Hepatitis: Taiwan

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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Chang KY, Chang JY, Yen Y. · National Institute of Cancer Research, National Health Research Institute, Taiwan. · J Natl Compr Canc Netw. · Pubmed #19406042 No free full text.

Abstract: Primary liver cancer is the sixth most common cancer and third most common cause of cancer death worldwide. Cholangiocarcinoma is the second most common primary liver tumor after hepatocellular carcinoma. Because the incidence of intrahepatic cholangiocarcinoma is rising in most areas worldwide, identification of the main causes of this problem is urgently needed. Despite well-known risk factors in the development of intrahepatic cholangiocarcinoma, recent reports focus on chronic hepatitis B and C viral infections because an increasing number of studies have observed an association. The relationship, however, is still not conclusive because of the diversity in clinical reports and the lack of in vitro evidences. This issue should be emphasized and further investigation is required for clarification.

Chen TJ, Lai PC, Yang LC, Kuo TT, Hong HS. · Department of Dermatology, Wanfang Medical Center and Taipei Medical University, Taipei, Taiwan. · Am J Clin Dermatol. · Pubmed #19354335 No free full text.

Abstract: Bullous pemphigoid (BP) is an autoimmune disease with chronic, recurrent bullous eruptions. BP has been reported to be associated with drugs, physical stimuli, malignancies, and immune abnormalities. Its association with renal transplant is rare and only four cases have been reported. We present a case of BP in a 52-year-old man with chronic hepatitis B and C infection who underwent a cadaveric renal transplant 13 years earlier. His graft was still functioning well when BP appeared. The occurrence of BP in our patient might be a result of drugs (furosemide or tacrolimus), viruses, or renal allograft. As the patient was receiving regular T-cell immunosuppressant therapy, his BP lesions were recalcitrant to corticosteroid treatment. We discuss the pathogenesis and treatment of such patients.

Yu ML, Chuang WL. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · J Gastroenterol Hepatol. · Pubmed #19335784 No free full text.

Abstract: The issue of best treatment for chronic hepatitis C virus (HCV) infection is in constant flux, not only in Western countries but also in Asia. Currently, pegylated-interferon plus ribavirin is the standard of care. Studies from Asia provide evidence to support the same broad treatment strategies for Asian patients as recommended in Western countries. Nevertheless, there is increasing evidence that Asians have a higher likelihood of achieving a sustained virological response (SVR) than their Caucasians counterparts when treated with the corresponding regimen. With the recommended 'standard dose and duration treatment regimens', SVR is achieved in Asia for around 70% of HCV genotype 1 (HCV-1) infected cases, approximately 90% of HCV-2/3, approximately 65% of HCV-4, and approximately 80% of HCV-6 patients. Difference of body weight in race might contribute the superior response in Asian patients. HCV genotype distribution in Asia also differs from North-America/Europe. HCV-6 and its variants, previously mistyped as HCV-1, needs accurate genotyping. Increasing data support the proposal that HCV genotype, baseline viral load and on-treatment virological response provide information for decision-making so that treatment can be individualized. Beyond the older recommendations, an abbreviated 24-week regimen could be suggested for HCV-1/4 patients with baseline viral loads < 400 000 IU/mL and a rapid virological response (RVR, HCV RNA undetectable at week 4), and an abbreviated 12-16 weeks of pegylated-interferon with weight-based doses of ribavirin could be suggested for HCV-2/3 patients with a RVR. Such tailored treatment regimens can reduce the costs of treatment and incidence of adverse events without compromising efficacy. Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis worldwide, and particularly in some countries of Asia (notably Japan) where it is now more prevalent than chronic hepatitis B virus infection. Hepatitis C virus infection can also lead to hepatocellular carcinoma (HCC). It is estimated that there are more than 170 million people chronically infected with HCV, and 3 to 4 million persons are newly infected each year. The risk for developing cirrhosis 20 years after initial HCV infection among those chronically infected varies between studies, but is estimated at around 10%-15% for men and 1-5% for women. Once cirrhosis is established, the rate of developing HCC is at 1%-4% per year. Approximately 280 000 deaths per year are related to HCV infection. Hepatitis C virus-related end-stage liver disease and HCC have become the leading cause for liver transplantation worldwide. In the Asia-Pacific area, the estimated prevalence of antibodies to HCV (anti-HCV) range from 0.3% in New Zealand to 5.6% in Thailand. In Japan, Middle East, Vietnam and Taiwan, several HCV hyper-endemic areas have been reported with an anti-HCV prevalence rate of 12% to as high as 58%. In addition to the well-known endemic status of HBV infection in most countries of the Asia-Pacific region, HCV infection presents another critical scenario of public health issue in this region, as outlined in Guidelines by the Asia-Pacific Association for Study of the Liver (APASL). Given the lack of an effective vaccine, optimal treatment of chronic HCV infection is now perceived as a 'must' in terms of public health strategies, as well as of the clinical setting for individual patients.

Liaw YF. · Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. · Antivir Ther. · Pubmed #19320233 No free full text.

Abstract: Studies published to date regarding on-treatment outcome prediction during chronic hepatitis B therapy were reviewed. Studies have shown that initial virological responses in terms of week 24 serum hepatitis B virus (HBV) DNA levels are associated with therapeutic outcomes of 1-year pegylated interferon-alpha and entecavir therapy, and weeks 52 or 104 of lamivudine and telbuvudine therapy. HBV DNA levels at week 48 are also associated with long-term adefovir therapy outcomes. Conceptual on-treatment adjustment and strategies have been proposed; however, this approach seems only necessary during therapy with nucleos(t)ide analogues with substantial risk of drug resistance. In addition, studies are needed to decide whether switching to or adding on a second drug, and with which drug, is the most cost-effective strategy.

Sun HY, Chen YJ, Chen IL, Gau CS, Chang SC, Luh KT. · Department of Internal Medicine, National Taiwan University Hospital, School of Pharmacy, Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. · J Formos Med Assoc. · Pubmed #19251545 links to  free full text

Abstract: BACKGROUND/PURPOSE: The present study prospectively investigated the incidence of and factors associated with hepatitis during antituberculous treatment in patients with tuberculosis and various underlying diseases. The results were compared with those of previously published studies. METHODS: Patients treated with antituberculous agents were enrolled from July 1, 2000 to July 31, 2001, in the divisions of chest and infectious diseases at National Taiwan University Hospital and followed until November 30, 2001. Hepatitis was defined as an aminotransferase level>5 times the upper limit of normal (ULN), or >3 times ULN in the presence of symptoms of hepatitis, or total bilirubin level>3 mg/dL. Studies reporting the incidence of hepatitis during antituberculous treatment were reviewed for comparison. RESULTS: Among 261 patients, median age was 58 years (range, 17-90 years), 17.7% had abnormal baseline liver function tests and 18.4% had concurrent hepatotoxic drug use. Fifteen patients (5.7%) had hepatitis B virus infection, 17 (6.5%) had hepatitis C virus infection, 14 (5.4%) had liver cirrhosis, and 15 (5.7%) had human immunodeficiency virus infection. Hepatitis occurred in 42 patients (16.1%), with 60% of the events in the first 2 months of treatment. Such an incidence was comparable to that in other Asian countries (5.3-18.2%) and slightly higher than that in Western countries (2.4-19%). In multivariate analysis, abnormal liver function tests at baseline and liver cirrhosis were independent factors for development of hepatitis. CONCLUSION: Elevation of liver function tests was not uncommon during antituberculous treatment, especially in the first 2 months. Patients with abnormal liver function tests at baseline or liver cirrhosis should be closely monitored.

Chang MH. · National Taiwan University Hospital, Taipei. · Recent Results Cancer Res. · Pubmed #19213561 No free full text.

Abstract: Chronic inflammation caused by persistent infection is closely related to a number of cancers; these include hepatitis B (HBV) or C and hepatoma, human papilloma virus and cervical cancer, and Helicobacter pylori and gastric cancer. The first evidence of cancer prevention by vaccination in humans was provided by HBV vaccination in infants. Chronic HBV is related to approximately 60%-90% of hepatocellular carcinomas (HCC) in adults and nearly 100% of childhood HCC in areas endemic for HBV infection. The first universal HBV vaccination program was launched in Taiwan and has continued for more than 20 years. Three or four doses of HBV vaccine were given to all infants starting from the first week of life. In addition, infants of high-risk mothers (with positive hepatitis B e antigen or high HBsAg titers) were given hepatitis B immunoglobulin within 24 h after birth. At 20 years after the launch of the HBV vaccination program in Taiwan, chronic HBV infection (HBsAg seropositive) rates in the general population below 20 years of age have revealed a remarkable reduction from 10%-17% before the vaccination program to 0.7%-1.7% after the program. HCC incidence rate in children 6-14 years old also fell from 0.52-0.54 to 0.13-0.20 per 100,000 (R.R. = 0.25-0.36). HCC prevention failure is mainly related to vaccine failure to prevent chronic HBV infection. The causes of vaccine failure have included intrauterine infection, vaccine escape mutants, genetic hyporesponsiveness, and poor compliance. Future efforts to reduce vaccine failure will improve the efficacy of liver cancer prevention by HBV vaccination. The experience of HCC prevention by HBV immunization may be applied to the prevention of other infection-related cancers.

Liaw YF. · Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. · Liver Int. · Pubmed #19207972 No free full text.

Abstract: Chronic hepatitis B virus (HBV) infection is a dynamic state of interactions among HBV, the hepatocytes and the immune system of the patient. Perinatally or early childhood-acquired chronic HBV infection has a long 'immune tolerant phase', when patients are young, and HBeAg seropositive with a high viral load but with no significant liver disease. Persistent or episodic liver injuries during the 'immune clearance phase' may lead to decompensation, fibrosis progression or cirrhosis development in some patients, but may eventually lead to HBV-DNA seroclearance with HBeAg seroconversion and entry into the 'inactive phase' with remission. Hepatitis may relapse, because of reactivation of HBV with precore or basal core promptor mutations, and develop 'HBeAg-negative chronic hepatitis', in some patients. In contrast, HBsAg seroclearance may occur in those with sustained remission. During the course, HBV replication is the key driver of disease progression including development of cirrhosis and hepatocellular carcinoma (HCC). Among the currently available anti-HBV drugs, the most extensive and longest experience has been gained with conventional interferon (IFN)-alpha and lamivudine. A finite course of IFN therapy has long-term benefit in achieving a cumulative response, increasing HBsAg seroclearance and reducing cirrhosis and/or HCC. Maintained virological response to lamivudine therapy has a similar long-term benefit in reducing disease progression. Pegylated IFN and newer nucleos(t)ide analogues may have even better long-term outcomes because of better therapeutic efficacy and/or a low risk of drug resistances. The treatment outcomes are still far from satisfactory. The development of safe and affordable anti-HBV agents/strategies is needed to further improve outcomes.

Chien RN, Liaw YF. · Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. · Best Pract Res Clin Gastroenterol. · Pubmed #19187868 No free full text.

Abstract: Studies in the past decades have shown that active hepatitis B virus (HBV) replication is the key driver of liver injury and disease progression, and thus sustained viral suppression is of paramount importance in the management of chronic HBV infection. The nucleos(t)ide analogues lamivudine, adefovir, entecavir, telbivudine and tenofovir are potent inhibitors of HBV polymerase/reverse transcriptase activity and are highly effective in the suppression of HBV replication, but rarely eliminate the virus. Long-term therapy is usually required to achieve sustained hepatitis B e antigen seroconversion, HBV DNA suppression, ALT normalization and fibrosis reversal. Maintained long-term therapy has been demonstrated to significantly lower the rate of hepatic decompensation and development of cirrhosis or hepatocellular carcinoma. However, drug resistance is a serious risk on prolonged nucleos(t)ide analogue therapy, and this poses a critical challenge. Prevention and proper management of drug resistance are crucial to ensure long-term success.

Liu PY, Yang Y, Shi ZY. · Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. · Jpn J Infect Dis. · Pubmed #19168962 links to  free full text

Abstract: Cryptococcus neoformans usually involves the central nervous system and the respiratory tract. We report a case of disseminated cryptococcosis with a liver abscess and meningoencephalitis in a patient with myelodysplastic syndrome. Computed tomography of the abdomen showed a 3-cm low-attenuated lesion in the left lobe of liver. Cultures from specimens of blood, the liver abscess, and the cerebrospinal fluid all yielded C. neoformans. The cryptococcal antigen titers for the serum and cerebral fluid were both 1:32. The patient was successfully treated with 1,335 mg of amphotericin-B followed by fluconazole. Most cryptococcal liver infections present as hepatitis, cholangitis, or microabscesses.

Koay LB, Tsai SL, Sun CS, Wu KT. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, 901 Chung Hwa Road, Yung Kang City, Tainan, Taiwan. · Hepatogastroenterology. · Pubmed #19102393 No free full text.

Abstract: A 66-year-old female presented with acute illness of severe hepatic dysfunction. She had a past history of chronic hepatitis of low disease activity. After admission and clinical investigation including liver biopsy, it showed an underlying chronic liver disease suggestive of autoimmune hepatitis (AIH) with early liver cirrhosis. Together with other clinical features, this patient was diagnosed as definite AIH type 1 by using the IAIHG (International Autoimmune Hepatitis Group) criteria. During this episode, superinfection by Epstein-Barr virus (EBV) was evidenced by positive PCR (polymerase chain reaction) test, and serial changes of EBV VCA IgM and IgG tests. Severe hepatic impairment was evidenced by markedly elevated AST level 3090 IU/L, high bilirubin level 26.4 mg/dL, and presence of ascites. The patient gradually recovered and liver function improved in agreement with the decline of EBV VCA titers. Immunosuppressive therapy resulted in further improvement of the aminotransferases levels. This is an unusual case of EBV superinfection on pre-existing AIH with early cirrhosis, which caused enhancement of the autoimmune disease process and resulted in severe hepatic decompensation and jaundice. We herein describe the case and briefly review the literature.

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.

Tsai HT, Tsai TH, Lu TM, Yang CC. · School of Nursing, Chung Shan Medical University, Taichung, Taiwan, Republic of China. · Int Rev Immunol. · Pubmed #19065350 No free full text.

Abstract: The interaction between immune responses and hepatitis B virus (HBV) is coordinated between innate and adaptive immunity. Anti-HBs antibodies protect the host by blocking the binding ability of HBV. Anti-HBc antibodies are detected with persistent HBV infection. The presence of anti-HBe antibodies is often associated with recovery from active diseases and is clinically used as a benchmark to assess response to treatment. Our studies have revealed that the anti-HBV immunoglobulins secreted are different in subclass patterns in different HBV infection status populations. These revelations may help to understand HBV escape and persistent infection and to develop strategies for prevention and therapeutic management of HBV infection.

Cheng PN, Chang TT. · National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan, ROC. · Expert Rev Anti Infect Ther. · Pubmed #18847396 No free full text.

Abstract: Entecavir has demonstrated safety and efficacy in the treatment of chronic hepatitis B infection. It is the prototype for the cyclopentane class of nucleoside/nucleotide chronic hepatitis B antiviral agents. It has a high potency and, due to its structural formula and mechanism of action, entecavir is associated with emergence of minimal resistance in the long-term treatment of nucleoside-naive patients. Research suggests that long-term treatment may be required for chronic hepatitis B patients, especially those who acquire HBV early in life, to achieve maximum viral suppression and improve outcomes. Several recent studies have evaluated the long-term safety, efficacy and development of resistance in nucleoside-naive patients treated with entecavir. Results indicate that the long-term use of entecavir is well tolerated and associated with continuous clinical improvement -- with an increasing number of patients achieving undetectable levels of HBV DNA, HBeAg seroconversion and minimal resistance. These data underscore the position of entecavir for first-line therapy and highlight its role in the long-term treatment of chronic hepatits B.

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.

Chu NS, Huang CC. · Department of Neurology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Lin-kou, Taiwan. · Acta Neurol Taiwan. · Pubmed #18686645 No free full text.

Abstract: Wilson's disease (WD) has been studied in Taiwan since 1960s. The study can be divided into three periods: (1) The first period was 1960s, represented by the work of Dr. JB Tu who worked in the U.S. Naval Medical Research Unit No. 2 (NAMRU-2); (2) The second period was 1970s, represented by the work of Dr. ML Leu who also worked in NAMRU-2. During these two periods, d-penicillamine was introduced to Taiwan via NAMRU-2, primarily as study drug; and (3) The third period was 1980s and afterwards. Tu and Leu reported the clinical manifestations, tissue concentrations of copper, and therapeutic effects of d-penicillamine including cupriuresis, reduction of copper content in tissues, and prognosis. Our studies after 1980s included clinical manifestations, evoked potentials to detect the extent of CNS involvement, effect of superimposed hepatitis B infection on clinical manifestations and prognosis, and WD with cerebral white matter involvement. The present review highlights above investigations.

Martin V, De Simone L, Lubroth J, Ceccato P, Chevalier V. · Emergency Centre for the Control of Transboundary Animal Diseases, FAO, Beijing, People's Republic of China. · Geospat Health. · Pubmed #18686251 links to  free full text

Abstract: Recent disease epidemics and their spread around the world have illustrated the weaknesses of disease surveillance and early warning systems (EWS), both at national and international levels. These diseases continuously threaten the livestock sector on a worldwide basis, some with major public health impact. EWS and accurate forecasting of new outbreaks of epidemic livestock diseases that may also affect wildlife, and the capacity for spread of such diseases to new areas is an essential pre-requisite to their effective containment and control. Because both the geographical and seasonal distribution of many infectious diseases are linked to climate, the possibility of using climaterelated environmental factors as predictive indicators, in association with regular disease surveillance activities, has proven to be relevant when establishing EWS for climate-related diseases. This article reviews the growing importance of using geographical information systems in predictive veterinary epidemiology and its integration into EWS, with a special focus on Rift Valley fever. It shows that, once fully validated in a country or region, this technology appears highly valuable and could play an increasing role in forecasting major epidemics, providing lead time to national veterinary services to take action to mitigate the impact of the disease in a cost-effective manner.

Su IJ, Wang HC, Wu HC, Huang WY. · Division of Clinical Research, National Health Research Institutes, Tainan, Taiwan. · J Gastroenterol Hepatol. · Pubmed #18505413 No free full text.

Abstract: The discovery of "ground glass" hepatocytes (GGH) that contain hepatitis B virus (HBV) surface antigens by Hadziyannis and Popper in 1973 represents a historical landmark in the pathology of chronic HBV infection. Different types of GGH have been correlated to the expression patterns of surface/core antigens and the stages of virus replication. The original two types (designated types I & II) of GGH were found to contain specific pre-S mutants with deletions over either pre-S1 or pre-S2 regions, respectively. Type II GGH consistently harbor pre-S2 deletion mutants, which can escape from immune attack and grow preferentially to form clusters. Both types of pre-S mutants can induce endoplasmic reticulum (ER) stress and oxidative DNA damage. The pre-S2 mutants, albeit inducing a weaker level of ER stress signals, could additionally initiate ER stress-independent retinoblastoma/adenovirus E2 promoter binding factor/cyclin A signaling through their interaction with c-Jun activation domain binding protein 1 to degrade p27, illustrating the growth advantage of type II GGH. The combined effects of genomic instability and the proliferation of hepatocytes harboring pre-S mutants could potentially lead to hepatocarcinogenesis over the decades of chronic HBV infection. The presence of pre-S mutants in sera was reported to carry a high risk of developing hepatocellular carcinoma (HCC). Furthermore, transgenic mice harboring pre-S2 mutant plasmids have been shown to develop a dysplastic change of hepatocytes and HCC. Therefore, in addition to being a histological marker of chronic HBV infection, GGH, particularly type II GGH, may represent the preneoplastic lesions of HBV-related HCC.

Wu IW, Wu MS, Lin JL. · Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC. · J Nephrol. · Pubmed #18446722 No free full text.

Abstract: Bentazone is a herbicide widely used in the agrochemical field and acts by interference in photosynthesis in plants. Case reports of bentazone poisoning in humans are rare, but hepatorenal damage and death have been described, though the mechanism of toxicity remains speculative. We describe 2 cases of acute bentazone poisoning and compare these with other literature reports. The clinical picture included nausea, vomiting, diarrhea, abdominal pain with gastrointestinal corrosive injury, dyspnea and acute hepatorenal dysfunction. Respiratory failure, acute hepatitis, acute renal failure requiring hemodialysis, and death occurred following a large ingested dose of 1,764 mg/kg. Bentazone may have direct organ toxicity, especially in liver and kidney, in subjects with renal hypoperfusion, rhabdomyolysis, preexisting renal disease or concomitant nephrotoxic drug consumption. Aggressive supportive therapy, hydration and measures to prevent renal hypoperfusion are essential to reverse acute renal failure.

Lee CM, Hung CH, Lu SN, Changchien CS. · Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niaosong Township, Kaohsiung, Taiwan, ROC. · Chang Gung Med J. · Pubmed #18419050 links to  free full text

Abstract: The incidence of hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) has been increasing in several countries including Taiwan. There are six main genotypes, each of which contains closely related subtypes. Molecular epidemiological studies have shown marked differences in the genotype distribution by geographical region and between patient groups. HCV genotype 1 may play a role in the development of HCC, although some studies have argued against this. A sustained virological response secondary to interferon monotherapy or interferon/ribavirin combination therapy may reduce the risk of HCC and improve survival in chronic hepatitis C patients. The HCV genotypes are associated with therapeutic response. Rapid virological response is also a predictor of therapeutic response. Although viral characteristics have consistently been shown to be important predictors of treatment response, identification of additional host immune and genetic factors involved in determining the outcome of antiviral therapy is necessary. Newly developed bio-techniques (microarray, proteomes, bioinformatics), drugs, and treatment strategies may elucidate the pathogenesis and improve the therapeutic response in HCV infection.

Chu CJ, Lee SD. · Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University, School of Medicine, Taipei, Taiwan. · J Gastroenterol Hepatol. · Pubmed #18397482 No free full text.

Abstract: Because of the shared modes of transmission, hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection is not uncommon in highly endemic areas and among subjects with a high risk of parenteral infections. The worldwide prevalence of HBV/HCV coinfection is unknown and might be underestimated with the phenomenon of silent (occult) HBV infection. HCV superinfection in patients with chronic HBV infection was the most common clinical features of coinfection in Asia-Pacific countries. Further, most, but not all, clinical observations suggested that interference between the two viruses was more frequently characterized by an inhibition of HBV replication exerted by HCV. However, longitudinal follow-up studies have demonstrated that the virological patterns in coinfection cases are widely divergent and have dynamic profiles over time. As compared with monoinfected patients, HBV/HCV coinfected persons tend to have more severe liver injury, a higher probability of liver cirrhosis and hepatic decompensation, and a higher incidence of hepatocellular carcinoma. Detailed serological and virological evaluations are required for coinfected patients before initiation of antiviral therapy. Previous studies demonstrated that HBV/HCV coinfected patients responded poorly to interferon (IFN) monotherapy. Currently, for patients with dominant HCV infection and low level HBV viremia (<10(4) IU/mL), IFN or pegylated IFN plus ribavirin can achieve comparable sustained virus response as expected with HCV monoinfection. However, phenomenon of reciprocal viral interference can happen, and resultant "flare" of hepatitis activity may cause liver function deterioration. For coinfected patients with dually-active HBV/HCV, the optimal regimen for therapy remains unclear although adding oral nucleos(t)ide analogs to pegylated IFN and ribavirin seems a reasonable empiric option.

Tan A, Yeh SH, Liu CJ, Cheung C, Chen PJ. · Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan. · Liver Int. · Pubmed #18251977 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is a worldwide health issue that has started receiving attention but is still poorly understood. However, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) are known to be two major causative agents of HCC. They differ in their modes of infection, their treatment options, their genomes and their carcinogenic abilities. However, both share a link with HCC through alterations of the host genome. In order to continue in our search for the mechanisms behind viral hepatocarcinogenesis, the individual entities (HBV, HCV, HCC and host), their natural history, treatment options and genomic properties must be further understood. Additionally, an understanding of the genomics, the link between the entities, is crucial for the success of the ongoing search for therapeutic options for HCC. Similar to most types of cancer, hepatocarcinogenesis is a multistep process involving different genetic alterations that ultimately lead to malignant transformation of the hepatocyte. As technology advances and research continues, the genetic changes and influences among these entities will prove essential to improved diagnostic and therapeutic options. It remains a challenge to provide a clear picture of the connection between virus and cancer. We review (i) the epidemiological link between HBV/HCV infection to HCC; (ii) prevention and control of chronic hepatitis B or C in reducing HCC risk; and (iii) genetic characters of viruses and hosts and the mechanisms associated with HCC susceptibilities, with the intention of providing a direction for future research and treatment.

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.

Yu ML, Huang CF, Dai CY, Huang JF, Chuang WL. · Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. · Oncology. · Pubmed #18087178 No free full text.

Abstract: Hepatitis C virus infection frequently causes chronic liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) and has become the main indication for liver transplantation. Interferon (IFN)-based therapy has been used in the treatment of chronic hepatitis C (CHC) for viral clearance. Several earlier studies showed long-term beneficial effects of IFN monotherapy in reducing the progression of cirrhosis, hindering HCC development, and prolonging survival among both sustained virological responders and nonresponders. However, the benefits of preventing disease progression in CHC patients without sustained virological response (SVR) no longer existed over a longer observation period. Both IFN monotherapy and IFN-ribavirin combination therapy were shown to reduce significantly the complications of liver disease, in terms of development of cirrhosis, HCC and liver-related mortality. The significance disappeared after response to antiviral treatment was taken into account. The benefits were obtained mainly from successful antiviral treatment but were not related to the antiviral regimens, suggesting that the magnitude of this preventive effect could increase through the significant improvement of SVR rate by using a more effective regimen, such as interferon-ribavirin or peginterferon-ribavirin combination therapy. Nevertheless, about one-third of patients remain resistant to the current recommended antiviral regimens. More effective treatment is needed for the population.

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.