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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.
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.
Serial serologic changes of hepatitis D virus in chronic hepatitis B patients receiving nucleos(t)ides analogues therapy
(1970-01-01)
Jang, Tyng-Yuan
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Wei, Yu-Ju
;
Hsu, Cheng-Ting
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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.
Direct-acting antivirals response in hepatocellular carcinoma: Does the presence of hepatocellular carcinoma matter?
(2019-06-01)
Huang, Chung-Feng
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Yu, Ming-Lung
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生物科技學院
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生醫工程研究所
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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.
An Open-Label, Randomized, Active-Controlled Trial of 8 Versus 12 Weeks of Elbasvir/Grazoprevir for Treatment-Naive Patients With Chronic Hepatitis C Genotype 1b Infection and Mild Fibrosis (EGALITE Study): Impact of Baseline Viral Loads and NS5A Resistance-Associated Substitutions
(2019-08-15)
Huang, Chung-Feng
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Hung, Chao-Hung
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Cheng, Pin-Nan
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Bair, Ming-Jong
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Huang, Yi-Hsiang
Background. A 12-week grazoprevir/elbasvir regimen is highly effective against hepatitis C virus genotype 1 (HCV-1) infection. The efficacy of an 8-week regimen for treatment-naive HCV-1-infected patients with mild fibrosis has not been determined. Methods. Treatment-naive HCV-1b-infected patients with mild fibrosis were randomly assigned to receive 8 (n = 41) or 12 (n = 41) weeks of grazoprevir/elbasvir therapy. The primary end point was a sustained virologic response, defined as an HCV RNA level of < 12 IU/mL, at posttreatment week 12 (SVR12). Results. SVR12 was achieved by 87.8% of patients (36 of 41) in the 8-week arm and 100% (41 of 41) in the 8-week arm of the full-analysis population and by 90.0% (36 of 40) and 100% (41 of 41), respectively, in the per-protocol population (all P = .055). In the 8-week arm, a significantly lower SVR12 rate was observed among patients with a high HCV-1b load, defined as >= 1 500 000 IU/mL (79% vs 100%; P =.042), and among those with a baseline Y93H resistance-associated substitution (RAS) frequency of >15% in HCV nonstructural protein 5A (NS5A; 40.0% vs 97.1%; P = .004). Between-group analysis demonstrated that, among patient with a high HCV-1b load and a baseline Y93H RAS frequency of >15%, those in the 8-week arm had a substantially lower SVR12 rate than those in the 12-week arm (40.0% vs 100.0%). All 4 HCV-1b relapses had a Y93H RAS frequency of >99% at posttreatment week 12. Conclusions. Twelve weeks of grazoprevir/elbasvir therapy is highly effective for treatment-naive patients with mild fibrosis. A truncated, 8-week grazoprevir/elbasvir regimen might be applied for those with low viral loads or without a significant NS5A RAS frequency.
Improvement of hyperuricemia in chronic hepatitis C patients receiving directly acting antiviral agents
(1970-01-01)
Jang, Tyng-Yuan
;
Huang, Ching-, I
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Yeh, Ming-Lun
;
Liang, Po-Cheng
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Tsai, Pei-Chien
Background and Aim Hepatitis C virus eradication via the use of antivirals ameliorates metabolic profiles. The changes in serum uric acid (SUA) levels in chronic hepatitis C patients who receive antivirals are not well understood. We aimed to address this issue by comparing the SUA changes before and after the achievement of a sustained virological response (which is defined as hepatitis C virus RNA seronegativity at 12 weeks after the end of treatment). Methods Two hundred and thirteen sustained virological response patients who were treated by directly acting antivirals were consecutively enrolled. Pretreatment and post-treatment SUA levels were compared. Hyperuricemia was defined as a uric acid level > 7.0 mg/dL in men and > 6.0 mg/dL in women. Results The SUA levels significantly decreased after treatment, as compared to the pretreatment levels (5.6 +/- 1.5 vs 6.0 +/- 1.7 mg/dL, respectively; P < 0.001). The proportion of hyperuricemia incidences significantly decreased after treatment (25.8% vs 35.7%, respectively; P = 0.001). The improvement was only observed in patients with a fibrosis-4 index (FIB-4) < 6.5 (25.7% vs 37.1%, P = 0.001) but not in those patients with a FIB-4 >= 6.5 (26.3% vs 28.9%, P = 1.00). A multivariate analysis revealed that the factor that was associated with significantly decreased SUA levels was FIB-4 < 6.5 (odds ratio [OR]/95% confidence interval [CI]: 3.22/1.04-9.95, P = 0.04) and estimated glomerular filtration rate < 60 mL/min/1.73 m(2) (OR/CI: 4.34/1.94-9.73, P < 0.001). There existed a trend of a higher proportion of patients with significant SUA improvement along with the decrement of FIB-4 (29.7%, 25%, and 10.5% in patients with FIB-4 < 3.25, 3.25-6.5, and > 6.5, respectively; trend P = 0.03). Conclusions SUA levels were significantly decreased in chronic hepatitis C patients after viral eradication. The improvement was particularly enhanced in patients with mild liver disease.
Ribavirin facilitates early viral kinetics in chronic hepatitis C patients receiving daclatasvir/asunaprevir
(1970-01-01)
Huang, Chung-Feng
;
Yeh, Ming-Lun
;
Huang, Ching-, I
;
Liang, Po-Cheng
;
Lin, Yi-Hun
Background and Aim Ribavirin (RBV) remains crucial in difficult-to-cure chronic hepatitis C patients receiving directly acting antivirals (DAAs). The current study aimed to address whether RBV enhanced early viral kinetics in patients with DAAs. Methods Hepatitis C virus (HCV) genotype-1b patients were allocated to daclatasvir/asunaprevir +weight-based RBV (1000-1200 mg/day) for 12-24 weeks. HCV RNA levels were compared at day 1, week 1, week 2, and week 4 of treatment. Results The sustained virological response rate was 100% (67/67) and 96.7% (59/61) in the RBV and non-RBV group, respectively. The HCV RNA levels at treatment week 2 (W2) were significantly lower in the RBV group than in the non-RBV group (0.42 +/- 0.81 log IU/mL vs 0.79 +/- 1.03 log IU/mL, P = 0.04). Among the intermediate responders who remained to have detectable RNA after W1 of treatment, patients with RBV had a significantly higher rate of undetectable HCV RNA (71.4% vs 36.0%, P = 0.003) and lower HCV RNA level at W2 (0.55 +/- 0.89 log IU/mL vs 1.32 +/- 1.04 log IU/mL, P = 0.001). A more significant magnitude of HCV RNA reduction was also noted from baseline to day 1 (3.15 +/- 0.38 log IU/mL vs 2.80 +/- 0.70 log IU/mL, P = 0.009) and W1 to W2 (1.40 +/- 0.65 log IU/mL vs 0.88 +/- 0.78 log IU/mL, P = 0.007) in the RBV group compared to the non-RBV group among the intermediate responders. Logistic regression analysis revealed that adding RBV independently predicted undetectable HCV RNA at W2 (odds ratio/confidence interval: 4.74/1.54-14.57, P = 0.007) in the intermediate responders. Conclusions Adding RBV to DAAs improved early viral kinetic, in particular, for intermediate responders.
Elevated interleukin-4 levels predicted advanced fibrosis in chronic hepatitis C
(2019-04-01)
Batsaikhan, Batbold
;
Lu, Ming-Ying
;
Yeh, Ming-Lun
;
Huang, Ching-, I
;
Huang, Chung-Feng
Background: Cytokine imbalance has been associated with chronic hepatitis C virus (HCV) infection. We hypothesized that cytokines have an important role in fibrosis development in HCV infection. Methods: Data of 92 patients were analyzed retrospectively. Fluorescent Bead immunoassay was used to measure the following serum cytokine levels: Interferon , tumor necrosis factor , interleukin (IL)-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-12. Various statistical analyses were used as appropriate. Results: Of the 92 HCV-infected patients, 49 (53.3%) were male, 23 (25%) patients had advanced (fibrosis grades 3-4) fibrosis, and the mean age of the study population was 51.9 9.4 years. Elevation of baseline IL-4 level (>490 pg/mL) was associated with liver fibrosis grade by (2) test (odds ratio [OR] = 2.99; 95%, CI = 1.02-8.78; p = 0.042) and multivariate logistic regression (OR = 4.26; 95% CI = 1.13-16.02; p = 0.032). Also, IL-4 had strong diagnostic value in advanced liver fibrosis by using area under receiver operating characteristics curve analysis. Assessment of fibrosis score was consequently developed from our findings and compared with other noninvasive serum markers to assess liver fibrosis. Conclusion: This study provides evidence that increased IL-4 expression predicted advanced liver fibrosis in treatment of naive HCV-infected patients. The newly developed FIL4 score had good predictive value for advanced fibrosis before treatment and this value was even strong in HCV-genotype 1b patients.
Equal treatment efficacy of direct-acting antivirals in patients with chronic hepatitis C and hepatocellular carcinoma? A prospective cohort study
(2019-05-01)
Huang, Chung-Feng
;
Yeh, Ming-Lun
;
Huang, Ching-I
;
Liang, Po-Cheng
;
Lin, Yi-Hung
Objective The treatment outcome of direct-acting antivirals (DAAs) in chronic hepatitis C patients with hepatocellular carcinoma (HCC) is controversial. The current study aimed to address the treatment efficacy and safety of DAAs in patients with curative or active HCC, compared with those of patients without HCC. Design A prospective cohort study Setting A medical centre and two regional hospitals in Taiwan Participants A total of 713 Taiwanese patients (601 non-HCC, 74 curative HCC and 38 active HCC patients) who received standard-of-care DAAs were consecutively enrolled in the study. Main outcome measurement The primary objective was to determine treatment efficacy, defined as undetectable hepatitis C virus RNA throughout 12 weeks of the post-treatment follow-up period (sustained virological response 12 [SVR12]). Results The overall SVR12 rate was 96.9%. The SVR12 rate was similar between the patients with HCC and those without HCC (95.5% vs 97.2%, p=0.37). The HCC patients were divided into two groups, those with curative HCC and those with viable HCC; a substantially but not significantly lower SVR rate, 92.1% (35/38), was observed in the patients with viable HCC compared with the SVR rate, 97.3% (72/74), in those with curative HCC (p=0.33). Compared with the patients with curative HCC, the patients with viable HCC had a significantly higher proportion of serious adverse events (10.5% vs 1.0%, p=0.002), early treatment discontinuation (10.5% vs 2.8%, p=0.03) and mortality (5.3% vs 0.1%, p=0.008). Conclusions An equivalently high SVR rate was observed in patients with either past or active HCC compared with those without HCC. The safety concerns in the HCC patients did not compromise treatment efficacy.

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🏛️國立陽明交通大學機構典藏

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