Hepatitis: Kao JH

Liu CJ, Kao JH. · No affiliation provided · J Gastroenterol Hepatol. · Pubmed #18318819 No free full text.

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Liu CH, Liu CJ, Kao JH. · No affiliation provided · Nephrology (Carlton). · Pubmed #17295654 No free full text.

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Kao JH. · No affiliation provided · J Gastroenterol Hepatol. · Pubmed #11966938 No free full text.

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Kao JH. · Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 10002, Taiwan. · Expert Rev Gastroenterol Hepatol. · Pubmed #19072403 No free full text.

Abstract: Hepatitis B virus (HBV) infection is an important health problem and the major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) worldwide. The natural history of chronic HBV infection can be divided into four dynamic phases in HBV carriers who acquire the virus early in life. Diagnosis of HBV infection is usually through serological and virological markers. Hepatitis B surface antigen (HBsAg) is the hallmark of HBV infection and is the first serological marker to appear in acute hepatitis B, and persistence of HBsAg for more than 6 months suggests chronic HBV infection. Hepatitis B e antigen (HBeAg) usually indicates active HBV replication and risk of transmission of infection. Recently, occult HBV infection is recognized as the absence of circulating HBsAg in individuals positive for serum or tissue HBV DNA, irrespective of other HBV serological markers. Meanwhile, monitoring the serum HBV DNA level is valuable for assessing liver disease activity, differentiating other etiologies of hepatitis activity in HBV carriers, predicting risk of HCC development or liver-related mortality, deciding to administer antiviral therapy, determination of the response to antiviral treatment, predicting the risk of developing drug resistance, and detecting the emergence of drug-resistant mutants. On the other hand, HBV genotype C, basal core promoter mutant and pre-S deletion mutant are reported to be associated with increased risk of HCC development. The roles of quantitative HBV serology and intrahepatic HBV covalently closed circular (ccc)DNA deserve further studies. In conclusion, it is particularly important for physicians to screen for HBV infection in HBV-endemic areas and to monitor liver disease progression in HBV carriers by using both serological and virological markers, so that effective treatment can be initiated early before the development of advanced liver disease.

Liu CJ, Kao JH. · Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan. · Antivir Ther. · Pubmed #18771045 No free full text.

Abstract: Hepatitis B virus (HBV) infection is a global health issue. Effective and individualized treatment of chronic hepatitis B to prevent progression to end-stage liver diseases and hepatocellular carcinoma is needed. HBV can be classified into eight genotypes (A-H) on the basis of genome sequence divergence. In addition, several naturally occurring HBV mutants have also been identified. The epidemiology of HBV genotypes and their implications for response to antiviral therapy have become increasingly recognized. Recent studies suggested that responses to standard interferon treatment in patients with genotype A or B are better than those with genotype C or D; however, conflicting results exist regarding the response to pegylated interferon. The influence of dose and duration on interferon-based therapy remains to be clarified. In addition to genotype, naturally occurring mutations such as precore and core promoter mutations have also attracted much attention, because they have been shown to affect the disease progression of HBV-related chronic liver disease and possibly the response to antiviral therapy. Here, we review the differences in antiviral theraputic response among HBV genotypes and discuss the role of precore or core promoter mutations in response to antiviral therapy.

Liu CJ, Kao JH. · Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. · Recent Pat Antiinfect Drug Discov. · Pubmed #18221137 No free full text.

Abstract: Five drugs are approved for the treatment of chronic hepatitis B: conventional interferon (IFN) alfa, lamivudine, adefovir dipivoxil, pegylated interferon (peginterferon) alfa-2a and entecavir. Conventional IFN monotherapy has a narrow range of efficacy, should be administered subcutaneously and is commonly associated with adverse effects. Lamivudine is cheaper and well tolerated, but the virological response may not be durable and prolonged lamivudine treatment is commonly associated with the emergence of drug-resistant mutants. Adefovir dipivoxil is potent but with nephrotoxicity at higher doses. Entecavir is active against both lamivudine- and adefovir dipivoxil-naïve and -resistant HBV, however, its long-term efficacy remains to be evaluated. Peginterferon alfa-2a has recently been shown to be superior to conventional IFN and lamivudine in the treatment of both HBeAg-positive and -negative chronic hepatitis B. By using peginterferon alfa-2a monotherapy, the overall virological and serological responses are around 30%-44%. However, peginterferon alfa-2a in combination with lamivudine does not improve the results at the end of follow-up. Adverse effects are usually tolerable and comparable with conventional IFN. Similar efficacy of peginterferon alfa-2b has also been demonstrated in HBeAg-positive chronic hepatitis B. These observations suggest an important and even a primary role of peginterferon alfa in the treatment of chronic HBV infection.

Lin CL, Kao JH. · Department of Gastroenterology, Ren-Ai branch, Taipei City Hospital, Taipei, Taiwan. · J Biomed Sci. · Pubmed #18058038 No free full text.

Abstract: Hepatitis B virus (HBV) infection is an important health problem and the major cause of chronic hepatitis, cirrhosis as well as hepatocellular carcinoma (HCC) worldwide. The natural history of chronic HBV infection can be divided into 4 dynamic phases in HBV carriers who acquire the virus early in life. In general, the frequency and severity of hepatitis flares in the immune clearance or reactivation phase predict disease progression in HBV carriers, and early HBeAg seroconversion typically confers a favorable outcome. In contrast, late or absent HBeAg seroconversion after multiple hepatitis flares accelerates the progression of chronic hepatitis to cirrhosis. Recently, several hepatitis B viral factors predictive of clinical outcomes have been identified. For example, serum HBV DNA level at enrollment is the best predictor of adverse outcomes (cirrhosis, HCC and death from liver disease) in adults with chronic HBV infection. In addition, HBV genotype C, basal core promoter (BCP) mutant and pre-S deletion mutant are associated with increased risk of HCC development. In conclusion, hepatitis B viral factors such as serum HBV DNA level, genotype and mutants have already been clarified to influence disease progression of chronic hepatitis B. Further studies are needed to investigate the pathogenic mechanism of each viral factor.

Liu CJ, Kao JH. · Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, R.O.C. · J Chin Med Assoc. · Pubmed #17475593 links to  free full text

Abstract: Chronic hepatitis B virus (HBV) infection is the primary risk factor for the development of hepatocellular carcinoma worldwide. After decades of chronic hepatitis, about 30-40% of patients progress into liver cirrhosis, and of them, around 1-5% subsequently develop hepatocellular carcinoma (HCC) annually. Since the carcinogenic process involves the interplay between the hepatitis virus and the host hepatocytes, both genomes contribute to the final pathogenic outcome, either individually or synergistically. Studying the genetic factors predisposing hepatocarcinogenesis in both host and viral genomes will help illuminate the critical carcinogenic mechanisms, and create molecular targets for future therapy. In this article, we thus review the epidemiology of HBV-related HCC and viral factors involved in hepatocarcinogenesis.

Liu CJ, Kao JH, Chen DS. · Department of Internal Medicine, Division of Gastroenterology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. · Liver Int. · Pubmed #16343058 No free full text.

Abstract: BACKGROUND/AIMS: Hepatitis B virus (HBV) is a global health problem. In addition to the implementation of universal hepatitis B vaccination, effective and individualized treatment of chronic hepatitis B to prevent progression into end-stage liver diseases and hepatocellular carcinoma is still needed. HBV has been designated eight genotypes (A-H) based on genome sequence divergence. The epidemiology of HBV genotypes and their implications on the responses to antiviral therapy have become increasingly recognized in both Asian and Western countries. METHODS: Published data are thus reviewed. Results: Each genotype has its distinct geographical and ethnic distribution. Genotypes A and D occur frequently in Africa, Europe, and India, while genotypes B and C are prevalent in Asia. Genotype E is restricted to West Africa, and genotype F is found in Central and South America. The distribution of genotypes G and H is less clear. Accumulating evidence indicates a better sustained response to conventional interferon in patients with genotype B than those with C, and in patients with genotype A than those with D. In contrast, conflicting results exist regarding the response to pegylated interferon. On the other hand, the therapeutic responses to nucleoside/nucleotide analogues are comparable among patients with different HBV genotypes. The impact of HBV subgenotypes, mixed genotype infections, and recombinants of different genotypes on the response to antiviral treatments awaits further examinations. CONCLUSION: Remarkable clinical and pathogenic differences do exist among HBV genotypes; however, researches on molecular and virologic mechanisms underlying the clinical phenotypes of different HBV genotypes are urgently needed.

Kao JH, Chen DS. · Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan. · Liver Int. · Pubmed #15998418 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and has a marked difference in geographic distribution. More than 80% of HCC cases occur in developing countries, especially the Far East and Southeast Asia. Although immunization has been successful against hepatitis B virus (HBV), a changing disease burden of HCC has been observed in many parts of the world because of the increasing prevalence and duration of hepatitis C virus (HCV) infection in these countries. In addition, the age-specific incidence of HCC has progressively shifted toward younger people. Hepatitis B genotypes B and C are prevalent in the Far East and Southeast Asia, and the clinical relevance of HBV genotypes has become increasingly recognized. Compared with genotype C, genotype B is associated with earlier hepatitis B e antigen seroconversion, slower progression to cirrhosis and less frequent development of HCC. By using periodic examinations of serum alfa-fetoprotein levels and abdominal ultrasonography, small HCC can be detected and treated earlier. However, prevention of HBV and HCV infections as well as effective treatment of the chronic viral infections with timely interventions are still needed for the global control of HCC, particularly in the Far East and Southeast Asia.

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.

Kao JH. · Graduate Institute of Clinical Medicine, Department of Internal Medicine and Department of Medical Research, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan. · Intervirology. · Pubmed #14688459 No free full text.

Abstract: With phylogenetic analysis of hepatitis B virus (HBV) isolates, eight different genotypes (A to H) have been recognized worldwide. The impact of HBV genotypes on the clinical aspects of HBV infection in Taiwan, including the clinical outcome of chronic infection and therapeutic response to antiviral treatments, has been clarified. Our data showed that genotypes B and C are the predominant HBV strains in Taiwan, and genotype C is associated with more severe liver disease including cirrhosis and hepatocellular carcinoma (HCC), whereas genotype B is associated with the development of HCC in young noncirrhotic patients. Serologically, genotype C tends to have a higher frequency of hepatitis B e antigen (HBeAg) positivity and a higher serum HBV DNA level than genotype B. In addition, genotype C patients, compared to genotype B patients, have a delayed HBeAg seroconversion in the immune clearance phase of chronic HBV infection. Virologically, genotype C bears a higher frequency of basal core promoter mutation than genotype B. Our recent data further indicated that patients with basal core promoter mutation are significantly more associated with the development of HCC than those without, which applies to both genotypes B and C. In addition, the prevalence of basal core promoter mutation in young HCC patients is comparable to older HCC patients but is significantly higher than that in age-matched inactive carriers, irrespective of genotypes. Although superinfection of HBV on hepatitis B carriers indeed occurs in Taiwan, it is rarely associated with acute exacerbations. As to the response to antiviral treatments, genotype C is associated with a lower response rate to interferon therapy compared to genotype B. In addition, genotype B seems to have a better virological response to lamivudine as compared to genotype C, but both genotypes have a similar risk in the development of lamivudine resistance. These lines of evidence highlight the remarkable differences in the clinical and virological characteristics between Taiwanese patients infected with different genotypes. In conclusion, pathogenic and therapeutic differences do exist among HBV genotypes in Taiwan, and determining the genotype in patients with chronic HBV infection would help gain further information in anthropologic, clinical, virological and prognostic investigations.

Kao JH, Chen DS. · Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan. · Lancet Infect Dis. · Pubmed #12127351 No free full text.

Abstract: Worldwide about 350 million people are chronic carriers of the hepatitis B virus (HBV). The infection can cause acute and chronic liver disease including cirrhosis and hepatocellular carcinoma (HCC). Hepatocellular injuries of HBV infection are predominantly immune-mediated, and the natural history of chronic infection can be divided into three phases based on virus-host interactions-namely, immune tolerance, immune clearance, and viral integration phases. Four serotypes (adw, ayw, adr, and ayr) and seven genotypes (A to G) of HBV have been identified, and they show some distinct geographic distributions. The HBV genotypes may have clinical relevance and are currently under investigation. On the basis of disease burden and the availability of safe and effective vaccines, the WHO recommended that by the end of the 20th century hepatitis B vaccine be incorporated into routine infant and childhood immunisation programmes for all countries. The efficacy of universal immunisation has been shown in different countries, with striking reductions of the prevalence of HBV carriage in children. Most important, hepatitis B vaccination can protect children against HCC and fulminant hepatitis, as has been shown in Taiwan. Nevertheless, the implementation of worldwide vaccination against HBV requires greater effort to overcome the social and economic hurdles. Safe and effective antiviral treatments are available but are still far from ideal, a situation that, hopefully, will be improved soon. With hepatitis B immunisation, the global control of HBV infection is possible by the end of the first half of 21st century.

Kao JH, Chen DS. · Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei,Taiwan. · J Formos Med Assoc. · Pubmed #12101859 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is responsible for significant morbidity and mortality throughout the world, and is clearly linked to viral infections. Mass vaccination programs against hepatitis B virus have reduced the incidence of HCC in Taiwanese children, and are likely to yield similar benefits elsewhere. In many countries, a definite increase in the incidence of HCC has been reported, largely attributable to the increasing incidence of hepatitis C virus infection. Although the major viral and environmental risk factors for the development of HCC have been determined, the oncogenic pathways leading to malignant transformation of liver cells have long remained obscure. HCC is also extremely difficult to manage. Although patients at risk can be identified and early detection of HCC is feasible, the current management of HCC is confusing due to the lack of well-designed, randomized clinical trials comparing various treatment modalities. New surgical techniques and postoperative therapies may improve the outcome in some resectable cancers; however, the vast majority of patients have unresectable tumors. Local ablation treatments may shrink or necrose tumors, but the clear benefit of such therapies remains to be seen. Further elucidation of the genetic and molecular features of HCC may lend insight that will lead to the development of innovative strategies to manage this cancer. In this article, the current understanding of HCC with respect to etiologic factors, genetic mechanisms responsible for hepatocarcinogenesis, diagnosis, therapy, and prevention are reviewed.

Kao JH. · Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei 100, Taiwan. · J Gastroenterol Hepatol. · Pubmed #12100608 No free full text.

Abstract: Hepatitis B virus (HBV) infection is a global health problem and the clinical outcome of chronic HBV infection depends on the frequency and severity of hepatitis flares in the immune clearance phase. Currently, four subtypes and seven genotypes of HBV are identified and most have specific geographic distributions. The impact of HBV genotypes on the clinical outcome of chronic HBV infection has been partially clarified. In Taiwan, genotype C is associated with more severe liver disease and genotype B is associated with the development of hepatocellular carcinoma (HCC) in young non-cirrhotic patients. In contrast, genotype B has a relatively good prognosis in Japan and China and is rarely associated with the development of HCC. Similarly, genotype D is associated with more severe liver disease than genotype A in India and may predict occurrence of HCC in young patients. Although superinfection of HBV on top of hepatitis B carriers occurs in Taiwan, it is rarely associated with acute exacerbations. As to the response to antiviral treatment, genotypes C and D are associated with a lower response rate to interferon therapy compared with genotypes B and A. In addition, the subtype adw is reported to be associated with a higher risk of lamivudine resistance than ayw. In HBV subtype adw-infected HCC patients, genotype B responds better to embolization therapy and has a lower rate of HCC recurrence than genotype C. In summary, pathogenic and therapeutic differences do exist among HBV genotypes and determining the genotype in patients with chronic HBV infection would help gain further information for etiologic, clinical, virologic and anthropologic investigations. Further studies to clarify the molecular virological factors that contribute to these differences are awaited.

Kao JH, Chen DS. · Graduate Institute of Clinical Medicine, Hepatitis Research Center, National Taiwan University Hospital and College of Medicine,7 Chung-Shan South Road, Taipei 100, Taiwan. · Int J Cancer. · Pubmed #11774275 No free full text.

This publication has no abstract.

Kao JH, Chen DS. · Graduate Institute of Clinical Medicine, Department of Internal Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Taipei. · J Gastroenterol Hepatol. · Pubmed #10921389 No free full text.

Abstract: Hepatitis C virus (HCV) infection is a major public health problem. The epidemiology of HCV infection in different parts of Asia is similar, with an average seroprevalence of hepatitis C antibody (anti-HCV) less than 2.5% in healthy adults. The infection is rarely seen in children. The major routes of HCV transmission in Asia during the past few decades have been through administration of therapeutic blood products and injecting drug use, similar to the pattern observed in other parts of the world. However, obvious parenteral routes of transmission only account for 30-60% of anti-HCV-positive cases, depending on the geographic area. Other inapparent parenteral or per-mucosal exposures, including medical intervention, tattooing, acupuncture, vertical and sexual transmission, accidental needlestick and household contact, are also possible routes of HCV transmission. Although screening of blood donors for anti-HCV and improvements in infection control have significantly decreased the exposure to HCV, it is believed that HCV is still spreading in some areas of Asia because of the lack of routine screening of donated blood, injecting drug usage, traditional medicine practices or medical treatment under suboptimal hygienic conditions that involve blood contamination, and tattooing. Accordingly, until effective and safe immunoprophylaxis is available, interruption of transmission routes, such as implementation of blood donor screening for anti-HCV, adequate sterilization of surgical instruments or the use of disposable medical instruments, especially needles and syringes, and avoidance of sharing personal grooming aids remains the mainstay to prevent HCV infection in Asia today.

Kao JH, Heptonstall J, Chen DS. · Department of Internal Medicine, National Taiwan University College of Medicine, Taipei. · Occup Environ Med. · Pubmed #10658557 links to  free full text

Abstract: Over the past decade, several molecular techniques for the detection of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) have been developed that have implications for occupational health practice. This review describes the techniques used for qualitative and quantitative detection of the viral genome, and briefly explains nucleic acid sequencing and analysis of phylogenetic trees. The review also discusses the current and potential uses of these techniques in investigations of transmission of bloodborne viruses by patient to worker and worker to patient, in the management of occupational exposure to blood, in research, and in the development of guidance and policy on infected healthcare workers who perform procedures prone to exposure.

Hsu CS, Liu CJ, Lai MY, Chen PJ, Kao JH, Chen DS. · Department of Hepatogastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, Taiwan. · Intervirology. · Pubmed #17622791 No free full text.

Abstract: OBJECTIVES: Early hepatitis C viral (HCV) kinetics following pegylated interferon-alpha (PEG-IFN) and ribavirin help to assess treatment in the Western world. Whether this functions in Taiwanese patients remains unknown. Studying the early HCV kinetics in Taiwanese patients may clarify this issue. METHODS: Six chronic hepatitis C patients were enrolled. A PEG-IFN-alpha dose was administered at week 1, then it was administered weekly with daily ribavirin for 24 weeks. Serum HCV RNA levels were determined frequently during the trial and qualitatively at week 49. Kinetic parameters epsilon (effectiveness at inhibiting viral production)and delta (loss rate of infected cells) were estimated from viral loads and alanine aminotransferase (ALT) kinetics, respectively. RESULTS: All serum HCV RNA levels became undetectable at week 12. The epsilon ranged from 0.4128 to 0.9904 and delta from 0.0019 to 0.1245. The log values of viral load differences between day 7 and 14 ranged from 0.15 to 1.21. Only 1 patient had an abnormal ALT level at week 49. CONCLUSIONS: Viral kinetic parameters in Taiwanese patients were similar to those in Western studies. However, the early viral decline pattern and viral negativity rate in Taiwanese patients might be different from Caucasian patients. Further large-scale studies to clarify this issue are ongoing.

Liu CJ, Kao JH, Chen PJ, Chen TC, Lin FY, Lai MY, Chen DS. · Department of Internal Medicine, Division of Gastroenterology, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan. · J Viral Hepat. · Pubmed #16842441 No free full text.

Abstract: Adefovir dipivoxil is effective against lamivudine-resistant hepatitis B virus (HBV) strains. Whether short-term overlap lamivudine is beneficial remains unknown, particularly in patients with decompensated chronic hepatitis B. We enrolled 30 patients who underwent 48-week adefovir treatment (10 mg daily) for exacerbation of hepatitis B, associated with lamivudine-resistant mutants. Nineteen (63.3%) patients had baseline evidence of hepatic decompensation. Lamivudine was combined for <or=1 month in eight (group I), 2-5 months in 10 (group II) and >or=6 months in 12 (group III). We analysed their serial alanine aninotransferase (ALT) levels, Child-Pugh (CP) score, serum viral load and lamivudine-resistant strains. We found that serum ALT became normalized in 20 (66.7%) and HBV-DNA decreased to <or=100 copies/mL in eight (26.7%) at the end of the 48-week treatment. The log(10) reduction of serum HBV-DNA was significantly smaller in group I patients compared with group II and III patients at week 24 and 48 of treatment [median (range): 3.0 (1.5-5.6) vs 4.5 (1.5-7.4), P = 0.032; and 3.4 (0.9-4.7) vs 5.2 (2.2-7.7), P = 0.008 respectively]. In contrast, the virologic responses at the end of the 48-week therapy were similar between group II and III patients. The improvement in serum ALT and CP score at week 48 was similar irrespective of baseline decompensation, liver cirrhosis and the duration of overlap lamivudine therapy. Our findings suggested that an overlap of lamivudine for >or=2 months might lead to better virological but not biochemical outcomes in patients receiving adefovir for lamivudine-resistance HBV. As our sample size was small and the study was not randomly controlled, further studies are needed.

Lu JY, Chuang LM, Yang WS, Tai TY, Lai MY, Chen PJ, Kao JH, Lee CZ, Lee HS. · Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan. · Liver Int. · Pubmed #15998426 No free full text.

Abstract: AIMS: The study was designed to survey the change of adiponectin levels before and after interferon-alpha (IFN-alpha) therapy in patients with chronic hepatitis B and C infections. METHODS: Twenty-one biopsy-proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-alpha for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN-alpha therapy. Insulin suppression test was conducted before and within 1 week after IFN-alpha therapy. RESULTS: The change of adiponectin levels differed significantly between responders (eight cases) and non-responders (13 cases) to IFN-alpha treatment (-4.8+/-2.2 vs. 0.5+/-1.0 microg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN-alpha (P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9+/-3.2 vs. 10.8+/-3.0 microg/ml, P=0.02, n=4) and HBV responders (17.7+/-4.1 vs. 9.2+/-1.0 microg/ml, P=0.10, n=4). In addition, a significant decrease of steady-state plasma glucose in insulin suppression test was noted in responders (13.6+/-1.8-11.7+/-1.2 mmol/l, P=0.03), but not in non-responders (12.3+/-1.1-11.0+/-1.0 mmol/l, P=0.20), after IFN-alpha therapy. CONCLUSIONS: IFN-alpha resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down-regulation of the virus or viral antigens in responders to IFN-alpha treatment, contributes to the lowering of adiponectin levels needs to be further investigated.

Huang GT, Lee PH, Tsang YM, Lai MY, Yang PM, Hu RH, Chen PJ, Kao JH, Sheu JC, Lee CZ, Chen DS. · Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. · Ann Surg. · Pubmed #15973099 links to  free full text

Abstract: OBJECTIVE: To compare disease recurrence and survival among patients with small hepatocellular carcinoma after surgical resection or percutaneous ethanol injection therapy, 2 treatments that have not been evaluated with a prospective study. METHODS: A total of 76 patients were randomly assigned to 2 groups based on treatment; all had one or 2 tumors with diameter </=3 cm, with hepatitis without cirrhosis or Child class A or B cirrhosis without evident ascites or bleeding tendency. RESULTS: Follow-up ranged from 12 to 59 months. Among percutaneous injection patients, 18 had recurrence 1 to 37 months after treatment (true recurrence, 11; original safety margin inadequate, 3; limitation of imaging technology to detect tiny tumors, 4). Three injection therapy patients died of cancer 25, 37, and 57 months after treatment. For the surgical resection group, 15 had recurrence 2 to 54 months after treatment (true recurrence, 12; limitation of imaging, 2; neck metastasis, 1). Five resection patients died of cancer at 11, 20, 23, 26, and 52 months, respectively. By Cox regression model and Kaplan-Meier survival analysis, there is no statistical significance for recurrence and survival between treatment groups. However, tumor size larger than 2 cm and alpha-fetoprotein over 200 ng/mL correlated with higher recurrence rate, and Child class B liver cirrhosis correlated with shorter survival. CONCLUSIONS: Percutaneous ethanol injection therapy appears to be as safe and effective as resection, and both treatments can be considered first-line options for small hepatocellular carcinoma.

Liu CJ, Chen PJ, Lai MY, Chen TC, Wang HY, Huang WL, Kao JH, Chen DS. · Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. · Antivir Ther. · Pubmed #15651748 No free full text.

Abstract: BACKGROUND/AIMS: In chronic hepatitis B, both host and viral factors may predict the response to interferon (IFN) treatment. Whether IFN sensitivity-determining regions exist within the hepatitis B virus (HBV) genomic background remains largely unknown. We therefore performed full-length viral genomic comparison between HBVs obtained from IFN responders and non-responders. METHODS: We enrolled 18 HBV genotype Ba patients who had received 24-week IFN 5 MU three times weekly and were followed monthly for 12 months post-treatment. There were 10 responders and eight non-responders. Pretreatment full-length viral nucleotide consensus sequence was obtained. In six non-responders and four responders, post-treatment viral nucleotide sequence was further compared with their corresponding pre-treatment specimens. In addition, the average number of nucleotide substitutions of the HBV quasispecies was compared between three responders and three non-responders. RESULTS: HBV nucleotide consensus sequence was identical between responders and non-responders. We found 0-15 (mean 7.7) nucleotide substitutions in the post-treatment HBV genome in the six non-responders and 0-14 (mean 3.8) nucleotide substitutions in the four responders, respectively. Genetic complexity of HBV quasispecies was comparable between responders and non-responders. CONCLUSIONS: Our results suggest that an IFN sensitivity-determining region might not exist within the genome of HBV genotype Ba. Host factors and virus-host interactions may be more important in determining the response to IFN treatment.

Liu CJ, Huang WL, Chen PJ, Lai MY, Kao JH, Chen DS. · Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, China. · World J Gastroenterol. · Pubmed #15534909 links to  free full text

Abstract: AIM: Attaining hepatitis B e antigen (HBeAg) seroconversion during lamivudine treatment is associated with fewer relapses in HBeAg-positive patients. In HBeAg-negative patients, predictors for post-treatment relapse remain largely unknown. We therefore studied whether end-of-treatment virologic response correlated with relapse after lamivudine treatment. METHODS: We prospectively analyzed 12 HBeAg-negative patients and 14 HBeAg-positive patients with chronic hepatitis B, who received at least 9 mo of lamivudine treatment and were followed up for 12 mo post-treatment. Relapse of hepatitis B activity was defined by an elevation of serum ALT level above twice the upper limit of normal as well as reappearance of serum HBV DNA by the branched DNA assay or HBeAg during the follow-up period. The serum viral loads during and at the end of treatment were further determined by a quantitative real-time polymerase chain reaction assay. RESULTS: Relapse occurred in 6 (50.0%) HBeAg-negative patients within 12 mo post-treatment. Two relapsers had end-of-treatment serum viral load <1 000 copies/mL, the proportion was not significantly different from that in the 6 non-relapsers (33.3% vs 16.7%; P = 1.00). Hepatitis B virus (HBV) DNA levels did not correlate with post-treatment relapse in HBeAg-positive patients either. However, genotype C patients tended to have a lower relapse rate than genotype B patients (14.3% vs 57.9%, P = 0.08). CONCLUSION: Our results suggest that end-of-treatment virologic response cannot predict post-treatment relapse in patients with HBeAg-negative or -positive chronic hepatitis B. The impact of HBV genotype on the response to lamivudine treatment awaits further studies.

Kao JH, Liu CJ, Chen DS. · No affiliation provided · J Hepatol. · Pubmed #11830346 No free full text.

This publication has no abstract.