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Background: Hepatocellular carcinoma (HCC) tends to recur after curative treatment. This study aimed to identify the clinical factors associated with HCC recurrence after initial curative therapy. Methods: We retrospectively included patients with early stage HCC Barcelona Clinic Liver Cancer (BCLC) stages 0 and A who received curative surgical resection or local ablation at three different Chang Gung Memorial Hospitals in Taiwan (527 patients from Linkou, 150 patients from Keelung, and 127 patients from Chiayi) from 2000 to 2009. Pretreatment clinical data were subjected to univariate and multivariate logistic analyses to identify the risk factors for HCC recurrence within five years after the primary curative treatment. Recurrence and survival rates were assessed using Kaplan–Meier curves and log-rank tests. Results: Patients with a history of nucleoside analog or peg-interferon treatment for hepatitis B or hepatitis C infection had lower HCC recurrence rates than did those without such treatment. By contrast, alcohol drinking habits (p = 0.0049, hazard ratio (HR): 1.508, 95%CI: 1.133–2.009), a platelet count of < 14 × 104/μL (p = 0.003, HR: 1.533, 95%CI: 1.155–2.035), and a serum alanine aminotransferase level > 40 U/L (p = 0.0450, HR: 1.305, 95%CI: 1.006–1.694) were independent risk factors for HCC recurrence. The five-year HCC recurrence rates did not differ between patients who received either local radiofrequency ablation or surgical resection at BCLC stages 0 and A. Conclusions: Factors contributing to persistent hepatitis activity and advanced fibrosis precipitate tumor recurrence. Active intervention to discontinue liver injury or hepatitis could reduce HCC recurrence. [ABSTRACT FROM AUTHOR]

Background/purpose: The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR.Methods: Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12).Results: 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P < 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common.Conclusion: LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations. [ABSTRACT FROM AUTHOR]

Background: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients.Methods: Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg-IFN-α2a) at 180 μg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 μg (n = 23), 360 μg (n = 21), 450 μg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24).Results: SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg-IFN-α2a 180 μg, Ropeginterferon alfa-2b 270 μg, 360 μg, and 450 μg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively.Conclusion: Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg-IFN-α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing. [ABSTRACT FROM AUTHOR]

Background/purpose: Genotype 2 (GT2) hepatitis C virus infection is the second common genotype in Taiwan. Real-world experience of ledipasvir/sofosbuvir (LDV/SOF) for GT2 infection is limited. The aim of this study is to evaluate the effectiveness and safety of LDV/SOF in patients with GT2 chronic hepatitis C (CHC) infection.Methods: CHC patients with GT2 infection receiving 12 weeks LDV/SOF from three hospitals were enrolled. HCV RNA was checked at baseline, end-of-treatment and 12 weeks after completing treatment. Demographic data, adverse events, renal function and metabolic profiles were recorded.Results: Among 392 enrolled patients, 33 patients (8.4%) were cirrhotic. Sustained virological response (SVR) rate was 96.7% (379/392) by intention-to-treat analysis and 97.2% (379/390) by per-protocol analysis. The SVR rate was lower in cirrhotic patients than in non-cirrhotic patients (90.6% vs 97.8%, p = 0.053). Two cirrhotic patients who took LDV/SOF plus ribavirin both achieved SVR. Neither drug-related severe adverse events nor discontinuation due to drug-related adverse event were reported. The estimated glomerular filtration rate (eGFR) remained stable in patients with chronic kidney disease 3a/3b.Conclusion: Twelve weeks of LDV/SOF treatment provided an excellent and safe regimen for GT2 CHC infection, particularly in non-cirrhotic patients. [ABSTRACT FROM AUTHOR]

Despite the excellent antiviral effects of direct acting antivirals (DAAs) for hepatitis C virus (HCV) infection with subsequent decrease of morbidity and mortality, a small proportion (5%) of the treated patients do not respond to first-line DAAs and have persistent viremia. Rescue therapy for patients with DAA failures is thus mandatory from both clinical and public health perspectives. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX), a fixed-dose pangenotypic rescue agent, has been approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA) for retreating HCV patients who fail prior DAA therapies. However, this agent has not been licensed by health authorities of Taiwan. Herein we reported two cases who successfully cleared HCV by using SOF/VEL/VOX plus ribavirin (RBV) after virologic failures to first-line pangenotypic SOF/VEL. Furthermore, we discussed the current unmet medical needs and clinical implications of SOF/VEL/VOX on the perspectives of HCV elimination in Taiwan. [ABSTRACT FROM AUTHOR]

Background/purpose: While direct-acting antiviral regimens have been approved for chronic hepatitis C (CHC) patients in Taiwan, reimbursement is limited to certain populations. Thus, pegylated interferon plus ribavirin (PEG-IFN/RBV) remains the standard of care for many patients. The aim of this study was to investigate the percentage of CHC patients who were recommended and willing to receive PEG-IFN/RBV, and to identify reasons why patients were not recommended or unwilling to receive treatment.Methods: 822 Taiwanese CHC patients were enrolled from May-August 2016 in this cross-sectional study. PEG-IFN/RBV recommendation and patient willingness to receive treatment were evaluated through surveys. Patient characteristics associated with treatment recommendation and willingness were assessed.Results: 311 (37.8%) patients were recommended PEG-IFN/RBV while 102 (12.4%) were willing to follow treatment recommendation. Rates of recommendation and willingness were lower in treatment-experienced, hepatitis C virus genotype 1 (GT1) and cirrhotic patients, and those treated in Northern Taiwan. Multivariate analyses found factors such as prior treatment experience, GT1, cirrhosis and low hemoglobin levels to be associated with lower recommendation rates while advanced age, GT1 and low baseline viral loads were associated with lower willingness rates. Physicians' top reasons for not recommending PEG-IFN/RBV included the wish to wait for better treatment options (60.3%), prior treatment failure (21.3%) and patients' advanced age (20.9%). Patients were unwilling to receive treatment mainly due to concerns about side effects (91.4%), the wish to wait for better treatment options (71.3%) and inconvenience (25.4%).Conclusion: A minority of Taiwanese CHC patients were recommended PEG-IFN/RBV, of which few were willing to receive treatment. [ABSTRACT FROM AUTHOR]

Background and Purpose: Sofosbuvir (SOF) and daclatasvir (DCV) treatment achieves excellent efficacy and safety in treating chronic hepatitis C (CHC) with various genotypes. Real world experience of SOF/DCV regimen to treat genotype 2 CHC was scanty in Asia. This study aimed to evaluate the effectiveness and safety of SOF/DCV with or without ribavirin to treat genotype 2 CHC patients in real world practice in Taiwan.Methods: Patients with genotype 2 CHC treated with 12-week of SOF/DCV or SOF/DCV/ribavirin were enrolled prospectively. Effectiveness was evaluated by sustained virological response (SVR) which was defined as undetectable hepatitis C virus (HCV) RNA at post-treatment week 12. Adverse events were recorded for safety analysis.Results: In total of 32 patients were enrolled from October 2016 to June 2017. All were infected with genotype 2 HCV. Sixteen patients (50%) exhibited cirrhosis including 6 patients with decompensation. Regimens of SOF/DCV and SOF/DCV/ribavirin were used to treat 14 and 18 patients, respectively. SVR was achieved in all 31 patients (100%) who completed follow-up. Significantly higher levels of cholesterol (p = 0.013) and higher low density lipoprotein-cholesterol (p = 0.015) were exhibited after successful viral clearance. SOF/DCV/ribavirin regimen resulted in more adverse events, significantly higher bilirubin levels, and decline of hemoglobin during treatment than SOF/DCV regimen. Four patients with chronic kidney disease maintained renal function during treatment. Overall, SOF/DCV or SOF/DCV/ribavirin treatment was well tolerated.Conclusion: SOF/DCV with or without ribavirin is highly effective and safe for patients with genotype 2 HCV infection in real-world experience in Taiwan. [ABSTRACT FROM AUTHOR]

Background/purpose: Treatment with daclatasvir plus asunaprevir (DCV + ASV) for 24 weeks provided a sustained virologic response (SVR) rate of over 90% in hepatitis C virus genotype 1b (HCV-1b) infected patients without non-structural 5A (NS5A) resistance-associated substitutions (RASs) at the L31 and Y93 sites. In this study, we investigated whether adding ribavirin to the DCV + ASV combination could shorten the original treatment regimen to 12 weeks without compromising the treatment efficacy for HCV-1b patients without NS5A RASs.Methods: In the prospective, open-label, single-arm, nationwide multi-center phase III study, a total of 70 interferon-naïve or interferon-experienced HCV-1b patients without baseline L31/Y93 RASs received daclatasvir (60 mg/day) and asunaprevir (100 mg twice daily) plus weight-based ribavirin (1000-1200 mg/day) for 12 weeks, with a 12-week post-treatment follow-up. The primary end-point was the rate of undetectable HCV RNA 12 weeks post-treatment (SVR12).Results: The SVR12 rate was 97.1% (68/70) and 100% (68/68) in the full-analysis-set and the per-protocol population, respectively. None of the 68 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. Two patients withdrew from the study at treatment days 21 and 34 due to anorexia and fatigue, which were considered ribavirin-related and resolved post medication cessation. A total of 4 serious adverse events were reported and considered treatment-unrelated. No deaths or grade 4 adverse events requiring hospitalization was observed throughout the study.Conclusion: Truncated regimen of DCV + ASV plus ribavirin for 12 weeks was highly effective and safe in HCV-1b patients without NS5A L31/Y93 RAS. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV)-infected patients who achieved sustained virologic response (SVR) may still develop hepatocellular carcinoma (HCC). The characteristic of HCC and the prognosis between SVR and non-SVR patients were not well known.Methods: Among 1884 HCV-infected patients who were treated with pegylated IFN plus ribavirin therapies, 122 patients developed HCC during follow-up were enrolled in this study. Laboratory data were collected before and at least 1 year after IFN-based therapy, as well as the latest follow-up.Results: Both SVR and non-SVR patients had similar risk factors to develop HCC, but with a little difference. Liver cirrhosis plays a key role in HCC occurrence in both groups. Among the patients who developed HCC, non-SVR patients had significantly higher total bilirubin, higher FIB-4, lower pre-treatment platelet count, higher pre-treatment AFP levels and higher proportion of cirrhosis than SVR patients before occurrence of HCC. After curative treatment, SVR patients had lower recurrence and longer overall survival than non-SVR patients by Kaplan-Meier analysis. Multivariate analysis revealed that APRI ≥0.7 was the independent risk factor for HCC recurrence; and AFP ≥20 ng/ml post IFN therapy, as well as HCC recurrence were the independent risk factors of mortality.Conclusion: Liver cirrhosis plays a key role in HCC occurrence after antiviral therapies. SVR patients may have lower HCC recurrence and longer survival rates than non-SVR patients. Only APRI was associated with HCC recurrence; and post-IFN AFP and HCC recurrence were predictive of subsequent mortality independently. [ABSTRACT FROM AUTHOR]

Background/purpose: The role of directly-acting antivirals (DAA)-containing regimens in the treatment of patients dually-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) remains unclear. The pilot study aimed to explore the safety and efficacy of a protease inhibitor, boceprevir, in combination with peginterferon/ribavirin for HCV genotype 1 (HCV-1)/HBV dually-infected patients refractory to prior peginterferon/ribavirin.Methods: Twelve peginterferon-experienced patients dually-infected with HCV-1/HBV were assigned to receive boceprevir 800 mg, twice a day, plus peginterferon-α 2b 1.5 μg/kg/week and ribavirin 800-1400 mg/day for 36 or 48 weeks. The primary endpoint was HCV sustained virological response (SVR, HCV RNA undetectable 24 weeks after end-of-treatment).Results: Five patients terminated treatment early due to adverse events (one at week 4, one at week 46), virological failures (one non-response and one breakthrough), and patient request (n = 1). Eight patients achieved HCV SVR (66.7% in full-analysis set and 72.7% in modified intention-to-treat population). The HCV SVR rate was 71.4% (5/7) in prior relapsers, 60.0% (3/5) in prior null responder; 75% in non-cirrhotic and 50% in cirrhotic patients. All four patients of prior non-cirrhotic relapsers received 36-week regimen and achieved HCV SVR. There was no HBV-related hepatic flare. All patients experienced at least one adverse event. Two had serious adverse events.Conclusion: Boceprevir plus peginterferon/ribavirin is effective in the treatment of HCV-1/HBV dually infected patients' refractory to prior peginterferon/ribavirin combination therapy. [ABSTRACT FROM AUTHOR]

Background/purpose: Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients.Methods: A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated.Results: We demonstrated that the average cost per SVR achieved was $13,722 in treatment-experienced CHC patients. Especially, patients with HCV G1 infection, baseline viral loads > 400,000 IU/mL, advanced hepatic fibrosis, not achieving a rapid viral response at week 4 or complete early viral response at week 12, had poorer cost-effectiveness for PegIFN/RBV retherapy, ranging from around $15,520 to as high as $72,546 per SVR achieved.Conclusion: In the current study, we explored the real-world cost-effectiveness data of PegIFN/RBV for different subgroups of treatment-experienced HCV patients. These findings provide information for policy-makers for making decisions on treatment strategies of costly direct-acting antiviral agents for retreating CHC patients. [ABSTRACT FROM AUTHOR]

Background/purpose: Daclatasvir is a nonstructural protein 5A inhibitor with potent activity against hepatitis C virus genotypes 1-6 in vitro, and asunaprevir is a nonstructural protein 3 protease inhibitor with activity against genotypes 1, 4, 5, and 6. Despite a 90% sustained virologic response (SVR) rate, the SVR rate in patients with baseline NS5A-L31/Y93H polymorphisms decreased to around 40%. Therefore, an alternative regimen under the consideration of cost-effectiveness would be important. Whether the addition of ribavirin could improve the SVR rate among this group of patients remains unknown and hence our case series was reported.Methods: For six adult chronic hepatitis C 1b patients with a pre-existing NS5A-Y93H (>20%) polymorphism, we added ribavirin (800 mg/d) to daclatasvir/asunaprevir for 24 weeks and followed through 12-weeks post-treatment. Four of these patients received interferon/ribavirin treatment before but relapsed, while the other two were naïve cases. Two of them had liver cirrhosis and one had hepatocellular carcinoma postcurative therapy. The primary efficacy end-point was undetectable hepatitis C virus RNA (hepatitis C virus RNA level of<25 IU/mL) at 12 weeks after the end of the treatment (SVR12).Results: In total, five cases reached SVR12 eventually (SVR rate: 83%; 95% confidence interval: 18.6-99.1%). However, the viral load of one remaining patient rebounded from the 24th week of treatment. No patients developed significant adverse effects during and after the treatment.Conclusion: In genotype 1b chronic hepatitis C patients with NS5A-Y93H polymorphism, the addition of ribavirin to daclatasvir/asunaprevir may increase the SVR12 rate with minimal side effects, and thus deserves more comprehensive trials in resource-limited areas. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is a global public health issue. Adequate treatment for hepatitis C patients is important, but anticipated side effects make patients fearful of receiving treatment. Little is known about the experiences of hepatitis C patients who have completed treatment with pegylated interferon and ribavirin. The purpose of this study was to explore the experiences of hepatitis C patients who had undergone therapy with pegylated interferon and ribavirin and gain an understanding of what factors contributed to completion of treatment.Method: This was a qualitative study with 21 adult hepatitis C patients purposively sampled from outpatient liver clinics of a medical university hospital in Taichung City, Taiwan. Participants had completed 6-12 months of therapy with pegylated interferon and ribavirin. Data were collected through individual, face-to-face, in-depth interviews conducted in the participants' homes from June-October 2013. Data were analysed using conventional content analysis.Results: Data analysis revealed three themes that described the strategies employed to alleviate and ease symptoms and manage the processes involved: restructuring their lifestyle, adopting a positive attitude, and seeking support.Conclusion: Hepatitis C patients face many challenges during treatment with pegylated interferon and ribavirin. These findings provide knowledge that can be used in designing effective programs to help other Hepatitis C patients manage the side effects of pegylated interferon and ribavirin therapy, complete treatment and improve quality of life. [ABSTRACT FROM AUTHOR]

Dual hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is not rare in HBV or HCV endemic areas, and can be found in populations at risk of parenteral viral transmission. Clinical observatory studies suggest a higher risk of liver disease progression in patients with dual HCV/HBV infection than in HBV or HCV monoinfected patients. Recent trials confirmed that combination therapy of peginterferon alfa-2a or alfa-2b and ribavirin was effective and safe in dually infected patients with positive HCV RNA. Moreover, about 30% of the dually infected patients cleared hepatitis B surface antigen within 5 years after the start of peginterferon-based therapy. The optimal treatment strategies for dually infected patients with active hepatitis B, with decompensated cirrhosis, or in other clinical situations should be explored in further studies. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may lead to the development of strategies for the treatment of dually infected patients with active hepatitis C, particularly for those not tolerating or not eligible for peginterferon-based therapy. Notably, direct-acting antivirals would not have any activity against HBV infection; simultaneous or on-demand nucleos(t)ide analogs would be needed if clinically indicated. [ABSTRACT FROM AUTHOR]

Background/purpose: Recent studies have shown that serum vitamin D deficiency is a negative predictor of response to peginterferon plus ribavirin therapy for Caucasian patients with chronic hepatitis C (CHC). Whether vitamin D receptor (VDR) gene polymorphisms associate with antiviral response in Asian CHC patients remains unclear.Methods: We recruited 139 Asian patients with CHC genotype-1 who achieved 80/80/80 adherence of response-guided peginterferon plus ribavirin therapy. BsmI rs1544410, ApaI rs7975232, and TaqI rs731236 were genotyped and related to clinical and virological features and to treatment outcome.Results: Patients carrying bAt [CCA] haplotype (p=0.033), ApaI CC genotype (p = 0.033), and TaqI AA genotype (p = 0.037) had a higher HCV load as compared to those with other haplotypes, ApaI CA/AA genotype and TaqI AG genotype, respectively. A sustained virological response (SVR) was achieved in 74 (53%) of the patients. Polymorphisms in VDR gene did not correlate with rapid virological response and SVR achievement. Stepwise logistic regression analysis showed that rs12979860 CC type [odds ratio (OR): 5.56, p=0.007], platelet counts ≥ 15 × 10(10)/L (OR: 4.80, p=0.001), and rapid virological response achievement (OR: 8.36, p<0.001) were independent factors of SVR.Conclusion: Despite their associations with high hepatitis C virus load, VDR gene polymorphisms are not related to the response to peginterferon plus ribavirin therapy in Asian CHC patients. [ABSTRACT FROM AUTHOR]

Background: Rapid virological response (RVR) strongly predicts sustained virological response (SVR) in patients with chronic hepatitis C (CHC), and abbreviates antiviral therapy in some patients. Objectives: To identify factors predicting virological relapse (VR) in CHC patients who attained RVR. Patients and Methods: Medical records of 133 CHC patients with an RVR after completing 24 weeks of antiviral therapy (a combination of pegylated interferon-α and ribavirin) were analyzed. Baseline characteristics and on-treatment responses were compared between the patients with an SVR and those with VR. Patients with normal alanine aminotransferase (ALT) levels at weeks 4 and 12 and at the end- of-treatment (EoT) and patients with elevated, but constantly decreasing, ALT levels were classified as having favorable patterns of ALT change. A trend of increasing ALT levels either between weeks 4 and 12 or between weeks 12 and EoT was classified as unfavorable. A high viral load (HVL) was defined as a baseline HCV RNA ≥ 600000 IU/mL. Results: In total, 116 (87.2%) patients had a SVR and 14 (10.5%) had VR. The VR rates were comparable between patients with genotype-1 (13.1%) and genotype-2 infection (8.7%) (P = 0.572). Multivariate analysis revealed that HVL (P = 0.015; odds ratio [OR] = 14.7 54; 95% confidence interval (CI) = 1.671-130.240), and unfavorable ALT patterns (P = 0.039; OR = 4.397; 95% CI = 1.078-17.930) independently predicted VR. In subgroup analysis, low viral load (LVL) patients had a minimal VR rate (1.8%). Among the HVL patients, the VR rate of those using peg-IFN-α- 2a was relatively low (9.1%). Patients using peg-IFN-α-2b had a slightly higher VR rate (23.8%; P = 0.128), and patients with f avorable patterns of ALT changes had a lower VR rate (10.3%) compared to the 53.8% in patients with unfavorable ALT patterns (P = 0.005). Conclusions: In southern Taiwan, 24 weeks of antiviral therapy achieved a high SVR rate in patients with CHC attaining RVR, except in the subgroup of patients treated with peg-IFN-α-2b with HVL and on-treatment unfavorable ALT patterns. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate whether polymorphisms in the guanine nucleotide binding (G protein), beta polypeptide 1 (GNB1) gene are associated with a rapid virological response (RVR) among HCV genotype 1 (HCV-1) and 2 (HCV-2) infected patients receiving peginterferon plus ribavirin treatment (PEG-IFN?-RBV). Methods: We analyzed the association between RVR to PEG-IFNα-RBV therapy and 4 tagging single nucleotide polymorphisms (SNPs) of the GNB1 gene. This study included 265 HCV-1 and 195 HCV-2 infected patients in a Chinese population in Taiwan. Results: Among the GNB1 SNPs examined, the combination of genotypes G/G and G/T populations of rs12126768 was significant inversely correlated with RVR in HCV-1 infected patients (P = 0.0330), whereas HCV-2 infected patients, combination of A/A and A/C genotypes populations at rs4648727 responded better to the PEG-IFNα-RBV treatment (P = 0.0089). However, there were no significant differences in the allele frequencies of those SNPs between RVR responders and non-responders. Several RVR susceptibility GNB1 haplotypes were identified, and the ACAT haplotype of the 4 SNPs may increase the successful outcomes of HCV-1 and HCV-2 infected patients (P = 0.0261 and P = 0.0253, respectively). Conclusion: The data for GNB1 SNPs and the association of RVR showed that GNB1 polymorphisms might be associated with the therapeutic outcomes of HCV-1 and HCV-2 infected patients under standard of care (SOC) treatment. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the efficacy, advantage, and safety of a 24-week regimen with high-dose interferon-α (INF-α; 6 million units thrice weekly) plus ribavirin (1000–1200 mg/day) combination therapy for 46 Taiwanese chronic hepatitis C (CHC) patients with persistently normal or near-normal alanine aminotransferase (PNALT) levels. Methods: Ninety-two age- and sex-matched CHC patients with elevated ALT levels (>2 times the upper limit of normal range) with a ratio of 1:2, treated with the same regimen, served as a control. Results: The sustained virologic response (SVR) rate was comparable between PNALT (67.4%) and elevated ALT (65.2%) groups (intention-to-treat analysis). The two groups had similar rates of discontinuation and incidence of adverse effects. Viral genotype 1b, baseline viral loads, body mass index, and age were significant factors negatively associated with SVR. Further decline of ALT levels throughout the follow-up period was observed in sustained responders of the PNALT group. None of the eight patients with ALT flares developed icteric hepatitis. The virologic efficacy was sustained in a 3-year extended follow-up period. Conclusion: high-dose INF-α with ribavirin combination therapy is effective, safe, and well tolerated in CHC patients with PNALT levels. The ALT assay might not be used as a single biochemical marker for determination of treatment consideration. [ABSTRACT FROM AUTHOR]

Background Different peg-interferon alpha-2b plus ribavirin treatment strategies are more effective in treating hepatitis C. However, no cost-effectiveness data have been published using the clinical data from the peg-interferon alpha-2b and ribavirin in the treatment of patients with hepatitis C in Taiwan. Aim To estimate the cost-effectiveness of different treatments with peg-interferon alpha-2b plus ribavirin for the initial treatment of patients with different genotype chronic hepatitis C. Methods Individual patient level data from a randomized clinical trial with peg-interferon plus ribavirin were applied to a Markov model to project lifelong clinical outcomes. Economic estimates and quality of life were based on published data and Taiwan patient data. We used a societal perspective and applied a 3% annual discount rate. Results Compared with different combination therapy strategies, peg-interferon alpha-2b plus weight-based dosing of ribavirin in all patients for 24 weeks is the most cost-effective treatment strategy. If the sustained virological response of peg-interferon plus ribavirin treatment for 48 weeks therapy in genotype 1 patients was higher than 67.8%, the best strategy of treating patients will be the peg-interferon plus weight-based dosing of ribavirin therapy for 48 weeks in genotype 1 patients and for 24 weeks in non-genotype 1 patients. Conclusions Peg-interferon alpha-2b plus ribavirin combination for 24 weeks therapy in all genotype patients should reduce the incidence of liver complications, prolong life, improve quality of life and be cost-effective for the initial treatment of chronic hepatitis C. [ABSTRACT FROM AUTHOR]

To assess the efficacy of 24- or 48-week peginterferon/ribavirin treatment of Taiwanese patients with chronic hepatitis C virus genotype-1b (HCV-1b) infection, and to identify subgroups of patients in whom the 48-week treatment has benefits. Methods: We assigned 60 patients receiving peginterferon-α-2b (80–100 mcg/week) plus ribavirin (1000–1200 mg/day), depending on body weight, for 24 or 48 weeks, with a 3:1 randomization ratio. Results: The sustained virological response (SVR) rate was significantly higher in the 48-week (80.0%, 12/15) than in the 24-week group (48.9%, 22/45, P<0.05). The 60 patients were classified into two subgroups according to the presence of unfavorable baseline predictors: viral loads ≥400 000 IU/ml or a hepatic fibrosis score of 3–4. In 19 patients without an unfavorable predictor, the SVR rate was comparable in the 24-week (78.6%) and 48-week (75.0%) groups; in patients with either unfavorable predictors, the SVR rate was significantly higher in the 48-week (81.1%, 9/11) than in the 24-week group (36.7%, 11/30, P=0.015). The discontinuation rate was significantly higher in the 48-week (20.0%, 3/15) than in the 24-week group (2.2%, 1/45, P<0.05). Conclusion: A 48-week course of peginterferon-α-2b/ribavirin was more effective than a 24-week course in Taiwanese HCV-1b patients, mainly in those with high viral loads and/or advanced hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection, including its sequelae, is an important healthcare problem in Taiwan. The seroprevalence of HCV infection in first-time blood donors in Taiwan is 1.2% and an estimated 2–5% in the general population, with a great geographic variation. Genotype 1b is the most prevalent HCV genotype in Taiwan, with a prevalence rate of 50–70%. An increasing incidence of hepatocellular carcinoma (HCC) is mainly attributed to HCV infection, while the declining role of HBV is observed in Taiwan. The seroprevalence of hepatitis B surface antigen among patients with HCC was 90% three decades ago, while recently, chronic HCV infection accounts for more than 30% of HCC patients in the National Taiwan University Hospital. With the advent of a combined conventional interferon (IFN)-α and ribavirin therapy, to which Taiwan has contributed in the early study phase, the sustained virological response rate has been greatly improved compared with IFN monotherapy. The sustained virological response rate in Taiwanese patients treated with the combination therapy for 6 months has reached up to 50–60%, which is higher than that reported in patients from the Western countries receiving a 12-month regimen. It is necessary to searche for the underlying mechanisms for the better treatment outcome with IFN plus ribavirin combination therapy in Taiwanese patients. Whether long-term effects of IFN plus ribavirin therapy can reduce the incidence of HCC needs to be established. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

With the favorable result of interferon (IFN)-ribavirin combination therapy for 24 weeks among naive Taiwanese chronic hepatitis C (CHC) patients, the optimal regimens of re-treatment for CHC patients who failed initial IFN monotherapy is not well-established. The study evaluated the effectiveness of re-treatment for 24 weeks with 3 different regimens and predictors for sustained virological response (SVR). Methods: Total 120 Taiwanese CHC patients (81 males, 70 relapsers, mean age: 48.6 years) who failed initial IFN monotherapy were enrolled. They were assigned randomly (with a ratio of 1:1:2) to receive one of the three regimens for re-treatment for 24 weeks; group A: IFN 6 million units (MU) monotherapy (N = 30), group B: combination therapy with ribavirin and IFN 3 MU (N 30) or group C: combination therapy with ribavirin and IFN 6 MU (N = 60). The intention-to-treat rate of sustained virological response (SVR) was 38.3%. The SVR rate in group C (53.3%) was significantly higher than group A (16.7%, P<0.005) and group B (30%, P<0.05). Drop-out rates were similar between the three groups. Patients achieving SVR had significant improvement histologically. Hepatitis C virus (HCV) genotype non-lb infection, lower pretreatment HCV RNA levels, combined with ribavirin and with higher IFN dose, and relapsers were independent predictors for SVR. Conclusion: We concluded that more than one-third Taiwanese CHC patients achieved SVR after 24 weeks re-treatment and combination therapy, especially with higher dose of IFN, yielded higher efficacy. [ABSTRACT FROM AUTHOR]

Yang S-S, Lai M-Y, Chen D-S, Chen G-H, Kao J-H. Mutations in the NS5A and E2-PePHD regions of hepatitis C virus genotype 1b and response to combination therapy of interferon plus ribavirin. Liver International 2003: 23: 426–433. © Blackwell Munksgaard, 2003 Combination therapy with interferon (IFN) and ribavirin is the current standard treatment for chronic hepatitis C, but the efficacy is still not satisfactory, especially for genotype 1b. NS5A and E2 proteins of hepatitis C virus (HCV) may repress the IFN-induced RNA-dependent protein kinase (PKR), and thus have the potential to influence the response of HCV to IFN therapy; however, this issue remains controversial. Nucleotide sequences of the PKR-eIF2α phosphorylation homology domain (E2-PePHD) and PKR-binding domain (NS5A-PKR bd) of the HCV genome were analyzed by amplification and direct sequencing in 30 HCV genotype 1b patients who had been treated with IFN and ribavirin. Nine (30%) patients achieved a sustained virological response (SVR) to combination therapy. Pretreatment variables and amino acid substitutions were compared between responders and non-responders. The responders were younger than non-responders (37.2±10.4 vs. 45.4±9.5 years, P=0.017), whereas no significant statistical differences were found in the number of amino acid substitutions in NS5A and E2-PePHD regions between the two groups. Genetic heterogeneity in NS5A and E2-PePHD regions of the HCV genome may not serve as a predictor for treatment outcome with combination therapy in Taiwanese patients with chronic HCV genotype 1b infection. [ABSTRACT FROM AUTHOR]

Background/purpose: The major dose-limiting toxicity of ribavirin is hemolytic anemia. We investigated the incidence, risk factors and impact on virological response of anemia in chronic hepatitis C genotype 2 patients receiving sofosbuvir plus ribavirin therapy., Methods: This was a retrospective real-world analysis of a single center including 293 chronic hepatitis C genotype 2 patients treated with sofosbuvir plus ribavirin for 12 weeks. Severe anemia was defined as hemoglobin concentration <10 g/dl., Results: Treatment was completed in 285 (97%) of patients, of whom one withdrew due to severe anemia. Ribavirin dose reduction was required in 88 (30%) of patients. After excluding those with baseline hemoglobin <10 g/dl, 79 (29%) patients had developed severe anemia during therapy. Stepwise logistic regression analysis identified that chronic kidney disease (odds ratio [OR] = 3.970, p < 0.001), baseline hemoglobin level (OR = 0.475, p < 0.001) and baseline platelet count (OR = 0.992, p = 0.022) were independent factors. The sustained viral response 12 weeks off therapy (SVR 12 ) rate was 93.9% in the per-protocol population. Multivariate analyses showed that history of hepatocellular carcinoma significantly reduced the efficacy of sofosbuvir plus ribavirin therapy (OR = 0.172, p = 0.001). Severe anemia, dose reduction or average dose (mg/kg/day) of ribavirin was not associated with SVR 12 ., Conclusion: Severe anemia was not uncommon during sofosbuvir plus ribavirin therapy for chronic hepatitis C genotype 2 patients. Careful monitoring of anemia is necessary in patients with chronic kidney disease and low baseline hemoglobin level and platelet count., (Copyright © 2019. Published by Elsevier B.V.)

Background: This study aimed to investigate the occurrence and risk factors of thyroid dysfunction (TD) in patients with chronic hepatitis C (CHC) infection in Taiwan. Methods: The data in this study were obtained from the Taiwan National Health Insurance Research (Taiwan NHIR) database between 2001 and 2013. CHC patients treated with pegylated interferon/ribavirin (PEG-IFN/RBV) were enrolled as case patients, and nontreated CHC patients were enrolled as controls and were matched at a control:case ratio of 3:1 by index date, age (± 3 years), and sex. We compared the cumulative incidence of TD between the cohorts at follow-up until 2013. Results: During the study period, 3810 cases and 9393 controls were included in the study. Among the study subjects, 173 (4.5%) case patients and 244 (2.6%) controls were diagnosed with TD during the follow-up period. The types of TD were hypothyroidism (42.9%), hyperthyroidism (31.2%), and thyroiditis (25.9%). Compared to controls during the 13-year follow-up, patients treated with PEG-IFN/RBV had a higher incidence rate of TD (P < 0.0001), as determined using the Kaplan-Meier method. Cox proportional hazards regression analysis showed that female sex (adjusted hazard ratio (HR): 1.49; 95% confidence interval (CI): 1.23–1.75; P < 0.001), treatment with PEG-IFN/RBV (HR: 1.68; 95% CI: 1.38–2.06; P < 0.001), hyperlipidemia (HR: 1.38; 95% CI: 1.12–1.71; P < 0.001), and past history of goiter (HR: 6.40; 95% CI: 5.00–8.18; P < 0.001) were independent predictors for the development of TD. Conclusions: PEG-IFN/RBV treatment may be an independent risk factor for thyroid dysfunction among patients with hepatitis C virus (HCV) infection. Monitoring thyroid function keenly during PEG-IFN/RBV therapy in patients with chronic HCV infection is recommended for clinicians, especially for female patients and for patients with a history of hyperlipidemia and goiter. [ABSTRACT FROM AUTHOR]

The article reports on a study to examine the efficacy of ribavirin to pegylated interferon-alpha2a therapy in case of patients with hepatitis C virus genotype 1 receiving hemodialysis. The study was carried on patients with chronic hepatitis C who were receiving hemodialysis for end-stage renal disease in Taiwan. The study found that patients who received low-dose ribavirin and pegylated interferon-alpha2a were found conquering of their hepatitis C infection.

The viral load of hepatitis C virus (HCV) in chronic hepatitis C patients affects clinical outcomes and response to interferon treatment. Various factors may be involved in determining the viral load, including host genetic factors. The aim of this study was to investigate the relationship between HCV viral load and human leukocyte antigen (HLA) class I and class II alleles. One hundred and six HCV RNA positive subjects were enrolled, and viral load was measured. HLA-A, -B, -C, -DR, and -DQ loci were determined by sequence-based genotyping. Univariate analysis indicated that HLA-B(*)40 and HLA-C(*)07 alleles had significantly higher HCV RNA levels (P<0.05). Patients with the HLA-C(*)15 allele exhibited a trend toward a lower HCV viral load (P=0.06). After controlling for confounding factors, multivariate analysis revealed that only HLA-C(*)15 allele was identified as a significant determinant for HCV-RNA level (slope=-0.91, 95% CI: -1.58, -0.24; Holm's P<0.01). Patients expressing the HLA-C(*)15 allele had significantly lower HCV RNA levels. HCV genotype 1 was significantly associated with high HCV RNA levels (P<0.05 by Mann-Whitney U test). In conclusion, HLA-C(*)15 is an important host immunogenetic factor with an inverse association to HCV viral load in CHC patients in Taiwan. HCV genotype 1 is the viral factor that associated with high viral load., (Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)