HBV and Hepatocellular Carcinoma Recurrence after Resection Surgery and Liver
Transplantation
By
Liz Highleyman  | |
The Hepatitis B virus (HBV) attacks the liver, causing lifelong infection,
cirrhosis (scarring) of the liver, liver cancer, liver failure and death. |
|
Hepatocellular
carcinoma (HCC) is a possible long-term consequence of chronic
hepatitis B virus (HBV) infection that may necessitate partial liver resection
(surgery) to remove tumors or complete liver transplantation. In
2 recent studies, researchers reported that people with a high HBV viral load
at the time of resection were more likely to experience HCC relapse, and conversely,
that people with HCC have a higher risk of HBV recurrence following liver
transplantation. Study
1
In
the first study, published in the July 2008 American Journal of Gastroenterology,
researchers from Hong Kong looked at risk factors for recurrence of HBV-related
HCC recurrence after resection.
The study included 72 patients who underwent
liver resection for HBV-related HCC; about 80% were men and the median age was
53 years. Demographic, biochemical, tumor, and viral factors at the time of resection
were evaluated using univariate and multivariate analyses to identify risk factors
associated with cancer relapse. Participants were followed for a median of 18.9
months.  | | What
is Hepatocellular Carcinoma? Most primary liver cancers are classified as hepatocellular
carcinoma. Hepatocellular carcinoma is a malignant tumor composed of cells resembling
hepatocytes ; however, the resemblance varies with the degree of differentiation
. Hepatocellular carcinoma is commonly associated with cirrhosis |
|
Results
•
Factors significantly
associated with an increased risk of HCC recurrence after resection were:
•
Age > 60 years;
•
Tumor
size > 5 cm;
•
Poorly differentiated tumors;
•
Lymphovascular permeation of cancer;
•
Presence of microsatellite lesions;
•
Alpha-fetoprotein (AFP) level > 1,000 ng/mL;
•
HBV DNA viral load > 2,000 IU/mL (4 log10 copies/mL) at the time of resection;
•
HBV genotype C;
•
Presence of HBV core promoter mutation;
•
Lack of antiviral treatment after resection.
•
In a multivariate analysis,
the following remained independent risk factors for HCC recurrence:
•
HBV viral load > 2,000 IU/mL (odds ratio [OR] 22.3; P = 0.001);
•
AFP > 1,000 ng/mL (OR 7.4; P = 0.02);
•
Tumor size > 5 cm (OR 5.1; P= 0.02);
•
Age > 60 years (OR 4; P = 0.01).
Based
on these findings, the study authors concluded, "Viral load of > 2,000
IU/mL (4 log10 copies/mL) is the most important correctable risk factor for HCC
recurrence after resection."
"Whether antiviral therapy in these
patients can decrease tumor recurrence requires further investigations,"
they added.
Study 2
In
a related study described in the June 2008 issue of Gastroenterology, French researchers
assessed the association between presence of HCC prior to orthotopic liver transplantation
and HBV recurrence after the transplant.
As background, the authors noted
that the risk of HBV recurrence after liver transplantation is significantly reduced
by prophylaxis with hyperimmune globulin antibodies (HBIG) and antiviral drugs
such as lamivudine (Epivir-HBV); the influence of HCC on HBV recurrence, however,
remains unclear.
The study included 99 hepatitis B surface antigen (HBsAg)
positive patients who underwent transplantation due to cirrhosis. The median follow-up
period was 43 months. All patients received HBIG and 51 also received lamivudine
and/or adefovir (Hepsera). Of these 99 patients, 31 had HCC before liver transplantation.
Total HBV DNA and covalently closed circular (ccc) DNA were measured in
tumor and non-tumor tissues from the explanted (removed) livers of 16 of these
patients, and also in 3 patients who experienced HBV/HCC recurrence.
Results
•
14
patients (14.1%) developed HBV recurrence within a median period of 15 months
post-transplantation.
•
Factors
independently associated with HBV recurrence after transplantation were: •
HCC at the time of transplantation;
•
Pre-transplant HBV DNA of 100,000 copies/mL or greater;
•
Prophylaxis with HBIG monotherapy.
•
11
of 31 patients (35.5%) with HCC at the time of transplantation experienced HBV
recurrence, compared with 3 of 68 patients (4.4%) without HCC (P < 0.0001).
•
HBV
recurrence was much more frequent in patients who experienced HCC relapse (7 of
8 patients; 87.5%) than in those who did not (4 of 23 patients; 17.4%) (P <
0.0001).
•
In
the 16 explanted livers, cccDNA was detectable in HCC cells from 11 patients and
in non-tumor cells from 12 patients.
•
cccDNA
was detected in 2 of the 3 patients who developed HBV/HCC recurrence.
In
conclusion, the study authors wrote that the associations of HCC prior to liver
transplantation, HCC relapse with HBV recurrence post-transplant, and the detection
of HBV DNA and cccDNA in liver tumors suggest that HBV replication in tumor cells
may contribute to HBV recurrence after transplantation.
7/25/08
References IF
Hung, RT Poon, CL Lai, and others. Recurrence of hepatitis B-related hepatocellular
carcinoma is associated with high viral load at the time of resection. American
Journal of Gastroenterology 103(7): 1663-1673. July 2008. LC
Faria, M Gigou, AM Roque-Afonso, and others. Hepatocellular carcinoma is associated
with an increased risk of hepatitis B virus recurrence after liver transplantation.
Gastroenterology 134(7): 1890-1899. June 2008. (Abstract) |
| |
FDA-approved
Treatments
