Tung-Hung Su
National Taiwan University, Internal Medicine, Faculty Member
Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC),... more
Oral antiviral therapy may reduce the disease progression of chronic hepatitis B (CHB) patients. We aimed to further investigate the efficacy of long-term entecavir therapy in reduction of the risk of hepatocellular carcinoma (HCC), cirrhotic events and mortality in a large group of CHB-related cirrhosis patients. The C-TEAM (Cirrhosis-Taiwanese EntecAvir Multicenter) study was a nationwide, multicenter, retrospective-prospective cohort study in Taiwan. We enrolled treatment-naïve patients with CHB-related cirrhosis and baseline HBV-DNA≥2000 IU/mL receiving long-term entecavir therapy and compared the development of HCC, cirrhotic events and mortality with that of a historical untreated cohort. In total, 1315 entecavir-treated and 503 untreated patients with cirrhosis were enrolled, with median treatment and follow-up durations of 4 and 6 years respectively. Compared with the untreated cohort, entecavir therapy was associated with a 60% HCC risk reduction [hazard ratio (HR): 0.40, 95% confidence interval (CI): 0.28-0.57]. Additionally, an older age, the male gender, HBeAg positivity, alpha-fetoprotein (AFP)≥7 ng/mL before therapy were independent predictors of HCC development. Further analysis showed that entecavir therapy significantly reduced risks of variceal bleeding, spontaneous bacterial peritonitis, and liver-related and all-cause mortality. These findings were confirmed by propensity score-matched cohorts in sensitivity analysis. In patients under entecavir therapy, an older age, the male gender, HBeAg positivity, AFP level ≥7 ng/mL before therapy, and 1-year virological response were predictive of HCC development. Four-year entecavir therapy significantly reduces the risk of HCC, cirrhotic events and mortality in patients with CHB-related cirrhosis.
Research Interests: Gastroenterology, Medicine, Multivariate Analysis, Prospective studies, Humans, and 15 moreInternal Medicine, Liver Cirrhosis, Liver, Female, Male, Hepatocellular Carcinoma, Clinical Sciences, Middle Aged, Adult, Retrospective Studies, Hepatitis B virus, Proportional Hazards Models, Antiviral Agents, Esophageal and gastric varices, and Liver neoplasms
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Data are limited on the effectiveness and safety of peginterferon plus ribavirin in HIV-infected Asian patients with acute or chronic HCV infection. HIV-infected Taiwanese patients with acute HCV infection received peginterferon plus... more
Data are limited on the effectiveness and safety of peginterferon plus ribavirin in HIV-infected Asian patients with acute or chronic HCV infection. HIV-infected Taiwanese patients with acute HCV infection received peginterferon plus weight-based ribavirin for 24 weeks (n = 24), and those with chronic HCV genotype 1 or 6 (HCV-1/6) and HCV genotype 2 or 3 (HCV-2/3) infection received response-guided therapy for 12-72 and 24-48 weeks, respectively (n = 92). The primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA 24 weeks off-therapy. The SVR rates were 83% and 72% in patients with acute and chronic HCV infection (p = 0.30), and 68% and 72% in patients with chronic HCV-1/6 and HCV-2/3 infection (p = 0.48), respectively. While no factors predicted SVR in acute HCV and chronic HCV-2/3 infection, age (odds ratio [OR] per 1-year increase: 0.88, 95% confidence interval [CI]: 0.78-0.99, p = 0.04), HCV RNA (OR per 1-log10 increase: 0.18, 95% CI: 0.03-0.98, p = 0.03), IL28B genotype (OR: 5.52, 95% CI: 1.55-12.2, p = 0.02), and RVR (OR: 9.62, 95% CI: 3.89-15.3, p = 0.007) predicted SVR in chronic HCV-1/6 infection. In conclusion, the SVR rates of peginterferon plus ribavirin for 24 weeks and for response-guided 12-72 weeks are satisfactory in HIV-infected Taiwanese patients with acute and chronic HCV infection.
Chronic hepatitis C virus (HCV) infection has been associated with non-Hodgkin's lymphoma (NHL); however, the results are inconsistent among regions with different HCV prevalence rates. The temporal relationship, risk estimates and... more
Chronic hepatitis C virus (HCV) infection has been associated with non-Hodgkin's lymphoma (NHL); however, the results are inconsistent among regions with different HCV prevalence rates. The temporal relationship, risk estimates and association between HCV and lymphoid-neoplasms remain unclear. This study investigated the temporal relationship between HCV infection and lymphoid-neoplasms by using a nationwide population-based cohort. Patients with chronic HCV infection were retrieved from the Taiwan National Health Insurance Research Database during 2001-2005 and designated as the HCV cohort. Those with prior malignancies or coinfected with hepatitis B or human immunodeficiency virus were excluded. The age, sex, and comorbidities-including rheumatological disorders and diabetes were matched by propensity scores to another non-HCV cohort. Both cohorts were followed longitudinally until 2009 for the new diagnosis of any lymphoid-neoplasms or NHL. A total of 11,679 HCV and 46,716 no...
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Tests for hepatitis B virus DNA are expensive, and levels of hepatitis B surface antigen (HBsAg) can help determine risk for hepatocellular carcinoma (HCC) in patients with chronic HBV infection. We investigated how adding data on level... more
Tests for hepatitis B virus DNA are expensive, and levels of hepatitis B surface antigen (HBsAg) can help determine risk for hepatocellular carcinoma (HCC) in patients with chronic HBV infection. We investigated how adding data on level of HBsAg or excluding measurement of HBV DNA affected the accuracy of the REACH-B scoring system in determining risk for HCC. We collected data from 3584 patients with chronic HBV infection who were positive for HBsAg, free of cirrhosis, and participated in the community-based REVEAL-HBV cohort (208 cases of HCC) from 1991 through 1992; they were followed until December 31, 2008. Data from this cohort was used to derive our scoring system. We validated our system using data from 2688 HBsAg-seropositive patients (191 cases of HCC) who participated in the hospital-based ERADICATE-B study at the National Taiwan University Hospital from 1985 through 2000; they were followed until December 31, 2010. We also validated the system using data from 426 patients with chronic HBV infection who participated in the Chinese University of Hong Kong (CUHK) study (46 cases of HCC) from 1997 through 2000; patients were followed for a median of 225 weeks. Discrimination and calibration were evaluated using area under the receiver operating characteristic (AUROC) curves and calibration charts. When data on HBsAg were added to the REACH-B scoring system, it identified patients in the ERADICATE-B study who developed HCC within 3, 5, and 10 years with AUROC curve values of 0.92 (95% confidence interval [CI], 0.82-1.02), 0.78 (95% CI, 0.70-0.86), and 0.80 (95% CI, 0.76-0.84), respectively. It identified patients in the CUHK study who developed HCC in 3, 5, and 10 years with AUROC curve values of 0.85 (95% CI, 0.75-0.95), 0.82 (95% CI, 0.70-0.93), and 0.78 (95% CI, 0.70-0.870), respectively. When data on HBV DNA were removed from the REACH-B scoring system, it identified patients in the ERADICATE-B cohort who developed HCC in 3, 5 and 10 years with AUROC curve values of 0.90 (95% CI, 0.81-1.0), 0.76 (95% CI, 0.68-0.85), and 0.78 (95% CI, 0.73-0.82), respectively. It identified patents in the CUHK cohort who developed HCC in 3, 5, and 10 years with AUROC values of 0.84 (95% CI, 0.79-0.92), 0.81 (95% CI, 0.71-0.91), and 0.79 (95% CI, 0.72-0.87). These modified systems identified patients who developed HCC with similar levels of accuracy as the original REACH-B score (P>.05 in tests of non-inferiority). Including data on serum level of HBsAg or removing data on level of HBV DNA do not alter the accuracy of the REACH-B scoring system in determining HCC risk in patients with chronic HBV infection without cirrhosis. It might be cost effective to replace the test for HBV DNA with assays to HBsAg in determining HCC risk. These modified scoring systems might replace the REACH-B system in specific situations.
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The impact of ribavirin (RBV) dosage on sustained virologic response (SVR) rates remains elusive in hepatitis C virus genotype 2 (HCV-2) rapid responders receiving 16 weeks of peginterferon (Peg-IFN) plus RBV. Treatment-naïve HCV-2... more
The impact of ribavirin (RBV) dosage on sustained virologic response (SVR) rates remains elusive in hepatitis C virus genotype 2 (HCV-2) rapid responders receiving 16 weeks of peginterferon (Peg-IFN) plus RBV. Treatment-naïve HCV-2 patients with rapid virologic response (RVR) received Peg-IFN alfa-2a 180 μg/week plus weight-based RBV (1,000 or 1,200 mg/day; cut-off body weight: 75 kg) for 6 weeks, and then randomly received Peg-IFN alfa-2a 180 μg/week plus weight-based (1,000 or 1,200 mg/day; n = 247) or flat-dose (800 mg/day; n = 246) RBV for additional 10 weeks. The primary endpoint was SVR24. Patients receiving weight-based and flat-dose RBV therapies had comparable SVR24 rates (93.5% versus 91.9%, P = 0.49). The risk differences (RDs) of SVR24 receiving weight-based and flat-dose RBV arms were 7.1% [95% CI: 0.7% to 13.6%] in males, and -5.8% [95% CI: -12.1% to 0.5%] in females (interaction P = 0.01). The SVR24 rate was higher in males receiving ≥13 mg/kg/day than those receiving...
The efficacy of entecavir (ETV) in treatment-experienced chronic hepatitis-B-virus (CHB) patients remains unclear. We evaluated the therapeutic responses and virological breakthrough following ETV treatment in hepatitis B e-antigen... more
The efficacy of entecavir (ETV) in treatment-experienced chronic hepatitis-B-virus (CHB) patients remains unclear. We evaluated the therapeutic responses and virological breakthrough following ETV treatment in hepatitis B e-antigen (HBeAg)-positive CHB patients with prior exposure to interferon or nucleos(t)ide analogue and treatment-naïve patients. This was a retrospective, multi-center study of treatment (>1 year) with 0.5 mg ETV in 248 treatment-naïve and 48 treatment-experienced HBeAg-positive CHB patients (70.5% male; mean age, 40.5 years). The rates of undetectable HBV DNA, HBeAg loss, and virological breakthrough were analyzed. The median duration of ETV treatment was 27.3 months (18.4 to 34.5 months). The rate of HBeAg loss was 41.9% (104/248) in treatment-naïve and 45.8% (22/48) in treatment-experienced patients. The baseline serum HBV DNA and alanine aminotransferase levels were significant predictors for HBeAg loss (P = 0.01 and P = 0.04, respectively). There was no statistical difference between the groups in the rates of undetectable HBV DNA and HBeAg loss at any time point. Virological breakthrough occurred in 1.6% (4/248) of treatment-naïve and 8.3% (4/48) of treatment-experienced patients. The four treatment-experienced patients with virological breakthrough had prior lamivudine treatment. After excluding those treated with interferon, lamivudine-experienced patients had a significantly greater of virological breakthrough compared to treatment-naïve patients (log-rank test, P = 0.034; univariate Cox regression, P = 0.047). ETV-treatment efficacy, including virological response and HBeAg loss, was comparable between treatment-naïve and treatment-experienced HBeAg-positive CHB patients. Lamivudine-experienced patients had a higher risk of virological breakthrough than treatment-naïve patients. This article is protected by copyright. All rights reserved.
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Hepatitis C virus genotype 2 (HCV-2) slow responders poorly respond to 24 weeks of peginterferon (Peg-IFN) plus ribavirin (RBV). We evaluated the efficacy of extended 48-week regimen and the role of interleukin-28B (IL-28B) genotype in... more
Hepatitis C virus genotype 2 (HCV-2) slow responders poorly respond to 24 weeks of peginterferon (Peg-IFN) plus ribavirin (RBV). We evaluated the efficacy of extended 48-week regimen and the role of interleukin-28B (IL-28B) genotype in this clinical setting. Treatment-naïve HCV-2 patients not achieving rapid virologic response (RVR) by Peg-IFN alfa-2a 180 μg/week plus weight-based RBV (1,000-1,200 mg/day, cutoff body weight of 75 kg) were randomly assigned to receive a total duration of 48 (n = 94) or 24 (n = 93) weeks of therapy. The primary endpoint was sustained virologic response (SVR). Baseline patient characteristics to predict SVR were analyzed. Patients receiving 48 weeks of treatment had a greater SVR rate than those receiving 24 weeks of treatment (70.2% versus 46.2%, P = 0.001). Compared to patients treated for 24 weeks, the SVR rate in those treated for 48 weeks increased by 10.9% [95% CI: -5.9% to 27.7%] and 65.6% [95% CI: 44.5% to 86.7%] if they had IL-28B rs8099917 TT...
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Signal transducer and activator of transcription 3 (STAT3) had been involved in liver fibrogenesis. We aimed to explore the antifibrotic activities of sorafenib and its derivative SC-1 (devoid of Raf kinase inhibition activity) both in... more
Signal transducer and activator of transcription 3 (STAT3) had been involved in liver fibrogenesis. We aimed to explore the antifibrotic activities of sorafenib and its derivative SC-1 (devoid of Raf kinase inhibition activity) both in vivo and in vitro with special focus on the STAT3 pathway in hepatic stellate cells (HSCs). The clinical role of STAT3 in chronic hepatitis B (CHB) was also investigated. Experimental fibrosis mouse models were established by thioacetamide injection and bile duct ligation in Balb/C mice and treated with sorafenib and SC-1. Rat and human HSCs were used for mechanistic investigations. Forty CHB patients were enrolled to quantify the hepatic phospho-STAT3 (p-STAT3) levels and correlated with liver fibrosis. Both sorafenib and SC-1 ameliorated liver fibrosis in vivo and promoted HSC apoptosis in vitro. p-STAT3 and downstream signals were down-regulated after sorafenib and SC-1 treatment in HSC. STAT3 overexpression in HSC enhanced cell proliferation and u...
Research Interests: Multidisciplinary, Cell line, Humans, Liver Cirrhosis, Mice, and 4 moreAnimals, Male, Hepatic Stellate Cells, and Rats
Genotyping/subtyping of 225 samples with HCV genotype 1, 2, 3, or 6 infection were determined using VERSANT-LiPA 2.0 and Abbott RealTime HCV GT II, taking direct sequencing at NS5B and 5' UTR regions as the reference standards. The... more
Genotyping/subtyping of 225 samples with HCV genotype 1, 2, 3, or 6 infection were determined using VERSANT-LiPA 2.0 and Abbott RealTime HCV GT II, taking direct sequencing at NS5B and 5' UTR regions as the reference standards. The concordance rates were > 99.2% for genotypes, and 96.1% for subtypes 1a/1b. Both Abbott RealTime and VERSANT-LiPA assays can accurately determine HCV genotypes.
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Timely diagnosis and prompt treatment can reduce the complications of scrub typhus. It is thus important to find easy laboratory tests to help in the diagnosis, especially in patients without eschar at initial presentation. Because serum... more
Timely diagnosis and prompt treatment can reduce the complications of scrub typhus. It is thus important to find easy laboratory tests to help in the diagnosis, especially in patients without eschar at initial presentation. Because serum aminotransferase elevation is common in scrub typhus, its associated factors and clinical implications need further investigations. We conducted a retrospective study in Kinmen, Taiwan, to collect clinically suspected scrub typhus patients notified to Taiwan Centers for Disease Control for confirmation during 2005-2010. Scrub typhus was diagnosed and Orientia tsutsugamushi was genotyped by serological or molecular assays. The laboratory data and clinical information were recorded for analysis. Overall, 344 suspected scrub typhus patients were reported to Taiwan Centers for Disease Control and 288 of them were certified scrub typhus. Scrub typhus patients had significantly more thrombocytopenia, serum aminotransferase elevation (76% vs. 54%, p = 0.00...
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Clinical implications of persistent alanine aminotransferase (ALT) elevation and associated factors in chronic hepatitis C (CHC) patients who achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon plus ribavirin... more
Clinical implications of persistent alanine aminotransferase (ALT) elevation and associated factors in chronic hepatitis C (CHC) patients who achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon plus ribavirin (peg-IFN/RBV) therapy remain unknown. A total of 1113 CHC patients with undetectable HCV RNA during peg-IFN/RBV therapy were enrolled. Baseline characteristics associated with persistent on-treatment ALT elevation (POAE), and its impact on treatment outcomes, were investigated. Of 1113 CHC patients, 254 (22.8%) had POAE. Among patients with HCV genotype 1 (HCV-1) who had complete early virologic response (EVR) and received 48 weeks of therapy, patients with POAE had a lower rate of sustained virologic response (SVR) than those without POAE (44.1% vs 74.0%; P = .0002). Multivariate analyses showed that body mass index ≥ 27 kg/m(2), ALT level ≥3 times the upper limit of normal, aspartate aminotransferase to platelet ratio index score ≥1.5, hepatic fib...
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Aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 index are noninvasive biomarkers to evaluate hepatic fibrosis. However, their usefulness in chronic hepatitis B (CHB) patients remains unclear. A total of 631 CHB... more
Aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 index are noninvasive biomarkers to evaluate hepatic fibrosis. However, their usefulness in chronic hepatitis B (CHB) patients remains unclear. A total of 631 CHB patients were enrolled and randomly divided into a training set (n=420) and a validation set (n=211). Areas under receiver operating characteristic (AUROC) curves for FIB-4 index and APRI were compared to evaluate their diagnostic values in identifying significant fibrosis and cirrhosis. The AUROC of FIB-4 index for the diagnosis of significant fibrosis and cirrhosis in the entire cohort was higher than that of APRI (0.769 vs. 0.704, P=0.0003 and 0.869 vs. 0.706, P<0.0001). By using cutoff APRI of 0.38 and 4.04 in the validation set, the diagnostic accuracy for absence of significant fibrosis and presence of cirrhosis was 67.7% and 76.8%. At cutoff FIB-4 index of 0.87 and 3.40 in the validation set, the diagnostic accuracy for absence of significant fib...
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Clearance of hepatitis B surface antigen (HBsAg) indicates clinical control of hepatitis B virus (HBV) infection. However, little is known about the impact of viral genomic variations on HBsAg loss. We explored the association between... more
Clearance of hepatitis B surface antigen (HBsAg) indicates clinical control of hepatitis B virus (HBV) infection. However, little is known about the impact of viral genomic variations on HBsAg loss. We explored the association between viral genomic factors and HBsAg loss in 2121HBeAg-negative patients. HBV pre-core stop codon (1896) and basal core promoter (BCP) (1762/1764) sequences were determined in patients with HBV DNA ≥200 IU/mL (N = 1693). The effect of HBV genotype on HBsAg loss was further validated in the whole cohort of 3445 HBsAg carriers. The cumulative lifetime (age 28-75 years) incidence of HBsAg loss was 50.4% in 2121 HBeAg-negative patients. We found that genotype C, but not pre-core stop codon or BCP mutants, was associated with HBsAg loss. Compared to genotype B patients, genotype C patients had higher lifetime chance of HBsAg loss, with hazard ratio of 1.8 (95% confidence interval: 1.4-2.4). Multivariable analysis showed that male sex, elevated ALT levels, lower ...
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ABSTRACT Background Clinical trials and real-world data confirm the efficacy of entecavir treatment for chronic hepatitis B (CHB); however, the factors associated with a favorable response remain unknown. Methods In a retrospective... more
ABSTRACT Background Clinical trials and real-world data confirm the efficacy of entecavir treatment for chronic hepatitis B (CHB); however, the factors associated with a favorable response remain unknown. Methods In a retrospective multicenter study, 132 treatment-naïve hepatitis B e antigen (HBeAg)-positive CHB patients (71% male; median age, 40.2 years) received entecavir therapy for &gt;2 years. At baseline, 15% of these patients had cirrhosis. The primary endpoint was HBeAg loss at 2 years of entecavir treatment. Results The rates of serum alanine aminotransferase (ALT) normalization at treatment Year 1 and Year 2 were 86% and 88%, respectively. The cumulative rate of HBeAg loss at treatment Year 1 and Year 2 were 17% and 33.3%, respectively. The rates of undetectable levels of serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) at treatment Year 1 and Year 2 were 64% and 80.8%, respectively. In univariate analysis, HBeAg loss at 2 years was associated with a young age (≤35 years; p = 0.007) and a high baseline ALT level (p &lt; 0.001). Multivariate analysis after adjusting for age, sex, and ALT level [&gt;5 times the upper limit of normal (ULN)] showed that a young age (odds ratio, 2.66; 95% confidence interval, 1.2–5.92) and male sex (odds ratio, 0.36; 95% confidence interval, 0.16–0.83) were independent factors associated with HBeAg loss at 2 years of therapy. Conclusion Two-year entecavir therapy has good biochemical and virologic responses; however, the rate of HBeAg loss is modest in HBeAg-positive CHB patients. A young age (i.e., ≤35 years) and female sex were also associated with a better serologic response.
The clinical significance of serum microRNA-122 (miR-122) has been shown in viral hepatitis B and C, respectively. Specifically, miR-122 stimulates hepatitis C virus (HCV) replication but suppresses hepatitis B virus (HBV) replication.... more
The clinical significance of serum microRNA-122 (miR-122) has been shown in viral hepatitis B and C, respectively. Specifically, miR-122 stimulates hepatitis C virus (HCV) replication but suppresses hepatitis B virus (HBV) replication. The profile and clinical significance of serum miR-122 in patients with dual chronic hepatitis B and C would be an interesting and important clinical issue. A total of 76 patients with HBV/HCV dual infection, 105 with HCV monoinfection and 39 with HBV monoinfection were enrolled. All patients received peginterferon alfa-2a (PEG-IFN)-based treatment. Serum miR-122 levels were quantified by using a sensitive hybridization-based assay. At baseline, the serum miR-122 level was lower in HCV-monoinfected patients than in HBV-monoinfected patients, whereas HBV coinfection increased the expression of miR-122. In multivariate analysis, the serum miR-122 level was positively correlated with the serum HBsAg level in patients with HBV/HCV dual infection and those with HBV monoinfection. In dually infected patients who received PEG-IFN-based treatment, a high baseline miR-122 level was positively correlated with a greater reduction of the posttreatment serum HBsAg level. In summary, the serum miR-122 level is highly correlated with the HBsAg level in HBV/HCV dually infected patients and may serve as a biomarker to predict posttreatment HBsAg decline.
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PURPOSE: A significant portion of HBeAg-negative chronic hepatitis B patients have persistently normal serum alanine aminotransferase levels (PNALT). We thus investigated host genetic variants and virological features in HBeAg-negative... more
PURPOSE: A significant portion of HBeAg-negative chronic hepatitis B patients have persistently normal serum alanine aminotransferase levels (PNALT). We thus investigated host genetic variants and virological features in HBeAg-negative hepatitis B carriers. METHODS: Baseline clinical and virological features of 133 HBeAg-negative hepatitis B carriers (77 with PNALT and 56 with chronic hepatitis activity) with follow-up for more than 5 years were investigated. Three single nucleotide polymorphisms (SNPs) located within or around human leukocyte antigen (HLA)-DPA1, HLA-DPB1, and interleukin (IL) 28B loci were genotyped. RESULTS: The genotype frequencies of these SNPs were comparable between hepatitis B carriers with PNALT and those with chronic hepatitis. Compared with hepatitis B carriers with PNALT, those with chronic hepatitis had significantly higher baseline serum HBV-DNA levels (4.96 vs. 4.04 log(10) IU/ml, P = 0.001). Baseline serum HBV-DNA level &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 2000 IU/ml (OR, 8.42; 95% CI, 2.74-25.90, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) were the only independent factor associated with chronic hepatitis activity. Changes of serum HBV-DNA in 30 hepatitis B carriers with PNALT had showed a significant reduction of viral load from baseline to last visit (mean difference of paired HBV-DNA levels: -0.78 log(10) IU/ml, 95% CI: -1.57 to -0.013, P = 0.047). In contrast, no significant reduction of viral load was found in 28 patients with chronic hepatitis. CONCLUSIONS: The results indicate that lower baseline serum HBV-DNA level and viral load reduction over time are associated with long-term biochemical remission in HBeAg-negative hepatitis B carriers.
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Research Interests: Treatment Outcome, Cell line, Humans, Liver, Mutation, and 21 moreTaiwan, Female, Male, Phenotype, Clinical Sciences, Prevalence, Middle Aged, Genotype, Adult, Time Factors, Biological markers, Combination drug therapy, Transfection, Hepatitis B virus, Recombinant Proteins, Cross Sectional Studies, Polyethylene Glycols, Ribavirin, Antiviral Agents, Interferon Alpha, and Viral Load
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Research Interests: Adolescent, Multivariate Analysis, Humans, Female, Male, and 13 moreConfidence intervals, Young Adult, Clinical Sciences, GASTROENTEROLOGY AND HEPATOLOGY., Aged, Middle Aged, Adult, Retrospective Studies, Hepatitis B virus, Proportional Hazards Models, Antiviral Agents, Alanine Transaminase, and Viral Load
The level of hepatitis B surface antigen (HBsAg) has been shown to complement hepatitis B virus (HBV)-DNA level in predicting disease progression in hepatitis B e antigen (HBeAg)-negative patients, especially those with low viral loads.... more
The level of hepatitis B surface antigen (HBsAg) has been shown to complement hepatitis B virus (HBV)-DNA level in predicting disease progression in hepatitis B e antigen (HBeAg)-negative patients, especially those with low viral loads. Whether this finding could be seen in spontaneous HBeAg seroconverters remains unclear. A retrospective cohort of 390 Taiwanese spontaneous HBeAg seroconverters with a mean follow-up period of 7.4 years was enrolled. The relationships between HBV-DNA/HBsAg levels and HBeAg-negative hepatitis/active viral replication (HBV-DNA level ≥ 2000 IU/mL) were investigated. In the overall cohort, serum HBV-DNA level served as a better predictor for HBeAg-negative hepatitis compared with HBsAg level. However, in those with HBV-DNA level &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 2000 IU/mL, a higher HBsAg level was associated with a higher risk of HBeAg-negative hepatitis (P = 0.015). Multivariate analysis showed the hazard ratio of HBsAg level ≥ 1000 IU/mL versus &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 1000 IU/mL was 4.1 (95% confidence interval: 1.3-13.6). When using the end-point of active viral replication, HBsAg ≥ 1000 IU/mL remained as an independent risk factor, with a hazard ratio of 2.5 (95% confidence interval: 1.1-5.9). In spontaneous HBeAg seroconverters with HBV-DNA level &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 2000 IU/mL, HBsAg level ≥ 1000 IU/mL is associated with increased risks of HBeAg-negative hepatitis and active viral replication. Combining HBV-DNA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 2000 IU/mL and HBsAg level &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 1000 IU/mL may be used to define minimal viral activity.
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Research Interests: Hepatology, Humans, Liver Cirrhosis, Female, Male, and 14 moreHepatocellular Carcinoma, Follow-up studies, Incidence, Recurrence, Clinical Sciences, Middle Aged, Adult, Prognosis, Biological markers, Hepatitis B virus, Proportional Hazards Models, Predictive value of tests, Cohort Studies, and Viral Load
Chronic hepatitis B patients with high viral loads are at increased risk of cirrhosis and hepatocellular carcinoma (HCC). In patients with low viral loads, higher hepatitis B surface antigen (HBsAg) levels have been shown to predict HCC... more
Chronic hepatitis B patients with high viral loads are at increased risk of cirrhosis and hepatocellular carcinoma (HCC). In patients 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. A total of 1,068 Taiwanese hepatitis B e antigen (HBeAg)-negative HBV carriers with serum HBV DNA level &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2,000 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. 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 an HBsAg level ≥ 1,000 versus &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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 patients with low levels of HBV DNA, HBsAg, and ALT. In HBeAg-negative patients with low viral loads and genotype B or C virus infection, a higher HBsAg level can predict disease progression. HBsAg &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1,000 IU/mL in combination with low levels of HBV DNA and ALT help define minimal-risk HBV carriers.
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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... more
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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). However, when we evaluated hepatitis B e antigen-negative patients with levels of HBV DNA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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.