[procaare] Hepatitis B hasn't gone away and may come back

["AIDSMAP" <procaare@healthnet.org>]

Hepatitis B hasn't gone away and may come back 
AIDSMAP - Monday, June 08, 2009 
Gus Cairns
http://www.aidsmap.com/en/news/4E0FC681-F3E8-4C16-8A9B-C68C87592C43.asp
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People with HIV who have been vaccinated for hepatitis B may still
become infected, the fifth Annual Workshop on HIV and Hepatitis
Co-infection in Lisbon heard this week. The conference also heard of a
case where starting interferon-based hepatitis C therapy in a person
with HIV apparently caused a reactivation of a dormant hepatitis B
infection. 

The conference also heard that HIV/hepatitis B co-infected people
have considerably faster CD4 declines than people co-infected with HIV
and hepatitis C or HIV alone, that rates of hepatitis B co-infection in
HIV positive African immigrants are as high as they are in gay men and
often go undetected, and that hepatitis B patients with high viral
loads have a very high rate of liver cancer. 

The good news is that at least two-thirds of patients treated with
tenofovir and FTC or 3TC develop undetectable hepatitis B viral loads.
However the 10-30% of patients who fail to respond are not always the
same as those who fail HIV therapy, showing that transmitted drug
resistance is becoming important in people with hepatitis B too. 

One presentation from Toronto (Wong) discussed four cases of people
with HIV who developed new hepatitis B infections despite previous
hepatitis B vaccination. In two cases they developed chronic hepatitis
B infection â an unusually high rate given that only about 10-15% of
people with HIV who acquire hepatitis B normally go on to develop the
chronic disease. 

In one case the patient had had three full courses of hepatitis B
vaccination, one before he acquired HIV, but had failed to develop
immunity. Three years after being diagnosed with HIV he developed acute
hepatitis with high liver enzymes, but was able to get rid of the
infection. In the second case, the patient acquired hepatitis B in 2007
despite having been vaccinated and having immunity to hepat
gnosed with HIV. He also resolved his infection. 

In the other two cases, however, the patients developed chronic
infections. In both cases the patients had had hepatitis B vaccination
but their immunity status was unknown. The third case was vaccinated in
2004 at the time of his HIV diagnosis but presented with hepatitis
symptoms a year later. He refused antiretroviral drugs and went on to
develop chronic hepatitis B. 

In the final case a long-term survivor of HIV (diagnosed in the 1980s)
was vaccinated for hepatitis B in 2005 but presented with hepatitis
symptoms in 2009. It was thought these were due to his HIV therapy (he
was multi-drug-resistant and was on etravirine, darunavir and
raltegravir, none of which work against hepatitis B), so this was
stopped. However it later turned out he had had acute hepatitis B and
went on to develop the chronic disease. He is now taking tenofovir/FTC (Truvada) for his hepatitis B but remains off HIV therapy. 

Emma Page from Londonâs Chelsea and Westminster Hospital presented a
case where hepatitis C therapy apparently caused a flare-up of
hepatitis B infection in a patient, despite their having been
vaccinated for hepatitis B (and hepatitis A) at the time of HIV
diagnosis. It was known he had had hepatitis B infection many years
previously but his immunity to it had waned, though there was no sign
of chronic infection. He developed acute hepatitis C just a few months
after his HIV diagnosis and was put on pegylated interferon and
ribavirin for hepatitis C, but not on HIV therapy as he had a high CD4
count. 

A couple of months into his treatment he developed hepatitis symptoms
and very high liver enzyme levels (and also anaemia) and was found to
have an acute hepatitis B infection. It was concluded that this was not
a new infection but a resurgence of his original infection from years
back. Dr Page hypothesised that the interferon therapy had caused a
form of IRIS. In hepatitis C and A the liver damage is caused directly
by the virus but in hepatitis B the damage is ca
uppresses hepatitis C may, it appears,
sometimes reactivate hepatitis B. 

Dr Vincent Soriano of Carlos III Hospital in Madrid outlined some
of the serious consequences of unchecked hepatitis B infection. In a
cohort of 3500 HIV/hepatitis B co-infected patients, 10% developed
liver cancer in 11 years and 5% (184 patients) liver cancer. 

In America, David Thomas of Johns Hopkins University told the
conference that patients co-infected with HIV and hepatitis B had an
annual mortality rate due to liver disease of 1.4%; in contrast in
people with HIV alone annual liver-related mortality was 0.17% and in
people with hepatitis B alone 0.08%. 

Evidence has also been accumulating that hepatitis B infection
exacerbates CD4 decline in patients with HIV. Sorriano said that in the
SMART Trial, patients in the âDrug Conservationâ arm who stopped
therapy at 350 CD4 cells/ml3 and resumed it at 250 were much more likely to resume therapy if they
had hepatitis B: after 18 months, nearly 80% of HIV/hepatitis B
co-infected patients had resumed therapy compared with 45% with HIV
alone and 48% co-infected with hepatitis C. 

However Thomas told the conference that patients with HIV and hepatitis
B who started HIV therapy had exactly the same increases in CD4 count. 

Worldwide, hepatitis B is most prevalent in sub-Saharan African and
central and east Asia. A substantial proportion of Africans with HIV
also have hepatitis B, though the majority of them get hepatitis B
through mother-to-child transmission and then HIV through sex in adult
life, whereas in the developed world both viruses are acquired most
often sexually. 

A team from Londonâs Royal Free Hospital surveyed its patients with
chronic hepatitis B and found that 38% were African; a third were women
compared with only 4% of the non-African group. African patients were
three times less likely to have the hepatitis B e antigen, an indicator
of current liver inflammation, than non-African patients but seven
times more likely to have liver cirrhosis, an indicator of thei
rs commented that the high prevalence of chronic hepatitis B
and the advanced nature of liver disease in African patients had
implications for antiretroviral rollout in Africa, with the most
commonly-available drugs either inactive against hepatitis B or, in the
case of 3TC, causing resistance when given as monotherapy. 

All patients in the Royal Free were on HIV regimens that contained
drugs active against hepatitis B (tenofovir plus either FTC or 3TC) and
seven out of every eight patients (87.5%) had an undetectable hepatitis
B viral load (under 1000 copies/ml3). 

There is however no standard definition of âundetectableâ and a study
from the Chelsea and Westminster Hospital found that only 66% of
patients were undetectable according to the stricter definition of
below 34 copies/ml3, with another 23% partially suppressed (between 34 and 10,000 copies/ml3)
and 11% over 10,000. However 74% of patients on tenofovir/FTC or
tenofovir/3TC had fully suppressed viral loads; the lower average
figure was due to less suppressive regimens. 

While some hepatitis B treatment failures are due to poor adherence to
what for most patients is essentially two-thirds of their HIV drug
regimen, some is due to drug-resistant hepatitis B. A study of 119
HIV/hepatitis B co-infected patients in Portuguese clinics of whom 87%
were on tenofovir/FTC, 9% on 3TC monotherapy and 4% on solo tenofovir
found that 18% had detectable hepatitis B. Eight of these (38% of
failures) had poor adherence. But two patients taking solo 3TC and 10
patients on tenofovir/FTC had one to three drug resistance mutations
(57% of failures), mainly due to previous 3TC monotherapy. 

Can chronic hepatitis B infection be cured? In the Portuguese cohort
just three patients developed antibodies to the surface antigen of
hepatitis B, which would indicate immunity if they were vaccinated. One
Italian case achieved hepatitis B immunity and no sign of hepatitis B
DNA sustained for over a year by adding a yearâs course of interferon
to antiviral drugs. 


References
e fifth International Workshop on HIV and Hepatitis Co-infection in Lisbon, 4-6 June 2009. 

Wong D et al. Acute hepatitis B infection in hIV-infected patients despite prior HBV vaccination. Poster presentation P_40. 
Page, E. Clinical case presentation on acute HCV. 

Soriano, V. Invited lecture: HBV therapies. 

Thomas, D. Review of data from major cohorts in U.S. 

Armenis K et al. HIV/HBV co-infection: a comparison of viral
characteristics and liver disease in African patients and Caucasian
patients in Europe â implications for ART rollout in sub-Saharan Africa. Poster presentation P_46. 

Nelson M et al. How successful are we at treating hepatitis B? Poster presentation P_45. 

Corte-Real R et al.Evaluation of HBV treatment efficacy in patients co-infected with HIV and hepatitis B. Poster presentation P_41. 

Angeli E at al. Complete cure of chronic hepatitis B in a
HIV-positive patient with sequential therapy based on tenofovir and 48
weeks of pegylated interferon alpha-2a. Poster presentation P_39.