Chronic Hepatitis E in HIV Patients: Rapid Progression to Cirrhosis and Response to Oral Ribavirin
Karin Neukam
1
2
3
Pablo Barreiro
0
2
Juan Macas
1
2
3
Ana Avelln
2
4
Celia Cifuentes
1
2
3
Luz Martn-Carbonero
0
2
Jos M. Echevarra
2
4
Julio Vargas
1
2
3
Vicente Soriano
0
2
Juan A. Pineda
1
2
3
0
Department of Infectious Diseases, Hospital Carlos III
,
Madrid
1
Instituto de Biomedicina de Sevilla
2
Received 8 December 2012; accepted 30 March 2013; electronically published 10 April 2013. loga,
Hospital Universitario de Valme
, Avda de Bellavista, 41014 Sevilla,
Spain
3
Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme
, Seville
4
National Center for Microbiology, Instituto de Salud Carlos III
, Majadahonda,
Spain
Chronic hepatitis E virus infection with rapid progression to cirrhosis is reported in 2 human immunodeficiency virus (HIV)-infected patients with severe immunosuppression. Monotherapy with ribavirin led to temporary viral response and marked improvement of liver damage. Chronic hepatitis E should be regarded as another opportunistic event within HIV infection.
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Hepatitis E virus (HEV) is a leading cause of epidemic or
sporadic waterborne acute hepatitis in developing countries.
For years, acute hepatitis E was considered a subclinical and
self-limiting disease [1]. In Western countries, autochthonous
cases of HEV genotype 3 (HEV-3) infection are increasingly
reported, mostly in relation to sporadic foodborne exposure to
undercooked swine products [1]. Immunosuppression has been
shown to facilitate chronicity of HEV infection, HIV infection
being one of the possible causes for HEV persistence [2], and
there are reports of high HIV/HEV coinfection rates for
particular regions [3, 4]. In Spain, for instance, the prevalence of
HEV antibodies in the general population ranges between 2.2%
and 7.3% [5, 6]. Although exposure to HEV seems comparable
between HIV-infected patients and the general population,
chronic HEV-3 infection has been described in HIV-infected,
immunosuppressed patients [2, 710].
There are data to suggest that HEV may enhance the
progression of liver disease from other causes [11]. However,
information on the natural history of chronic HEV infection, especially
regarding the velocity of progression to cirrhosis, is scarce.
Likewise, data on the treatment of HEV in HIV-infected patients
have only been described in 2 cases, which were treated with
pegylated interferon ( peg-IFN) alone [2] or in combination
with ribavirin (RBV) [7]. Because in some regions
monoinfection with HEV or HIV represents a common health problem,
HIV/HEV coinfection may become a relevant issue. It is thus of
the highest importance to clarify the natural history, as well as
treatment options, for chronic hepatitis E in HIV infection.
We report 2 cases of chronic hepatitis E in HIV-infected
patients with severe immunosuppression, the response to RBV
monotherapy, and the course of fibrosis progression before and
after therapy.
CASE REPORT 1
A 47-year-old, white homosexual man was first seen at a
hospital in Seville in 2003, presenting with plasma HIV RNA of
21 000 copies/mL and a CD4 count of 17 cells/L. In 1995 he
had been classified as category C under the Centers for Disease
Control and Prevention HIV classification system. Despite
undetectable plasma HIV RNA after starting antiretroviral
therapy (ART), CD4 counts remained <100 cells/L during the
first years on treatment. In April 2008, he presented with a
peak in alanine aminotransferase (ALT) level of 482 IU/mL but
was otherwise asymptomatic (Figure 1A). Serology for hepatitis
A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus
(HCV) was negative, whereas serum immunoglobulin M (IgM)
antibodies against HEV were positive. In January 2009 ALT
levels normalized, only to increase again 1 month later,
remaining elevated with fluctuations thereafter (Figure 1A). Liver
stiffness (LS) as assessed by transient elastometry increased from
4.9 kPa in April 2006 to 17.1 kPa in April 2011 (Figure 1A). In
November 2011, liver biopsy confirmed macro-micronodular
cirrhosis with significant steatosis. No esophageal varices were
detected. HAV, HBV, and HCV serology remained negative,
and CD4 counts did not exceed 200 cells/L throughout the
follow-up period. The patient reported occasional alcohol
consumption (50100 mg/day with infrequent binge drinking) in
2009. In 2011, he was abstinent.
globulin M.
Retrospective analysis of frozen serum samples confirmed
acute HEV-3 infection in March 2008 (Figure 1A). No source
of infection was recognized. In November 2011, a 24-week
course of treatment with RBV 1200 mg/day was initiated. In
December 2011 the patient showed normal liver enzymes and
undetectable plasma HEV RNA, with detectable IgM and
immunoglobulin G (IgG) against HEV. At the end of treatment
and 3 months thereafter, no HEV RNA could be detected in
plasma or feces (Figure 1A), liver enzymes remained normal,
and LS declined to 14 kPa. In October 2012, however, HEV
RNA was detectable in plasma.
CASE REPORT 2
A 53-year-old homosexu (...truncated)