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Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection
(2020-07-01)
Yeh, Ming-Lun
;
Huang, Chung-Feng
;
Huang, Ching-, I
;
Holmes, Jacinta A.
;
Hsieh, Meng-Hsuan
dynamics of HBsAg and HBV virological reactivation, among patients coinfected with HCV receiving direct-acting antivirals (DAAs) remains unclear. Thus, we aimed to analyze HBV-related outcomes in these patients. Methods: Serial HBsAg and HBV DNA levels were measured in 79 HBV/HCV-coinfected patients receiving DAAs (13 receiving anti-HBV nucleot(s)ide analog [NUC] therapy simultaneously). The endpoints included HBsAg dynamics and seroclearance, HBV reactivation (HBV DNA >1 log increase or >100 IU/ml if undetectable at baseline) and HBV-related clinical reactivation. Results: HBsAg levels declined from a median of 73.3 IU/ml at baseline to 16.2 IU/ml at the end-of-DAA treatment and increased to 94.1 IU/ml at 12 months post-treatment. During a mean 11.1-months of follow-up, 8 (10.1%) patients experienced HBsAg seroclearance and 30 (38.0%) HBV reactivation (12-month cumulative incidence, 10.3% and 40.4%, respectively). Patients with pre-treatment HBsAg <= 10 IU/ml had a significantly higher rate of HBsAg seroclearance (hazard ratio [HR] 8.52; 95% CI 1.048-69.312) and lower risk of HBV reactivation than those with pre-treatment HBsAg >10 IU/ml (HR 2.88; 95% CI 1.057-7.844) in multivariate analyses. Six patients (4 cirrhotics) not receiving NUC therapy experienced HBV-related clinical reactivation; 3 of the 4 cirrhotics developed liver failure and 2 died despite immediate NUC therapy. Compared to untreated HBV-monoinfected patients, HBV/HCV-coinfected patients without NUC prophylaxis had a similar rate of HBsAg seroclearance, but a significantly higher risk of HBV reactivation following DAA therapy (HR 6.59; 95% CI 2.488-17.432). Conclusions: DAA-treated HBV/HCV-coinfected patients had significantly higher rates of HBV seroclearance, particularly among those with low pre-treatment HBsAg titer, but were at higher risk of HBV reactivation, particularly among those with higher pretreatment HBsAg titer. Prophylactic anti-HBV therapy is essential for cirrhotic patients, irrespective of baseline HBV DNA levels. Lay summary: We studied outcomes relating to hepatitis B virus (HBV) in patients coinfected with both hepatitis B and C. Patients receiving direct-acting antiviral treatment for hepatitis C were more likely to experience seroclearance (or functional cure of HBV), but were also more likely to experience HBV reactivation, which can lead to hepatitis, liver failure and death. In coinfected cirrhotic patients being treated for HCV, prophylactic treatment for HBV is mandatory. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.
Severe acute exacerbation of HCV infection in cancer patients who undergo chemotherapy: Some issues
(1970-01-01)
Dai, Chia-Yen
;
Huang, Jee-Fu
;
Chuang, Wan-Long
;
Yu, Ming-Lung
;
生物科技學系
Clusters of Circulating let-7 Family Tumor Suppressors Are Associated with Clinical Characteristics of Chronic Hepatitis C
(2020-07-01)
Tsai, Yi-Shan
;
Yeh, Ming-Lun
;
Tsai, Pei-Chien
;
Huang, Ching-, I
;
Huang, Chung-Feng
Hepatitis C virus (HCV) infections can cause permanent liver-related diseases, including hepatocellular carcinoma (HCC). Low mortality and incidence of HCC have been observed in patients with chronic hepatitis C undergoing direct-acting antiviral therapy. Tumor suppressive let-7 family members are down-regulated in HCC. The present study, therefore, aimed to investigate whether expression levels for the full spectrum of let-7 family members (let-7a, 7b, 7c, 7d, 7e, 7f, 7g, 7i, and miR-98) in the circulatory system are useful as surveillance biomarkers for liver-related diseases to monitor treatment efficacy during HCV infection. To this end, we measured the levels of mature circulating let-7 family members using quantitative reverse transcription-PCR in 236 patients with HCV infection, and 147 age- and sex-matched controls. Using hierarchical cluster analysis and principal component analysis, three clusters were obtained after measuring expression levels of let-7 family members in the patients and controls. Cluster 1 included let-7a/d/e/g, Cluster 2 comprised let-7b and let-7i, and Cluster 3 comprised let-7c/f/miR-98. Let-7b/c/g represented the three clusters and showed the best survival response to liver cancer when analyzed with respect to patient data. Therefore, considering the circulating levels of let7 b/c/g as representatives of the let-7 family may facilitate effective monitoring of liver-related disease.
Cure or curd: Modification of lipid profiles and cardio-cerebrovascular events after hepatitis C virus eradication
(1970-01-01)
Huang, Chung-Feng
;
Dai, Chia-Yen
;
Yeh, Ming-Lun
;
Huang, Ching-, I
;
Lee, Hsiang-Chun
Hepatitis C virus (HCV) eradication deteriorates lipid profiles. Although HCV eradication may reduce the risk of vascular events as a whole, whether deteriorated lipid profiles increases the risk of cardio-cerebral disease in certain patients is elusive. Serial lipid profiles were measured before, during, at and 3 months after the end of direct-acting antivirals (DAAs) therapy, and annually thereafter in chronic hepatitis C patients who achieved a sustained virological response (SVR, undetectable HCV RNA at posttreatment week 12). The primary end-point was the occurrence of the events. A total of 617 patients were included, with a mean follow-up period of 26.8 months (range: 1-65 months). The total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels increased significantly from treatment week 4 to 2 years after treatment. Logistic regression analysis revealed that the factors independently associated with a significant cholesterol increase included age (odds ratio [OR]/95% confidence intervals [CIs]:1.02/1.006-1.039,P= .007) and smoking (OR/CI:3.21/1.14-9.02,P= .027). Five patients developed cardio-cerebral diseases during 1376 person-years follow-up period. Compared to patients without vascular events, a significantly higher proportion of those with vascular events experienced an LDL-C surge >40% (80% vs 19.9%,P= .001). Cox-regression analysis revealed that an LDL-C surge >40% was the only factor predictive of vascular events (HR/CI: 15.44/1.73-138.20,P= .014). Dyslipidemia occurred after HCV eradication, and it was associated with the risk of cardio-cerebrovascular diseases. Attention should also be paid to the extrahepatic consequence beyond liver-related complications in the post-SVR era.
Risk of hepatitis C virus infection in injecting and noninjecting drug users receiving opioid substitution therapy
(2020-05-01)
Wang, Chih-Wen
;
Chuang, Hung-Yi
;
Chiang, Hung-Che
;
Huang, Po-Chin
;
Yu, Ming-Lung
Background: Hepatitis C virus (HCV) is the most common viral infection among illicit drug users in the world. Although intervention of needle and syringe program and opioid substitution therapy had engaged to prevent HCV infection, the prevalence of HCV infection does not seem to decline. The aim of this study was to estimate the risk of HCV infection in injecting drug users (IDUs) and noninjecting drug users (NIDUs) receiving opioid substitution therapy. Methods: We recruited 1179 heroin-dependent patients (age: 20-66 years) under opioid substitution therapy from 2012 to 2015 in a Psychiatric Center, Southern Taiwan. The data of HCV, hepatitis B virus and HIV infection and liver biochemical examination were obtained. We used multivariate logistic regression analysis to predict the risk of HCV infection. Results: There were 93.1% of IDUs and 68.1% of NIDUs positive for HCV infection. In IDUs, HIV infection, age of heroin initiation, duration and dose of heroin use, frequency of detoxification, and number of criminal conviction were significantly associated with HCV infection. In NIDUs, snort/sniff heroin exhibited a significantly increased risk of HCV infection. Intravenous injecting (odds ratio [OR] = 23.10, 95% CI = 8.04-66.40, p < 0.001), intravenous injecting combined snort/sniff (OR = 12.95, 95% CI = 3.90-42.97, p < 0.001), and snort/sniff (OR = 4.14, 95% CI = 1.30-13.18, p = 0.016) were significantly associated with increased risk of HCV infection compared with smoking. The trend was significant (p for trend <0.001). Conclusion: In Taiwan, IDUs had harmful characteristics compared with NIDUs and both had extremely high prevalence of HCV infection. We provided evidence that snort/sniff is a possible way of leak in HCV infection despite needle-syringes supplement program been provided. Opioid substitution therapy program should include HCV assessment and treatment in the new direct-acting antiviral therapy era.
Serial serologic changes of hepatitis D virus in chronic hepatitis B patients receiving nucleos(t)ides analogues therapy
(1970-01-01)
Jang, Tyng-Yuan
;
Wei, Yu-Ju
;
Hsu, Cheng-Ting
;
Hsu, Po-Yao
;
Liu, Ta-Wei
Background and Aim The serial serologic changes of hepatitis D virus (HDV) infection among chronic hepatitis B virus (HBV) infected patients who received oral nucleotide/nucleoside analogues are elusive. Methods Serum anti-HDV and HDV RNA among chronic hepatitis B (CHB) patients were tested at the time of initiating anti-HBV therapy and subsequently during the follow-up period. Results The seropositive rate of anti-HDV and HDV RNA among 2850 CHB patients, was 2.7% and 0.9%, respectively. Factors associated with anti-HDV seropositivity were platelet counts (odds ratio [OR]/95% confidence intervals [CI]: 0.995/0.992-0.999; P = 0.006), HBV DNA levels (OR/CI: 0.81/0.70-0.94; P = 0.005), and hepatitis B e-antigen (HBeAg) seropositivity (OR/CI: 0.22/0.05-0.95; P = 0.04). The only factor associated with HDV RNA positivity among anti-HDV seropositive patients was age (OR/CI: 0.95/0.90-1.00; P = 0.03). The spontaneous clearance rate of serum anti-HDV antibody was 3.0 per 100 person-years with a median follow-up period of 3.5 years (range 2-12 years), whereas the seroclearance rate of HDV RNA was 4.3 per 100 person-years among anti-HDV seropositive patients after a median follow-up period of 6.0 years (range 2-11 years). A baseline anti-HDV titer < 0.5 cut-off index was the only factor predictive of anti-HDV seroclearance (hazard ratio [HR]/CI: 30.11/3.73-242.85; P = 0.001). Conclusions HDV infection was not common among patients treated for HBV in Taiwan. Seroclearance of anti-HDV and HDV RNA did occur over time, albeit the chance is rare.
Higher NAFLD fibrosis score is associated with impaired eGFR
(2020-01-01)
Hsieh, Meng-Hsuan
;
Wu, Kuan-Ta
;
Chen, Yi-Yu
;
Yang, Jeng-Fu
;
Lin, Wen-Yi
Background/Purpose: Chronic kidney disease (CKD) has become a worldwide health problem, leading to high morbidity and mortality, and non-alcoholic fatty liver disease (NAFLD) is considered a risk factor for CKD. The aim of this study was to explore the relationship between NAFLD fibrosis score (NFS) and the estimated glomerular filtration rate (eGFR), and identify possible risk factors related to the NFS among Taiwanese subjects. Methods: Subjects were enrolled from the database of the Department of Preventive Medicine of Kaohsiung Municipal Hsiao-Kang Hospital. The eGFR was calculated according to the Taiwanese Modification of Diet in Renal Disease (TMDRD) equation, and the NFS was employed to evaluate the fibrotic level. Results: In total, 11,376 subjects were enrolled in this study, with a mean age of 52.0 +/- 6.81 years, including 4529 (39.8%) males. A fasting sugar level >= 100 mg/dL (OR = 1.70, 95% CI = 1.52-1.87) and an abnormal waist circumference (OR = 1.81, 95% CI = 1.65-1.99) were significant factors associated with NFS (p < 0.05). Trends of a decreasing TMDRD score and an increasing NFS with increasing age were noted (p < 0.05). The NFS was significantly negatively correlated with the TMDRD score (standard coefficients: -0.067, p < 0.001). Conclusion: A higher NFS is associated with an impaired eGFR in Taiwanese subjects. Controlling risk factors, especially fasting sugar level and waist circumference, may be useful in preventing NFS deterioration, which is negatively correlated with the eGFR. Copyright (C) 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC.
Direct-acting antivirals response in hepatocellular carcinoma: Does the presence of hepatocellular carcinoma matter?
(2019-06-01)
Huang, Chung-Feng
;
Yu, Ming-Lung
;
生物科技學院
;
生醫工程研究所
;
College of Biological Science and Technology
During the clinical trial development of directly acting antivirals (DAAs), evidence regarding the treatment efficacy in chronic hepatitis C patients with hepatocellular carcinoma (HCC) was scarce because these patients have always been excluded. Apart from the clinical trials, more HCC patients are currently being treated in daily practice, given that these treatments are highly effective and involve well-tolerated regimens. Large scale, real-world studies have demonstrated potentially suboptimal antiviral treatment efficacy in HCC patients who received DAAs. It is postulated that the impairment of the bioavailability of DAAs may account for the inferior treatment response. However, the results could not be generalized across all studies. The differing results were attributed to diverse patient characteristics, suboptimal regimens or imprecise definitions of active cancer statuses at the time of treatment initiation. Additional large-scale studies that utilize the treatment of choice in clearly defined HCC patients with different disease severities are warranted to clarify the issue.
APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation
(2019-11-01)
Kanda, Tatsuo
;
Lau, George K. K.
;
Wei, Lai
;
Moriyama, Mitsuhiko
;
Yu, Ming-Lung
In the direct-acting antiviral (DAA) era for hepatitis C virus (HCV) infection, sustained virological response (SVR) is very high, but close attention must be paid to the possible occurrence of hepatocellular carcinoma (HCC) and reactivation of hepatitis B virus (HBV) in patients with co-infection who achieved SVR in short term. HCC occurrence was more often observed in patients with previous HCC history. We found occurrence of HCC in 178 (29.6%) of 602 patients with previous HCC history (15.4 months mean follow-up post-DAA initiation) but, in contrast, in only 604 (1.3%) of 45,870 patients without previous HCC history (18.2 months mean follow-up). Thus, in these guidelines, we recommend the following: in patients with previous HCC history, surveillance at 4-month intervals for HCC by ultrasonography (US) and tumor markers should be performed. In patients without previous HCC history, surveillance at 6- to 12-month intervals for HCC including US is recommended until the long-term DAA treatment effects, especially for the resolution of liver fibrosis, are confirmed. This guideline also includes recommendations on how to follow-up patients who have been infected with both HCV and HBV. When HCV was eradicated in these HBsAg-positive patients or patients with previous HBV infection ( anti-HBc and/ or anti-HBs-positive), it was shown that HBV reactivation or HBV DNA reappearance was observed in 67 (41.4%) of 162 or 12 (0.9%) of 1317, respectively. For these co-infected patients, careful attention should be paid to HBV reactivation for 24 weeks post-treatment.
Pharmacokinetics and pharmacodynamics of pegylated interferon for the treatment of hepatitis B
(2019-10-03)
Yeh, Ming-Lun
;
Huang, Jee-Fu
;
Dai, Chia-Yen
;
Yu, Ming-Lung
;
Chuang, Wan-Long
Introduction: Interferon (IFN) had both antiviral and immunomodulatory effects, and was one of the approved treatments for hepatitis B virus (HBV). Herein, we reviewed the pharmacokinetics and pharmacodynamics of pegylated IFN-? (PegIFN-?) for the treatment of HBV. Areas covered: The steady-state serum levels of PegIFN-? were reached within 5 to 8?weeks, and the week 48 mean trough concentrations were approximately 2-fold higher than week 1. There was also no difference of the pharmacokinetics in male or female, healthy volunteers or patients with hepatitis B or C infection. PegIFN-? did not affect the metabolism of the cytochrome P450 (CYP) isozymes, except inhibition of CYP1A2. There was also no pharmacokinetic interaction between PegIFN-? and HBV nucleot(s)ide analogues (NUCs). Forty-eight weeks of PegIFN-? achieved 32% of HBeAg seroconversion, 32-43% of HBV DNA suppression, 41-59% of ALT normalization, and 3% of HBsAg seroconversion rate with a post-treatment durable response up to 80% in the initial responders. Expert opinion: On-treatment HBsAg titer guided the treatment of HBV with PegIFN-?. The recommendation of PegIFN-? and NUC combination or switch remained controversial. New immunotherapeutic agents are now in development. Although, PegIFN-? should continue to play a role in the treatment of HBV.

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