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1.
J Infect Dis ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396638

RESUMO

BACKGROUND: Prophylaxis with nucleos(t)ide analogue (NA) is recommended to prevent hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-positive patients receiving rituximab-based B cell depletion therapy. However, little is known about the risk of clinical relapse following withdrawal of NA. PATIENTS: and Methods: We retrospectively analyzed 77 non-cirrhotic, HBsAg carriers with haematological malignancies who received rituximab-containing chemotherapy. All of them received either prophylactic entecavir or tenofovir therapy. The risk of clinical relapse and hepatic decompensation after cessation of NA was explored. RESULTS: Clinical relapse and hepatic decompensation developed in 25 (32.5 %) patients and 11 (14.3 %) patients, respectively, and 2 patients died of hepatic decompensation. Most of the hepatic events occurred within 1 year (20/25; 80.0%) after stopping NA. A higher pretreatment viral load (≥2000 vs. <2000 IU/mL) was associated with increased risks of clinical relapse (HR: 3.47, 95% CI: 1.56-7.73) and hepatic decompensation (HR: 9.91, 95% CI: 2.14-45.92). Of 51 patients with pretreatment viral load <2000 IU/mL, 10 (19.6 %) experienced clinical relapse and 2 (3.9%) developed hepatic decompensation. CONCLUSIONS: Pretreatment HBV DNA ≥2000 IU/mL is associated with increased risk of liver-related morbidities after cessation of prophylactic NA therapy in patients who received rituximab-containing chemotherapy.

2.
J Formos Med Assoc ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32284164

RESUMO

BACKGROUND: Patients with different hepatitis C virus (HCV) genotype infections are associated with varying metabolic disorders. Although alteration of lipid metabolism has been confirmed as a virus-induced metabolic derangement in chronic hepatitis C patients, the impact of various HCV genotypes on hepatic cholesterol metabolism remains elusive. In this study, we thus investigated the HCV genotype-specific lipogenic and cholesterol metabolism profiles in an in vitro cell culture system. METHODS: We first conducted HCV cell culture system (HCVcc) assays by infecting Huh7.5.1 cells with multiple infection-competent HCV strains, including the genotype 2a JFH1 and JFH1-based intergenotypic recombinants 1b and 3a. We then examined the expression levels of various lipid and cholesterol-related genes. RESULTS: The data showed that infection with individual HCV genotypes exerted unique gene expression regulatory effects on lipoproteins and cholesterol metabolism genes. Of note, all HCV strains suppressed cholesterol biosynthesis in hepatocytes through downregulating the expression of HMG-CoA reductase (HMGCR) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1) - two essential enzymes for cholesterol biosynthesis. These HCV-mediated inhibitory effects could be reversed by treatment with sofosbuvir, a pangenotypic NS5B inhibitor. In addition, overexpression of HCV genotype 1b, 2a or 3a core protein significantly suppressed HMGCR mRNA transcription and translation, thus diminished cellular cholesterol biosynthesis. Nonetheless, the core protein had no effect on FDFT1 expression. CONCLUSION: Although HCV infection regulates host lipid metabolism in a genotype-specific manner, its inhibition on hepatocellular cholesterogenic gene expression and total cholesterol biosynthesis is a common effect among HCV genotype 1b, 2a and 3a.

3.
Mol Ther Nucleic Acids ; 20: 480-490, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32278307

RESUMO

Current antiviral therapy fails to cure chronic hepatitis B virus (HBV) infection because of persistent covalently closed circular DNA (cccDNA). CRISPR/Cas9-mediated specific cleavage of cccDNA is a potentially curative strategy for chronic hepatitis B (CHB). However, the CRISPR/Cas system inevitably targets integrated HBV DNA and induces double-strand breaks (DSBs) of host genome, bearing the risk of genomic rearrangement and damage. Herein, we examined the utility of recently developed CRISPR/Cas-mediated "base editors" (BEs) in inactivating HBV gene expression without cleavage of DNA. Candidate target sites of the SpCas9-derived BE and its variants in HBV genomes were screened for generating nonsense mutations of viral genes with individual guide RNAs (gRNAs). SpCas9-BE with certain gRNAs effectively base-edited polymerase and surface genes and reduced HBV gene expression in cells harboring integrated HBV genomes, but induced very few insertions or deletions (indels). Interestingly, some point mutations introduced by base editing resulted in simultaneous suppression of both polymerase and surface genes. Finally, the episomal cccDNA was successfully edited by SpCas9-BE for suppression of viral gene expression in an in vitro HBV infection system. In conclusion, Cas9-mediated base editing is a potential strategy to cure CHB by permanent inactivation of integrated HBV DNA and cccDNA without DSBs of the host genome.

4.
Hepatology ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171027

RESUMO

BACKGROUND & AIMS: Early recurrence of hepatocellular carcinoma (HCC) after surgical resection compromises the patient survival. Timely detection of HCC recurrence and its clonality is required to implement salvage therapies appropriately. This study examined the feasibility of virus-host chimera DNA (vh-DNA), generated from junctions of hepatitis B virus (HBV) integration in the HCC chromosome, as a circulating biomarker for this clinical setting. APPROACH & RESULTS: HBV integration in 50 HBV-related HCC patients was determined by the capture-next generation sequencing (NGS) platform. For individual HCC, the vh-DNA was quantified by specific droplet digital PCR (ddPCR) assay in plasma samples collected before and two months after surgery. HBV integrations were identified in 44 out of 50 HBV-related HCC patients. Tumor-specific ddPCR was developed to measure the corresponding vh-DNA copy number in baseline plasma from each patient immediately before surgery. vh-DNA was detected in 43 patients (97.7%), and the levels correlated with the tumor sizes (detection limit at 1.5 cm). Among the plasma collected at 2 months after surgery, 10 cases (23.3%) still contained the same signature vh-DNA detected at baseline, indicating the presence of residual tumor cells. Nine of them (90%) experienced HCC recurrence within one year, supporting vh-DNA as an independent risk factor in predicting early recurrence. Analysis of circulating vh-DNA at recurrence further helped identify the clonal origin. 81.8% of recurrences came from original HCC clones sharing the same plasma vh-DNA, whereas 18.2% were from de novo HCC. CONCLUSIONS: vh-DNA was shown to be a new circulating biomarker for detecting the tumor load in majority of HBV-related HCC patients and aided in monitoring residual tumor and recurrence clonality after tumor resection.

5.
Proc Natl Acad Sci U S A ; 117(12): 6717-6725, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32139604

RESUMO

Most hepatocellular carcinomas (HCCs) develop in patients with chronic hepatitis, which creates a microenvironment for the growth of hepatic progenitor cells (HPCs) at the periportal area and subsequent development of HCCs. We investigated the signal from the inflammatory liver for this pathogenic process in the hepatic conditional ß-catenin knockout mouse model. Senescent ß-catenin-depleted hepatocytes in aged mice create an inflammatory microenvironment that stimulates periportal HPC expansion but arrests differentiation, which predisposes mice to the development of liver tumors. The release of complement C1q from macrophages in the inflammatory niche was identified as the unorthodox signal that activated the ß-catenin pathway in periportal HPCs and was responsible for their expansion and de-differentiation. C1q inhibitors blocked the ß-catenin pathway in both the expanding HPCs and the liver tumors but spared its orthodox pathway in pericentral normal hepatocytes. This mechanism has been validated in human liver specimens from patients with chronic hepatitis. Taken together, these results demonstrate that C1q- mediated activation of ß-catenin pathway in periportal HPCs is a previously unrecognized mechanism for replenishing hepatocytes in the inflammatory liver and, if unchecked, for promoting hepatocarcinogenesis. C1q may become a new target for blocking carcinogenesis in patients with chronic hepatitis.

6.
J Hepatol ; 72(6): 1105-1111, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32006586

RESUMO

BACKGROUND & AIMS: Acute HEV infection causes varying degrees of liver damage. Although liver-related death due to HEV infection alone is rare in healthy individuals, it is unclear whether HEV superinfection is associated with worse outcomes in patients with chronic HBV infection. Thus, we explored whether HEV superinfection was associated with increased incidence of liver-related death, cirrhosis, and hepatocellular carcinoma (HCC). METHODS: Serum and data were collected from 2 independent retrospective cohorts of patients with chronic HBV infection, comprising 2,123 patients without cirrhosis and 414 with cirrhosis at baseline, respectively. All the patients were negative for HEV-IgG at enrolment and HEV superinfection was defined by the presence of HEV-IgG seroconversion. RESULTS: In the non-cirrhotic cohort, 46 of 2,123 patients developed HEV superinfection. Though HEV superinfection was only associated with increased incidence of liver-related death in the overall cohort, it was a risk factor for all 3 endpoints (liver-related death, cirrhosis, and HCC) in a subgroup of 723 HBeAg-negative patients with chronic HBV infection. In addition, the 1-year mortality rate after HEV superinfection was higher in 4 patients who developed cirrhosis during the follow-up than in those who did not (50% vs. 2.4%, p = 0.001). To elucidate the perceived relationship between HEV superinfection and risk of mortality, an independent cohort of cirrhotic patients (n = 414) was further analyzed to control for the inherent increase in mortality risk due to cirrhosis. The 10 cirrhotic patients with HEV superinfection had a higher 1-year mortality rate than those without (30% vs. 0%, p <0.001). CONCLUSIONS: In both cohorts of patients with chronic HBV infection, acute HEV superinfection increases the risk of liver-related death, especially in those with cirrhosis. LAY SUMMARY: The mortality caused by acute hepatitis E virus infection is usually low in the healthy population, but it is unclear how it affects patients with chronic hepatitis B virus infection, as they already have compromised liver function. Our data show that the 1-year mortality rate is 35.7% in patients with hepatitis B-related cirrhosis who contract hepatitis E virus. Hepatitis E may accelerate disease progression in patients with chronic hepatitis B.

8.
J Viral Hepat ; 27(6): 568-575, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31981264

RESUMO

Data are limited regarding the real-world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI). We aimed to evaluate the performance of GLE/PIB in patients with chronic kidney disease (CKD) stage 4 or 5 in Taiwan. 108 chronic HCV patients with CKD stage 4 (n = 32) or 5 (n = 76) receiving GLE/PIB for 8-12 weeks were retrospectively recruited at 4 academic centres in Taiwan. The effectiveness was determined by sustained virologic response at off-therapy week 12 (SVR12 ) for evaluable (EP) and per-protocol populations (PP). The safety profiles were also assessed. By EP and PP analyses, the SVR12 rate was 99.1% (107 of 108 patients; 95% confidence interval (CI): 94.9%-99.8%) and 100% (107 of 107 patients; 95% CI: 96.5%-100%). The SVR12 rates were 100% (95% CI: 89.3%-100%) and 98.7% (95% CI: 92.9%-99.8%) in patients with CKD stage 4 and 5, respectively. One patient, who declined off-therapy follow-up after permanently discontinuing GLE/PIB at on-treatment week 9 due to scheduled cardiac surgery, had nonvirologic failure. Sixteen (14.8%) patients had serious adverse events (AEs), which were judged not related to GLE/PIB. The three most common AEs were pruritus (19.4%), fatigue (15.7%) and nausea (13.9%). None had ≥3-fold upper limit of normal for total bilirubin and alanine aminotransferase levels. None of the 9 patients with hepatitis B virus (HBV) coinfection developed HBV-associated hepatitis. In conclusion, GLE/PIB for 8-12 weeks is effective and well-tolerated in HCV patients with severe RI.

9.
J Infect Dis ; 221(4): 589-597, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31574141

RESUMO

BACKGROUND: To investigate serum Mac-2-binding protein glycosylation isomer (M2BPGi) levels in predicting hepatocellular carcinoma (HCC) and mortality at virological remission (VR, HBV DNA <20 IU/mL) following antiviral therapy in chronic hepatitis B (CHB) patients with cirrhosis. METHODS: This retrospective cohort study included patients with CHB-related Child-Pugh A cirrhosis undergoing long-term antiviral therapy. Serum M2BPGi levels were quantified and multivariable Cox proportional hazards regression models were used to identify risk predictors for HCC and death. RESULTS: A total of 126 and 145 patients were included in the derivation and validation cohorts, respectively. The mean age was 56, and the mean M2BPGi level was 1.86 cut-off index (COI) in the derivation cohort. After adjustment for confounders, a higher M2BPGi level at VR significantly predicted HCC (hazard ratio [HR]: 1.58, 95% confidence interval [CI]: 1.19-2.10, P=0.002) and death (HR: 2.17, 95% CI: 1.02-4.62, P=0.044). The M2BPGi ≥3 COI significantly increased the risk of HCC and death in the derivation and validation cohorts. Serial M2BPGi levels declined significantly (P=0.0001) in non-HCC patients only, and remained significantly lower than those who developed HCC afterwards (P=0.039). CONCLUSIONS: Serum M2BPGi levels at antiviral therapy-induced VR predict HCC development and death in patients with CHB-related Child-Pugh A cirrhosis.

10.
Lancet Gastroenterol Hepatol ; 5(2): 167-228, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31852635

RESUMO

The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.

11.
J Hepatol ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31790766

RESUMO

BACKGROUND & AIMS: Data regarding the nephrotoxicity of sofosbuvir (SOF) remain controversial. We compared the evolution of estimated glomerular filtration rate (eGFR) in patients with chronic HCV infection receiving SOF-based or SOF-free direct-acting antivirals (DAAs). METHODS: A total of 481 patients with compensated liver diseases and eGFR ≥30 ml/min/1.73m2, receiving SOF-based (n = 308) or SOF-free (n = 173) DAAs for 12 weeks, were prospectively enrolled. The eGFR was assessed from baseline to off-treatment week 24 using the chronic kidney disease (CKD)-epidemiology collaboration equation. Differences in the evolution of eGFR between regimens were compared by a generalized linear mixed-effects model. Multivariate analysis was performed for factors affecting eGFR evolution. RESULTS: Patients receiving SOF-based DAAs experienced a significant on-treatment decline in eGFR (adjusted slope coefficient difference: -1.24 ml/min/1.73m2/month; 95% CI -1.35 to -1.13; p <0.001) and a significant off-treatment improvement (adjusted slope coefficient difference: 0.14 ml/min/1.73m2/month; 95% CI 0.08 to 0.21; p = 0.004) compared to patients receiving SOF-free DAAs. Multivariate analysis showed age per 1-year increase (adjusted slope coefficient difference: -0.05 ml/min/1.73m2/month; 95% CI -0.05 to -0.04; p <0.001), SOF-based DAAs (adjusted slope coefficient difference: -0.33 ml/min/1.73m2/month; 95% CI -0.49 to -0.17; p <0.001), and CKD stage (adjusted slope coefficient difference: -1.44 ml/min/1.73m2/month; 95% CI -1.58 to -1.30; p <0.001 for stage 3 vs. 1, and -3.59 ml/min/1.73m2/month; 95% CI -3.88 to -3.30; p <0.001 for stage 2 vs. 1) were independent factors affecting eGFR evolution from baseline to off-treatment week 24. CONCLUSIONS: Patients receiving SOF-based DAAs exhibited a quadratic trend, with eGFR worsening on treatment and improving off treatment. Increasing age, SOF-based DAAs, and more advanced baseline CKD stage are independently associated with a decline in eGFR in patients with HCV receiving DAAs. LAY SUMMARY: While the efficacy of sofosbuvir for the treatment of hepatitis C virus is clear, data regarding its possible nephrotoxicity are controversial. Herein, we showed that sofosbuvir worsened on-treatment kidney function but led to an off-treatment improvement. Our findings suggest that treating physicians should be alert to risk factors for kidney dysfunction before initiating direct-acting antiviral treatment for patients with hepatitis C virus infection. CLINICAL TRIAL NUMBER: NCT04047680.

12.
Int J Cancer ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31853972

RESUMO

To identify the risk factors of oral cancer, we investigated the association between chronic hepatitis C (CHC) and oral cancer, and the development of oral cancer after anti-hepatitis C virus (HCV) therapy. We conducted a nationwide, population-based cohort study from 2004 to 2012 from the Taiwan National Health Insurance Research Database. CHC patients without anti-HCV therapy were matched with those non-HCV patients by age, sex and comorbidities. Moreover, CHC patients who underwent pegylated interferon and ribavirin (PegIFN/RBV) anti-HCV therapy were matched with CHC patients without anti-HCV therapy. A total of 100,058 patients were included in the HCV cohort and non-HCV cohorts, respectively. Their mean age was 59 years and 50% of these were male. CHC infection significantly increased the cumulative incidence of lichen planus and oral cancer. After adjustment for confounders and competing mortality, CHC infection significantly increased the risk of oral cancer (hazard ratio [HR]: 1.677, 95% confidence interval [CI]: 1.392-2.020, p < 0.001). Another 23,735 CHC patients without anti-HCV therapy were matched with 23,735 CHC patients in the treatment cohort. After adjustment for confounders and competing for mortality, the risk of oral cancer was significantly reduced in CHC patients receiving anti-HCV therapy (HR: 0.652, 95% CI: 0.479-0.887, p = 0.007). To minimize the inclusion of pre-existing unidentified oral cancer, we excluded oral cancer developed within the first year of CHC or anti-HCV therapy and found these associations remained statistically significant. In conclusion, CHC significantly increases the risk of oral cancer. Moreover, PegIFN/RBV antiviral therapy significantly reduces the risk of HCV-related oral cancer.

13.
Liver Int ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710759

RESUMO

BACKGROUND & AIMS: Large-scale data regarding the real-world effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) for patients with chronic hepatitis C virus (HCV) infection were limited in East Asia. We aimed to evaluate the clinical performance of GLE/PIB in different HCV populations in Taiwan. METHODS: A total of 658 chronic HCV patients with compensated liver diseases receiving GLE/PIB for 8 (n = 549), 12 (n = 103) or 16 (n = 6) weeks were retrospectively enrolled. The effectiveness was determined by sustained virologic response at off-therapy 12 weeks (SVR12 ). Patient characteristics potentially related to SVR12 and the safety profiles were also assessed. RESULTS: By evaluable population (EP) and per-protocol (PP) analyses, the overall SVR12 rate was 98.2% (95% confidence interval (CI): 96.8%-99.0%) and 99.4% (95% CI: 98.4%-99.8%). The SVR12 rates were 98.9% (95% CI: 97.6%-99.5%), 94.2% (95% CI: 87.9%-97.3%) and 100% (95% CI: 60.1%-100%) in patients receiving 8, 12 and 16 weeks of treatment respectively. A total of 656 (99.7%) patients completed the scheduled treatment. The SVR12 rates were comparable regardless of baseline characteristics or week 4 viral decline. Twenty (3.0%) patients had serious adverse events (AEs), but none were not related to GLE/PIB. The two most common AEs were pruritus (7.8%) and fatigue (5.5%). Two (0.3%) and no patients had ≥3-fold upper limit of normal (ULN) for total bilirubin and alanine aminotransferase (ALT) levels. CONCLUSIONS: GLE/PIB for 8-16 weeks is effective and well-tolerated for patients with chronic HCV infection in Taiwan.

14.
Gastroenterology ; 157(6): 1518-1529.e3, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31470004

RESUMO

BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC). Serum levels of HB core-related antigen (HBcrAg) have been associated with active replication of HBV. We investigated whether HBcrAg levels are associated with development of HCC, especially in patients who do not require antiviral treatment. METHODS: We collected data from 2666 adults positive for hepatitis B surface antigen (HBsAg), infected with HBV genotypes B or C, and without liver cirrhosis, who had long-term follow-up at the National Taiwan University Hospital from 1985 through 2000. None of the patients received antiviral treatment during the follow-up. Baseline levels of HBV DNA, HBsAg, and HBcrAg were determined retrospectively and participants were followed for a mean of 15.95 years. The primary end point was an association between serum level of HBcrAg and HCC development. RESULTS: HCC developed in 209 patients in the cohort (incidence rate, 4.91 cases/1000 person-years). We found a positive association between baseline level of HBcrAg and HCC development; HBcrAg level was an independent risk factor in multivariable analysis. In the subgroup of hepatitis B e antigen-negative patients with HBV DNA levels from 2000 to 19,999 IU/mL (intermediate viral load [IVL]) and normal levels of alanine aminotransferase, HBcrAg levels of 10 KU/mL or more identified patients at increased risk of HCC (hazard ratio, 6.29; confidence interval, 2.27-17.48). Patients with an IVL and a high level of HBcrAg had a risk for HCC that did not differ significantly from that of patients with a high viral load (≥20,000 IU/mL). Patients with an IVL but a low level of HBcrAg had a low risk of HCC, with an annual incidence rate of 0.10% (95% confidence interval, 0.04%-0.24%). CONCLUSIONS: In a long-term follow-up study of 2666 patients with chronic HBV infection (genotypes B or C), level of HBcrAg is an independent risk factor of HCC. Moreover, HBcrAg level of 10 KU/mL identifies patients with an IVL who are at high risk for HCC.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Antígenos da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Neoplasias Hepáticas/epidemiologia , Adulto , Biomarcadores/sangue , Carcinoma Hepatocelular/virologia , DNA Circular/sangue , DNA Viral/sangue , Feminino , Seguimentos , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Incidência , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Carga Viral
16.
J Formos Med Assoc ; 118(8): 1187-1192, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279502

RESUMO

BACKGROUND: Glecaprevir/pibrentasvir (GLE/PIB) is a pangenotypic direct-acting antiviral agent for the treatment of chronic hepatitis C virus (HCV) infection. Real-world data of GLE/PIB in Asian patients other than Japanese are limited. We thus investigated the effectiveness and safety profile of GLE/PIB in Taiwanese patients with chronic hepatitis C (CHC). METHODS: CHC patients who received 8, 12, or 16 weeks of GLE/PIB between August and October of 2018 were consecutively enrolled. The treatment duration was determined according to drug label. The hepatic fibrosis was staged according to liver histology, transient elastography, fibrosis index based on 4 factors (FIB-4), or findings of ultrasonography/endoscopy. The primary endpoint was sustained virological response at week 12 off therapy (SVR12). The safety profiles were also assessed. RESULTS: A total of 110 CHC patients with 51% of males were enrolled. The median age was 70 years. A majority (82%) of patients were infected with HCV genotype 2. Forty-six (42%) and 64 (58%) patients had advanced hepatic fibrosis and compensated cirrhosis, respectively. Forty-five (41%) non-cirrhotic patients were treated for 8 weeks. The overall SVR12 rates were 100%, regardless of baseline clinical characteristics. The common adverse events (AEs) were pruritus (12%), anorexia (6%), and fatigue (5%). Nine (8%) serious AEs unrelated to GLE/PIB occurred. Three (2%) patients had Grade 3 elevation of total bilirubin level. None had premature treatment termination, hepatic decompensation, or death. CONCLUSION: Interferon-free GLE/PIB regimen is highly effective and safe for Asian chronic hepatitis C patients with advanced hepatic fibrosis or compensated cirrhosis.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/virologia , Quinoxalinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Quimioterapia Combinada , Feminino , Hepacivirus/efeitos dos fármacos , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Estudos Retrospectivos , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Taiwan
17.
Aliment Pharmacol Ther ; 50(3): 306-316, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31271463

RESUMO

BACKGROUND: Maternal anti-viral treatment prevents mother-to-infant transmission of hepatitis B virus (HBV), but the role of neonatal viremia on subsequent HBV infection is not clear. AIMS: To investigate the effect of maternal anti-viral treatment on neonatal serum HBV DNA and hepatitis B surface antigen (HBsAg) in infants born to highly viremic mothers and the roles of neonatal markers in predicting chronic HBV infection in children. METHODS: Serum HBV DNA and HBsAg were tested in children. Of the 201 pregnant mothers, 110 received tenofovir during the third trimester. Chronic infection in children was defined by HBsAg seropositivity at 6 or 12 months lasting more than 6 months. RESULTS: The maternal HBV viral loads from baseline to delivery were 8.25 ± 0.48 to 4.29 ± 0.98 log10  IU/mL; and 8.29 ± 0.49 to 8.12 ± 0.68 log10  IU/mL in the tenofovir and control group respectively. Of the 208 children, those in the tenofovir group had a lower rate of neonatal HBV DNA seropositivity at birth (5.22% vs 30.11%, P < 0.0001) and HBsAg seropositivity at 6 months (1.74% vs 11.83%, P = 0.003) and 12 months (1.74% vs 10.75%, P = 0.007). In a first multivariate analysis, maternal HBV DNA level at delivery (odds ratio = 1.70, P = 0.0172) and neonatal HBsAg positivity (odds ratio = 19.37, P < 0.0001) were significantly associated with children's chronic HBV infection. In a second model, neonatal HBV DNA positivity was a strong independent influence variable (odds ratio = 61.89, P = 0.0002). CONCLUSIONS: Maternal tenofovir therapy decreased maternal viral load and neonatal viremia. Positive neonatal HBV DNA was highly correlated with chronic HBV infection in children. Clinical Trial Identifier: NCT01312012.

18.
J Gastroenterol Hepatol ; 34(12): 2179-2186, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31062879

RESUMO

BACKGROUND AND AIM: The NIACE score provides prognostic values for hepatocellular carcinoma (HCC) in European studies. We aim to evaluate the prognostic value of the NIACE score in Asian patients. METHODS: Patients with HCC were retrospectively enrolled from a tertiary medical center in Taiwan during 2009-2014, and their clinical information were collected. The NIACE score was calculated according to the Nodular numbers, tumor Infiltration, Alpha-fetoprotein level, Child-Pugh score, and Eastern Cooperative Oncology Group score. The prognostic values of NIACE score for overall survival according to individual treatment and the Barcelona clinic liver cancer (BCLC) staging were analyzed. RESULTS: A total of 468 patients were included with a median follow-up of 30 months. A greater NIACE score correlated with lower median survival and higher BCLC staging. Regardless of treatment modalities, NIACE scores (0, 1-1.5, 2.5-3, and 4-7) significantly predicted survival between groups (log-rank P < 0.001). Specifically, NIACE score (0, 1-1.5, 2.5-3, and 4-7) significantly predicted survival in patients receiving transarterial chemoembolization (log-rank P < 0.001). NIACE score 1, 2.5, and 4 further distinguished overall survival in BCLC A, B, and C patients, respectively (all log-rank P < 0.01). After adjustment of the confounders and the BCLC staging, NIACE score of 2.5-3 and 4-7 (vs 0) had a significantly increased risk of mortality with a hazard ratio of 4.04 (95% confidence interval: 2.14-7.64, P < 0.001) and 7.45 (95% confidence interval: 3.22-17.23, P < 0.001), respectively. CONCLUSIONS: The NIACE score helps refine differential prognosis among BCLC A, B, and C subgroups of Asian patients with HCC, especially in those receiving transarterial chemoembolization.

19.
J Gastroenterol Hepatol ; 34(11): 1977-1983, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30931537

RESUMO

BACKGROUND AND AIM: Data regarding the efficacy and safety of paritaprevir/ritonavir, ombitasvir plus dasabuvir (PrOD) for East Asian non-cirrhotic hepatitis C virus genotype 1b (HCV GT1b) patients receiving hemodialysis were limited. METHODS: Forty-six HCV GT1b non-cirrhotic patients receiving hemodialysis who received PrOD for 12 weeks were prospectively enrolled in seven academic centers in Taiwan. The primary efficacy endpoint was sustained virologic response 12 weeks off-therapy (SVR12 ). Patients' baseline characteristics, early virokinetics, and HCV resistance-associated substitutions (RASs) potentially related to SVR12 were analyzed. The safety profiles were also assessed. RESULTS: The SVR12 rate was 100% (46 of 46 patients). Patients' baseline characteristics, on-treatment viral decline, and baseline HCV resistance-associated substitutions did not affect SVR12 . All patients tolerated treatment well. One patient with folliculitis temporarily discontinued treatment, and another two patients had serious adverse events (SAEs), which were considered not related to PrOD treatment. The common adverse events were pruritus (19.6%), fatigue (15.2%), and upper respiratory tract infection (6.5%). Twelve (19.6%) and one (2.2%) patients had hemoglobin levels < 10 and 8.5 g/dL, respectively, which were related to renal impairment. Five (10.9%) patients had on-treatment total bilirubin level of 1.5-3.0 mg/dL, but none developed hepatic decompensation. The bilirubin levels peaked at week 1 of treatment and then declined with continuous treatment. CONCLUSION: Treatment with PrOD for 12 weeks is efficacious and well-tolerated for East Asian non-cirrhotic HCV GT1b patients receiving hemodialysis.

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Lancet Infect Dis ; 19(5): 466-467, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31034387
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