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Editorial Board: Emmet B. Keeffe, MD (Chair); |
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HBV
Watch™ |
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Timely Information for Practicing Physicians |
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NOVEMBER 2005
LIVER
Transplantation for Hepatitis B virus (hbv) infection
Prevention of HBV reinfection after liver transplantation. Combination prophylaxis using
hepatitis B immune globulin (HBIG) and lamivudine has reduced the incidence of HBV
reinfection after liver transplantation to between 5% and 15%. Despite the
availability of three nucleoside analogs with proven activity against HBV, HBIG
remains a key component in the prophylactic regimen against HBV reinfection
after liver transplantation. Early attempts to discontinue HBIG 6 to 12 months
after transplantation failed because of a high rate of lamivudine-resistant
mutations. A major problem with the long-term use of HBIG is its cost. Various
investigators have examined whether active immunization with HBV vaccine
(standard or with a more potent adjuvant) can replace HBIG. Four studies in
addition to Starkel’s have been reported. All included patients who had
undergone transplantation at least 1 or 2 years earlier; most patients were hepatitis
B e antigen (HBeAg)- and/or HBV DNA-negative prior to transplantation, and a
disproportionately high percentage had fulminant hepatitis or hepatitis D virus
superinfection. Despite favorable features, the overall success of HBV vaccine
in inducing protective levels of hepatitis B surface antibody (anti-HBs) was
low. Strategies that optimize the efficacy of antiviral therapy are being
explored to determine if they can eliminate the need for, or reduce the
required dosage of, HBIG. These include de novo therapy with an antiviral agent
that has a low risk of drug resistance, such as adefovir, tenofovir, or
entecavir, and a combination of two antiviral agents that are not cross-resistant,
such as lamivudine or emtricitabine plus adefovir or tenofovir.
HBV vaccine permits
withdrawal of HBIG prophylaxis. Starkel and colleagues conducted a study in
which 15 liver transplant recipients (five with nonviral liver disease and ten
with HBV infection on HBIG monotherapy) received a hepatitis B surface antigen
vaccine with a novel adjuvant (HBsAg/AS04). Patients received a double dose of
vaccine at 0, 1, 2, 6, and 12 months. Sustained response, defined as anti-HBs
titers of >500 mIU/L without further need for HBIG for ≥12 months, was
achieved in eight patients (53%). Four (40%) of the patients in the HBV group (two
of two with fulminant disease and two of eight with chronic infection) achieved
a sustained response. No HBV recurrence, rejection episodes, or side effects
occurred in responding patients during follow-up. These data suggest that an
effective vaccine may allow long-term discontinuation of HBIG in a small
percentage of liver transplant recipients with HBV infection. (Starkel P, et
al. Liver Transpl. 2005;11:1228–1234.)
Adefovir
Resistance
Association with viral
rebound and hepatic decompensation. Fung and coworkers reported the
development of adefovir-resistant mutations (rtA181V/T or rtN236T) in eight
male patients with HBV and preexisting lamivudine resistance. Adefovir
resistance was associated with an increase of HBV DNA to ≥5 log10
copies/mL in seven patients and hepatic decompensation in two patients, one of
whom died. Salvage therapy with lamivudine, entecavir, or tenofovir was given
to seven patients, and a reduction in HBV DNA by ≥3 log10 was
seen in three patients. These findings indicate that significant viral rebound
and hepatic decompensation can be associated with adefovir resistance. (
HBV-Associated
Polyarteritis Nodosa (HBV-PAN)
Clinical characteristics
and outcome. HBV- PAN is a typical form of classic PAN, a disease thought to be
due to immune complex deposition and antigen excess. Recently Guillevin and
colleagues reviewed the clinical findings of 115 patients with HBV-PAN who had
participated in various trials organized by the French Vasculitis Study Group between
1972 and 2002. A cohort of 226 patients with PAN without HBV, followed during
the same period, served as controls. Prior to 1983, patients were treated with
corticosteroids with or without cyclophosphamide (n = 35). After 1983, patients
received corticosteroids followed by antiviral therapy combined with plasma
exchanges (n = 80). The most common initial clinical symptoms at the onset of
PAN included asthenia, weight loss, fever, peripheral neuropathy, arthralgias,
and myalgias. Glomerulonephritis due to vasculitis was not reported, and
antineutrophil cytoplasmic antibodies were not detected. Remission was achieved
in 93 patients (80.9%). Remission rates and event-free and overall survival did
not differ between patients who did and did not receive antiviral therapy. However,
when HBeAg seroconversion was achieved, clinical remission of PAN was also
attained and no relapses occurred. (Guillevin L, et al. Medicine. 2005;84:313–322.)
HEPATOCELLULAR
CARCINOMA (HCC)
Risk of HBV exacerbation
after transcatheter arterial chemoembolization (TACE). Systemic chemotherapy
may lead to reactivation of HBV infection. Park and others prospectively
investigated 69 patients with HBV-related HCC who underwent a course of TACE (performed
with doxorubicin 20 to 60 mg and iodinated oily contrast medium 2 to 20 mL) to
determine if the localized hepatic arterial infusion of chemotherapy aggravates
chronic HBV infection. Twenty patients with HBV-related HCC who were awaiting
TACE therapy or were in prolonged follow-up after TACE were enrolled in the
control arm. HBV reactivation occurred in three patients (4.3%) in the TACE
group and two patients (10%) in the control group. A greater-than-twofold
increase in serum HBV DNA levels was detected in 21 patients (30.4%) in the
TACE group and four patients (20%) in the control group (P = 0.361). Exacerbation of HBV infection occurred in four patients
in the TACE group but no patients in the control group. These data indicate
that the risk of HBV exacerbation is low following one course of TACE therapy
in patients with HBV-related HCC. However, other studies have reported higher
rates of reactivation among patients who received multiple courses of TACE. (Park
J-W, et al. Am J Gastroenterol.
2005;100:2194–2200.)
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