Evaluation of Impact of Serial Hepatitis B Virus DNA Levels on Development of Hepatocellular Carcinoma
|
|
- Sherman Warner
- 6 years ago
- Views:
Transcription
1 JOURNAL OF CLINICAL MICROBIOLOGY, June 2009, p Vol. 47, No /09/$ doi: /jcm Copyright 2009, American Society for Microbiology. All Rights Reserved. Evaluation of Impact of Serial Hepatitis B Virus DNA Levels on Development of Hepatocellular Carcinoma Henry Lik-Yuen Chan,* Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Angel Mei-Ling Chim, Larry Hin Lai, and Joseph Jao-Yiu Sung Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong Received 6 January 2009/Returned for modification 30 March 2009/Accepted 10 April 2009 We aimed to investigate the impact of hepatitis B virus (HBV) DNA on the development of hepatocellular carcinoma (HCC). We conducted a case/control study based on 506 chronic HBV patients followed up since Forty-one patients developed HCC, and each of them was age and gender matched with two simultaneously recruited controls without HCC. HBV DNA was measured at the initial visit, at yearly intervals, and at the last visit. Patient age at the time of HCC development was 55 9 years. Forty-nine (40%) patients experienced antiviral treatment. The median time from diagnosis to the development of HCC was 17 months, and the control patients were followed for 92 months. At the trough level (defined as lowest level among all studied visits), more (27 patients; 66%) HCC patients had HBV DNA levels of >10,000 copies/ml than the controls (17 patients; 21%). The area under the receiver operating characteristic curve of the trough log HBV DNA level for HCC was 0.79 (95% confidence interval [CI], 0.69 to 0.89). Trough log HBV DNA (odds ratio, 11.4; 95% CI, 3.6 to 37.6; P < ) and liver cirrhosis (odds ratio, 11.4; 95% CI, 3.6 to 36.2; P < ) levels were independently associated with HCC after an adjustment for age, gender, antiviral treatment, and HBV genotype. The difference in the trough HBV DNA level was more obvious among untreated patients ( log copies/ml in HCC patients versus log copies/ml in control patients; P < ) than among those who had received antiviral treatment ( log copies/ml in HCC patients versus log copies/ml in control patients; P 0.38). A high trough HBV DNA level was associated with a higher risk of HCC. Whether antiviral treatment could prevent HCC was uncertain. * Corresponding author. Mailing address: Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, Ngan Shing Street, Shatin, Hong Kong. Phone: Fax: hlychan@cuhk.edu.hk. Published ahead of print on 22 April Chronic hepatitis B virus (HBV) infection is the commonest cause of hepatocellular carcinoma (HCC) in Southeast Asia (8). In addition to the host factors, including an older age and male gender, viral factors such as being positive for HBV e antigen (HBeAg) and having high HBV DNA levels, genotype C HBV (particularly subgenotype Ce), and basal core promoter mutations have been suggested to associate with a higher risk of HCC (7, 9, 10, 11, 14, 28). In several cohort studies in Taiwan, China, and Hong Kong, a single high HBV DNA level higher than 4 log to 4.5 log copies/ml was associated with an increased HCC risk in the subsequent 10 years (7, 9, 10, 11). In addition, patients who had persistently high HBV DNA levels at the last follow-up visit also had an increased risk of developing HCC (10). In all previous studies, there was no information on the HBV DNA levels during the years between the first and last follow-up visits. As HBV DNA levels tend to fluctuate, particularly in HBeAg-negative patients, an assessment at a single time point cannot accurately reflect the severity of liver disease (6, 12, 13). In recently published management guidelines, antiviral treatment is recommended in patients with liver cirrhosis when the HBV DNA level is higher than 4 log copies/ml (15, 21, 23). This recommendation was based primarily on a multicentered, placebo-controlled trial among Asian chronic HBV patients who suffered from severe liver fibrosis (20). In this study, lamivudine treatment was demonstrated to reduce the risk of liverrelated complications in 3 years. However, the benefit of prevention of HCC development among lamivudine-treated patients became dubious after excluding patients who developed HCC within the first year. In an Italian series, HBV DNA suppression by lamivudine and adefovir could not prevent the development of HCC among patients with decompensated liver cirrhosis (18). In this study, we aimed to investigate the impact of changes in HBV DNA on the development of HCC, either in the natural course of disease or as a result of antiviral treatment. To address this question, we studied the HBV DNA levels at different time intervals of follow-up among a cohort of chronic HBV patients before the development of HCC compared to those of simultaneously recruited controls. MATERIALS AND METHODS Patients. This case/control patient study was based on two cohorts of patients followed up at the hepatitis clinic at Prince of Wales Hospital. One cohort consisted of 426 consecutive chronic HBV patients who were recruited between December 1997 and July 2000 and were followed up thereafter (1, 7). Another cohort consisted of 80 chronic HBV patients who have participated in a placebocontrolled, randomized trial of lamivudine since 1999 (20). All patients were ethnically Chinese and were positive for HBV surface antigen for over 6 months. All patients had no history of alcoholism over 20 g per week or hepatitis C virus coinfection. Patients who had other possible causes of hepatitis or liver cirrhosis, including autoimmune liver disease, primary biliary cirrhosis, Wilson s disease, and hemochromatosis, were also excluded. At initial presentation, an ultrasound of the abdomen was performed to exclude any preexisting HCC. Patients were prospectively followed up every 3 to 6 months, or more frequently if clinically indicated, with monitoring of liver biochemistry and HBeAg and anti-hbe status as well as alpha-fetoprotein levels. An ultrasound of the abdomen, computerized tomography, hepatic angiogram, and/or liver biopsy would be performed when- 1830
2 VOL. 47, 2009 SERIAL HBV DNA AND HCC 1831 ever the alpha-fetoprotein level was on a rising trend over 20 g/liter to confirm the diagnosis of HCC. For patients with normal alpha-fetoprotein levels, an ultrasound of the abdomen was performed every 1 to 2 years. Clinical liver cirrhosis was defined as ultrasonic features of liver cirrhosis plus evidence of hypersplenism (splenomegaly with a platelet count of less than /liter or a white cell count of less than /liter), clinical ascites, varices, and/or hepatic encephalopathy (1). Antiviral treatment was started according to the physician s decision or the clinical trial protocol. The database was frozen on 30 December Forty-one patients developed HCC during the follow-up period. For each case patient, we randomly selected two control subjects from the same cohort of chronic HBV patients who were alive and had not been diagnosed with HCC throughout the follow-up period. As the age of the patient at the time of HCC development is a major confounding factor, the control subjects were individually matched to the case patients by the gender and age of the patient at the last follow-up (or when HCC was diagnosed) within 5 years. In other words, these patients were recruited at the same period of time, with the time of HCC diagnosis matched to that of the last follow-up of the controls. Other clinical factors, including liver cirrhosis and antiviral treatment, were not matched due to an insufficient number of matched patients to serve as controls in our database. HBV DNA was measured at the initial visit, at yearly intervals, and at the last follow-up visit (or when HCC developed if serum samples were available). Laboratory tests. Residual serum samples were stored in a 80 C freezer. HBV DNA was measured in the initial visit, then every year until the last follow-up visit. HBV genotyping was performed with the initial serum sample at the time of patient enrollment. HBV DNA was extracted by using a Qiagen QIAamp DNA minikit (Qiagen, Inc., Chatsworth, CA) according to the instructions of the manufacturer. Serology assays. HBV surface antigen (HBsAg) and anti-hepatitis C virus antibodies (third-generation assay) were tested using commercially available enzyme-linked immunosorbent assay kits (Abbott GmBH Diagnostika, Wiesbaden-Delkenheim, Germany). HBeAg and anti-hbe were measured by using an enzyme-linked immunosorbent assay (Sanofi Diagnostics, Pasteur, France). HBV DNA. HBV DNA was quantified by using a TaqMan real-time PCR assay as described previously (3, 22). This assay was standardized by serial dilution of EUROHEP genotype D HBV standard which contained viral copies/ ml. The range of HBV DNA detection was from 10 2 to 10 9 copies/ml with a correlation coefficient of the standard curve routinely greater than HBV genotyping. HBV genotyping was determined by PCR amplification and restriction fragment length polymorphism as described previously (4). All samples with inconclusive findings were confirmed by bidirectional sequencing of the HBV surface gene and compared to the published sequences in GenBank (9). Statistical analysis. Statistical analysis was performed by using SPSS version 13.0 (Chicago, IL). Continuous variables were expressed as the mean with the standard deviation or the median with the interquartile range as appropriate. HBV DNA and alanine aminotransferase (ALT) levels were analyzed at the first visit, the peak, the trough, and the last visit (or the visit when HCC was first diagnosed). The peak level was defined as the highest level of HBV DNA and ALT among all the studied visits, and the trough level was defined as the lowest level of HBV DNA and ALT among all the studied visits. Continuous variables were compared by using Student s t test or the Mann-Whitney U test as appropriate, and categorical variables were compared by using the chi-square test. Logistic regression analysis was used to determine the independent effects of HBV DNA and liver cirrhosis on the risk of HCC. The area under the receiver operating characteristic (ROC) curve (with a 95% confidence interval [95% CI]) was used to evaluate the predictive levels of HBV DNA and ALT to diagnose HCC. All statistical tests were two-sided, and s of less than 0.05 were considered statistically significant. RESULTS Clinical characteristics. The age of patients at the time of HCC development in the case cohort was 55 9 years. One hundred two (83%) of the patients were male. Thirteen (32%) case patients and 36 (44%) control patients had experienced antiviral treatment. Twelve HCC patients had received lamivudine treatment, which was changed to/supplemented with adefovir for 4 patients and changed to entecavir for 1 patient, and one HCC patient had received telbivudine treatment. All 36 control patients had received lamivudine treatment, which TABLE 1. Clinical characteristics of patients Variable a HCC (n 41) Non-HCC (n 82) Age of first visit (yr) Age of last visit (yr) No. (%) of males 34 (83) 68 (83) 1.00 Cirrhosis present at recruitment 27 (66) 20 (24) Initial hemoglobin (g/dl) Initial platelet (10 9 /mm 3 ) Initial albumin (g/liter) Initial bilirubin (mmol/liter) Initial international normalized ratio Creatinine ( mol/liter) ALT (IU/liter) level at: First visit 63 (55 104) 61 (40 96) Last visit 57 (37 121) 38 (25 59) Peak 210 ( ) 152 (84 268) Trough 35 (23 44) 26 (20 32) HBV DNA (log copies/ml) level at: First visit Last visit Peak Trough Positive for HBeAg b First visit 15 (37) 20 (24) 0.13 Last visit 14 (35) 12 (15) 0.01 HBV genotype C (vs B) c 33 (81) 53 (65) 0.10 Antiviral treatment 13 (32) 36 (44) 0.19 Follow-up duration (mo) 17 ( ) 92 (78 99) No. of visits 3 (2 7) 9 (8 9) a Continuous variables are expressed as means standard deviations or medians (interquartile ranges) as appropriate, except where indicated otherwise. b One patient with HCC was missing HBeAg data at all visits. c Two patients in the control group had negative HBV DNA in all visits, and no genotyping results were available. was changed to/supplemented with adefovir for 12 patients, changed to entecavir for 1 patient, and changed to telbivudine for 1 patient. At the time of recruitment, case patients had a higher proportion of clinical liver cirrhosis and tended to have more advanced liver disease (lower serum albumin, higher serum bilirubin, worse clotting profile, lower platelet count) (Table 1). There were more patients infected by genotype C HBV among patients with HCC than controls but the difference did not reach statistical significance. The median time from diagnosis to HCC was 17 months, and 14 (34%) patients had HCC diagnosed during the first year of follow-up. The median number of serum samples available for the case patients was three, while nine (22%) case patients had only one
3 1832 CHAN ET AL. J. CLIN. MICROBIOL. FIG. 1. ROC curves of log HBV DNA at different time points for HCC. The area under the ROC curve for the first log HBV DNA (LogDNA_first) is 0.65 (95% CI, 0.50 to 0.71; P 0.059). The area under the ROC curve for the last log HBV DNA (LogDNA_last) is 0.72 (95% CI, 0.62 to 0.81; P ). The area under the ROC curve for the peak log HBV DNA (LogDNA_peak) is 0.51 (95% CI, 0.41 to 0.61; P 0.88). The area under the ROC curve for the trough log HBV DNA (LogDNA_trough) is 0.79 (95% CI, 0.69 to 0.89; P ). serum sample for analysis. The control patients had a significantly longer follow-up duration (median, 92 months) and more serum samples (median, nine) for analysis than the case patients. All control patients were followed up for more than 12 months. Relationship of HBV DNA and ALT with HCC. Patients who developed HCC had higher HBV DNA and ALT levels at the trough and the last visit than the control patients (Table 1). The higher HBV DNA at the last visit was accompanied by a higher proportion of HBeAg among patients with HCC. The peak and first HBV DNA and ALT levels had no association with HCC. Comparing the areas under the ROC curves, the trough log HBV DNA level offered the best prediction for HCC (0.79; 95% CI, 0.69 to 0.89; P ), followed by the last log HBV DNA level (0.72; 95% CI, 0.62 to 0.81; P ) (Fig. 1). The areas under the ROC curves for the trough ALT level (0.66; 95% CI, 0.55 to 0.76; P 0.005) and the last ALT level (0.68; 95% CI, 0.57 to 0.78; P 0.002) were generally lower than those of the corresponding log HBV DNA levels (Fig. 2). At the trough, more (27 patients; 66%) HCC patients had HBV DNA levels of 4 log copies/ml than control patients (17 patients; 21%) (Table 2). Although the median trough ALT level was within the laboratory limit for both case and control patients, significantly more HCC patients (29 patients; 71%) had serum ALT levels of 0.5 times the upper limit of the laboratory normal than the controls (31 patients; 38%). A similar but less contrasting difference between the two groups was observed for HBV DNA and ALT levels at the last visit. To avoid the potential bias of occult HCC, we performed a sensitivity analysis on HBV DNA by excluding the 14 patients who developed HCC within the initial 12 months of follow-up. In this analysis, the trough log HBV DNA level ( log FIG. 2. ROC curves of ALT at different time points for HCC. The area under the ROC curve for the first ALT (ALT_first) is 0.59 (95% CI, 0.48 to 0.69; P 0.13). The area under the ROC curve for the last ALT (ALT_last) is 0.67 (95% CI, 0.57 to 0.77; P 0.002). The area under the ROC curve for the peak ALT (ALT_peak) is 0.60 (95% CI, 0.50 to 0.71; P 0.063). The area under the ROC curve for the trough ALT (ALT_trough) is 0.66 (95% CI, 0.55 to 0.76; P 0.005). copies/ml) of HCC patients was still significantly higher than that of the control subjects ( log copies/ml; P ). Fifteen of 27 (56%) HCC patients had trough HBV DNA levels of 4 log copies/ml (versus 21% in control patients; P 0.001). The log HBV DNA level at the first visit became statistically significantly higher among the HCC patients ( log copies/ml) than the control patients ( log copies/ml; P 0.024), but the peak log HBV DNA levels were still comparable between the two groups ( log copies/ml in HCC patients versus log copies/ml in control patients; P 0.23). Relationship of HBV DNA and liver cirrhosis. As patients who had HCC tended to have more liver cirrhosis and more advanced liver disease than control patients, we further analyzed the independent effect of the trough HBV DNA level and presence of clinical liver cirrhosis on HCC. On multivariate analysis adjusted for age, gender, and antiviral treatment, the trough log HBV DNA level (odds ratio, 11.4; 95% CI, 3.6 to 37.6; P ) and presence of liver cirrhosis (odds ratio, 11.4; 95% CI, 3.6 to 36.2; P ) were independent factors associated with HCC. Patients who had either liver cirrhosis or trough HBV DNA levels of 4 log copies/ml had a moderately increased risk (odds ratio, 14.8 to 20.2), while patients who had both liver cirrhosis and high HBV DNA levels had a markedly increased risk (odds ratio, 201.5) of HCC (Table 3). Effect of antiviral treatment on HCC. The effect of antiviral treatment on the trough HBV DNA levels and HCC is shown in Table 4. Among patients who did not receive any antiviral treatment, HCC patients had significantly higher trough HBV DNA and ALT levels than the control patients. Thirteen HCC patients and 36 control patients had received antiviral treatment for months and months, respectively (P 0.092). Among patients who had received antiviral treat-
4 VOL. 47, 2009 SERIAL HBV DNA AND HCC 1833 Visit HBV DNA (log copies/ml) TABLE 2. Categories of HBV DNA and ALT levels with respect to status of HCC a ALT level HCC (n 41) Non-HCC (n 82) (ULN) HCC (n 41) Non-HCC (n 82) First 4 2 (5) 16 (20) (0) 9 (11) to 6 11 (27) 26 (32) (37) 30 (37) 6 28 (68) 40 (49) (44) 28 (34) (17) 13 (16) 5 1 (2) 2 (2) Last UD 4 (10) 29 (35) (15) 25 (31) UD to 4 5 (12) 19 (23) (37) 34 (42) 4 to 6 12 (29) 48 (22) (20) 17 (21) 6 20 (49) 16 (20) (27) 6 (7) 5 1 (2) 0 (0) Peak 4 1 (2) 6 (7) (0) 2 (2) to 6 6 (15) 19 (23) (5) 10 (12) 6 34 (83) 57 (70) (22) 18 (22) (37) 34 (42) 5 15 (37) 18 (22) Trough UD 8 (20) 46 (56) (29) 52 (63) UD to 4 6 (15) 19 (23) (66) 25 (31) 4 to 6 16 (39) 16 (20) (5) 5 (6) 6 11 (27) 1 (1) (0) 0 (0) 5 0 (0) 0 (0) a UD, undetectable; ULN, upper limit of laboratory normal. ment, the differences in trough log HBV DNA and ALT levels between the HCC and control patients were less obvious. Numerically, the log HBV DNA was higher among the HCC patients, but the proportions of patients with undetectable HBV DNA were comparable between the two groups. Eight of 13 (62%) HCC patients and 20 of 36 (56%) patients without HCC had undetectable amounts of HBV DNA at the trough level (P 0.71). Among the 41 patients who developed HCC, 13 of them received antiviral treatment and 28 patients did not. Treated patients have significantly lower trough log HBV DNA levels ( copies/ml) than the untreated patients ( copies/ml) (P 0.001). However, all (100%) of the treated patients but only 14 (50%) of the untreated patients had liver cirrhosis (P 0.001). Although the duration of follow-up was longer for the treated patients (54 33 months) than the untreated patients (24 31 months; P 0.004), there was no difference in their ages at the time of HCC development (53 7 versus 55 4 years; P 0.40). The male gender ratio (10 patients [77%] versus 24 patients [86%]; P 0.66) and levels of HBV genotype C (12 patients [92%] versus 21 patients [75%]; P 0.40) and first log HBV DNA ( versus copies/ml; P 0.87) were comparable between the treated and untreated patients. DISCUSSION In this case/control patient study among patients who were prospectively followed up before the development of HCC, we have provided supportive evidence that high HBV DNA and ALT levels were associated with a higher cancer risk. As we have studied the serial HBV DNA levels during the follow-up period and our control patients had a median follow-up of up to 8 years, we were able to demonstrate that the trough HBV DNA level was more important than the peak level or a random time point (such as the first or last visit) measurement to predict HCC. The impact of a high HBV DNA level on HCC was more prominent among patients who have not received any antiviral treatment, as reported by most of the previous studies (10, 11). However, our results have cast a slight doubt on the effectiveness of antiviral treatment to prevent HCC as the difference of the trough HBV DNA levels, which reflected treatment efficacy, between the case and control patients became less obvious. To study the effect of HBV DNA on HCC development, longitudinal studies with HBV DNA measurements well before the development of HCC are preferred. This study design was ideal but difficult due to the low incidence of HCC. The annual incidence of HCC was approximately 500 to 1,000 per Amt of trough HBV DNA TABLE 3. Relationship between trough HBV DNA level and presence of liver cirrhosis and the risk of HCC a No. of cases/ no. of controls With cirrhosis Adjusted odds ratio (95% CI) No. of cases/no. of controls Without cirrhosis Adjusted odds ratio (95% CI) 4 log copies/ml 2/50 Referent 12/ ( ) 4 log copies/ml 12/ ( ) 15/ (19.4 2,090.0) a Adjusted for age of last visit (continuous variable), gender (male or female), and whether or not the patient was receiving antiviral therapy.
5 1834 CHAN ET AL. J. CLIN. MICROBIOL. Treatment TABLE 4. Trough HBV DNA and ALT levels with respect to antiviral treatment among patients with and without HCC a HBV DNA (log copies/ml) ALT level (ULN) HCC (n 28) Non-HCC (n 46) HCC (n 28) Non-HCC (n 46) None b UD 0 (0) 19 (41) (18) 30 (65) UD to 4 5 (18) 14 (30) (75) 15 (33) 4 to 6 12 (43) 12 (26) (7) 1 (2) 6 11 (39) 1 (2) Mean SD Antiviral c UD 8 (62) 27 (75) (54) 22 (61) 0.28 UD to 4 1 (8) 5 (14) (46) 10 (28) 4 to 6 4 (31) 4 (11) (0) 4 (11) 6 0 (0) 0 (0) Mean SD a UD, undetectable; ULN, upper limit of laboratory normal. b The numbers of patients in the HCC and non-hcc groups were 28 and 46, respectively. c The numbers of patients in the HCC and non-hcc groups were 13 and 36, respectively. 100,000 patients in tertiary referral centers where the prevalence of active hepatitis and liver cirrhosis was much higher than that in the general population (7, 19, 25). In most longitudinal series, a very large number of patients were studied with a long follow-up and yet only a small minority developed HCC (9, 10, 11). As the risk of HCC could be influenced by various host (age, gender), disease (ALT level, cirrhosis, antiviral treatment), and virus (HBeAg, HBV DNA, HBV genotype) factors, it was almost impossible to study the independent effect of HBV DNA at different time intervals in detail. With the low event rate, it would be undesirable to study the entire cohort of patients as the statistical adjustment might overpower the model. To address these challenges, we have decided to study the newly diagnosed HCC patients in prospective databases against simultaneously recruited age- and gender-matched controls. Unfortunately, we were unable to match the liver cirrhosis status, treatment status, and HBV genotype due to the availability of patients in the database. Although the proportion of patients receiving antiviral treatment could not be matched, nearly all treated patients received lamivudine as the initial antiviral treatment, and the importance of the trough HBV DNA level remained significant after adjustment for the treatment factor. We were not able to match the follow-up as all patients were recruited at the same time frame while data for HCC patients were censored at the time of tumor development. In other words, patients with HCC inevitably had a shorter duration of follow-up and fewer clinic visits than the controls. As most Asian patients acquire HBV infection at birth or at a very early age, the matching of the age at the last visit has matched the duration of infection until HCC development. As liver biopsy was not a routine procedure, most patients lacked liver fibrosis scores for adjustment. Our small sample size might be the reason why we could not demonstrate the difference in HCC development between genotype B and C HBV infection (9, 10). In line with previous reports, HBV DNA levels higher than 10,000 copies/ml were found to be associated with an increased risk of HCC in this study (9, 10, 11). Furthermore, a high trough HBV DNA level was most significantly associated with an increased HCC risk. In other words, patients who had intermittent viremia and disease reactivation probably had a lower risk of HCC than others who had persistently active viral replication. The observation that HBV DNA and liver cirrhosis were independent risk factors of HCC with comparable odds ratios supported direct viral mechanisms for HCC in addition to liver necroinflammation and fibrosis (8). On the other hand, the presence of liver cirrhosis is probably secondary to previous hepatic necroinflammation, which is an indirect effect of a high level of HBV replication. One particular point of note was that most HCC patients were HBeAg negative and in their 50s, as in other series. Although patients in these studies have been followed up for up to 10 years, we could at most draw the conclusion that a high HBV DNA level was associated with a higher HCC risk among middle-aged chronic HBV patients. Nonetheless, we believe that it would be inappropriate to extrapolate our findings to young immunotolerant chronic HBV patients who usually are positive for HBeAg and have very high HBV DNA levels (5). ALT is a laboratory parameter commonly used to screen for disease activity of liver disease (17). In HBeAg-negative, chronic HBV patients, elevated ALT levels are usually associated with more active disease progression (2, 26). However, patients with ALT at a high range of reference levels were found to have increased liver-related mortality in a study of 142,055 healthy Korean individuals 35 to 59 years old in an insurance program (16). In an Italian study, lowering the upper limit of the ALT normal standard to 30 IU/liter for men and 19 IU/liter for women could differentiate normal healthy subjects from those suffering from chronic hepatitis C and nonalcoholic fatty liver disease (24). Among a cohort of 1,197 Chinese HBeAg-negative chronic HBV patients, ALT levels higher than 0.5 times the upper limit of the laboratory reference range were associated with an increased risk of liver cirrhosis (27). In a large-scale longitudinal study in Hong Kong, a single ALT level between 0.5 and two times the upper limit of the laboratory reference range was associated with an increased risk of
6 VOL. 47, 2009 SERIAL HBV DNA AND HCC 1835 liver-related complications among chronic HBV patients in the subsequent follow-up (29). In this study, we have shown that higher ALT levels, especially the trough ALT level, were also associated with increased HCC risk. Also, the risk started to increase when the ALT was greater than 0.5 times the upper limit of the normal laboratory reference range. Therefore, our results supported the need to reevaluate the normal range of ALT levels among patients suffering from chronic HBV. In most treatment guidelines, antiviral treatment was recommended when HBV DNA levels were elevated, particularly when there was clinical evidence of active hepatic necroinflammation and/or liver cirrhosis (15, 21, 23). There was little controversy on the benefit of successful viral suppression for the prevention of hepatic decompensation and progression of liver cirrhosis (18, 20). However, the lowering of HBV DNA levels by antiviral treatment did not seem to effectively prevent the development of HCC. In this study, patients who developed HCC also had a dramatic reduction of HBV DNA, though to a slightly lesser extent than the controls. One possible explanation was the delayed commencement of treatment after hepatocarcinogenesis had been triggered by the virus. In our patients, the mean duration of antiviral treatment prior to HCC development was only 40 months, and it might be too short to prevent HCC development. Another possible reason would be the carcinogenic effect of the integrated HBV in the host genome, which might not respond to viral suppression by antiviral treatment. In summary, we have demonstrated that high levels of HBV DNA at the trough, which reflected a persistently active viremia, were associated with a higher risk of HCC, independent of the presence of liver cirrhosis among middle-aged chronic HBV patients. Whether antiviral treatment commenced at this time of life could effectively prevent the development of HCC was uncertain. Our findings raised a query about the optimal timing of commencement of antiviral treatment. Future studies should address whether antiviral treatment should be started at an earlier age among patients who failed to clear the virus spontaneously before histologic evidence of severe fibrosis or cirrhosis has set in. And we recommend close HCC surveillance for patients at high risk even if they have good response to antiviral treatment. ACKNOWLEDGMENTS This study is supported by a research fund for the Control of Infectious Diseases, Food, and Health Bureau, Hong Kong, Special Administrative Region (application number ) to H.L.-Y.C. H.L.-Y.C. is an advisory board member of Schering-Plough, Bristol- Myers Squibb, Pharmasset, and Novartis Pharmaceutical. REFERENCES 1. Chan, H. L. Y Changing scene in hepatitis B serology interpretation. Hosp. Med. 63: Chan, H. L. Y., N. W. Y. Leung, M. Hussain, M. L. Wong, and A. S. Lok Hepatitis B e antigen-negative chronic hepatitis B in Hong Kong. Hepatology 31: Chan, H. L. Y., Y. Hui, N. W. Y. Leung, J. Y. L. Ching, F. K. L. Chan, and J. J. Y. Sung Risk factors for active liver disease in HBeAg-negative chronic hepatitis B virus (HBV) infected patients. Am. J. Gastroenterol. 95: Chan, H. L. Y., A. K. K. Chui, W. Y. Lau, F. K. L. Chan, M. L. Wong, C. H. Tse, A. R. N. Rao, J. Wong, and J. J. Y. Sung Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation. J. Med. Virol. 68: Chan, H. L. Y., S. W. C. Tsang, C. T. Liew, C. H. Tse, M. L. Wong, J. Y. L. Ching, N. W. Y. Leung, J. S. L. Tam, and J. J. Y. Sung Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection. Am. J. Gastroenterol. 97: Chan, H. L. Y., M. L. Wong, A. Y. Hui, L. C. T. Hung, F. K. L. Chan, and J. J. Y. Sung Use of hepatitis B virus DNA quantitation to predict hepatitis B e antigen reversion in cases of chronic hepatitis B. J. Clin. Microbiol. 41: Chan, H. L. Y., A. Y. Hui, M. L. Wong, A. M. L. Tse, L. C. T. Hung, V. W. S. Wong, and J. J. Y. Sung Genotype C hepatitis B virus infection is associated with increased risk of hepatocellular carcinoma. Gut 53: Chan, H. L. Y., and J. J. Y. Sung Hepatocellular carcinoma and hepatitis B virus. Semin. Liver Dis. 26: Chan, H. L. Y., C. H. Tse, F. Mo, J. Koh, V. W. S. Wong, G. L. H. Wong, S. L. Chan, W. Yeo, J. J. Y. Sung, and T. S. K. Mok High viral load and hepatitis B virus subgenotype Ce are associated with increased risk of hepatocellular carcinoma. J. Clin. Oncol. 26: Chen, C. J., H. I. Yang, J. Su, C. L. Jen, S. L. You, S. N. Lu, G. T. Huang, U. H. Iloeje, and the REVEAL-HBV Study Group Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295: Chen, G., W. Lin, F. Shen, U. H. Iloeje, W. T. London, and A. A. Evans Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study. Am. J. Gastroenterol. 101: Chu, C. J., M. Hussain, and A. S. F. Lok Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology 36: Hadziyannis, S. F., and D. Vassilopoulos Hepatitis B e antigennegative chronic hepatitis B. Hepatology 34: Kao, J. H., P. J. Chen, M. Y. Lai, and D. S. Chen Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology 124: Keeffe, E. B., D. T. Dieterich, S. H. B. Han, I. M. Jacobson, P. Martin, E. R. Schiff, H. Tobias, and T. L. Wright A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin. Gastroenterol. Hepatol. 4: Kim, H., C. Nam, S. Jee, K. Han, D. Oh, and I. Suh Normal serum aminotransferase concentration and risk of mortality from liver disease. BMJ 328: Kim, W. R., S. L. Flamm, A. M. Di Bisceglie, H. C. Bodenheimer, Jr., and the Public Policy Committee of the American Association for the Study of Liver Disease Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology 47: Lampertico, P., M. Vigano, E. Manenti, M. Iavarone, E. Sablon, and M. Colombo Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients. Gastroenterology 133: Liaw, Y. F., D. I. Tai, C. M. Chu, D. Y. Lin, I. S. Sheen, T. J. Chen, and C. C. Pao Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. A prospective study. Gastroenterology 90: Liaw, Y. F., J. J. Y. Sung, W. C. Chow, G. Farrell, C. Z. Lee, H. Yun, T. Tanwandee, Q. M. Tao, K. Shue, O. N. Keene, J. S. Dixon, F. Gray, J. Sabbat, and the Cirrhosis Asian Lamivudine Multicentre Study Group Lamivudine for patients with chronic hepatitis B and advanced liver disease. N. Engl. J. Med. 351: Liaw, Y. F., N. Leung, J. H. Kao, T. Piratvisuth, E. Gane, K. H. Han, R. Guan, G. K. K. Lau, S. Locarnini, and the Chronic Hepatitis B Guideline Working Party of the Asian-Pacific Association for the Study of the Liver Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol. Int. 2: Loeb, K. R., K. R. Jerome, J. Goddard, M. L. Huang, A. Cent, and L. Corey High-throughput quantitative analysis of hepatitis B virus DNA in serum using the TaqMan fluorogenic detection system. Hepatology 32: Lok, A. S. F., and B. J. McMahon Chronic hepatitis B. Hepatology 45: Prati, D., E. Taioli, A. Zanella, E. Della Torre, S. Butelli, E. Del Vecchio, L. Vianello, F. Zanuso, F. Mozzi, S. Milani, D. Conte, M. Colombo, and G. Sirchia Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann. Intern. Med. 137: Sherman, M., K. M. Peltekian, and C. Lee Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology 22: Sung, J. J. Y., H. L. Y. Chan, M. L. Wong, C. H. Tse, S. C. H. Yuen, J. S. L. Tam, and N. W. Y. Leung Relationship of clinical and virological factors with hepatitis activity in hepatitis B e antigen-negative chronic hepatitis B virus-infected patients. J. Viral Hepat. 9:
7 1836 CHAN ET AL. J. CLIN. MICROBIOL. 27. Wong, G. L. H., V. W. S. Wong, P. C. L. Choi, A. W. H. Chan, A. M. L. Chim, K. K. L. Yiu, H. Y. Chan, F. K. L. Chan, J. J. Y. Sung, and H. L. Y. Chan Evaluation of alanine transaminase and hepatitis B virus DNA to predict liver cirrhosis in hepatitis B e antigen-negative chronic hepatitis B using transient elastography. Am. J. Gastroenterol. 103: Yang, H. I., S. N. Lu, Y. F. Liaw, S. L. You, C. A. Sun, L. Y. Wang, C. K. Hsiao, P. J. Chen, D. S. Chen, C. J. Chen, and the Taiwan Community- Based Cancer Screening Project Group Hepatitis B e antigen and the risk of hepatocellular carcinoma. N. Engl. J. Med. 347: Yuen, M. F., H. J. Yuan, D. K. Wong, J. C. Yuen, W. M. Wong, A. O. Chan, B. C. Wong, K. C. Lai, and C. L. Lai Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut 54:
Chronic hepatitis B is one of the leading causes of hepatocellular. Surrogate End Points and Long-Term Outcome in Patients With Chronic Hepatitis B
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2009;7:1113 1120 Surrogate End Points and Long-Term Outcome in Patients With Chronic Hepatitis B VINCENT WAI SUN WONG,*, GRACE LAI HUNG WONG,*, ANGEL MEI LING CHIM,*,
More informationHepatitis B Virus Genotype C Is Associated With More Severe Liver Fibrosis Than Genotype B
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2009;7:1361 1366 Hepatitis B Virus Is Associated With More Severe Liver Fibrosis Than HENRY LIK YUEN CHAN, GRACE LAI HUNG WONG, CHI HANG TSE, ANGEL MEI LING CHIM,
More informationNatural History of HBV Infection
Natural History of HBV Infection Joseph JY Sung MD PhD Institute of Digestive Disease Department of Medicine & Therapeutics Prince of Wales Hospital The Chinese University of Hong Kong HBV Infection 2
More informationChronic hepatitis B (CHB) is the leading cause of
GASTROENTEROLOGY 2013;144:933 944 CLINICAL LIVER Accuracy of Risk Scores for Patients With Chronic Hepatitis B Receiving Entecavir Treatment GRACE LAI HUNG WONG, 1,2 HENRY LIK YUEN CHAN, 1,2 HOI YUN CHAN,
More informationManagement of Chronic Hepatitis B in Asian Americans
Management of Chronic Hepatitis B in Asian Americans Myron J Tong; UCLA, CA Calvin Q. Pan; Mount Sinai, NY Hie-Won Hann; Thomas Jefferson, PA Kris V. Kowdley; Virginia Mason, WA Steven Huy B Han; UCLA,
More informationRole of Hepatitis B Virus Genotypes in Chronic Hepatitis B Exacerbation
BRIEF REPORT Role of Hepatitis B Virus Genotypes in Chronic Hepatitis B Exacerbation Man-Fung Yuen, 1 Erwin Sablon, 2 Danny Ka-Ho Wong, 1 He-Jun Yuan, 1 Benjamin Chun-Yu Wong, 1 Annie On-On Chan, 1 and
More informationThe Impact of HBV Therapy on Fibrosis and Cirrhosis
The Impact of HBV Therapy on Fibrosis and Cirrhosis Jordan J. Feld, MD, MPH Associate Professor of Medicine University of Toronto Hepatologist Toronto Centre for Liver Disease Sandra Rotman Centre for
More informationC hronic hepatitis B (CHB) virus infection affects more
161 HEPATITIS Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications MF Yuen, HJ Yuan, D KH Wong, J CH Yuen, WM Wong, A OO Chan, B CY Wong, KC Lai, CL Lai... See end of article
More informationOriginal article On-treatment monitoring of liver fibrosis with transient elastography in chronic hepatitis B patients
Antiviral Therapy 2011; 16:165 172 (doi: 10.3851/IMP1726) Original article On-treatment monitoring of liver fibrosis with transient elastography in chronic hepatitis B patients Grace Lai-Hung Wong 1,2,
More informationAntiviral Therapy 14:
Antiviral Therapy 14:679 685 Original article Combination of baseline parameters and on-treatment hepatitis B virus DNA levels to start and continue patients with lamivudine therapy Man-Fung Yuen 1 *,
More informationCornerstones of Hepatitis B: Past, Present and Future
Cornerstones of Hepatitis B: Past, Present and Future Professor Man-Fung Yuen Queen Mary Hospital The University of Hong Kong Hong Kong 1 Outline Past Natural history studies Development of HBV-related
More informationChronic hepatitis B virus (HBV) infection remains a major
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:541 545 Hepatitis B Virus DNA Level Predicts Hepatic Decompensation in Patients With Acute Exacerbation of Chronic Hepatitis B WEN JUEI JENG, I SHYAN SHEEN,
More informationCURRENT TREATMENT. Mitchell L Shiffman, MD Director Liver Institute of Virginia Bon Secours Health System Richmond and Newport News, Virginia
CURRENT TREATMENT OF HBV Mitchell L Shiffman, MD Director Liver Institute of Virginia Bon Secours Health System Richmond and Newport News, Virginia CHRONIC HBV INFECTION DEMOGRAPHICS IN THE USA Estimated
More informationJournal of Antimicrobial Chemotherapy Advance Access published April 25, 2013
Journal of Antimicrobial Chemotherapy Advance Access published April 25, 213 J Antimicrob Chemother doi:1.193/jac/dkt147 Virological response to entecavir reduces the risk of liver disease progression
More informationPhylogenetic, Virological, and Clinical Characteristics of Genotype C Hepatitis B Virus with TCC at Codon 15 of the Precore Region
JOURNAL OF CLINICAL MICROBIOLOGY, Mar. 2006, p. 681 687 Vol. 44, No. 3 0095-1137/06/$08.00 0 doi:10.1128/jcm.44.3.681 687.2006 Copyright 2006, American Society for Microbiology. All Rights Reserved. Phylogenetic,
More informationReceived 30 May 2004/Returned for modification 6 August 2004/Accepted 12 August 2004
JOURNAL OF CLINICAL MICROBIOLOGY, Nov. 2004, p. 5036 5040 Vol. 42, No. 11 0095-1137/04/$08.00 0 DOI: 10.1128/JCM.42.11.5036 5040.2004 Copyright 2004, American Society for Microbiology. All Rights Reserved.
More informationDoes Viral Cure Prevent HCC Development
Does Viral Cure Prevent HCC Development Prof. Henry LY Chan Head, Division of Gastroenterology and Hepatology Director, Institute of Digestive Disease Director, Center for Liver Health Assistant Dean,
More informationLong-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease
Antiviral Therapy 12:1295 133 Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease Man-Fung Yuen, Wai-Kay
More informationE pidemiological studies have shown a strong association
1494 LIVER Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma H L-Y Chan, A Y Hui, M L Wong, A M-L Tse, L C-T Hung, V W-S Wong, J J-Y Sung... See end
More informationHepatitis B Treatment Pearls. Agenda
Hepatitis B Treatment Pearls Fredric D. Gordon, MD Vice Chair Dept. of Transplantation and Hepatobiliary Diseases Lahey Hospital & Medical Center Associate Professor of Medicine Tufts Medical School Boston,
More informationHepatitis B virus (HBV) infection is a global
VIRAL HEPATITIS Serum Hepatitis B Surface Antigen Levels Help Predict Disease Progression in Patients With Low Hepatitis B Virus Loads Tai-Chung Tseng, 1,3,8 Chun-Jen Liu, 2,3 Hung-Chih Yang, 2,6 Tung-Hung
More informationChronic hepatitis B - New goals, new treatment. New England Journal Of Medicine, 2008, v. 359 n. 23, p
Title Chronic hepatitis B - New goals, new treatment Author(s) Lai, CL; Yuen, MF Citation New England Journal Of Medicine, 2008, v. 359 n. 23, p. 2488-2491 Issued Date 2008 URL http://hdl.handle.net/10722/59270
More informationHepatitis B Virus therapy. Maria Buti Hospital Universitario Valle Hebron Barcelona Spain
Hepatitis B Virus therapy Maria Buti Hospital Universitario Valle Hebron Barcelona Spain Disclosures Advisor: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp &
More informationManagement of Decompensated Chronic Hepatitis B
Management of Decompensated Chronic Hepatitis B Dr James YY Fung, FRACP, MD Department of Medicine The University of Hong Kong Liver Transplant Center Queen Mary Hospital State Key Laboratory for Liver
More informationManagement of hepatitis B virus
Journal of Antimicrobial Chemotherapy Advance Access published May 14, 2008 Journal of Antimicrobial Chemotherapy doi:10.1093/jac/dkn188 Management of hepatitis B virus Nidhi A. Singh and Nancy Reau* Section
More informationHepatitis B Virus therapy. Maria Buti Hospital Universitario Valle Hebron Barcelona Spain
Hepatitis B Virus therapy Maria Buti Hospital Universitario Valle Hebron Barcelona Spain Disclosures Advisor: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp &
More informationAntiviral Therapy 2012; 17: (doi: /IMP1945)
Antiviral Therapy 2012; 17:387 394 (doi: 10.3851/IMP1945) Original article HBV DNA level at 24 weeks is the best predictor of virological response to adefovir add-on therapy in patients with lamivudine
More informationHepatitis B Update. Jorge L. Herrera, M.D. University of South Alabama Mobile, AL. Gastroenterology
Hepatitis B Update Jorge L. Herrera, M.D. University of South Alabama Mobile, AL Deciding Who to Treat Is hepatitis B a viral disease or a liver disease? Importance of HBV-DNA Levels in the Natural History
More informationNatural History of Chronic Hepatitis B
Natural History of Chronic Hepatitis B Anna SF Lok, MD Alice Lohrman Andrews Professor in Hepatology Director of Clinical Hepatology Assistant Dean for Clinical Research University of Michigan Ann Arbor,
More informationViral hepatitis and Hepatocellular Carcinoma
Viral hepatitis and Hepatocellular Carcinoma Hashem B. El-Serag, MD, MPH Dan L. Duncan Professor of Medicine Chief, Gastroenterology and Hepatology Houston VA & Baylor College of Medicine Houston, TX Outline
More informationHepatitis B. What's the impact on the risk? Dr Himanshu Bhatia, Asia Chief Medical Officer ALUCA, Brisbane, Sept 2013
Hepatitis B What's the impact on the risk? Dr Himanshu Bhatia, Asia Chief Medical Officer ALUCA, Brisbane, Sept 2013 Some quick facts about Hepatitis B Worldwide: 350-400 Million are chronic infections
More informationLong-term Clinical Outcomes and Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Patients with HBsAg Seroclearance
Long-term Clinical Outcomes and Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Patients with HBsAg Seroclearance Gi-Ae Kim, Han Chu Lee *, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim,
More informationChoice of Oral Drug for Hepatitis B: Status Asokananda Konar
Choice of Oral Drug for Hepatitis B: Status 2011 Asokananda Konar Chronic hepatitis B (CHB) is a global public health challenge with an estimated 350 to 400 million people with chronic HBV infection, despite
More informationTreatment of patients with chronic hepatitis B who have failed previous antiviral treatment with pegylated interferon α2a (40 kda; PEGASYS )
Original article Antiviral Therapy 13:555 562 Treatment of patients with chronic hepatitis B who have failed previous antiviral treatment with pegylated interferon α2a (40 kda; PEGASYS ) Henry L-Y Chan*,
More informationDisclaimer. Presenter Release are for reactive use by Medical Information only internal learning/educational use only
Disclaimer Presenter Release are for reactive use by Medical Information only internal learning/educational use only Any unsolicited request from HCP must be forwarded to Medical Information Housekeeping
More informationWho to Treat? Consider biopsy Treat. > 2 ULN Treat Treat Treat Treat CIRRHOTIC PATIENTS Compensated Treat HBV DNA detectable treat
Who to Treat? Parameter AASLD US Algorithm EASL APASL HBV DNA CRITERIA HBeAg+ >, IU/mL > 2, IU/mL > 2, IU/mL >, IU/mL HBeAg- > 2, IU/mL > 2, IU/mL > 2, IU/mL > 2, IU/mL ALT CRITERIA PNALT 1-2 ULN Monitor
More informationManagement of chronic hepatitis B : recent advance in the treatment of antiviral resistance
anagement of chronic hepatitis B : recent advance in the treatment of antiviral resistance / 김강모 연수강좌 anagement of chronic hepatitis B : recent advance in the treatment of antiviral resistance 김강모 울산대학교의과대학서울아산병원소화기내과
More informationWhat have we learned from HBV clinical cohorts?
PHC 2015: Hepatitis B What have we learned from HBV clinical cohorts? Jia-Horng Kao MD, Ph D Graduate Institute of Clinical Medicine, Hepatitis Research Center, Department of Internal Medicine, National
More informationSupplementary materials: Predictors of response to pegylated interferon in chronic hepatitis B: a
Supplementary materials: Predictors of response to pegylated interferon in chronic hepatitis B: a real-world hospital-based analysis Yin-Chen Wang 1, Sien-Sing Yang 2*, Chien-Wei Su 1, Yuan-Jen Wang 3,
More informationPegasys Hepatitis B. Pegasys (peginterferon alfa-2a) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.03.02 Subject: Pegasys Hepatitis B Page: 1 of 5 Last Review Date: September 18, 2015 Pegasys Hepatitis
More informationChronic Hepatitis B Infection
Chronic Hepatitis B Infection Mohssen Nassiri Toosi, MD Imam Khomeinin Hospital Tehran University of Medical Sciences Chronic Hepatitis B Infection Virus : HBs Ag Positive Host Liver Health Chronic Hepatitis
More informationDevelopment of Hepatocellular Carcinoma After Seroclearance of Hepatitis B Surface Antigen
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2009;7:889 893 Development of Hepatocellular Carcinoma After Seroclearance of Hepatitis B Surface Antigen MYRON JOHN TONG,*, MICHAEL ONG NGUYEN, LORI TERESE TONG,
More informationHepatitis B virus (HBV) is a major public health
Hepatocellular Carcinoma Risk in Chronic Hepatitis B Virus Infected Compensated Cirrhosis Patients With Low Viral Load Dong Hyun Sinn, 1 Junggyu Lee, 1 Juna Goo, 2 Kyunga Kim, 2 Geum-Youn Gwak, 1 Yong-Han
More informationViral Hepatitis. Dr Melissa Haines Gastroenterologist Waikato Hospital
Viral Hepatitis Dr Melissa Haines Gastroenterologist Waikato Hospital Viral Hepatitis HAV HBV HCV HDV HEV Other viral: CMV, EBV, HSV Unknown Hepatitis A Hepatitis A Transmitted via the faecal-oral route
More information29th Viral Hepatitis Prevention Board Meeting
29th Viral Hepatitis Prevention Board Meeting Madrid, November 2006 Treatment of chronic hepatitis B José M. Sánchez-Tapias Liver Unit Hospital Clínic University of Barcelona Spain CHRONIC HBV INFECTION
More informationHepatocellular Carcinoma: Can We Slow the Rising Incidence?
Hepatocellular Carcinoma: Can We Slow the Rising Incidence? K.Rajender Reddy M.D. Professor of Medicine Director of Hepatology Medical Director of Liver Transplantation University of Pennsylvania Outline
More informationChronic Hepatitis B: management update.
Chronic Hepatitis B: management update. E.O.Ogutu Department of clinical medicine & therapeutics, University of Nairobi. Physicians meeting,kisumu 2011. Background epidemiology Chronic hepatitis B (CHB)
More informationTreatment of chronic hepatitis B: Evolution over two decades_
doi:10.1111/j.1440-1746.2010.06545.x REVIEW Treatment of chronic hepatitis B: Evolution over two decades_6545 138..143 Man-Fung Yuen and Ching-Lung Lai Department of Medicine, the University of Hong Kong,
More informationHBV NATURAL HISTORY. Mitchell L. Shiffman, MD Director Liver Institute of Virginia Bon Secours Health System Richmond and Newport News, Virginia
HBV NATURAL HISTORY AND MANAGMENT Mitchell L. Shiffman, MD Director Liver Institute of Virginia Bon Secours Health System Richmond and Newport News, Virginia IVer Liver Institute of Virginia Education,
More informationAlam MM 1, Mahtab MA 1, Akbar SMF 2, Kamal M 3, Rahman S 1
Bangladesh Med Res Counc Bull 2014; 40: 92-56 Hepatic necroinflammation and severe liver fibrosis in patients with chronic hepatitis B with undetectable HBV DNA and persistently normal alanine aminotransferase
More informationJ.C. WANG, L.L. HE, Q. CHEN 1. Introduction. Abstract. BACKGROUND: Either combination. European Review for Medical and Pharmacological Sciences
European Review for Medical and Pharmacological Sciences Comparison of re-treatment outcomes of lamivudine plus adefovir or entecavir in chronic hepatitis B patients with viral relapse after cessation
More informationWhite Nights of Hepatology 2016
White Nights of Hepatology 2016 Saint Petersburg, 3 June 2016 Long-term treatment of Chronic hepatitis B - a key to HCC prevention Massimo Colombo Chairman Department of Liver, Kidney, Lung and Bone Marrow
More informationHow to use pegylated Interferon for Chronic Hepatitis B in 2015
How to use pegylated Interferon for Chronic Hepatitis B in 215 Teerha Piratvisuth NKC Institute of Gastroenterology and Hepatology Prince of Songkla University, Thailand ASIAN-PACIFIC CLINICAL PRACTICE
More informationNATURAL HISTORY OF HEPATITIS B
NATURAL HISTORY OF HEPATITIS B AND DIAGNOSTIC: STATE OF THE ART O. BAHRI LABORATORY OF MEDICAL BIOLOGY AZIZA OTHMANA HOSPITAL TUNIS, TUNISIA The 2 nd Congress of The Federation of Arab Societies of Clinical
More informationRisk Factors and Preventive Measures for Hepatocellular carcinoma (HCC) 울산의대울산대병원소화기내과박능화
Risk Factors and Preventive Measures for Hepatocellular carcinoma (HCC) 울산의대울산대병원소화기내과박능화 Risk factors for HCC development (I) Environmental factors Infectious HBV HCV HDV Alimentary Alcohol Diet High
More informationTreatment as a form of liver cancer prevention The clinical efficacy and cost effectiveness of treatment across Asia
Treatment as a form of liver cancer prevention The clinical efficacy and cost effectiveness of treatment across Asia Prof. Henry LY Chan Head, Division of Gastroenterology and Hepatology Director, Institute
More informationViral Hepatitis The Preventive Potential of Antiviral Therapy. Thomas Berg
Viral Hepatitis The Preventive Potential of Antiviral Therapy Thomas Berg Therapeutic and preventive strategies in patients with hepatitis virus infection Treatment of acute infection Treatment of chronic
More informationDrug Class Monograph
Drug Class Monograph Class: Chronic Hepatitis B Drug: Baraclude (entecavir), Epivir (lamivudine), Hepsera (adefovir), Intron A (interferon alfa- 2b), Pegasys (peginterferon alfa-2a), Tyzeka (telbivudine),
More informationResponse-guided antiviral therapy in chronic hepatitis B: nucleot(s)ide analogues vs. pegylated interferon
Response-guided antiviral therapy in chronic hepatitis B: Sang Hoon Ahn, M.D., Ph.D. Department of Internal Medicine, Yonsei University College of Medicine, Institute of Gastroenterology, Liver Cirrhosis
More informationThe presence of hepatitis B e antigen (HBeAg) is
Assessment of Current Criteria for Primary Nonresponse in Chronic Hepatitis B Patients Receiving Entecavir Therapy Young-Joo Yang, 1 Ju Hyun Shim, 2 Kang Mo Kim, 2 Young-Suk Lim, 2 and Han Chu Lee 2 A
More informationInteraction of Adipokines and Hepatitis B Virus on Histological Liver Injury in the Chinese
132 ORIGINAL CONTRIBUTIONS nature publishing group Interaction of Adipokines and Hepatitis B Virus on Histological Liver Injury in the Chinese Vincent Wai-Sun Wong, MD1, 2, Grace Lai-Hung Wong, MD 1, 2,
More informationOur better understanding of the natural
TREATMENT OF CHRONIC HEPATITIS B: MASTERING THE BASICS ON A COMPLEX TOPIC Ke-Qin Hu, MD* ABSTRACT The availability of newer antiviral agents, as well as comprehensive treatment recommendations, has equipped
More informationHepatitis B Prior Authorization Policy
Hepatitis B Prior Authorization Policy Line of Business: Medi-Cal P&T Approval Date: November 15, 2017 Effective Date: January 1, 2018 This policy has been developed through review of medical literature,
More informationTherapeutic Guidelines on Management of Chronic Hepatitis B in Asia
SPECIAL FEATURE Vol.6 No.2 (April 2001) Therapeutic Guidelines on Management of Chronic Hepatitis B in Asia Abstract Dr. Nancy Leung Department of Medicine and Therapeutics, Prince of Wales Hospital, The
More informationSerum Hepatitis B Surface Antigen Levels Help Predict Disease Progression in Patients With Low Hepatitis B Virus Loads. Hepatology Feb 2013
Serum Hepatitis B Surface Antigen Levels Help Predict Disease Progression in Patients With Low Hepatitis B Virus Loads Hepatology Feb 2013 Hepatitis B Surface Antigen HBsAg is the glycosylated envelope
More informationHepatitis B. ECHO November 29, Joseph Ahn, MD, MS Associate Professor of Medicine Director of Hepatology Oregon Health & Science University
Hepatitis B ECHO November 29, 2017 Joseph Ahn, MD, MS Associate Professor of Medicine Director of Hepatology Oregon Health & Science University Disclosures Advisory board Gilead Comments The speaker Joseph
More informationPrediction of HBsAg Loss by Quantitative HBsAg Kinetics during Long-Term 2015
THAI J 16 GASTROENTEROL Treatment with Nucleos(t)ide Original Analogues Article Prediction of HBsAg Loss by Quantitative HBsAg Kinetics during Long-Term Treatment with Nucleos(t)ide Analogues Sombutsook
More informationARTICLE IN PRESS. A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: An Update
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2006;4:xxx REVIEW A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: An Update EMMET B. KEEFFE,* DOUGLAS T. DIETERICH,
More informationentecavir, 0.5mg and 1mg film-coated tablets and 0.05 mg/ml oral solution, Baraclude SMC No. (747/11) Bristol-Myers Squibb Pharmaceuticals Ltd
entecavir, 0.5mg and 1mg film-coated tablets and 0.05 mg/ml oral solution, Baraclude SMC No. (747/11) Bristol-Myers Squibb Pharmaceuticals Ltd 09 December 2011 The Scottish Medicines Consortium (SMC) has
More informationPersonalized treatment of hepatitis B
pissn 2287-2728 eissn 2287-285X Review Clinical and Molecular Hepatology 2015;21:1-6 Personalized treatment of hepatitis B Anna S. Lok Division of Gastroenterology and Hepatology, University of Michigan,
More informationChanges in Serum Levels of HBV DNA and Alanine Aminotransferase Determine Risk for Hepatocellular Carcinoma
GASTROENTEROLOGY 2011;141:1240 1248 Changes in Serum Levels of HBV DNA and Alanine Aminotransferase Determine Risk for Hepatocellular Carcinoma CHUEN FEI CHEN,*, WEN CHUNG LEE,* HWAI I YANG,, HUNG CHUEN
More informationIt is estimated that there are 1.25 million individuals
Treatment Recommendations for Chronic Hepatitis B: An Evaluation of Current Guidelines Based on a Natural History Study in the United States Myron John Tong, 1,2 Carlos Hsien, 2 Leeyen Hsu, 2 Hai-En Sun,
More informationRelative predictive factors for hepatocellular carcinoma after HBeAg seroconversion in HBV infection
PO Box 2345, Beijing 123, China World J Gastroenterol 25;11(43):6848-6852 www.wjgnet.com World Journal of Gastroenterology ISSN 17-9327 wjg@wjgnet.com E L S E V I E R 25 The WJG Press and Elsevier Inc.
More informationMedInform. HBV DNA loss in Bulgarian patients on NUC therapy. Speed related factors. (NUC related speed of HBV DNA loss in Bulgaria) Original Article
DOI: 10.18044/Medinform.201852.897 ISSUE 3, 2018 HBV DNA loss in Bulgarian patients on NUC therapy. Speed related factors. (NUC related speed of HBV DNA loss in Bulgaria) Donika Krasteva, Radosveta Tomova,
More informationChronic infection with hepatitis B virus (HBV) is still a
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2012;10:527 534 Incidence and Determinants of Spontaneous Hepatitis B e Antigen and DNA in Patients With Chronic Hepatitis B HWAI I YANG,*,, HSIU LIAN HUNG, MEI
More informationPegasys Pegintron Ribavirin
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.01.47 Subsection: Anti-infective nts Original Policy Date: January 1, 2019 Subject: Pegasys Pegintron
More informationGlobal Perspective on the Natural History of Chronic Hepatitis B: Role of Hepatitis B Virus Genotypes A to J
97 Global Perspective on the Natural History of Chronic Hepatitis B: Role of Hepatitis B Virus Genotypes A to J Chun-Jen Liu, MD, PhD 1,2,3 Jia-Horng Kao, MD, PhD 1,2,3,4 1 Graduate Institute of Clinical
More informationNH2 N N N O N O O P O O O O O
N N NH 2 N N O O P O O O O O O James Watson and Francis Crick Double Helix 1953 Baruch Blumberg, MD, PhD 1925-2011 Australia Antigen 1965 Hepatitis B Virus (HBV) Hepadnaviridae member that primarily infects
More informationManagement of Hepatitis B - Information for primary care providers
Management of Hepatitis B - Information for primary care providers July 2018 Chronic hepatitis B (CHB) is often a lifelong condition. Not everyone infected needs anti-viral therapy. This document outlines
More informationNovedades en el tratamiento de la hepatitis B: noticias desde la EASL. Maria Buti Hospital Universitario Valle Hebrón Barcelona
Novedades en el tratamiento de la hepatitis B: noticias desde la EASL Maria Buti Hospital Universitario Valle Hebrón Barcelona Milestones in CHB treatment Conventional IFN 1991 Lamivudine (LAM) 1998 Adefovir
More informationLong-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men
Carcinogenesis vol.29 no.1 pp.106 112, 2008 doi:10.1093/carcin/bgm252 Advance Access publication November 13, 2007 Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular
More informationTreatment of chronic hepatitis B 2013 update
22 February 213 Treatment of chronic hepatitis B 213 update Pietro Lampertico 1st Gastroenterology Unit Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico Università di Milano EASL 212 Clinical
More informationFebruary 8, World Journal of Gastroenterology. Re: ESPS Manuscript No Dear Dr. Qi:
February 8, 2017 World Journal of Gastroenterology Re: ESPS Manuscript No. 32025 Dear Dr. Qi: My co-authors and I respectfully submit the accompanying revised manuscript, Early hepatitis B viral DNA clearance
More informationIntron A HEPATITIS B. Intron A (interferon alfa-2b) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.03.01 Subject: Intron A Hepatitis B Page: 1 of 8 Last Review Date: September 18, 2015 Intron A HEPATITIS
More informationAlimentary Pharmacology and Therapeutics SUMMARY. Background Metabolic syndrome is a known risk factor of cirrhosis in chronic hepatitis B (CHB).
Alimentary Pharmacology and Therapeutics Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B a prospective cohort study with paired transient
More informationHBV Therapy in Special Populations: Liver Cirrhosis
HBV Therapy in Special Populations: Liver Cirrhosis Universitätsklinikum Leipzig Thomas Berg Sektion Hepatologie Klinik und Poliklinik für Gastroenterologie und Rheumatologie Leber- und Studienzentrum
More informationChronic hepatitis B virus (HBV) infection affects
GASTROENTEROLOGY 2009;136:505 512 Predictive Factors for Early HBeAg Seroconversion in Acute Exacerbation of Patients With HBeAg-Positive Chronic Hepatitis B HYOUNG SU KIM,* HA JUNG KIM, WOON GEON SHIN,*
More informationHBeAg-negative chronic hepatitis B. with a nucleos(t)ide analogue?
4 th PARIS HEPATITIS CONFERENCE HBeAg-negative chronic hepatitis B Why do I treat my chronic hepatitis B patients with a nucleos(t)ide analogue? George V. Papatheodoridis, MD 2nd Department of Internal
More informationDNA 2 91% (185/203), 82% (75/91), 75% (47/63), 62% (26/42) 200,000, 20, ,999, 2,000-19,999, <2,000 ( P
Is There a Meaningful Serum Hepatitis B Virus DNA Cutoff Level for Therapeutic Decisions in Hepatitis B e Antigen Negative Chronic Hepatitis B Virus Infection? George V. Papatheodoridis, 1 Emanuel K. Manesis,
More informationScreening for HCCwho,
Screening for HCCwho, how and how often? Catherine Stedman Associate Professor of Medicine, University of Otago, Christchurch Gastroenterology Department, Christchurch Hospital HCC Global Epidemiology
More informationNeed for long-term evaluation of therapy in Chronic Hepatitis B
Need for long-term evaluation of therapy in Chronic Hepatitis B VHPB meeting Budapest 18/03/2010 Solko Schalm & Mehlika Toy Licensed Therapy Chronic hepatitis B Drug Date of Efficacy Disease Clinical Mortality
More informationHepatitis B. Epidemiology and Natural History and Implications for Treatment
Hepatitis B Epidemiology and Natural History and Implications for Treatment Norah Terrault, MD Professor of Medicine and Surgery Director, Viral Hepatitis Center University of California San Francisco
More informationChronic hepatitis B in Asia new insights from the past decade_
doi:10.1111/j.1440-1746.2010.06544.x REVIEW Chronic hepatitis B in Asia new insights from the past decade_6544 131..137 Henry Lik-Yuen Chan* and Jidong Jia *Department of Medicine and Therapeutics and
More informationPathological Features and Prognosis in Chronic Hepatitis B Virus Carriers
The Journal of International Medical Research 2011; 39: 71 77 Pathological Features and Prognosis in Chronic Hepatitis B Virus Carriers ZH LU, W CHEN, ZC JU, H PEI, XJ YANG, XB GU AND LH HUANG Department
More informationIdentification of hepatitis B virus DNA reverse transcriptase variants associated with partial response to entecavir
Title Identification of hepatitis B virus DNA reverse transcriptase variants associated with partial response to entecavir Author(s) Wong, DKH; Fung, JYY; Lai, CL; Yuen, RMF Citation Hong Kong Medical
More informationDon t interfere My first choice is always nucs!
Don t interfere My first choice is always nucs! Robert G Gish MD Professor Consultant Stanford University Medical Director, Hepatitis B Foundation Singapore Viral Hepatitis Meeting 2014 1 Disclosures Dr
More informationHepatitis B virus genotypes, precore and core promoter variants among predominantly Asian patients with chronic HBV infection in a Canadian center
Liver International 2006: 26: 796 804 r 2006 The Author Journal compilation r 2006 Blackwell Munksgaard Clinical Studies DOI: 10.1111/j.1478-3231.2006.01297.x Hepatitis B virus genotypes, precore and core
More informationY. Xiang*, P. Chen*, J.R Xia and L.P. Zhang
A large-scale analysis study on the clinical and viral characteristics of hepatitis B infection with concurrence of hepatitis B surface or E antigens and their corresponding antibodies Y. Xiang*, P. Chen*,
More informationMarch 29, :15 PM 1:15 PM San Diego, CA Convention Center Ballroom 20D
March 29, 2017 12:15 PM 1:15 PM San Diego, CA Convention Center Ballroom 20D Provided by #IM2017 This lunch symposium is not part of the official Internal Medicine Meeting 2017 Education Program. #IM2017
More informationESCMID Online Lecture Library. by author
Pro-Con: To stop or not to stop hepatitis B treatment? To Stop HBV Treatment Resat Ozaras, MD, Professor Istanbul University, Cerrahpasa Medical School, Infection Dept. HBV Therapy Nucleos(t)ide analogues
More information