Infection with hepatitis E virus should be considered as a
possible cause of unexplained elevations in liver enzymes in HIV-positive
patients, Swiss investigators suggest in Emerging
Approximately 3% of their patients with persistently elevated alanine aminotransferase
(ALT) levels had antibodies to hepatitis E. None of
these patients were co-infected with either hepatitis B or hepatitis C.
Screening for hepatitis E RNA found evidence of the
infection in two patients with very low CD4 cell counts.
The study was undertaken because unexplained elevations in
liver enzyme levels are common in patients with HIV.
Hepatitis E infection originates in pigs and the main mode of
transmission in Europe is via contaminated meat from pigs or wild animals. It is also transmitted through food or water contaminated by faeces containing the virus.
The virus can cause disturbances in liver
function. Infection is usually cleared within a few weeks, as with hepatitis A, but may be more severe in people with suppressed immunity. Cases of the infection have been detected in HIV-positive
Investigators from the Swiss HIV Cohort Study wanted to see
if hepatitis E infection was the cause for persistent elevations in ALT levels.
To be eligible for the study, patients were required to have
two consecutive ALT measurements above 60 iu/l. Individuals with hepatitis B or
hepatitis C were excluded.
Blood samples were tested for antibodies to hepatitis E and
for hepatitis E RNA.
A total of 735 patients met the inclusion criteria and were
included in the investigators’ analysis.
A total of 19 patients (2.6%) had antibodies to hepatitis E
virus. The co-infection was associated with female sex (p = 0.059) and Asian
origin (p = 0.007).
There was no evidence that age, HIV risk group, lowest ever
CD4 cell count, HIV viral load, body mass index, or ALT values.
However, after adjustment for age and sex, the investigators
found that patients with a CD4 cell count between 100 and 350 cells/mm3
were 4.7 times more likely to have hepatitis E antibodies than individuals with
a CD4 cell count below 100 cells/mm3 (OR = 4.68; 95% CI, 1.26-17.29;
p = 0.02).
Duration of ALT elevation was also associated with hepatitis
E coinfection (OR = 1.01; 95% CI, 1.00-1.002; p = 0.02).
In 16 of the 19 coinfected patients, additional blood
samples obtained a median of 6.6 months before the first ALT elevation were
available. Seroconversion from a previous hepatitis E test was found in five
One of the patients with antibodies to the infection also
had evidence of hepatitis E RNA . The virus was detected over a 24-month
period, even though the individual was hepatitis E antibody-negative for half
this period. The patient was a 46-year-old gay man who was diagnosed with HIV
in June 2001. He started antiretroviral therapy with a CD4 cell count of only 34
cells/mm3. At this time his ALT level was normal, but increased one
month later. He was positive for hepatitis E’s genetic material between August
2001 and December 2004. However, this was no longer detectable after his CD4
cell count reached 83 cells/mm3. His liver function normalised six
months later, after his CD4 cell count had increased to above 100 cells/mm3.
The investigators were concerned that hepatitis E antibody
tests may perform less well in patients with severe immune suppression. Therefore blood samples from 53
hepatitis E virus antibody-negative patients with a low CD4 cell count (below
150 cells/mm3) were retested for hepatitis E viral load.
The virus’s genetic material was detected in one patient, a
59-year-old gay man who started antiretroviral therapy in October 1996 when his
CD4 cell count was 140 cells/mm3. Despite HIV therapy, his CD4 cell
count remained below 250 cells/mm3 for the next twelve years. He had
hepatitis E RNA testing between March 2002 and April 2008. The virus’s genetic
material was identified from 2005 to 2006.
“Taken together, our results suggest that serologic
screening alone may be insufficient to diagnose hepatitis E virus infection in
HIV-infected patients with very low CD4 count because seroconversion may be
delayed or not occur,” comment the investigators.
Even though the prevalence of hepatitis E infection was low,
the authors conclude, “when investigating unexplained, elevated ALT level in
HIV-infected patients, we propose that hepatitis E virus infection should be