Does treatment with interferon-based therapy improve the natural history of chronic hepatitis B infection?
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Antiviral Agents↗
Biomedical subjects
George K K Lau
Publications and source records attributed to George K K Lau.
Colonoscopy demand and practice in a regional hospital over 9 years in Hong Kong: resource implication for cancer screening.
BACKGROUND: The incidence of colorectal cancer (CRC) in Hong Kong is rising. The trend of colonoscopy demand is uncertain. AIM: To investigate colonoscopy demand and practice in a Hong Kong regional hospital over the past nine years. METHODS: Colonoscopy data from 1st January 1997 to 31st August 2005 were retrieved and divided into two equal periods for comparison. Colonoscopy practice and findings between the two periods were compared. RESULTS: There was no change in the number of endoscopists and colonoscopy sessions in the two periods. The number of colonoscopy done in the two periods was 2,681 and 2,871, respectively. The indications for screening of CRC/polyp (9.3 vs. 24.7%, p < 0.0001) and surveillance of CRC/polyp (4.7 vs. 10.9%, p < 0.0001) were increased, but decreased for diarrhea (18 vs. 10.2%, p < 0.0001) and per rectal bleeding (19 vs. 8.1%, p < 0.0001). The waiting time was lengthened from 2 to 4 weeks (p < 0.0001). The percentage of colonic adenomas (19.9 vs. 27.2%, p < 0.0001) was increased. A right-shift was observed in both CRC (37 vs. 50%, p = 0.018) and adenoma (21.6 vs. 38.1%, p < 0.0001). CONCLUSION: The number of colonoscopies performed was governed by capacity partly through lengthening of waiting time to cope with demand. Ways to improve capacity for colonoscopies is needed.
Adolescent↗
Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy.
BACKGROUND & AIMS: De novo hepatitis B virus (HBV)-related hepatitis after chemotherapy results in high morbidity and mortality. We evaluate the clinical course of de novo HBV-related hepatitis after chemotherapy. METHODS: Two hundred forty-four consecutive hepatitis B surface antigen (HBsAg)-negative lymphoma patients treated with chemotherapy were followed up for a median of 12.4 (range, 0.1-65.0) months. Serially collected serum samples were analyzed for hepatitis, serum HBV DNA, and HBsAg seroreversion. RESULTS: Eight of the 244 patients (3.3%) developed de novo HBV-related hepatitis. A 100-fold increase in serum HBV DNA preceded de novo HBV-related hepatitis by a median of 18.5 (range, 12-28) weeks. All 8 patients had normal serum alanine aminotransaminase level when the 100-fold increase in serum HBV DNA occurred. Patients with de novo HBV-related hepatitis were more likely to have occult HBV infection before chemotherapy. Direct sequencing results showed that these 8 patients had de novo HBV-related hepatitis from reactivation of occult HBV infection. Three of the 8 patients with de novo HBV-related hepatitis compared with 6 of the 236 patients without de novo HBV-related hepatitis developed fulminant hepatic failure (37.5% vs 2.5%, respectively, P < .001). On multivariate Cox analysis, de novo HBV-related hepatitis was independently associated with a higher risk of fulminant hepatic failure (relative risk, 29.854; 95% confidence interval: 4.844-183.980; P < .001). CONCLUSIONS: Close surveillance for a 100-fold increase in HBV DNA is recommended for HBsAg-negative patients treated with chemotherapy so that early commencement of antiviral therapy can be initiated before the occurrence of de novo HBV-related hepatitis.
Adult↗
Current issues and future directions in treatment.
The clinical sequelae of chronic hepatitis B (CHB), such as liver cirrhosis and hepatocellular carcinoma, are determined mainly by the host immune response to the hepatitis B virus-encoded antigens. Disease remission in CHB has been associated with sustained viral suppression < 10 (4) to 10 (5) copies/mL. This can be achieved by either restoring the host immune control on the virus with immunomodulatory therapy, such as conventional or pegylated interferon-alfa therapy, or by continuous suppression of the viral replication by nucleos(t)ide therapy, such as lamivudine, adefovir dipivoxil, or entecavir treatment. Given that not all patients can tolerate or will respond to interferon-alfa-based therapy, maintenance therapy with nucleos(t)ide therapy is the alternative. However, this latter approach can lead to development of viral resistance and long-term safety concerns. Further improvement in CHB therapy is limited by a lack of understanding of the host immune characteristics associated with sustained disease remission.
Antiviral Agents↗
Comparison of real-time PCR assays for monitoring serum hepatitis B virus DNA levels during antiviral therapy.
The performance characteristics of the RealART and Molecular Beacons assays were compared with those of the Digene Hybrid Capture II assay (ultrasensitive). The results of the RealART and Digene Hybrid assays were related (r = 0.94; P < 0.001) and diverged by 2 orders of magnitude. The RealART assay can be used to effectively monitor serum hepatitis B virus DNA levels.
DNA, Viral↗
Fibrosis progression in chronic hepatitis C patients with occult hepatitis B co-infection.
Occult hepatitis B virus (HBV) infection in individuals without hepatitis B surface antigen (HBsAg) can be identified in hepatitis C virus (HCV) infected patients. However, its role in fibrosis progression remains uncertain. This retrospective study compared the fibrosis progression (defined as fibrosis progression by at least one stage) and progression to severe fibrosis (fibrosis stage 3 or 4) in HCV patients with occult HBV infection. Occult HBV infection was diagnosed by the detection of HBV DNA in the serum of 74 consecutive anti-HCV positive patients by PCR. Thirty-one patients (41.9%) had occult HBV infection. All 74 patients had a median of 2 (range 2-3) liver biopsies. The median time between the first and last liver biopsy was 57.7 (range 15.0-132.8) months. Eleven of the 31 patients with occult HBV infection compared with 12 of the 43 patients without occult HBV infection had fibrosis progression (35.5% versus 27.9%, respectively, p=0.608). Six of the 31 patients with occult HBV infection compared with 8 of the 43 patients without occult HBV infection developed severe fibrosis (19.4% versus 18.6%, respectively, p=0.946). In conclusion, chronic HCV patients with occult HBV co-infection does not seem to progress more than patients without occult HBV infection. However, more large-scale studies are needed before a definite conclusion can be obtained.
DNA, Viral↗
Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B.
BACKGROUND: Current treatments for chronic hepatitis B are suboptimal. In the search for improved therapies, we compared the efficacy and safety of pegylated interferon alfa plus lamivudine, pegylated interferon alfa without lamivudine, and lamivudine alone for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. METHODS: A total of 814 patients with HBeAg-positive chronic hepatitis B received either peginterferon alfa-2a (180 microg once weekly) plus oral placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), or lamivudine alone. The majority of patients in the study were Asian (87 percent). Most patients were infected with hepatitis B virus (HBV) genotype B or C. Patients were treated for 48 weeks and followed for an additional 24 weeks. RESULTS: After 24 weeks of follow-up, significantly more patients who received peginterferon alfa-2a monotherapy or peginterferon alfa-2a plus lamivudine than those who received lamivudine monotherapy had HBeAg seroconversion (32 percent vs. 19 percent [P<0.001] and 27 percent vs. 19 percent [P=0.02], respectively) or HBV DNA levels below 100,000 copies per milliliter (32 percent vs. 22 percent [P=0.01] and 34 percent vs. 22 percent [P=0.003], respectively). Sixteen patients receiving peginterferon alfa-2a (alone or in combination) had hepatitis B surface antigen (HBsAg) seroconversion, as compared with 0 in the group receiving lamivudine alone (P=0.001). The most common adverse events were those known to occur with therapies based on interferon alfa. Serious adverse events occurred in 4 percent, 6 percent, and 2 percent of patients receiving peginterferon alfa-2a monotherapy, combination therapy, and lamivudine monotherapy, respectively. Two patients receiving lamivudine monotherapy had irreversible liver failure after the cessation of treatment--one underwent liver transplantation, and the other died. CONCLUSIONS: In patients with HBeAg-positive chronic hepatitis B, peginterferon alfa-2a offers superior efficacy over lamivudine, on the basis of HBeAg seroconversion, HBV DNA suppression, and HBsAg seroconversion.
Adolescent↗
Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area.
BACKGROUND/AIMS: The acquisition of hepatitis B virus (HBV) infection following organ transplantation from donors with occult HBV infection is an important cause of morbidity and mortality. The aim of this study is to determine the prevalence of occult HBV in allogeneic hematopoietic stem cell (HSC) transplantation donors. METHODS: We performed a retrospective study on 124 consecutive hepatitis B surface antigen negative HSC donors. Their serum samples were analyzed by PCR for the pre-S/S, pre-core/core and X regions of the virus. Samples reactive by at least two PCR assays were considered HBV-DNA positive. RESULTS: Nineteen of the 124 HSC donors (15.3%) had occult HBV infection. Sixteen of these 19 donors with occult HBV infection (84.2%) tested positive for hepatitis B core antibody while 78 of 105 subjects (74.3%) without occult HBV infection were also positive (P=0.56). Fourteen of the 19 donors (73.7%) with occult HBV infection tested positive for hepatitis B surface antibody while 67 of the 105 subjects without occult HBV infection were also positive (P=0.45). CONCLUSIONS: The prevalence of occult HBV infection among HSC donors in Hong Kong is high. Anti-HBc and anti-HBs status had no significant correlation with the presence of occult HBV infection.
Adult↗
A long-term follow-up study on hepatitis B surface antigen-positive patients undergoing allogeneic hematopoietic stem cell transplantation.
The long-term hepatic complications after allogeneic hematopoietic stem cell transplantation (HSCT) in hepatitis B virus (HBV) endemic area are unknown. We examined the serological and liver-related outcome of 803 consecutive patients who received allogeneic HSCTs, with a median follow-up period of 83 months (range, 0.5-155 months). Late HBV-related hepatitis occurred in 2 of the 721 hepatitis B surface antigen-negative (HBsAg-) recipients compared with 16 of the 82 HBsAg+ recipients after HSCT (0.3% vs 19.5%; P < .001 by log-rank). Liver cirrhosis developed in 8 of the 82 HBsAg+ recipients compared with none of the 721 HBsAg- recipients (9.8% vs 0%; P < .001 by log-rank). Twenty of the 31 (64.5%) HBsAg+ recipients of hematopoietic stem cells from donors with natural immunity to HBV had sustained serologic clearance of HBsAg after HSCT. Eight of the 62 recipients without sustained HBsAg clearance compared with none of the 20 recipients with sustained HBsAg clearance developed liver cirrhosis (12.9% vs 0%; P = .02 by log-rank). Our study showed that long-term hepatic complications occur in a significant proportion of HBsAg+ patients after HSCT and the incidence of liver cirrhosis is reduced in those with sustained serologic clearance of HBsAg after HSCT.
Adolescent↗
Clinical significance of intrahepatic hepatitis B virus covalently closed circular DNA in chronic hepatitis B patients who received cytotoxic chemotherapy.
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Adult↗
Chronic hepatitis B: HBeAg seroconversion after pegylated interferon and nucleos(t)ide analogs.
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Antiviral Agents↗
Sexual transmission of hepatitis B infection despite the presence of hepatitis B virus immunity in recipients of allogeneic bone marrow transplantation.
BACKGROUND: After hematopoietic cell transplantation (HCT), hepatitis due to hepatitis B virus (HBV) rarely occurred beyond the initial 12 months after transplantation. OBJECTIVES: We investigated the cause of "late" hepatitis due to HBV infection in two recipients after allogeneic HCT. STUDY DESIGN: Two male patients with acute myeloid leukemia and light chain myeloma, respectively, developed HBV-related hepatitis more than 2 years after HCT. All serum samples collected from the recipients, donors and their respective spouses were tested for HBV DNA by nested PCR, and if positive further quantified by Digene Hybrid Capture assay II. The HBV genotype was determined by PCR and sequencing. RESULTS: Genotypic analysis suggested that the cause of "late" hepatitis was due to acute HBV infection transmitted from their respective spouse. CONCLUSION: Our findings suggested that sexual precautions should be taken in these patients after HCT. Alternatively, or even additionally, active vaccination should be delivered to these patients once they have lost their HBV immunity.
Adult↗
Immune system and hepatitis B virus infection.
The immune system plays an important role in determining the outcome of hepatitis B virus (HBV) infection. This is because recovery from of acute HBV infection is associated with a clear division in the profile of adaptive immune response. Multispecific antiviral CD4 and CD8 responses with a type 1 cytokine production can be observed in patients who recover from acute HBV infection. On the other hand, those who develop chronic infection tend to have a weak virus specific T cell response. Therapeutic strategies aimed at correcting this defective T cell reactivity could represent a complementary approach to the cure of chronic HBV infection.
Genetic Variation↗
Macrophage migration inhibitory factor expression correlates with inflammatory changes in human chronic hepatitis B infection.
BACKGROUND: Macrophage migration inhibitory factor (MIF) has emerged to be a pivotal cytokine in immune-mediated diseases. PATIENTS AND METHODS: To investigate the role of MIF in chronic hepatitis B infection, we studied two groups of hepatitis B surface antigen positive patients: group 1 (immune tolerant, n = 16) and group 2 (immune clearance, n = 16). Serum level of MIF was measured by enzyme-linked immunosorbent assay and intrahepatic expression of MIF, macrophage and T-cell localisation were detected by double immunohistochemistry. RESULTS: An increased serum MIF correlated significantly with increased serum alanine aminotransferase activity (r = 0.73, P < 0.001) and the severity of necroinflammatory injury (r = 0.642, P < 0.001). In group 2, there was marked MIF mRNA expression in all KP-1+ macrophages and CD45RO+ activated T cells and, to a lesser extent, in hepatocytes within inflammatory areas. In contrast to its mRNA expression, the cytoplasmic MIF protein level in hepatocytes, infiltrating macrophages and T cells within the inflammatory area was reduced, which probably contributed to the increased serum MIF level. CONCLUSIONS: Our data suggested that MIF played a role in sustaining cell-mediated hepatic injury during the immune-clearance phase of chronic hepatitis B infection.
Adult↗
Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update.
BACKGROUND/AIMS: A large amount of new data on the treatment of chronic hepatitis B has become available such that the 2003 consensus statement requires revision and update. METHODS: New data were presented, discussed and debated in an expert pre-meeting to draft a revision. The revised contents were finalized after discussion in a general meeting of APASL. RESULTS: Conceptual background, including the efficacy and safety profile of currently available and emerging drugs, was reviewed. Nineteen recommendations were formed and unresolved issues and areas for further study were suggested. CONCLUSION: The current therapy of chronic hepatitis B is modestly effective but not satisfactory. The development of new drugs and new strategies is required to further improve the outcomes of treatment.
Antiviral Agents↗
Effectiveness of prophylactic Anti-HBV therapy in allogeneic hematopoietic stem cell transplantation with HBsAg positive donors.
Use of hepatitis B surface antigen (HBsAg) positive donors for allogeneic hematopoietic stem cell transplantation (HSCT) causes serious hepatitis B virus (HBV)-related liver morbidity and mortality in the recipient. We compared the effectiveness of anti-HBV therapy in 29 recipients who underwent HSCT using HBsAg positive marrow (group I) against a historical control group of 25 patients who received HBsAg positive marrow without pre-HSCT prophylaxis (group II). Anti-HBV therapy consisted of lamivudine for HBsAg-positive donors and all recipients (n = 29) as well as HBV vaccination to all HBsAg-negative recipients (n = 10) before HSCT. After transplantation, HBV-related hepatitis was significantly higher in group II than group I recipients [12 of 25 recipients (48%) vs. 2 of 29 recipients (6.9%), p = 0.002] and in recipients whose donors had detectable serum HBV DNA by Digene Hybrid Capture II assay [8 of 14 recipients (57.1%) vs. 6 of 40 recipients (15.0%), p = 0.02]. Six recipients in group II and none in group I died of HBV-related hepatic failure (24.0% vs. 0%, p = 0.01). By multivariate Cox analysis, anti-HBV therapy effectively reduces post-HSCT HBV-related hepatitis (p = 0.01, adjusted hazards ratio 7.27, 95%CI 1.62-32.58). Our data support the use of prophylactic therapy in preventing HBV-related hepatitis after allogeneic HSCT from HBsAg-positive donor.
Adult↗
Clevudine for the treatment of chronic hepatitis B virus infection.
Chronic hepatitis B virus (HBV) infection is a major health problem that is responsible for < or = 1 million deaths and 500,000 cases of hepatocellular carcinoma worldwide each year. Drugs that are currently approved by the FDA for the treatment of chronic HBV consist of two groups: the immunomodulators, such as conventional IFN-alpha and pegylated IFN-alpha2a; and nucleoside/nucleotide analogues, such as lamivudine, adefovir dipivoxil and entecavir. However, due to the limitations of these agents, newer agents with improved efficacy are currently being developed. One nucleoside/nucleotide analogue that is drawing a wide range of interest is clevudine, which is an analogue of the unnatural beta-L configuration. In the woodchuck hepatitis virus (WHV), clevudine 10 mg/kg has proven to be effective in suppressing viral replication with < or = 9 log10 decreases in WHV. At this dose, a significant reduction of intrahepatic WHV RNA and covalently closed circular WHV DNA levels can also be observed. Treatment with clevudine 10 mg/kg can confer additional antiviral benefit in the form of a more sustained reduction in WHV replication, serum woodchuck hepatitis surface antigen and intrahepatic woodchuck hepatitis core antigen expression following the withdrawal of clevudine. In humans, clevudine 10, 50, 100 or 200 mg/day for 28 days can reduce the median HBV DNA by -2.5, -2.7, -3 and -2.6 log10, respectively. More importantly, this suppression of antiviral activity is maintained at 12 and 24 weeks post treatment. Based on the early results of clevudine, more large-scale human studies with clevudine monotherapy or combination therapy is eagerly awaited.
Animals↗
Peginterferon-alpha2a (40 kDa) (Pegasys) for hepatitis B.
Chronic hepatitis B virus is a serious and life threatening disease afflicting 350 million people worldwide, despite the availability of effective vaccines. Thus far, current monotherapy with conventional interferon-alpha, lamivudine and adefovir dipivoxil remains unsatisfactory. In addition, the use of conventional interferon-alpha needs to be administered subcutaneously three-times weekly and is associated with frequent adverse events. Although nucleoside/nucleotide analogs such as lamivudine and adefovir dipivoxil are well tolerated and can normalize serum alanine aminotransaminase rapidly, 1-year therapy with either lamivudine or adefovir dipivoxil results in low hepatitis B e antigen seroconversion rates. In hepatitis B e antigen-negative patients, most would relapse after lamivudine has been discontinued. Peginterferon-alpha2a, an immunomodulatory agent, is a new drug that has just completed Phase III clinical trials for the treatment of both hepatitis B e antigen-positive and -negative chronic hepatitis B virus infection. The advantage of peginterferon-alpha2a in achieving sustained virologic response over nucleoside/nucleotide analogs is particularly obvious in the hepatitis B e antigen-negative group. In both studies, sustained off-treatment response is superior to the use of monotherapy with lamivudine, and concomitant use of lamivudine and pegnterferon-alpha2a does not have advantages over the use of peginterferon-alpha2a alone. These recent data put peginterferon-alpha2a as the antihepatitis B virus therapy of choice, especially in young and motivated patients with chronic hepatitis B virus infection. However, despite the superiority of peginterferon-alpha2a over currently licensed nucleoside/nucleotide analogs, more research needs to be conducted in order to find the most optimal treatment regimen in our fight against chronic hepatitis B virus infection.
Antiviral Agents↗