Infection with hepatitis E virus (HEV) can
cause rapid liver fibrosis in people with HIV who have low CD4 cell counts,
case reports published in the online edition of Clinical Infectious Diseases show. Spanish investigators reported
two instances of HEV infection in gay men with HIV who had severe
immunosuppression. Treatment with ribavirin monotherapy led to normalisation of
liver function and temporary suppression of HEV replication.
“Chronic HEV…can lead to cirrhosis within
less than three years,” comment the authors. “In the setting of
immunosuppressed HIV-infected patients with chronic hepatitis E, progression to
cirrhosis may be even faster than that observed in HBV [hepatitis B virus] or
HCV [hepatitis C virus]/HIV coinfection.”
Hepatitis E is a leading cause of acute hepatitis
in resource-limited countries. Often there are no symptoms and the infection is
usually cleared by the body’s natural defences. Most infections are caused by
consumption of undercooked pork products.
Immunosuppression is a recognised risk
factor for the persistence of HEV infection, and high rates of HEV/HIV
co-infection have been reported in some countries. In Spain, between 2 and 7% of the general population have antibodies to HEV, and a similar
prevalence has been observed in people with HIV.
Doctors in Spain were concerned by two
cases of chronic HEV infection causing rapid liver damage involving
people with HIV who had low CD4 cell counts.
The first case involved a 47-year-old gay
man. He was diagnosed with HIV in 1995, at which time his CD4 cell count was
just 17 cells/mm3. Antiretroviral therapy suppressed his viral load
to undetectable levels, but his CD4 cell count remained persistently low, never
rising to above 100 cells/mm3 in the early years of therapy and
subsequently never increased above 200 cells/mm3.
In April 2008
monitoring of liver function revealed an ALT level of 482 iu/ml, well above the
upper-limit of normal. Tests for hepatitis A, B and C were all negative.
However, antibodies to hepatitis E were detected. The man’s liver function had
normalised by January 2009 but again spiked one month later. Liver stiffness
increased from 4.9 kPa in April 2006 to 17.1 kPa in April 2011, suggesting
rapid onset liver cirrhosis. This was confirmed by liver biopsy, which revealed
cirrhosis with significant steatosis (fatty liver). Screening tests for
hepatitis A, B and C remained persistently negative, and the man
reported only modest alcohol consumption.
Retrospective analysis of stored serum
samples confirmed acute infection with HEV genotype-3 in March 2008. The
patient initiated a 24-week course of ribavirin monotherapy (1200mg daily) in
November 2011. Within one month, his liver enzymes had normalised, HEV RNA was
suppressed to undetectable levels and antibodies to HEV were present. HEV viral
load was undetectable at the end of therapy and three months later. Liver
enzymes remained normal and liver stiffness declined to 14 kPa. However, in
October 2012, HEV RNA was once again detectable in plasma.
The second case involved a 53-year-old gay
man born in Cuba who had been resident in Spain since 1979. He was diagnosed
with HIV in 1999 when his CD4 cell count was 19 cells/mm3. HIV
therapy was immediately initiated, but the man frequently interrupted his
treatment. In April 2006, when his CD4
cell count was 88 cells/mm3, a flare in ALT to 261 was recorded. Screening
tests for hepatitis A, B and C were all negative.
A dramatic increase in liver stiffness from
6.7 kPa to 38.5 kPa was observed. An endoscopy revealed the presence of
esophageal varices. Tests also showed the presence of HEV antibodies.
Stored serum samples were negative for HEV
antibodies before the ALT spike, but positive thereafter. HEV RNA was
intermittently detectable in blood and persistently detectable in faeces.
Sequencing confirmed infection with HEV genotype-3. The infection was
attributed to the consumption of homemade pork liver pâté manufactured by his
relatives at their farm in northern Spain.
A 24-week course of ribavirin monotherapy
(1000mg daily) was initiated in September 2011. By January 2012, HEV viral load was
undetectable in both plasma and faeces. Liver function normalised, liver
stiffness declined and the man’s CD4 cell count increased to 289 cells/mm3.
Ten weeks after the end of treatment, HEV RNA was once again detectable in
plasma, but had disappeared by October 2012.
“In the setting of HIV carriers, HEV-3
infection should be regarded as an opportunistic infection, since it appears to
evolve differently in HIV infection,” comment the investigators. “A delay in
the diagnosis of HEV infection and, as a result, in starting antiviral therapy,
can lead to clinical complication and hazardous consequences for the patient.”
They conclude: “Screening for HEV in
HIV-infected individuals presenting unexplained transaminase elevations or with
hepatic fibrosis of unknown origin is warranted. A short course of ribavirin
may temporarily control viral replication, however, optimal treatment regimens
need to be defined.”