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Tung-Hung Su,
Chun-Jen Liu,
Hung-Chih Yang,
Yung-Ming Jeng,
Huei-Ru Cheng,
Chen-Hua Liu, Tai-Chung Tseng,
Thai-Yen Ling,
Pei-Jer Chen,
Ding-Shinn Chen,
Jia-Horng Kao
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ABSTRACT: BACKGROUND: Serum hepatitis B surface antigen (HBsAg) level is important in the management of chronic hepatitis B (CHB). However, it is unclear whether serum HBsAg reflects its expression in liver and the hepatic HBsAg evolution following interferon therapy. METHODS: Forty-five HBeAg-positive CHB patients receiving interferon-based therapy within a randomized, controlled, multicenter study during 1998-1999 were included. The hepatic HBsAg expressions were categorized into cytoplasmic, inclusion, marginal and negative patterns by immunohistochemical staining. The HBsAg-positive hepatocytes were quantified by image-based cytometry and correlated to HBV serological and virological profiles for clinical implications. The evolution of hepatic HBsAg levels was analyzed among 22 patients with paired liver biopsies before and after interferon therapy, sequentially. RESULTS: There was a positive correlation between pretreatment serum HBsAg and hepatic HBsAg levels (r = 0.67, P < 0.0001). The hepatic HBsAg expression pattern significantly evolved from cytoplasmic/inclusion pattern to marginal/negative pattern after interferon treatment. The serum HBV-DNA, HBsAg and hepatic HBsAg levels all decreased significantly after interferon therapy. Among 36 % patients with HBeAg loss after therapy, pretreatment hepatic HBsAg levels were significantly lower compared with those without HBeAg loss. After multivariate analysis, low pretreatment hepatic HBsAg levels rather than serum HBsAg titers were associated with a higher rate of HBeAg loss (OR: 4.97, 95 % CI: 1.12-22.00, P = 0.035). CONCLUSIONS: The serum HBsAg level positively reflects the HBsAg level in liver which evolves significantly after interferon therapy. A lower hepatic HBsAg level is associated with HBeAg loss after interferon treatment. Hepatic HBsAg may have clinical significance in CHB patients receiving interferon treatment.
Journal of Gastroenterology 06/2013; · 4.16 Impact Factor
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Tai-Chung Tseng,
Chun-Jen Liu,
Chi-Ling Chen,
Hung-Chih Yang,
Tung-Hung Su,
Chia-Chi Wang,
Wan-Ting Yang,
Stephanie Fang-Tzu Kuo,
Chen-Hua Liu,
Pei-Jer Chen,
Ding-Shinn Chen,
Jia-Horng Kao
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ABSTRACT: Background & Aims. Serum hepatitis B surface antigen (HBsAg) level can predict hepatocellular carcinoma (HCC) development in hepatitis B e antigen (HBeAg)-negative patients with HBV DNA level <2000 IU/mL. However, little is known regarding how well the combination of both viral biomarkers stratifies HCC risk.Methods. A total of 2165 Taiwanese HBeAg-negative non-cirrhotic patients were followed for 14.9 years. The predictive power of HBsAg level for HCC was analyzed for different viral load ranges.Results. In patients with HBV DNA level between 2000-19999 IU/mL (intermediate viral load), a positive correlation between HBsAg level and HCC development was identified after adjusting for other risk factors (P=.002). In contrast, no association was found between HBsAg level and HCC in patients with higher viral loads. HBsAg level was subsequently included to stratify HCC risk in patients with low and intermediate viral loads. Receiver operating characteristic curve analysis showed that combining HBV-DNA and HBsAg level better predicts 10-year HCC development compared to using HBV-DNA level alone in the overall cohort (P=.028).Conclusions. Serum HBsAg level helps stratify HCC risk in patients with intermediate viral loads. Combining HBV-DNA and HBsAg levels better predicts HCC risk.
The Journal of Infectious Diseases 05/2013; · 6.41 Impact Factor
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ABSTRACT: MicroRNA-122 (miR-122) facilitates hepatitis C virus replication in vitro. Serum miR-122 has been implicated as a biomarker for various liver diseases; however, its role in chronic hepatitis C remains unclear. To address this issue, 126 patients with chronic hepatitis C who completed pegylated IFN plus ribavirin therapy with sustained virologic response (SVR) or nonresponse (NR) were retrospectively included, and their pretreatment clinical profiles and treatment responses were collected. Serum miR-122 was quantified before and during treatment. Another 51 patients in SVR and NR groups were prospectively enrolled for validation. Serum miR-122 was found to be a surrogate for hepatic miR-122 and positively correlated with hepatic necroinflammation. Patients who showed complete early virologic response and SVR had significantly higher pretreatment serum miR-122 levels than those with NR (P = 0.001 and P = 0.008, respectively), especially in subgroups of patients with hepatitis C virus genotype 2 and IL-28B rs8099917 TT genotype. Patients with IL-28B TT genotype had significantly better treatment responses and higher pretreatment serum miR-122 level than those with GT or GG genotypes. Univariate analysis showed that pretreatment body mass index, γ-glutamyl transpeptidase, triglyceride, IL-28B TT genotype, and serum miR-122 are predictors for SVR. Multivariate analysis specifically in IL-28B TT genotype demonstrated that pretreatment serum miR-122 independently predicted SVR. The validation cohort confirmed a significantly greater pretreatment serum miR-122 level in patients with SVR compared with NR (P = 0.025). In conclusion, serum miR-122 may serve as a surrogate of hepatic miR-122, and a higher pretreatment serum miR-122 level can help predict virologic responses to pegylated IFN plus ribavirin therapy.
Proceedings of the National Academy of Sciences 04/2013; · 9.68 Impact Factor
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ABSTRACT: Quantitative HBsAg has been recognized to assist in the management of chronic hepatitis B virus (HBV) infection. However, its role in disease monitoring of HBeAg-negative patients remains unclear. We aimed to investigate the longitudinal HBsAg change in HBeAg-negative carriers with HBV genotype B or C infection.
This is a retrospective cohort study conducted in a university hospital. Treatment-naïve HBeAg-negative carriers followed for more than 3 years were recruited. Their hepatitis activities were categorized by longitudinal HBV-DNA levels into high viral-load (HVL: HBV-DNA >/ = 2000 IU/mL persistently), low viral-load (LVL: HBV-DNA <2000 IU/mL persistently) and fluctuated viral-load (FVL: HBV-DNA between HVL and LVL). The baseline and end-of-follow-up (EOF) HBsAg levels were quantified for analyses.
We recruited 187 patients with a median follow-up of 8 years. LVL patients had a significantly lower HBsAg at baseline and EOF and a significantly greater annualized HBsAg decline compared with the FVL and HVL. The longitudinal HBsAg change was independent of genotype B or C. The lower baseline HBsAg level predicted the HBsAg decline and HBsAg loss, whereas the higher baseline HBV-DNA predicted the hepatitis flare. A baseline HBsAg <50 IU/mL predicted subsequent HBsAg loss with a sensitivity of 82% and specificity of 67%. The annualized HBsAg decline appeared non-linear, and accelerated as the HBsAg level lowered (0.054, 0.091, 0.126 log(10) IU/mL in patients with baseline HBsAg >1000, 100-999, <100 IU/mL, respectively, P for trend = .014).
In genotype B or C HBeAg-negative carriers, baseline HBsAg levels correlate with future disease activities and help to predict HBsAg decline or loss. Inactive carriers with lower baseline HBsAg levels have a greater and accelerating HBsAg decline over time, regardless of HBV genotypes.
PLoS ONE 01/2013; 8(2):e55916. · 4.09 Impact Factor
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ABSTRACT: Spontaneous clearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients usually indicates a remission of hepatitis activity and a favorable outcome. Two single nucleotide polymorphisms (SNP), rs3077 near HLA-DPA1 region and rs9277535 near HLA-DPB1 region, have been shown to be associated with HBV persistence after acute HBV infection. However, little is known about the impact of these 2 SNPs on spontaneous HBsAg clearance in CHB patients. In this case-control study, a total of 100 male HBeAg-negative chronic HBV carriers who cleared HBsAg spontaneously (case group) and 100 age-matched HBeAg-negative male patients with persistent HBsAg positivity (control group) were enrolled. We investigated the relationship between these 2 SNPs and HBsAg clearance. There was a higher frequency of rs9277535 non-GG genotype in the case group (57% vs. 42%). Patients with rs9277535 non-GG genotype had a higher chance to clear HBsAg [Odds ratio (OR): 1.83, 95% confidence interval (CI): 1.04∼3.21, P = 0.034]. Compared to GG haplotype of rs3077 and rs9277535, GA haplotype had a higher chance of achieving spontaneous HBsAg loss (OR: 2.17, 95% CI: 1.14∼4.16, P = 0.030). In conclusion, rs9277535 non-GG genotype is associated with a higher likelihood of spontaneous HBsAg seroclearance in CHB patients.
PLoS ONE 01/2013; 8(1):e53008. · 4.09 Impact Factor
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Chung-Feng Huang,
Ming-Lung Yu,
Jia-Horng Kao, Tai-Chung Tseng,
Ming-Lun Yeh,
Jee-Fu Huang,
Chia-Yen Dai,
Zu-Yau Lin,
Shinn-Cherng Chen,
Liang-Yen Wang,
Suh-Hang Hank Juo,
Wan-Long Chuang,
Chen-Hua Liu
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ABSTRACT: BACKGROUND: Viral kinetics and host interleukin 28B (IL-28B) genotype determine treatment outcome in hepatitis C virus genotype 1 (HCV-1) infection. OBJECTIVES: We aimed to explore the interplay between interferon responsiveness at treatment week 4 and IL28B genotype in the achievement of a sustained virological response (SVR; undetectable HCV RNA 24-weeks after end-of-treatment). STUDY DESIGNS: Rs8099917 genotypes were determined in 528 HCV-1 patients with peginterferon/ribavirin. Interferon responsiveness were evaluated by the degree of week 4 viral reduction: <1 log(10) IU/mL, 1-2 logs(10) IU/mL, 2-3 logs(10) IU/mL, 3-4 logs(10) IU/mL and ≥4 logs(10) IU/mL reduction and/or undetectable HCV RNA, respectively. RESULTS: The SVR rate was significantly higher in patients with great interferon responsiveness at week 4. A great interferon responsiveness was associated with younger age (P<0.0001), lower body mass index (P=0.0056), lower aspartate aminotransferase levels (P=0.0009), higher hemogloblin concentration (P=0.0033), higher platelet counts (P<0.0001), male gender (P<0.0001) and rs809997 TT-genotype (P<0.0001). Comparing to non-TT genotype patients, TT genotype patients had a significantly higher SVR rate with moderate viral reduction (1-3 logs(10) IU/mL) at week 4 (58.9% vs. 18.2%, P<0.001), and the SVR rate did not differ between TT/non-TT patients on the extreme ends (<1 or >3 log(10) IU/mL reduction) of week 4 interferon responsiveness. For non-TT genotype carriers who were with <3 logs(10) reduction, none (0/15) could have a complete early virological response and only 10.9% (7/64) of the patients had an SVR. CONCLUSIONS: More profound interferon responsiveness is mandatory for HCV-1 patients with unfavorable IL-28B genotype.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 12/2012; · 3.12 Impact Factor
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Hung-Chih Yang,
Chi-Ling Chen,
Yueh-Chi Shen,
Cheng-Yuan Peng,
Chun-Jen Liu, Tai-Chung Tseng,
Tung-Hung Su,
Wan-Long Chuang,
Ming-Lung Yu,
Chia-Yen Dai,
Chen-Hua Liu,
Pei-Jer Chen,
Ding-Shinn Chen,
Jia-Horng Kao
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ABSTRACT: Precore (PC) (G1896A) and basal core promoter (BCP) (A1762T/G1764A) mutations of hepatitis B virus (HBV) genome often emerge in chronic hepatitis B (CHB) patients. Their roles in HBeAg seroconversion induced by interferon therapy remain controversial, partly because quantitative analysis for these mutants is lacking. This study aimed to develop a new assay to accurately quantify the PC and BCP mutant percentages and correlate their dynamic changes with interferon-induced HBeAg seroconversion in HBeAg-positive CHB patients. The PC and BCP mutant percentages were analyzed by PCR-pyrosequencing. Our results showed this quantitative assay for PC and BCP mutants achieved high accuracy (R(2) >0.99) within a range between 10% and 90% mutants. We examined dynamic changes of the PC and BCP mutant percentages following interferon treatment in 203 HBeAg-positive CHB patients. By multiple logistic regression analysis, we found that the chance of HBeAg seroconversion increased by 2.2% (OR=1.022, 95% CI: 1.009-1.034, P=0.001) and 2.3% (OR=1.023, 95% CI: 1.010-1.037, P =0.001) per 1% increase of the pretreatment PC and BCP mutant percentages, respectively, after adjustment for other predictors. However, only the pretreatment PC mutation percentage was significantly associated with HBeAg seroconversion with HBV DNA < 2,000 IU/mL (OR= 1.030, 95% CI: 1.014-1.047, P<0.001) . Furthermore, the mutant percentage of PC, but not BCP, in patients achieving HBeAg seroclearance with HBV DNA < 20,000 IU/mL increased significantly during interferon treatment (P=0.039). Interestingly, patients with HBeAg seroconversion who had a high PC mutant percentage at the end of interferon treatment tended to exhibit high viremia after seroconversion. Conclusion: Quantitative analysis of PC and BCP mutants can predict interferon-induced HBeAg seroconversion and demonstrate their distinct evolution patterns during HBeAg seroconversion. (HEPATOLOGY 2012.).
Hepatology 10/2012; · 11.66 Impact Factor
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ABSTRACT: Using commercial quantitative assays, quantitative hepatitis B surface antigen (qHBsAg) has improved our understanding and management of chronic hepatitis B (CHB). The HBsAg level is highest in the immune tolerance phase, starts to decline during the immune clearance phase, and decreases slowly but progressively after hepatitis B e antigen (HBeAg) seroconversion. The HBsAg level is lowest in individuals with an inactive carrier state but higher in those who develop HBeAg-negative hepatitis. It has been shown that a reduction of HBsAg by 1 log IU/mL or more reflects improved host immune control of HBV infection. A combination of HBsAg <1000 IU/mL and HBV-DNA <2000 IU/mL can identify a 3-year inactive state in a genotype D HBeAg-negative carrier population. In the Asian-Pacific region, where HBV genotypes B and C are dominant, HBsAg levels of ≤10-100 IU/mL predict HBsAg loss over time. As to the prediction of disease progression, low-viremic carriers with HBsAg >1000 IU/mL have been shown to be at higher risks of HBeAg-negative hepatitis, cirrhosis, and hepatocellular carcinoma than those with HBsAg <1000 IU/mL. Although qHBsAg has been widely used in CHB patients receiving pegylated interferon therapy, the HBsAg decline is slow and does not correlate with HBV-DNA levels during nucleos(t)ide analogue (NUC) therapy. However, a rapid HBsAg decline during NUC therapy may identify patients who will finally clear HBsAg. A 6- to 12-monthly assessment of HBsAg level could be considered during NUC therapy. Taking these lines of evidence together, qHBsAg can complement HBV-DNA levels to optimize the management of CHB patients in our daily clinical practice.
Journal of Gastroenterology 10/2012; · 4.16 Impact Factor
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ABSTRACT: BACKGROUND AND AIM: Although entecavir has been shown to have good efficacy and low resistance for the treatment of chronic hepatitis B (CHB), factors associated with a favorable response remain unknown. METHODS: This was a retrospective, multicenter study of 248 treatment-naïve HBeAg-positive patients (69.4% male; median age, 39.4 years) treated with entecavir for more than 1 year, and 15.7% of them had cirrhosis at baseline. The primary endpoints were HBeAg loss and/or seroconversion. RESULTS: The median baseline levels of alanine aminotransferase (ALT) and HBV DNA were 201 U/L (range, 27-2,415 U/L) and 7.6 log(10) IU/mL (range, 2.2-13.18), respectively. The median treatment period was 25.3 months (range, 12-69.6). The rates of ALT normalization at years 1, 2 and 3 were 83.1%, 87.9% and 94.9%, respectively. The cumulative rates of HBeAg loss at years 1, 2 and 3 were 20.3%, 38.0% and 48.9%, respectively. The rates of undetectable HBV DNA at years 1, 2 and 3 were 52.1%, 78.9% and 82.5%, respectively. Using Cox proportional hazards model, multivariate analysis showed that baseline ALT >5-time the upper limit of normal, and viral load were independent factors associated with HBeAg loss (hazard ratio: 1.81, and 0.812; 95% confidence interval: 1.062-3.085; 0.7-0.942, respectively). CONCLUSION: Entecavir treatment for 3 years can achieve good biochemical and virologic responses in HBeAg-positive CHB patients, but has a modest effect on HHBeAg loss and/or seroconversion. In addition, baseline serum ALT and HBV DNA levels are independent factors associated with favorable treatment responses.
Journal of Gastroenterology and Hepatology 09/2012; · 2.87 Impact Factor
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Tai-Chung Tseng,
Chun-Jen Liu,
Tung-Hung Su,
Hung-Chih Yang,
Chia-Chi Wang,
Chi-Ling Chen,
Stephanie Fang-Tzu Kuo,
Chen-Hua Liu,
Pei-Jer Chen,
Ding-Shinn Chen,
Jia-Horng Kao
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ABSTRACT: Background. It is unclear whether hepatitis B e antigen (HBeAg) seroconversion induced by nucleos(t)ide analogues (NUC) has a prognosis that is similar to that of spontaneous HBeAg seroconversion. Methods. A total of 148 noncirrhotic NUC-induced HBeAg seroconverters were consecutively enrolled. A historical control of 407 noncirrhotic spontaneous HBeAg seroconverters was also recruited. We compared the rates of HBeAg seroreversion and HBV reactivation between these 2 cohorts. Results. There were 1652.8 and 465.2 person-years of follow-up for spontaneous and NUC-induced HBeAg seroconverters, respectively. Compared with NUC-induced seroconverters, spontaneous seroconverters were younger when achieving HBeAg seroconversion. We thus compared these 2 cohorts according to their age at HBeAg seroconversion. In patients achieving HBeAg seroconversion before 30 years of age, NUC-induced seroconverters had a higher 2-year HBeAg seroreversion rate than spontaneous seroconverters (12.0% vs 2.9%; P = .004) and were at a higher risk of HBV reactivation (hazard ratio, 4.6; 95% confidence interval, 1.5-14.4). Using multivariate analysis, NUC-induced HBeAg seroconversion remained a risk factor of both endpoints in young HBeAg seroconverters. Conclusion. NUC-induced HBeAg seroconverters may not have durable response after stopping therapy. For patients achieving HBeAg seroconversion before 30 years of age, the risk of HBeAg seroreversion and HBV reactivation is higher in NUC-induced seroconverters than spontaneous HBeAg seroconverters.
The Journal of Infectious Diseases 09/2012; 206(10):1521-31. · 6.41 Impact Factor
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Ching-Sheng Hsu,
Chia-Chi Wang,
Pin-Chao Wang,
Hans Hsienhong Lin, Tai-Chung Tseng,
Chien-Hwa Chen,
Wei-Chih Su,
Chun-Jen Liu,
Chi-Ling Chen,
Ming-Yang Lai,
Pei-Jer Chen,
Ding-Shinn Chen,
Jia-Horng Kao
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Tai-Chung Tseng,
Chun-Jen Liu,
Hung-Chih Yang,
Tung-Hung Su,
Chia-Chi Wang,
Chi-Ling Chen,
Cheng-An Hsu,
Stephanie Fang-Tzu Kuo,
Chen-Hua Liu,
Pei-Jer Chen,
Ding-Shinn Chen,
Jia-Horng Kao
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ABSTRACT: BACKGROUND & AIMS: Chronic hepatitis B patients with high viral loads are at increased risk of cirrhosis and hepatocellular carcinoma (HCC). In those with low viral loads, higher hepatitis B surface antigen (HBsAg) levels have been shown to predict HCC development. However, little is known about the difference in risk for other hepatitis B virus (HBV)-related adverse outcomes with varying HBsAg levels. METHODS: A total of 1068 Taiwanese hepatitis B e antigen (HBeAg)-negative HBV carriers with serum HBV DNA level <2000 IU/mL at baseline were followed for a mean duration of 13.0 years. Patients were categorized based on their HBsAg levels, and the relationships between HBsAg level and development of HBeAg-negative hepatitis, hepatitis flare, and cirrhosis were investigated. RESULTS: Of the 1068 patients with low viral loads, 280 developed HBeAg-negative hepatitis with an annual incidence rate of 2.0%. HBsAg level, but not HBV DNA level, was found to be a risk factor for HBeAg-negative hepatitis. Multivariate analysis showed that the adjusted hazard ratio in patients with HBsAg level ≧1000 versus <1000 IU/mL was 1.5 (95% confidence interval, 1.2-1.9). The positive correlation was present when evaluating other endpoints, including hepatitis flare and cirrhosis, and remained consistent when the study population was restricted to those with normal alanine aminotransferase (ALT) level at baseline. The annual incidence rate of HBeAg-negative hepatitis was lowered to 1.1% in those with low levels of HBV DNA, HBsAg, and ALT. CONCLUSIONS: In HBeAg-negative patients with low viral loads and genotype B or C virus infection, a higher HBsAg level can predict disease progression. HBsAg <1000 IU/mL in combination with low levels of HBV DNA and ALT help define minimal-risk HBV carriers. (HEPATOLOGY 2012.).
Hepatology 09/2012; · 11.66 Impact Factor
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Chen-Hua Liu,
Cheng-Chao Liang,
Chun-Jen Liu, Tai-Chung Tseng,
Chih-Lin Lin,
Sheng-Shun Yang,
Tung-Hung Su,
Jou-Wei Lin,
Jun-Herng Chen,
Pei-Jer Chen,
Ding-Shinn Chen,
Jia-Horng Kao
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ABSTRACT: Pegylated interferon and ribavirin for 72 weeks improve sustained virological response (SVR) in HCV genotype 1 (HCV-1) slow viral responders. Whether interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and on-treatment viral responses can identify non-rapid virological response (RVR) patients who benefit from 48 or 72 weeks of therapy remains unclear.
Treatment-naive HCV-1 patients who failed to achieve RVR were randomly assigned to receive 48 (n=168) or 72 (n=167) weeks of therapy. Baseline factors and on-treatment virological responses at weeks 8 and 12 were evaluated for SVR in 289 compliant patients who received ≥80% of drug dosages and treatment duration, and had end of follow-up viral response. The stratified SVR rates for independent factors were compared by treatment duration.
Treatment duration, IL28B rs8099917 genotypes, cirrhosis, week-8 viral response (undetectable HCV RNA at treatment week 8) and complete early virological response (cEVR) predicted SVR. In week-8 viral response patients, the SVR rates of 72-week and 48-week treatment were similar (75-88%), regardless of IL28B SNP genotypes or cirrhosis. In non-week-8 viral response patients who achieved cEVR, the SVR rate of 72-week treatment was higher than that of 48-week treatment for non-cirrhotic patients, regardless of IL28B SNP genotypes (91-100% versus 13-44%; P=0.001).
Although IL28B SNP genotypes predict SVR, they play a minor role when on-treatment viral responses are taken into consideration. On-treatment viral responses at weeks 8 and 12 are the key determinants to decide the optimal treatment duration in HCV-1 patients without RVR.
Antiviral therapy 08/2012; 17(6):1059-67. · 3.16 Impact Factor
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ABSTRACT: Non-alcoholic fatty liver disease is associated with an increased risk of metabolic and cardiovascular diseases. Whether the severity of fatty liver on ultrasound correlates with metabolic or cardiovascular risk remains unclear. A total of 1000 people receiving health examinations were enrolled, and 126 were excluded due to the presence of HBsAg, anti-HCV, known hepatic disorders or alcohol use (>140 g/wk). Significant fatty liver consisted of moderate and severe fatty liver on ultrasound. The definition of central obesity was modified to a waist circumference of >90 cm in men and >80 cm in women. Framingham risk score was used to estimate the risk of cardiovascular disease. A total of 874 subjects (485 women and 388 men with a mean age of 52.07 ± 11.68 years) were included in the final analysis. By using logistic regression analyses stratified by gender, the odds ratio for the prevalence of diabetes mellitus, metabolic syndrome and risk of cardiovascular disease increased with increasing fatty liver status in both genders (p ≤ 0.001). The difference was not only present between individuals with fatty liver vs. non-fatty liver but also between the mild fatty liver and significant fatty liver groups (p < 0.05). In conclusion, the severity of fatty liver on ultrasound could be useful for the risk stratification of metabolic syndrome, diabetes mellitus and cardiovascular disease in clinical practice.
The Kaohsiung journal of medical sciences 03/2012; 28(3):151-60. · 0.61 Impact Factor
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ABSTRACT: Background and Aims: Asymptomatic erosive esophagitis (AEE) is an easily forgotten subgroup of gastroesophageal reflux disease due to its lack of warning symptoms, despite having the risk of developing complications, such as bleeding, stricture, or even esophageal adenocarcinoma.Methods: A total of 2843 potentially eligible patients were screened at the health management center of Buddhist Tzu Chi General Hospital. A total of 1001 patients responded to the survey and gave informed consent; 998 patients who completed the reflux disease diagnostic questionnaire were enrolled. Of them, 594 patients who had no reflux symptoms were included for final analysis. The presence and severity of erosive esophagitis was graded according to the Los Angeles classification. Active infection of Helicobacter pylori (H. pylori) was determined by the Campylo-like organism (CLO) test during endoscopies.Results: A total of 14.5% (86/594) of asymptomatic patients had endoscopic findings of erosive esophagitis. In the univariate analysis, male sex and hiatus hernia were significantly associated with AEE. Positive CLO tests had a trend association. Based on the multivariate analysis, male sex (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.35–3.98), hiatus hernia (OR: 4.48, 95% CI: 2.35–89.17), and positive CLO test (OR: 0.57, 95% CI: 0.34–0.95) were associated with AEE, as compared to the healthy controls.Conclusions: AEE is not a rare condition, and constitutes 14.5% of the asymptomatic population. Male sex, hiatus hernia, and H. pylori infection are factors associated with AEE. These findings are not only helpful in identifying such asymptomatic patients, but also provide information to improve understanding of the relationship between H. pylori infection, reflux symptoms, and erosive esophagitis.
Journal of Gastroenterology and Hepatology 02/2012; 27(3):586 - 591. · 2.87 Impact Factor
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Tai-Chung Tseng,
Chun-Jen Liu,
Hung-Chih Yang,
Tung-Hung Su,
Chia-Chi Wang,
Chi-Ling Chen,
Stephanie Fang-Tzu Kuo,
Chen-Hua Liu,
Pei-Jer Chen,
Ding-Shinn Chen,
Jia-Horng Kao
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ABSTRACT: Patients with chronic hepatitis B virus (HBV) infection have a high risk for developing hepatocellular carcinoma (HCC). Patients with lower levels of hepatitis B surface antigen (HBsAg) have higher chances of losing HBsAg than those with high levels. However, little is known about whether higher levels of HBsAg increase risk for HCC.
We followed 2688 Taiwanese HBsAg-positive patients without evidence of cirrhosis for a mean time period of 14.7 years. In addition to the known risk factors of HCC, we investigated the association between levels of HBsAg and development of HCC.
Of the patients followed, 191 developed HCC, with an average annual incidence rate of 0.5%. Baseline levels of HBsAg and HBV were associated with development of HCC, and risk increased with level. Compared to HBsAg level, by receiver operating characteristic curve analysis, HBV DNA level better predicted the development of HCC during 10-year and 15-year periods (both, P < .001). However, when we evaluated hepatitis B e antigen-negative patients with levels of HBV DNA <2000 IU/mL, factors that determined HCC risk included sex, age, and levels of alanine aminotransferase and HBsAg (≥1000 IU/mL), but not level of HBV DNA. Multivariate analysis showed that the adjusted hazard ratio for HCC in patients with levels of HBsAg ≥1000 IU/mL versus <1000 IU/mL was 13.7 (95% confidence interval: 4.8-39.3).
Among patients infected with HBV genotype B or C, determinants of HCC risk include their sex, age, hepatitis B e antigen status, HBV genotype, and levels of alanine aminotransferase and HBV DNA, but not level of HBsAg. Among hepatitis B e antigen-negative patients with low viral loads, HCC risk is determined by levels of HBsAg and alanine aminotransferase and age, but not HBV DNA.
Gastroenterology 02/2012; 142(5):1140-1149.e3; quiz e13-4. · 11.68 Impact Factor
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Hepatology 02/2012; 55(2):656-7. · 11.66 Impact Factor
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Ming-Lung Yu,
Chen-Hua Liu,
Chung-Feng Huang, Tai-Chung Tseng,
Jee-Fu Huang,
Chia-Yen Dai,
Zu-Yau Lin,
Shinn-Cherng Chen,
Liang-Yen Wang,
Suh-Hang Hank Juo,
Wan-Long Chuang,
Jia-Horng Kao
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ABSTRACT: The current stopping rule for peginterferon/ribavirin therapy in hepatitis C virus genotype-1 (HCV-1) patients is based on an early virological response (EVR, defined as >2 log(10) viral reduction at treatment week 12). We aimed to explore rapid stopping rules at week 4.
We randomly allocated 528 HCV-1 patients into training and validation sets (at a 1∶2 ratio). The interleukin-28B rs8099917 genotypes and on-treatment virological responses were evaluated to determine the negative predictive value (NPV) for achieving a sustained virological response (SVR, defined as undetectable HCV RNA 24 weeks after end-of-treatment). The study was approved by the ethics committees of the participating hospitals. All of the patients gave written informed consent before enrollment.
A poor week 4 response (W4R), defined as a HCV RNA reduction of <1 log(10) IU/mL at week 4 or a week 4 HCV RNA>10,000 IU/mL with interleukin-28B non-TT genotype, had the highest NPV (95%). In the complete sample, poor W4R could identify 43.4% (59/136) of the non-responders, with an NPV of 95% and a false negative rate of only 0.8% (3/396). The multivariate analysis revealed that a poor W4R was the most important negative predictor (odds ratio/95% confidence intervals: 49.01/13.70-175.37), followed by the lack of an EVR. In addition to HCV RNA<1 log(10) IU/mL reduction, using the criteria of HCV RNA>10,000 IU/mL/non-TT genotype helped identifying an additional one-third of non-SVR patients at W4.Using the strategy of sequential rapid stopping rule strategy could identify 53.7% (73/136) of the non-responders (43.4% at week 4 and an addition 11.3% at week 12), as compared to 40.4% for the classical week-12 early stopping rule.
Sequential rapid stopping rules using on-treatment virological responses and interleukin-28B genotype can rapidly identify additional peginterferon/ribavirin non-responders.
PLoS ONE 01/2012; 7(12):e52048. · 4.09 Impact Factor
