,
aCurrent research
“Severe Exacerbation of Chronic Hepatitis B after Emergence of Lamivudine Resistance in a Cirrhotic Patient: Immediate Switch to Adefovir Dipivoxil Appears to be Indicated.”
J. Wiegand1,6, J. J. W. Tischendorf1,6, B. Nashan2, J. Klempnauer2, P. Flemming3, P. Niemann4, P. Rohde5, M. P. Manns1, C. Trautwein1, H. L. Tillmann1
http://www.thieme-connect.com/DOI/DOI?10.1055/s-2004-812683
Developing lamivudine-resistant strains of Hepatitis B is a common problem when treating chronic hepatitis with lamivudine. This article profiles a case study of a 31-year old man suffering from chronic Hepatitis B infection and cirrhosis of the liver. After developing resistance to lamivudine, adefovir dipivoxil therapy was administered (10 mg per day) to treat the resulting subacute liver failure. The progression of liver failure was markedly slowed, and the viral load dropped significantly after the start of adefovir therapy. The patient eventually needed a liver transplant, although this could have been avoided had adefovir therapy begun earlier. In conclusion, adefovir dipivoxil is a promising drug to manage lamivudine-resistant strains of Hepatitis B and should be initiated as soon as resistance is suspected to avoid complications such as liver transplantation.
“Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B.”
Monika van Zonneveld 1, Pieter Honkoop 1, Bettina E. Hansen 2, Hubertus G.M. Niesters 3, Sarwa Darwish Murad 1, Robert A. de Man 1, Solko W. Schalm 1, Harry L.A. Jansse
http://www3.interscience.wiley.com/cgi-bin/fulltext/107630490/HTMLSTART
To investigate the effects of long-term alpha-interferon (Intron A ©) therapy, 165 patients (123/165 Caucasian) with chronic Hepatitis B who were treated with alpha-interferon therapy between 1978 and 2002 were included in this follow-up study. Long-term follow-up in essential to investigate the outcome of therapy associated with liver cancer (hepatocellular carcinoma or HCC), because HCC may take years to develop. The median treatment duration was 16 weeks, the median time lapse between treatment and follow-up was 8.8 years, and the median dosage was 30 megaunits/week. Survival was significantly higher in patients responded favorably to alpha-interferon therapy (33%). This trend may be explained by decreased incidence of HCC in responders. However, responders were twice as likely as nonresponders to develop cirrhosis. In general, the long-term effects of alpha-interferon therapy are favorable and lead to higher survival rates with less severe complications.
“Predicting relapse after cessation of Lamivudine monotherapy for chronic hepatitis B virus infection.”
Ito K, Tanaka Y, Orito E, Hirashima N, Ide T, Hino T, Kumashiro R, Kato A, Nukaya H, Sakakibara K, Mukaide M, Ito H, Sata M, Ueda R, Mizokami M.
Clin Infect Dis. 2004 Feb 15;38(4):490-5. Epub 2004 Jan 30
http://www.journals.uchicago.edu/CID/journal/issues/v38n4/31616/31616.html
This study investigated factors that could be used to predict relapse after lamivudine therapy (when taken alone to treat Hepatitis B) was stopped. 22 patients were involved in the study Results were generally inconclusive; the only independent predictive factor that was correlated with relapse after cessation of lamivudine therapy was the duration of nondetectable blood levels of HBV. Only if HBV cannot be detected in the blood for 6 months of longer is cessation of lamivudine therapy the recommended course of action. Shorter durations may encourage seroconversion to a resistant strain of Hepatitis B.
“Treatment of chronic Hepatitis B infection via oral immune regulation toward Hepatitis B proteins.”
Rifaat Safadi M.D.a,
Eran Israeli M.D.a,
Orit Papo M.D.b,
Oren Shibolet M.D.a,
Alaa Melhem M.D.a,
Aharon Bloch M.D.a,
Mina Rowe R.N.a,
Ruslana Alper B.Sc.a,
Athalia Klein M.A.a,
Nilla Hemed R.N.a,
Ori Segol M.D.c,
Barbara Thalenfeld Ph.D.c,
Dean Engelhardt Ph.D.d,
Elazar Rabbani Ph.D.d
and Yaron Ilan M.D.,
a
The American Journal of Gastroenterology
Volume 98, Issue 11 , November 2003, Pages
2505-2515
Administration of Hepatitis B virus envelope proteins is a novel therapy in chronic hepatitis B infection. Specifically, it combats the liver damage caused by the immune response to the virus. HBsAg, preS1 and preS2 were given orally three times per week for 20-30 weeks in this study, involving 42 patients with chronic Hepatitis B infections. Patients’ HBV-DNA levels were evaluated during and after the study, in addition to their liver enzymes and liver histology. In one third of patients, HBV viral load decreased significantly. Additionally, liver inflammation improved significantly in one third of the study participants. Proliferation of HBV-specific T cells – an essential factor in the immune response to an viral infection – increased in 78% of patients, and all patients experienced an increase in Natural Killer Cells, another key player in the immune response. Therefore, the therapy was effective at combating infection and inducing a stronger immune response Since an ineffective immune response mediates long-term liver damage in chronically-infected HBV patients, and since this therapy caused no adverse side effects, this is a promising therapy to reducing liver damage in that population.
“Specific mutations of hepatitis B virus in plasma predict liver cancer development.”
Kuang SY, Jackson PE, Wang JB, Lu PX, Munoz A, Qian GS,
Kensler TW, Groopman JD.
*Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe
Street, Baltimore, MD 21205; ()Qidong Liver Cancer Institute, Qidong 226200,
Jiangsu Province, People's Republic of China.
Proceedings of the Natonal Academy of Sciences, U S A. 2004 Feb 27.
This study compiled the results of several different research projects to evaluate the correlation between two specific mutations in the HBV genome – 1762(T) and 1764(A) - and the incidence of hepatocellular carcinoma (HCC). This double mutation is more common in genotype C of HBV, a strain commonly found in East Asia. The mutation alters the X protein, which plays a crucial but not-fully-understood role in the immune response to HBV and the subsequent development of HCC. There was a strong relationship between the double mutation and HCC, indicating that a test for this mutation could have predictive value as to whether HCC would develop, especially if used in combination with the less specific test for alpha-fetoprotein in HBV and HCV patients. By identifying patients at high-risk of developing HCC early, interventions could be more successful to managing or even preventing HCC.
http://www.pnas.org/cgi/reprint/0308232100v1.pdf
"Identification of hepatitis B virus vertical transmission from father to
fetus by direct sequencing."
Wang S, Peng G, Li M, Xiao H, Jiang P, Zeng N, Wang Z.
Department of Epidemiology, Medical Institute of Guangzhou Command PLA, Yanling,
Guangzhou, People's Republic of China. doctorxiao@163.net
Southeast Asian J Trop Med Public Health. 2003 Mar;34(1):106-13.
This article makes the surprising conclusion that father to fetus vertical transmission of HBV may be possible. HBV was isolated from the semen of 8 men and from their aborted fetuses. The mothers were all HBV-negative. By comparing the DNA sequences and point mutations of father to fetus, there is reason to conclude that the virus in the fetus originated from the father. In one case, the point mutation in the two was identical, and there were 11 total documented similar mutations. The small sample size, limits the generalizability of the results, but the conclusion that sperm may be a vector for HBV is interesting.