence of
portal hypertension. However liver failure leading to death or liver
transplantation has been described in some cases of
NCPH.8
Prognosis for patients with antiretroviral associated NCPH
has not been clearly described. In a published
cohort5 4/15 patients died of complications of
liver disease, either variceal haemorrhage or liver failure, over an average
follow-up period of 12 years. In addition NCPH is a rare but recognised cause of
decompensated liver disease requiring liver
transplantation.8 Ongoing monitoring of
patients with antiretroviral associated NCPH for these complications is
therefore warranted.
Although our patient declined liver biopsy, the Fibroscan
result excluded hepatic fibrosis or cirrhosis. Fibroscan is a well-validated
non-invasive method for detecting hepatic fibrosis or cirrhosis. A recent
meta-analysis of 50 studies examining the performance of Fibroscan showed that
cirrhosis could be excluded with a transient elasticity (TE) of less than
13.01kPa, and significant hepatic fibrosis (equivalent to a metavir score of F2
or greater on liver biopsy) with a TE less than 7.65
kPa.9
Didanosine has recently been implicated in the development
of NCPH.5 Its use in NZ has declined due to
well-documented toxicity issues such as lipodystrophy, pancreatitis and lactic
acidosis. Exposure to any ART medication appears to increase the risk of
developing NCPH, and this risk appears to be cumulative. ART commenced as mono
or dual therapy increases the risk when compared to three or more drugs. When
individual antiretrovirals were studied, didanosine stood out as a risk factor
for development of NCPH, with an odds ratio of 3.44.
Our report describes an HIV-positive patient treated with
didanosine for 8 years. He presented with variceal haemorrhage secondary to
portal hypertension, had no evidence of liver fibrosis or cirrhosis on Fibroscan
and had a negative screen for causes of chronic liver disease. This is the first
report of didanosine associated NCPH identified in NZ.
The population of individuals infected with HIV in NZ
remains small and current ART regimes are highly effective. Nevertheless, it is
important that clinicians remain vigilant for unusual complications of the
disease and its therapy.
Author information: Sara Temelkovski, House
Surgeon; James Irwin, Gastroenterology Registrar; Jim Brooker,
Gastroenterologist; Waikato Hospital, Hamilton
Acknowledgement: We thank Dr Graham Mills
(Consultant Physician in General Medicine and Infectious Diseases, Waikato
Hospital).
Correspondence: Dr Sara Temelkovski,
Waikato Hospital, Pembroke Street, Private Bag 3200, Hamilton 3240, New Zealand.
Email: saratemelkovski@gmail.com
References:
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