Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Chronic Hepatitis B”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1999

Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B, chronic hepatitis B and hepatitis B liver cirrhosis before and after liver transplantation.

BACKGROUND: Several studies have shown that hepatitis B immunoglobulin (HBIG) imposes a selection pressure on the hepatitis B virus (HBV) S gene, and that the emergence of mutations in this region would make reinfection after orthotopic liver transplantation (OLT) possible. AIMS: This study was undertaken to analyze the presence of HBV S-gene mutations in the different stages of HBV infection and the relationship between HBIG therapy and the emergence of mutations in liver transplant recipients. METHODS: The frequency and location of mutations in the coding region of the HBV S gene were studied by PCR and direct sequencing in 30 patients (7 with acute self-limited hepatitis B, 16 with chronic hepatitis B and 7 recipients of (OLT) for HBV-related end stage liver disease who became reinfected). RESULTS: The average number of amino acid changes was higher in patients with a more advanced stage of disease, 0.57 mutations/100 positions in acute hepatitis B and 1.57 in chronic hepatitis B (1.28 in HBeAg-positive and 1.8 in anti-HBe-positive patients). The average number of substitutions in the transplanted patients was 2.7 before OLT and 3 after OLT. No amino acid substitutions were detected in the "a" determinant of HBsAg in acute hepatitis B, however, 8 substitutions were observed in 6 chronic patients. In 3 OLT patients, 4 substitutions were observed in samples before and after OLT. One of these patients, who had protective levels of anti-HBs, showed 3 additional new amino acid substitutions after OLT, suggesting escape mutant selection by the effect of HBIG therapy. No changes were observed between the consensus sequences obtained several years before and after transplantation, indicating consensus sequence stability. CONCLUSION: These results show that there is an accumulation of HBV S-gene mutations in HBV-related end-stage liver disease. Prophylaxis with HBIG mainly obtained from acute self-limited hepatitis patients who have a highly homogeneous viral population, may be one factor underlying the reinfection after liver transplantation.

Acute Disease↗
PubMed2002

Update on the management of chronic hepatitis B.

Chronic hepatitis B virus infection is common and may cause significant disease morbidity, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatitis B surface antigen-positive patients should have a detailed serologic evaluation including determination of the level of replication. Patients with high levels of virus replication and those with co-infection should be considered for treatment. Interferon was the first approved therapy for chronic hepatitis B and remains one of the most effective options. Newer agents, such as lamivudine and adefovir dipivoxil, offer excellent antiviral activity and ease of administration, although drug resistance is common with lamivudine.

Adenine↗
PubMed1993

Historical treatment of chronic hepatitis B and chronic hepatitis C.

Interferon is currently considered to be the only accepted effective treatment for chronic viral hepatitis. A history of the treatment of chronic hepatitis B and C before the use of interferon is presented here. Hepatitis B virus does not seem to be directly cytopathic and the disease is known to be modulated largely by the host's immune response. Experience with immunosuppressant and immunostimulant drugs and a wide variety of antiviral agents, however, has indicated that none of these are of any benefit in patients with chronic hepatitis B, with the possible exception of adenine arabinoside. In view of the much more recent identification of the hepatitis C virus, studies of therapy for chronic hepatitis C are inevitably less extensive. A pilot study using acyclovir in patients with chronic non-A, non-B hepatitis did not show any benefit, although the treatment period may have been too short for the results to be conclusive. The only agent other than alpha interferon to be tried in chronic hepatitis C is ribavirin, which may have some activity. Many of the agents studied in chronic hepatitis B should also be investigated for the treatment of patients with chronic hepatitis C.

Adjuvants, Immunologic↗
PubMed2004

Review article: current management of chronic hepatitis B.

Chronic hepatitis B can be diagnosed in patients with increased aminotransferases, hepatitis B virus viraemia and necroinflammation with fibrosis on liver biopsy. Although, ideally, all patients with chronic hepatitis B should be treated, therapeutic intervention is currently recommended for cases with a relatively satisfactory likelihood of response and/or advanced disease. A realistic therapeutic approach aims to sustain hepatitis B e antigen (HBeAg) loss and hepatitis B e antibody (anti-HBe) seroconversion in HBeAg-positive chronic hepatitis B and to sustain biochemical and virological remission in HBeAg-negative chronic hepatitis B. Currently, three drugs are licensed for chronic hepatitis B: interferon-alpha, lamivudine and adefovir dipivoxil. In patients with HBeAg-positive chronic hepatitis B, all of these drugs achieve HBeAg loss (24-33%) and anti-HBe seroconversion (12-30%) rates significantly superior to those observed in untreated placebo controls. In patients with HBeAg-negative chronic hepatitis B, the sustained off-therapy response rate is 20-25% after a > or =12-month course of interferon-alpha and minimal (<10%), if any, after a 12-month course of lamivudine or adefovir. Long-term lamivudine induces an initial response in 70-90% of patients, but only 30-40% of patients remain in remission after the third year due to progressively increasing viral resistance. Long-term adefovir achieves a response in approximately 70% of patients at 12 months, which is maintained at 24 months with rare (<2%) drug resistance. Adefovir is also effective against lamivudine-resistant strains. Many other anti-viral agents, immunomodulatory approaches and combination therapies are currently being evaluated in chronic hepatitis B.

Antiviral Agents↗
PubMed2006

Natural course, therapeutic options and economic evaluation of therapies for chronic hepatitis B.

Chronic hepatitis B virus infection afflicts 400 million people worldwide and untreated will progress to cirrhosis in 15-40% of individuals, with an associated increased risk for the development of hepatocellular carcinoma. The 'inactive carrier state' carries a benign prognosis with a very low risk of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive chronic hepatitis state is an active disease state with increased risk for progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant variety of chronic hepatitis B has been associated with a higher incidence of cirrhosis at initial presentation and more frequent progression to hepatocellular carcinoma compared with the wild-type hepatitis B. Five medications are currently approved by the US FDA for the treatment of chronic hepatitis B: interferon-alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a. Interferon-alpha therapy has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but has significant adverse effects and is ineffective against the HBeAg-negative mutant. Lamivudine is a safely used, orally administered drug with good efficacy, but is associated with the development of a lamivudine-resistant (Lam-R) mutant in a large proportion of patients after long-term therapy. High relapse rates after lamivudine therapy make this medication less effective in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used, orally administered drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is effective against the wild-type and HBeAg-negative hepatitis B and has a very low incidence of resistance development. Entecavir is a highly potent and selective new oral drug against hepatitis B. It has demonstrated no resistance development in treatment-naive patients, but a low incidence of resistance in patients infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once weekly and has improved efficacy compared with standard interferon-alpha and lamivudine. However, it has a similar adverse-effect profile to standard interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in treating chronic hepatitis B patients compared with no therapy. However, results have been conflicting, with earlier studies showing a cost advantage of lamivudine over interferon-alpha and a more recent, comprehensive study favouring interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil 'salvage' after lamivudine resistance development in HBeAg-positive patients.

Antiviral Agents↗
PubMed2001

Diagnosis and management of pre-core mutant chronic hepatitis B.

Chronic hepatitis due to pre-core hepatitis B virus (HBV) mutants presents as hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). HBeAg-negative CHB represents a late phase in the natural course of chronic HBV infection that develops after HBeAg loss and seroconversion to anti-HBe. It is usually associated with pre-core stop codon mutation at nucleotide 1896 (mainly selected in non-A HBV genotypes), but also with other pre-core changes or with mutations in the basic core promoter region (mainly in HBV genotype A). In chronic HBV infections, pre-core mutants can be detected both in patients with HBeAg-negative CHB and in inactive hepatitis B surface antigen (HBsAg) carriers. The diagnosis of HBeAg-negative CHB is based on HBsAg positivity, HBeAg negativity, and mainly on increased alanine aminotransferase (ALT) and serum HBV-DNA levels and exclusion of other causes of liver disease. The differential diagnosis between patients with CHB and inactive HBsAg carriers can be made only by close follow-up of aminotransferase activity and viraemia levels, although the cut-off level of serum HBV DNA has not been definitely determined. IgM anti-HBc levels have also been suggested as an index that increases the diagnostic accuracy for transient hepatitis flares, while liver biopsy confirms the diagnosis and evaluates the severity of the liver disease. Interferon-alpha (IFN-alpha) and lamivudine are the two drugs that have been tried, mainly in the management of HBeAg-negative CHB. A 12-month course of IFN-alpha achieves sustained biochemical remission in about 20% of patients, which has been associated with improvement in the long-term outcome of this subset. A 12-month course of lamivudine is rather ineffective, maintaining remission in less than 15% of patients after cessation of therapy. Long-term lamivudine is associated with progressively increasing rate of virological and subsequent biochemical breakthroughs due to YMDD mutants, with approximately 30% of patients remaining in remission in the third year of therapy. Several other antiviral agents are currently being evaluated in this setting with combined regimens being the most reasonable step for the near future.

Antiviral Agents↗
PubMed2003

Thymosin in the treatment of HBeAg-negative chronic hepatitis B.

Chronic hepatitis B virus (HBV) infection, which can lead to cirrhosis and hepatocellular carcinoma, is a major health threat worldwide. Classic patients with chronic hepatitis B are positive for hepatitis Be-antigen (HBeAg) and HBV-DNA. In the Mediterranean basin, 30-80% of patients with chronic hepatitis B (CHB) are HBeAg-negative, in contrast to Northern European countries and the US, where only 10-40% of CHB patients are lacking HbeAg. HBeAg-negative CHB usually runs a progressive course. The greatest problem with the treatment of HBeAg-negative CHB is the high relapse rate. Their end treatment response rates are similar to those of classic CHB patients, but after discontinuation of treatment most of them relapse. All the data available in the literature show that more than 80% of patients with HBeAg-negative CHB do not respond to the current approved therapies. A literature review and our experience with thymosin indicate that the combination of IFN alpha2b and T-alpha1 is better tolerated and more likely to induce a sustained response in HbeAg-negative chronic hepatitis B patients when compared to other currently available therapies. As thymosin-alpha1 treatment is relatively free from adverse effects, future controlled trials are needed, with a longer follow-up, in order to fully evaluate the role of the combination therapy of thymosin-alpha1 with other emerging therapeutic agents.

2-Aminopurine↗
PubMed2000

Telomerase activity of peripheral blood lymphocytes in patients with chronic hepatitis B.

Chronic hepatitis B is the immunocompromising condition. The decrease of lymphocyte telomerase is linked to immunosenescence in hosts. To know whether telomerase activity of lymphocytes is involved in immunopathogenesis in patients with chronic hepatitis B, telomerase activity of peripheral lymphocytes was determined in such patients. The results showed that telomerase activity in resting peripheral lymphocytes of healthy subjects was detectable at low level, and obviously increased (P<0.001) after stimulation in vitro with phytohaemagglutinin (PHA). Telomerase activity of lymphocytes decreased with age in both groups with or without PHA stimulation. Telomerase activity of resting lymphocytes in patients with chronic hepatitis B was also observed at detectable level and markedly upregulated after PHA stimulation. The decreased telomerase activity of resting lymphocytes was found in patients with chronic hepatitis B (n=14, 0.32+/-0.27) compared to that in healthy subjects (n=17, 0. 52+/-0.28; P<0.05). However, there was no difference present between these two groups in telomerase activity of activated lymphocytes with PHA. In addition, no effect of recombinant human interleukin-12 (rhIL-12) on telomerase expression was observed in either the patient group or the healthy group. We concluded that the decreased telomerase activity of lymphocytes in chronic hepatitis B patients is present, which may be partly responsible for immunosuppressive condition in such patients.

Adolescent↗
PubMed2004

Thymalfasin for the treatment of chronic hepatitis B.

Chronic hepatitis B virus infection is a serious problem because of its worldwide distribution and possible adverse chronic sequelae, such as cirrhosis and hepatocellular carcinoma. Chronic hepatitis B infection is a dynamic state of interactions between the virus, hepatocyte and host immune response. Interferon-alpha and direct antiviral agents, such as lamivudine (Epivir, GlaxoSmithKline), are effective in the therapy of chronic HBV infection but the efficacy is far from satisfactory. Thymalfasin (thymosin alpha1; Talpha1, Zadaxintrade mark, SciClone Pharmaceuticals, Inc.) is a 28-amino acid polypeptide produced synthetically but originally isolated from thymosin fraction 5, a bovine thymus extract containing a number of immunologically active peptides. In vitro studies have shown that Talpha1 can influence T-cell production and maturation, stimulate production of Th1 cytokines such as interferon-gamma and interleukin-2, and activate natural killer cell-mediated cytotoxicity. Seven randomized controlled studies on Talpha1 monotherapy in patients with chronic hepatitis B showed that 6 months treatment with Talpha1 (1.6 mg twice-weekly) resulted in a significantly higher sustained response rate than untreated controls. The benefits of Talpha1 therapy is usually not immediately apparent during therapy. There is a trend for complete virological response to increase or accumulate gradually after the end of thymosin therapy. The results of Talpha1 and interferon combination therapy in two open-label trials were also promising. In terms of the mechanisms of action, a combination of Talpha1 and nucleoside or nucleotide analogs is a logical approach in the control of chronic HBV infection and a randomized control study is ongoing.

Animals↗
PubMed1996

Long-term effects of interferon-alpha in five HIV-positive patients with chronic hepatitis B.

Chronic hepatitis B viral infection is common in human immunodeficiency virus (HIV) carriers, but the effectiveness of interferon therapy is still unknown. We report the results of a long-term pilot study of five patients, who were infected with HIV and chronic hepatitis B, treated by interferon. Five males co-infected with HIV and hepatitis B virus (HBV) (mean age 27 years) were given a 6-month course of interferon (IFN)-alpha 2b 5 million units (MU) three times weekly. On initiating the treatment, their CD4 lymphocyte count was 340-553 mm-3, their CDC stage was IIa-III; all had histologically proven chronic hepatitis, with Knodell's score ranging from 6-10, and active HBV replication (HBV DNA and hepatitis B e antigen (HBeAg) were detectable). There was no associated hepatitis delta virus (H delta V) or hepatitis C virus (HCV) infection. Follow-up was for 53 months on average (24-74 months). After the treatment, hepatitis B e antibody (HBeAb) and hepatitis B s antibody (HBsAb) seroconversion was observed in one patient, HBeAb seroconversion alone in two patients, HBV DNA was absent from serum in three patients, and HBV DNA significantly decreased in one patient. The serum alanine aminotransferase (ALT) activity was normal in four patients. Histological improvement was obtained in four patients. The HIV stage remained unchanged in all patients during the whole follow-up. These preliminary results suggest that interferon can be successfully used in immunocompetent HIV carriers with chronic hepatitis B as well as in HIV-negative patients.

Acyclovir↗
PubMed2003

Anticardiolipin antibodies in chronic hepatitis B and chronic hepatitis D infection, and hepatitis B-related hepatocellular carcinoma. Relationship with portal vein thrombosis.

OBJECTIVE: To assess the presence of anticardiolipin antibodies (ACAs) in patients with chronic hepatitis B virus (HBV) infection, chronic hepatitis D virus (HDV) infection and HBV-related hepatocellular carcinoma (HCC) and to associate this with the incidence of portal vein thrombosis (PVT) in HCC patients. PATIENTS AND METHODS: Sixty-five cirrhotic patients with HBV-related HCC, 28 naive patients with chronic HBV infection and 14 naive patients with chronic HDV infection were enrolled prospectively in the study. Thirty-two healthy blood donors were used as controls. The ACAs (immunoglobulin G and immunoglobulin M) were measured using an enzyme-linked immunosorbent assay system. Statistical analysis used non-parametric methodology (chi-squared test, Student t-test and Fisher exact test, P value<0.05). RESULTS: Eleven of the 65 patients with HCC (16.9%) showed a positive ACA titre and 22 of the patients (34%) had PVT. Of these patients, eight (36%) had a positive ACA titre. In contrast, from the 43 patients without PVT, only three (11%) showed a positive titre. From the 28 HBV patients, six (21.5%) had a positive ACA titre, and six out of 14 (42.8%) HDV patients also showed a positive ACA titre. Three of the six ACA positive HBV patients presented an extrahepatic manifestation of the disease. One out of 32 control patients (3%) had positive ACAs. CONCLUSION: Both chronic HBV and chronic HDV infections are potent stimulants for the production of ACAs. The presence of ACAs in a great proportion of HBV-cirrhosis-related HCC patients with PVT suggests their possible participation in thrombotic mechanisms and in the hypercoagulable state that occurs in advanced liver disease and HCC.

Adult↗
PubMed2003

Agents in clinical development for the treatment of chronic hepatitis B.

Chronic hepatitis B remains a public health problem of global importance despite the availability of an effective vaccine. Between 350 and 400 million people, approximately 6% of the world's population, suffer from chronic hepatitis B and face a 30% likelihood of developing cirrhotic liver disease or hepatocellular carcinoma. Current treatment options include three monotherapies of subcutaneous interferon, oral nucleoside lamivudine and oral nucleotide adefovir dipivoxil. Unfortunately, these agents have not effectively and frequently been able to attain a 'cure' or complete eradication of the virus. Consequently, the expectation of current therapies is confined to the achievement of clinically beneficial and durable responses defined by lasting suppression of virus replication, histological improvement and increased survival for patients with decompensated liver diseases. Other disadvantages include the undesirable tolerability of interferon, the rapid resistance to lamivudine and the compromise between efficacy and toxicity that led to the development of the 10 mg dose of adefovir dipivoxil. Clearly, better therapeutics and treatment strategies are needed. Increased potency, activity against current treatment-refractory viruses, as well as efficacy in difficult-to-treat populations will be critical to meeting the therapeutic challenge of chronic hepatitis B.

Adjuvants, Immunologic↗
PubMed2004

Thymalfasin (thymosin-alpha 1) therapy in patients with chronic hepatitis B.

Chronic hepatitis B virus (HBV) infection is a serious clinical problem because of its worldwide distribution and potential adverse sequelae. Globally, there are approximately 350 million people infected with chronic HBV, 75% of whom live in the Asia-Pacific region. Interferon-alfa and direct antiviral agents such as lamivudine and adefovir are effective in the therapy of chronic HBV infection but the efficacy is far from satisfactory, particularly in perinatally infected patients, patients with lower ALT levels and those with HBeAg-negative chronic hepatitis B. Thymalfasin (thymosin-alpha1) is an immunoregulatory agent able to enhance Th1 response. It has been shown to trigger maturational events in lymphocytes, to augment T-cell function, and to promote reconstitution of immune defects. Studies are underway in both monotherapy and combination therapy with thymalfasin and interferon and results are promising.

Antiviral Agents↗
PubMed2004

Thymalfasin (thymosin-alpha 1) therapy in patients with chronic hepatitis B.

Chronic hepatitis B virus (HBV) infection is a serious clinical problem because of its world-wide distribution and potential adverse sequelae. Globally, there are approximately 350 million people infected with chronic HBV, 75% of whom live in the Asia-Pacific region. Interferon-alfa and direct anti-viral agents such as lamivudine and adefovir are effective in the therapy of chronic HBV infection but the efficacy is far from satisfactory, particularly in perinatally infected patients, patients with lower ALT levels and those with HBeAg-negative chronic hepatitis B. Thymalfasin (thymosin-alphal) is an immunoregulatory agent able to enhance Thl response. It has been shown to trigger maturational events in lymphocytes, to augment T-cell function, and to promote reconstitution of immune defects. Studies are underway in both monotherapy and combination therapy with thymalfasin and interferon and results are promising.

Adjuvants, Immunologic↗
PubMed2006

Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C.

The clinical manifestations of chronic hepatitis B (CH-B) and chronic hepatitis C (CH-C) are different. We previously reported differences in the gene expression profiles of liver tissue infected with CH-B or CH-C; however, the signaling pathways underlying each condition have yet to be clarified. Using a newly constructed cDNA microarray consisting of 9614 clones selected from 256,550 tags of hepatic serial analysis of gene expression (SAGE) libraries, we compared the gene expression profiles of liver tissue from 24 CH-B patients with those of 23 CH-C patients. Laser capture microdissection was used to isolate hepatocytes from liver lobules and infiltrating lymphoid cells from the portal area, from 16 patients, for gene expression analysis. Furthermore, the comprehensive gene network was analyzed using SAGE libraries of CH-B and CH-C. Supervised and nonsupervised learning methods revealed that gene expression was correlated more with the infecting virus than any other clinical parameters such as histological stage and disease activity. Pro-apoptotic and DNA repair responses were predominant in CH-B with p53 and 14-3-3 interacting genes having an important role. In contrast, inflammatory and anti-apoptotic phenotypes were predominant in CH-C. These differences would evoke different oncogenic factors in CH-B and CH-C. In conclusion, we describe the different signaling pathways induced in the livers of patients with CH-B or CH-C. The results might be useful in guiding therapeutic strategies to prevent the development of hepatocellular carcinoma in cases of CH-B and CH-C.

Adolescent↗
PubMed2006

[Treatment of chronic hepatitis B].

Chronic hepatitis B develops in 3 phases: immune tolerance, where viral replication is strong and there is little or no fibrosis; immune activity phase with low viral replication and rapidly developing fibrosis as well as an elevated risk of cirrhosis; low viral replication and remission, with a risk, nonetheless, of reactivation. Antiviral treatment is indicated in patients with moderate or severe levels of either fibrosis or activity (necrotic and inflammatory lesions). Standard interferon treatment produces a prolonged response rate on the order to 20-40%; side effects are frequent but generally mild and reversible when treatment stops. Pegylated interferon (standard interferon conjugated with polyethylene glycol) has substantially better efficacy and comparable tolerance. Lamivudine (a nucleoside analog) has several advantages over interferon: oral administration, excellent tolerance, and rapid antiviral effect. Its principal disadvantage is the frequency of resistant mutations. Adefovir and entecavir have oral administration, are well tolerated and associated with a low incidence of resistance. They induce a sustained response after withdrawal of therapy in only a minority of patients and therefore the treatment needs to be indefinitely administered in the majority of patients.

Adenine↗
PubMed2000

Role of steroid priming in the treatment of chronic hepatitis B.

Chronic hepatitis B is the result of the immunological response of the host to persistently replicating hepatitis B virus. Steroids can modulate this response; after steroid administration, viral replication increases and after drug withdrawal, it decreases in conjunction with a temporal increase in the transaminase level. Long-term decrease of the viral level is observed in some patients, but the beneficial effect of steroid withdrawal alone has not been confirmed. Interferon and other anti-viral agents can suppress virus replication, but the effect of these agents is still unsatisfactory. The combination of steroid priming and anti-viral treatment may be beneficial. Recent large-scale controlled trials indicate the utility of the combination therapy, but other randomized trials show no significant difference between therapy with or without steroid priming. Although steroid priming in combination with antiviral agents may be useful in some patients, it should be carefully performed due to the potential risk of liver failure.

Antiviral Agents↗