Hepatitis: Lau GK

Liaw YF, Leung N, Guan R, Lau GK, Merican I, Anonymous00265. · Liver Research Unit, Chang Gung University, Taipei, Taiwan. · J Gastroenterol Hepatol. · Pubmed #12603522 No free full text.

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Lau GK. · No affiliation provided · J Hepatol. · Pubmed #17112628 No free full text.

This publication has no abstract.

Lau GK. · Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. · Liver Int. · Pubmed #19207975 No free full text.

Abstract: Worldwide, chronic hepatitis B virus infection is a major cause of end-stage liver disease and hepatocellular carcinoma. While the past two decades have brought major advances in the availability of treatments to help delay or prevent these outcomes, treatment of chronic hepatitis B remains a serious challenge. With the recent availability of potent new nucleot(s)ide such as entecavir, tenofovir and telbuvidine, I still use pegylated interferon (PEG-IFN)-alpha for the treatment of chronic HBeAg-positive patients. This is based on its relatively higher effectiveness in restoring the host immune control on viral replication, resulting in sustained diseases remission in a proportion of patients, a finite course of therapy and the absence of viral resistance. The two major hindrances to its wide application are its lack of effectiveness in a large proportion of patients and its side-effect profile. The former shortcoming can be circumvented to a certain extent with the use of response predictor models. Recently, based on long-term follow-up study, the better durability of sustained response further enhances the confidence in the use of PEG-IFN-alpha in chronic HBeAg-positive patients.

Lai L, Hui CK, Leung N, Lau GK. · Department of Medicine, Caritas Medical Centre, Hong Kong SAR, China. · Int J Nanomedicine. · Pubmed #17717966 links to  free full text

Abstract: Chronic hepatitis B virus (HBV) is a serious and life-threatening disease afflicting 350 million of the world's population. So 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 daily or thrice 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 (HBeAg) seroconversion rates. In HBeAg negative patients, most of the patients would relapse after lamivudine has been discontinued. Pegylated interferon alpha-2a, an immunomodulatory agent, is a new drug that has just completed phase III clinical trials for the treatment of both HBeAg positive and HBeAg negative chronic HBV infection. The advantage of pegylated interferon alpha-2a in achieving sustained virological response over nucleoside-nucleotide analogs is particularly obvious in the HBeAg negative group. In both of these phase III studies, sustained off-treatment response is superior to the use of lamivudine. These recent data put pegylated interferon alpha-2a as the first choice of anti-HBV therapy, especially in young and motivated patients with chronic HBV infection.

Luk JM, Wang X, Liu P, Wong KF, Chan KL, Tong Y, Hui CK, Lau GK, Fan ST. · Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong. · Liver Int. · Pubmed #17696925 No free full text.

Abstract: Liver disease afflicts over 10% of the world population. This includes chronic hepatitis, alcoholic steatosis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC), which are the most health-threatening conditions drawing considerable attention from medical professionals and scientists. Patients with alcoholism or viral hepatitis are much more likely to have liver cell damage and cirrhosis, and some may eventually develop HCC, which is unfortunately, and very often, a fatal malignancy without cure. While liver surgery is not suitable in many of the HCC cases, patients are mostly given palliative support cares or transarterial chemoembolization or systemic chemotherapies. However, HCC is well known to be a highly chemoresistant tumour, and the response rate is <10-20%. To this end, alternative medicines are being actively sought from other sources with hopes to halt the disease's progression or even eliminate the tumours. Traditional Chinese herbal medicine has begun to gain popularity worldwide for promoting healthcare as well as disease prevention, and been used as conventional or complementary medicines for both treatable and incurable diseases in Asia and the West. In this article, we discuss the laboratory findings and clinical trial studies of Chinese herbal medicines (particularly small molecule compounds) for the treatment of liver disease ranging from fibrosis to liver cancer.

Hui CK, Lau GK. · Center for the Study of Liver Diseases, The University of Hong Kong, SAR, China. · Semin Liver Dis. · Pubmed #16673297 No free full text.

Abstract: 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.

Hui CK, Lau GK. · Department of Medicine, The University of Hong Kong, Hong Kong SAR, China. · J Clin Virol. · Pubmed #16461223 No free full text.

Abstract: 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.

Hui CK, Lau GK. · Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China. · Expert Opin Investig Drugs. · Pubmed #16185170 No free full text.

Abstract: 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.

Lau GK. · Department of Medicine, The University of Hong Kong, Hong Kong, SAR, China. · Med J Malaysia. · Pubmed #16108175 No free full text.

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Hui CK, Lau GK. · Department of Medicine, Center for the Study of Liver Diseases, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China. · Expert Rev Anti Infect Ther. · Pubmed #16107195 No free full text.

Abstract: 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.

Liaw YF, Leung N, Guan R, Lau GK, Merican I, McCaughan G, Gane E, Kao JH, Omata M, Anonymous00046. · Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan. · Liver Int. · Pubmed #15910483 No free full text.

Abstract: 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.

Hui CK, Zhang HY, Lau GK. · Division of Gastroenterology and Hepatology, University Department of Medicine, Queen Mary Hospital, 103 Pokfulam Road, Hong Kong SAR, China. · Gastroenterol Clin North Am. · Pubmed #15324946 No free full text.

Abstract: Current monotherapy with interferon (IFN), lamivudine, or adefovir remains unsatisfactory for most patients with chronic hepatitis B infection. Prolonged treatment with lamivudine monotherapy is needed in most patients with chronic hepatitis B infection and leads to an increased risk of developing lamivudine resistance. Recent data suggest that lamivudine resistance occasionally can result in serious clinical sequelae. On the other hand, conventional IFN treatment is ineffective in up to 70% of chronic hepatitis B patients.Adefovir resistance, although less frequent than lamivudine resistance,also has been identified. With the introduction of new nucleoside/nucleotide analogs such as entacavir, clevudine, LFd4C,tenofovir, and immunomodulatory agents such as pegylated IFN, new treatment options, either alone or in combination, are being investigated to increase the response rate in treatment-naïve and treatment-experienced chronic hepatitis B patients.

Cheng VC, Lo CM, Lau GK. · Department of Microbiology, Center for the Study of Liver Disease, University of Hong Kong Medical Center, Queen Mary Hospital, Hong Kong SAR, China. · Semin Liver Dis. · Pubmed #14523677 No free full text.

Abstract: In the Far East, fulminant hepatic failure is mainly due to viral hepatitis. In areas where hepatitis B infection is endemic, exacerbation of chronic hepatitis B infection, either spontaneously or on withdrawal of immunosuppressive therapy, is the major cause of fulminant hepatic failure. For hepatitis B surface antigen (HBsAg)-positive patients treated with intense immunosuppressive or cytotoxic therapy, preemptive use of lamivudine has drastically reduced the incidence of hepatitis due to hepatitis B exacerbation. Recently, the application of orthotopic liver transplantation, in particular living donor liver transplantation, has markedly improved the survival of patients with fulminant hepatic failure. In Hong Kong, the phenomenon of adoptive transfer of immunity to hepatitis B virus in liver transplantation has recently been reported. The mechanisms by which transfer of immunity occurs and its potential relationship with grafts from living related donors should be further explored.

Ma SY, Lau GK, Cheng VC, Liang R. · Division of Hematology, University Department of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China. · Leuk Lymphoma. · Pubmed #12952220 No free full text.

Abstract: Hepatitis due to reactivation of hepatitis B virus is an important cause of liver-related morbidity and mortality in hepatitis B surface antigen (HBsAg) positive patients undergoing autologous hematopoeitic cell transplantation. With the recent introduction of sensitive serum HBV DNA quantitation assay, the diagnosis of hepatitis B reactivation can now be made more reliably. As these hepatitis are driven by the host immune response to a surge of hepatitis B viral load, the availability of effective nucleoside analogues which can inhibit hepatitis B viral replication has opened up new approaches to this previously untreatable condition. Up till now, two such nucleoside analogues, lamivudine and adefovir dipivoxil, have been approved for the treatment of chronic hepatitis B infection. However, further studies are needed to determine which nucleoside analogues should be chosen in this transplant setting. Due to the high dose chemotherapy generally needed in autologous hematopoeitic cell transplantation, there is a high risk of post-transplant hepatitis B reactivation. Hence, all HBsAg positive patients undergoing autologous hematopoeitic cell transplantation should preferably be treated pre-emptively with nucleoside analogous. An alternative approach is to defer treatment with nucleoside analogous until there is evidence of hepatitis B virological reactivation. However, the latter approach would need the patient's hepatitis B viral load be monitored at a very close interval and might not be cost-effective.

Xunrong L, Yan AW, Liang R, Lau GK. · University Department of Medicine, Queen Mary Hospital, 102 Pokfulum Road, Hong Kong SAR, China. · Rev Med Virol. · Pubmed #11590667 No free full text.

Abstract: In an endemic area for chronic hepatitis B infection, reactivation of this virus is a serious cause of morbidity and mortality in patients undergoing cytotoxic or immunosuppressive therapy. Careful prospective serological testing has shown that hepatitis B virus reactivation is a two-staged process. The initial stage occurs during intense cytotoxic or immunosuppressive therapy and is characterised by enhanced viral replication, as reflected by increases in the serum levels of hepatitis B virus DNA, hepatitis B e antigen, hepatitis B virus DNA polymerase and infection of naïve hepatocytes with hepatitis B virus. The second stage is related to restoration of immune function following withdrawal of cytotoxic or immunosuppressive therapy, which causes rapid immune-mediated destruction of infected hepatocytes. Clinically, this can lead to hepatitis, hepatic failure and even death. The occurrence and severity of hepatitis B virus reactivation after various cytotoxic or immunosuppressive therapy is unpredictable and treatment has been disappointing, largely due to the late administration of therapy. Recently, pre-emptive treatment of chronic hepatitis B patients undergoing cytotoxic or immunosuppressive therapy, with potent nucleoside analogues has shown some promising results. Further controlled studies are needed to define the incidence and risk factors of hepatitis B reactivation so that pre-emptive treatment with nucleoside analogues could be administered to those patients at high risk of disease.

Lau GK. · University Department of Medicine, Queen Mary Hospital, Hong Kong, SAR, China. · Clin Liver Dis. · Pubmed #11385968 No free full text.

Abstract: Chronic HBV infection is a serious health threat in the Asian-Pacific region. The introduction of lamivudine has greatly improved the hope of these patients and is undoubtly a milestone in the management of chronic HBV infection. The combination of lamivudine with another nucleotide or nucleoside analogue or immunomodulatory agent to improve its therapeutic efficacy further must be investigated. Also, the use of lamivudine to prevent HBV reactivation on withdrawal of immunosuppressive therapy should be explored.

Lau GK. · University Department of Medicine, Queen Mary Hospital, Hong Kong SAR, China. · J Gastroenterol Hepatol. · Pubmed #10921382 No free full text.

Abstract: Chronic hepatitis B virus (HBV) infection is a major health threat in Asia. In order to design a better therapeutic regimen, the underlying mechanism of HBV viral persistence must be understood. Immunological studies have found that impaired HBV virus-specific T cell reactivity is the major cause of chronic infection, whereas strong and multispecific T cell responses to HBV are associated with long-term control, but not elimination of the virus. Furthermore, in the serological clearance of hepatitis B surface antigen (HBsAg) in allogeneic haematopoietic cell transplantation, HBsAg seroconversion is associated with activation of the donor's hepatitis B core antigen-specific CD4+ T lymphocytes. This suggests that the donor's hepatitis B core antigen-specific CD4+ T cells provide 'intermolecular T cell help' for the HBsAg seroconversion. These findings are relevant to the future development of therapeutic vaccines or DNA vaccine as immunotherapy for chronic hepatitis B. Apart from interferon-alpha, thymosin alpha1 (Talpha1) has been investigated for treatment of chronic hepatitis B. Meta-analysis of 4 randomized controlled studies investigating the safety and efficacy of Talpha1 monotherapy for the treatment of chronic hepatitis B showed that 6 months treatment with Talpha1 (1.6 mg twice weekly) almost doubles the sustained response rate (36%) compared with controls (19%; P=0.04). However, more specific immunological approaches are being developed; notably, hepatitis B core antigen-based therapeutic vaccine was found to induce T cell proliferative responses in chronically infected hepatitis B patients to the T helper epitope included in the construct. However, the cytokine profile observed suggested the induction of a T helper 0/T helper 2 CD4+ T cell response rather than T helper 1 response. Thus, its combination with interferon-gamma or interleukin-12, which might reverse the CD4+T cell response, should be considered. In the future, it is likely that different types of combination therapy may have to be tailor-made for chronic HBV infection with different virological and immunological profiles and different degrees of liver damage.

Lau GK, Lee CK, Liang R. · University Department of Medicine, Queen Mary Hospital, Hong Kong, SAR, People's Republic of China. · Crit Rev Oncol Hematol. · Pubmed #10532191 No free full text.

This publication has no abstract.

Liang R, Lau GK, Kwong YL. · Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong. · J Clin Oncol. · Pubmed #10458258 No free full text.

Abstract: In places where hepatitis B virus (HBV) infection is endemic, it is often necessary to give chemotherapy to or perform bone marrow transplantation for cancer patients who are also chronic HBV carriers. When standard chemotherapy was given to lymphoma patients, elevation of liver transaminases was observed in nearly half of those who were chronic HBV carriers. Ten percent of them became jaundiced, and the overall liver-related mortality was about 5%. There is currently no reliable way to predict the severity of HBV reactivation after chemotherapy. The risk is probably higher when the chemotherapy used is significantly immunosuppressive and the viral load in the liver is high. Different strategies have been used in an attempt to reduce the risk of HBV reactivation after chemotherapy, but they have not been very successful. Further studies will be required to determine the impact of newly available antiviral agents that are active against HBV. Recipients who are carriers of HBV or who receive hepatitis B surface antigen (HBsAg)-positive marrow are at increased risk of hepatitis B-related morbidity and mortality after bone marrow transplantation (BMT). There is evidence to suggest that prophylactic use of an active antiviral agent, such as famciclovir, may result in a significant decrease in the incidence and severity of HBV reactivation after BMT. Sustained serologic clearance of chronic HBV infection has also been reported in many HBsAg-positive marrow recipients receiving hepatitis B surface antibody-positive marrow from their allogeneic donors. There seems to be a transfer of both humoral and cellular immunity against HBV from donors to recipients. Further prospective studies are required to define the best approach to manage HBsAg-positive cancer patients receiving chemotherapy or BMT. It is recommended that all cancer patients be checked for their hepatitis B status before receiving chemotherapy or a bone marrow transplant, especially if they reside in or come from endemic areas of HBV infection.

Shi M, Fu J, Shi F, Zhang B, Tang Z, Jin L, Fan Z, Zhang Z, Chen L, Wang H, Lau GK, Wang FS. · Research Center for Biological Therapy, Beijing 302 Hospital, Beijing 100039, China. · Clin Immunol. · Pubmed #19328038 No free full text.

Abstract: Adoptive immune transfer plays an important role in clearance of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. However, it is unclear whether cytokine-induced killer (CIK) cells could suppress HBV replication in CHB patients, especially if drug resistance develops. In this study, functional CIK cells were efficiently generated from 21 CHB patients and were transfused in an autologous manner. We found that CIK cells from the CHB patients displayed substantial proliferation and function. Administration of the CIK cells closely correlated with the decrease in the serum HBV load and improvement in liver function in some patients. The virological response rate in patients with baseline serum alanine aminotransferase (ALT) levels of >40 U/L was higher than that in patients with baseline serum ALT levels of < or = 40 U/L. Moreover, patients who had HBeAg loss or showed seroconversion generally had baseline serum ALT levels of >40 U/L. No serious side effects were observed. This protocol represents an alternative immune therapeutic strategy for the disease.

Lim SG, Leung N, Hann HW, Lau GK, Trepo C, Mommeja-Marin H, Moxham C, Sorbel J, Snow A, Blum MR, Rousseau F, Marcellin P. · Department of Gastroenterology and Hepatology, National University Hospital, Yong Yoo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Rd, Singapore 119074. · Aliment Pharmacol Ther. · Pubmed #18363895 No free full text.

Abstract: BACKGROUND: Clevudine is a polymerase inhibitor that has the unusual feature of delayed viral rebound after therapy in some patients which may be related to its pharmacokinetics. AIM: To characterize pharmacokinetic and pharmacodynamic profile of clevudine, a potent hepatitis B polymerase inhibitor. METHODS: A multicenter, randomized study comparing 10, 30 and 50 mg clevudine once daily for 12 weeks with 24 weeks off-treatment follow-up. Patients had chronic HBV infection, were nucleoside-naïve without co-infection. HBV viral load (VL) was assayed using Digene Hybrid Capture II with a lower limit of detection of 4700 copies/mL (940 IU/mL). Clevudine levels were measured using a liquid chromatography/mass spectrometery method. RESULTS: A total of 31 patients were enrolled into the 10 mg (n = 10), 30 mg (n = 11) and 50 mg (n = 10) groups, respectively. At week 12, the median VL change was -3.2, -3.7 and -4.2 log(10) copies/mL (-0.64, -0.74 and -0.84 log(10) IU/mL) in the 10, 30 and 50 mg groups, respectively (P = 0.012). At week 12, one of 10, five of 11 and two of 10 patients had VL below the assay lower limit of detection. Clevudine was well tolerated with no severe/serious adverse events. The mean plasma half-life of clevudine was 70 h and consequently is not the cause of the delayed viral rebound seen in some patients. Through modelling, 97% of the maximal treatment effect was reached with a 30 mg daily dose. Six patients had genomic changes without viral rebound. CONCLUSION: Clevudine appears to be a potent and tolerable (over 12 weeks) anti-viral and the optimal dosage appears to be 30 mg once daily.

Marcellin P, Lau GK, Zeuzem S, Heathcote EJ, Pockros PJ, Reddy KR, Piratvisuth T, Farci P, Chow WC, Jia JD, Paik W, Wintfeld N, Pluck N. · Service d'Hépatologie & INSERM CRB3, University of Paris, Hôpital Beaujon, Clichy, France. · Liver Int. · Pubmed #18339074 No free full text.

Abstract: BACKGROUND/AIMS: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). METHOD: The HBV studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg-negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 microg peginterferon alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. RESULTS: Differences (HBV vs HCV) were observed in the incidence of AEs (88-89 vs 96-100%), serious AEs (4-5 vs 7-16%) and treatment withdrawals (6-8 vs 17-33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. CONCLUSIONS: The safety and tolerability of peginterferon alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression.

Lo CM, Lau GK, Chan SC, Fan ST, Wong J. · Centre for the Study of Liver Disease, The University of Hong Kong, Pokfulam, Hong Kong, China. · Am J Transplant. · Pubmed #17283489 No free full text.

Abstract: Lamivudine monoprophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants and second generation recombinant HBV vaccine is not effective. We studied the efficacy of two courses each of three double-doses (20 microg) of third-generation recombinant pre-S containing vaccine (Sci-B-Vac) in 20 patients on lamivudine prophylaxis at a median of 637 days (range, 390-2666 days) after transplantation. At enrollment, all patients were seronegative for HBsAg, anti-HBs and HBVDNA (by qPCR). Lamivudine (100 mg/day) was continued throughout the study. Five patients (25%) responded to the first course and five additional patients responded after the second course (overall response rate 50%). The response rate was 88% in patients younger than 50 years old and 25% in older patients (p = 0.02). The median peak anti-HBs titer was 153 mIU/mL with six responders having a titer >100 mIU/mL and seven sustained >6 months. Among seven previous nonresponders to second generation recombinant vaccine, three (44%) responded. At the end of the study, all patients remained seronegative for HBsAg. In conclusion, Sci-B-Vac is effective in about 50% of patients receiving lamividine prophylaxis and may prevent recurrence due to escape mutants.

Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried MW, Chow WC, Paik SW, Chang WY, Berg T, Flisiak R, McCloud P, Pluck N, Anonymous00057. · Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China. · N Engl J Med. · Pubmed #15987917 links to  free full text

Abstract: 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.

Lo CM, Liu CL, Lau GK, Chan SC, Ng IO, Fan ST. · Center for the Study of Liver Disease and the Departments of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. · Liver Transpl. · Pubmed #15973721 links to  free full text

Abstract: Lamivudine treatment in patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation. Emergence of lamivudine-resistant YMDD mutant is common. We report the results of liver transplantation in 16 patients with pretransplantation YMDD mutants after receiving lamivudine treatment for a median of 738 days (range, 400-1799 days). Adefovir dipivoxil (10 mg daily) was added on to lamivudine for a median of 20 days (range, 8-271 days) before (n = 11) or at (n = 5) liver transplantation, and the combination was continued indefinitely thereafter. Eight patients received additional intravenous hepatitis B immune globulin (HBIG) for a median of 24 months. Fifteen patients with known pre-adefovir HBV DNA levels had a median titer of 14,200 x 10(3) copies/mL (2 x 10(3) to 4,690,000 x 10(3) copies/mL), and 14 had HBV DNA >10(5) copies/mL. All but 1 patient remained positive for HBV DNA (by quantitative polymerase chain reaction [qPCR]) at the time of liver transplantation, and the titer was greater than10(5) copies/mL in 8 patients. The median follow-up after liver transplantation was 21.1 (range, 4.4-68.9) months. One patient (6%) died of an unrelated cause 12.2 months after transplantation, and 15 patients (94%) were alive with the original graft. All patients cleared HBV DNA and had no detectable HBV DNA by qPCR at the latest follow-up. Fourteen patients had cleared hepatitis B surface antigen (HBsAg), but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG remained HBsAg positive after 7.7 and 9.5 months. Serum HBV DNA, however, was negative, and there was no biochemical or histological evidence of recurrence. Adefovir dipivoxil was well tolerated with no significant renal toxicity. In conclusion, a combination of add-on adefovir dipivoxil plus lamivudine therapy provides effective prophylaxis in patients with pretransplantation YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined.