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1.
J Formos Med Assoc ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34625346

RESUMO

BACKGROUND/PURPOSE: Switching to a tenofovir alafenamide (TAF)-containing regimen has been reported to be associated with body weight gain in human immunodeficiency virus-infected subjects. We aimed to investigate the body weight change and virological, hepatic, and renal outcomes of TAF switching among chronic hepatitis B (CHB) patients. METHODS: This retrospective study included 121 CHB patients who were switched to TAF after >12 months of treatment with another nucleot(s)ide analog (NUC). All patients were monitored for 12 months. RESULTS: The cohort was mostly Asian (96.7%) with a mean age of 55 years, 72% male, 14% cirrhosis, 21% HBeAg positive, and 75% with prior use of tenofovir disoproxil fumarate. At 12 months after TAF switching, their body weight significantly increased from 66.4 ± 11.8 to 67.8 ± 12.3 kg (p < 0.001), and 21.1% of the subjects had a ≥5% weight gain. Patients without diabetes or hypertension were more likely to have a body weight gain. Meanwhile, the complete viral suppression rate increased significantly from 89.3% to 96.2% (p = 0.016). The rate of alanine aminotransferase normalization also increased significantly from 71.1% to 87.6% (p < 0.001) by local criteria and from 58.7% to 70.2% (p = 0.029) by AASLD criteria. The mean eGFR (mL/min/1.73 m2) did not change (88.2 ± 18.8 vs. 87.2 ± 17.5, p = 0.28). However, for the subgroup with GFR <90 at TAF switching, there was a significant improvement in eGFR (72.9 ± 12.0 vs. 75.7 ± 14.2, p = 0.027). CONCLUSION: In real-world NUC-experienced CHB patients, unexpected body weight gain was observed after TAF switching. The mechanism needs to be investigated in the future.

2.
Pathogens ; 10(10)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34684176

RESUMO

Hepatitis Delta Virus (HDV) is an RNA virus that requires the presence of hepatitis B surface antigen (HBsAg) to propagate into hepatocytes, with Genotype I being more prevalent globally. However, the prevalence of HDV genotypes in Taiwan is unknown. Accordingly, a cohort including 24 chronic HBV patients who received nucleos(t)ides (NUCs) between January 2002 and July 2018 was used to determine HDV genotypes and genotype specific serological association in chronic HBV carriers. HDV-positive genotypes in 18/24 (75%) males and 6/24 (25%) females were identified among chronic HBV patients. Viremia was lower in HDV-IV patients than in patients affected with other HDV genotypes (1.34 log10 copies/mL vs. 3.30 log10 copies/mL; p = 0.009). A logistics regression analysis revealed that HDV-IV was inversely proportional to HDV RNA (odds ratio [OR]/95% confidence intervals [CI]: 0.370/0.164-0.830; p = 0.017). The serologic association study indicated lower levels of creatinine (p = 0.047) and HDV-RNA (p = 0.009) in the HDV-IV group than the non-HDV-IV group but did not indicate any significant differences in the AST, ALT, bilirubin levels or other laboratory test factors. The three genotypes evident in Taiwan were HDV-I (4/24, 16.7%), HDV-II (6/24, 25.0%), and HDV-IV (14/24, 58.3%), and HDV-IV is the predominant HDV genotype in Taiwan. These results anticipate a clear understanding of HDV genotype serological association in chronic HBV carriers.

3.
Biomedicines ; 9(10)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34680563

RESUMO

BACKGROUND: A large amount of epidemiological evidence indicates that persistent HCV infection is the main risk factor for HCC. We aimed to study the effects of persistent HCV infection on the interaction of the virus and host cell to identify cancer gene profiles. METHODS: Next-generation sequencing (NGS) was used to identify differentially expressed genes between uninfected Huh7.5.1 control cells, short-term HCV (S-HCV), early long-term HCV (eL-HCV), and long-term HCV (L-HCV) infections, which were analyzed using different dynamic bioinformatics and analytic tools. mRNA expression was validated and quantified using q-PCR. One hundred ninety-six serum samples of HCV patients with IFN/RBV treatment were used to study chemokine levels. RESULTS: S-HCV activates an inflammatory response and drives cell death and apoptosis through cell cycle arrest via MAPK signaling. L-HCV promotes cell growth and alters cell adhesion and chemokine signaling via CXCL8-mediated-SRC regulation. A total of 196 serum samples from the HCV and HCV-HCC cohorts demonstrated significantly upregulated pro-inflammatory CXCL8 in non-SVR (persistent HCV infection) patients in the HCV-HCC group. CONCLUSIONS: Persistent infection with HCV induced pro-inflammatory CXCL8 and the oncogene SRC, thereby triggering and promoting hepatocarcinogenesis. CXCL8 may be a potential biomarker for monitoring HCV-related HCC progression.

4.
Am J Gastroenterol ; 116(9): 1924-1928, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465694

RESUMO

INTRODUCTION: We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. METHODS: Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). RESULTS: Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. DISCUSSION: Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C/tratamento farmacológico , Falência Renal Crônica/terapia , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Esquema de Medicação , Feminino , Fluorenos/administração & dosagem , Hepatite C/complicações , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Sofosbuvir/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento
5.
Hepatol Int ; 15(5): 1109-1121, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34365587

RESUMO

BACKGROUND AND AIM: The long-term outcome of hepatitis B virus (HBV) infection among patients dually infected with HBV and hepatitis C virus (HCV) remains unclear. We aimed to investigate the long-term liver outcomes of HBV/HCV-coinfected patients after antiviral therapy. METHODS: A total of 11,359 chronically HCV-infected patients with interferon-based therapy were registered in a nationwide Taiwanese Chronic Hepatitis C Cohort. A propensity score matched (PSM) cohort of HCV mono-infected (n = 7020) and HBV/HCV (n = 702) co-infected patients by age, sex, and fibrosis was recruited for outcome analysis. The primary outcome was liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation during a mean follow-up period of 4.44 years. RESULTS: Among HBV/HCV co-infected patients, patients without HCV-SVR had a significantly higher 10-year cumulative incidence of major liver-related complications than those with HCV-SVR. However, among patients with HCV-SVR in the PSM cohort, the risk of major liver-related complications, both HCC and liver decompensation, did not differ between HBV/HCV co-infected and HCV mono-infected patients. Similar results were observed among those without HCV-SVR. A substantial lower risk of major liver-related complications was found in HBV/HCV co-infected patients with HCV SVR and subsequent anti-HBV nucleot(s)ide analogues treatment. Overall, factors associated with major liver-related complications included age ≥ 65 year-old, BMI ≥ 27 kg/m2, FIB-4 ≥ 3.25, eGFR < 60 ml/min/1.73 m2, and non-HCV SVR, but not HBV co-infection. CONCLUSION: Interferon-based therapy reduced the long-term risk of major liver-related complications among HBV/HCV co-infected patients, as among HCV mono-infected patients. Nevertheless, post-HCV-SVR surveillance for major liver-related complications is mandatory among those high-risk groups.

6.
Hepatol Int ; 15(5): 1136-1147, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34386935

RESUMO

BACKGROUND: The efficacy and safety of insulin sensitizer in Asians with non-alcoholic steatohepatitis (NASH) remain elusive. AIMS: The double-blind, randomized, placebo-controlled trial was conducted aiming to investigate the efficacy and safety of pioglitazone in NASH patients. METHODS: A total of 90 NASH patients (66 males, age = 44.1 ± 12.7 years) were prospectively randomized into oral pioglitazone 30 mg/day (Arm A) or placebo (Arm B) for 24 weeks. The primary endpoint was the efficacy of pioglitazone in reducing inflammation and liver fat at end-of-treatment (EOT). NASH resolution/improvement without fibrosis worsening was also evaluated. RESULTS: At EOT, there was a significantly decline of alanine aminotransferase (86.9 ± 34.3 to 45.7 ± 35.8 IU/L, p = 0.003) level in Arm A patients. In intention-to-treat analysis among 66 patients who completed paired biopsies, The NAFLD activity score (NAS) of 30 Arm A patients significantly decreased from 4.27 ± 1.14 at baseline to 2.53 ± 1.63 at EOT (p < 0.0001), whereas there was no significant change in patients of Arm B (3.94 ± 1.41 vs 3.94 ± 1.51, p = 1.0). NASH improvement without worsening of fibrosis was achieved in 46.7% (14/30) patients in Arm A, compared to 11.1% (4/36) patients in Arm B (p = 0.002). Liver fat content reduced (20.2 ± 9.0 to 14.3 ± 6.9%, p < 0.0001) on MRI-PDFF in Arm A compared to their counterparts. No significant difference of adverse events occurred between groups. CONCLUSIONS: A 24-week pioglitazone treatment was well-tolerated and effective in improving liver histology and reducing liver steatosis in Asian NASH patients. (ClinicalTrials.gov number: NCT01068444).

8.
Artigo em Inglês | MEDLINE | ID: mdl-34333150

RESUMO

BACKGROUND & AIMS: Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. METHODS: The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non-sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). RESULTS: The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P < .001) and substantially recovered at EOF (88.8 mL/min/1.73 m2) but did not return to pretreatment levels (P < .001). Notably, a significant decrease in eGFR was observed only in patients with baseline eGFR ≥90 mL/min/1.73 m2 (from 112.9 to 106.4 mL/min/1.73 m2; P < .001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m2 (from 70.0 to 71.5 mL/min/1.73 m2; P < .001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR >90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 mL/min/1.73 m2; 95% confidence interval, -2.24 to -1.72; P < .001). The use of sofosbuvir was not an independent factor associated with eGFR change. CONCLUSIONS: Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.

9.
JGH Open ; 5(8): 929-940, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34386602

RESUMO

Background and Aim: Ropeginterferon alfa-2b (P1101) is a novel long-acting mono-PEGylated recombinant proline interferon (IFN) conjugated to a 40 kDa branched polyethylene glycol (PEG) chain at its N-terminus, allowing every-two-week injection. It received European Medicines Agency and Taiwan marketing authorization for the treatment of polycythemia vera in 2019 and 2020, respectively. This phase 2 study aimed to evaluate the pharmacokinetics, safety, and preliminary efficacy of ropeginterferon alfa-2b as compared with PEG-IFN-α2a in patients with chronic hepatitis C virus genotype 1 infection. Methods: One hundred six treatment naive patients were enrolled in this phase 2 study and randomized to four treatment groups: subcutaneous weekly PEG-IFN-α2a 180 µg (group 1), weekly ropeginterferon alfa-2b 180 µg (group 2), weekly ropeginterferon alfa-2b 270 µg (group 3), or biweekly ropeginterferon alfa-2b 450 µg (group 4) plus ribavirin for 48 weeks. Results: After multiple weekly administration, serum exposure (AUC0-τ) in ropeginterferon alfa-2b 180 µg was approximately 41% greater and the accumulation ratio of 2-fold greater than PEG-IFN-α2a 180 µg. The incidences of flu-like symptoms were 66.7% (18/27), 53.3% (16/30), 55.0% (11/20), and 48.3% (14/29), anxiety were 14.8% (4/27), 6.7% (2/30), 0%, and 0%, and depression were 25.9% (7/27), 13.3% (4/30), 0%, and 3.4% (1/29), for groups 1-4, respectively. Two grade 2 of 3 depression were noted in PEG-IFN-α2a arm, but none in ropeginterferon arms. The SVR24 rates were 77.8% (21/27), 66.7% (20/30), 80% (16/20), and 69% (20/29), respectively. Conclusions: Ropeginterferon alfa-2b showed longer effective half-life and superior safety profile than PEG-IFN-α2a. Biweekly injection of ropeginterferon alfa-2b will be studied in larger viral hepatitis patient population.

10.
Cancers (Basel) ; 13(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298669

RESUMO

The clinical presentation and survival of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication as compared to HCC in viremic patients are not well characterized. We aimed to investigate the characteristics and survival between HCV patients with and without viremia at HCC diagnosis.: We retrospectively analyzed overall survival outcomes in 1389 HCV-related HCC patients, including 301 with HCC developed after HCV eradication (post-SVR HCC) and 1088 with HCV viremia at HCC diagnosis (viremic HCC). We also evaluated overall survival in the two groups using propensity score-matching methods.: At HCC diagnosis, post-SVR HCC patients were older, less obese, less likely cirrhotic, with better liver function, lower alfa-fetoprotein levels, earlier BCLC stages, and higher rate of treatment with surgery. Overall, post-SVR HCC patients had higher median survival than viremic patients (153.3 vs. 55.6 months, p < 0.01), but post-SVR HCC was not independently associated with survival on multivariate analysis (adjusted HR: 1.05, 95% CI: 0.76-1.47). However, on sub-analysis, viremic HCC patients who subsequently received anti-viral treatment and achieved SVR had higher median survival than post-SVR HCC patients (p < 0.01). Viremic HCC with subsequent SVR was also significantly associated with lower mortality as compared to post-SVR HCC (adjusted HR: 0.18, 95% CI: 0.11-0.29). In addition, we observed similar findings in our analysis of the propensity score-matched cohorts.: The advantages in clinical and tumor characters at HCC diagnosis determined the better overall survival of post-SVR HCC patients; however, HCV eradication after HCC development was also associated with improved survival.

11.
PLoS One ; 16(7): e0254028, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34197557

RESUMO

BACKGROUND/AIMS: Hepatitis C Virus (HCV) infection is diagnosed by the presence of antibody to HCV and/or HCV RNA. This study aimed to evaluate the accuracy of anti-HCV titer (S/CO ratio) in predicting HCV viremia in patients with or without hepatitis B virus (HBV) dual infection. METHODS: Anti-HCV seropositive patients who were treatment-naïve consecutively enrolled. Anti-HCV antibodies were detected using a commercially chemiluminescent microparticle immunoassay. HCV RNA was detected by real-time PCR method. RESULTS: A total of 1321 including1196 mono-infected and 125 HBV dually infected patients were analyzed. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001). Of the entire cohort, the anti-HCV cut-off value of 10 provided the best accuracy, 96.8%, with the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96.3%, 98.9%, 99.7% and 87.3% respectively. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001) and 9.36 (AUROC 1.00, P<0.0001) in patients with HCV mono-infection and HBV dual-infection respectively. Among the HBV dually infected patients, the accuracy of anti-HCV titer in predicting HCV viremia reached up to 100% with the cut-off value of 9. All the patients were HCV-viremic if their anti-HCV titer was greater than 9 (PPV 100%). On the other hand, all the patients were HCV non-viremic if their anti-HCV titer was less than 9 (NPV 100%). CONCLUSIONS: Anti-HCV titer strongly predicted HCV viremia. This excellent performance could be generalized to either HCV mono-infected or HBV dually infected patients.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34318943

RESUMO

BACKGROUND AND AIM: Hepatitis B virus (HBV) surface antigen (HBsAg) seroreversion usually occurs during immunosuppressive therapy. The risk and factors of HBsAg seroreversion from resolved HBV infection in the general population remained unclear. METHODS: This retrospective study enrolled subjects with resolved HBV infection and who had received at least two times of screening in a longitudinal community screening program. HBsAg, hepatitis B surface antibody (anti-HBs), and hepatitis C virus antibody (anti-HCV) were tested every time in all subjects. The primary endpoint was HBsAg seroreversion. RESULTS: Of the 7630 subjects enrolled, 5158 (67.6%) subjects had positive anti-HBs at baseline. HBsAg seroreversion occurred in 84 subjects during 42 815-person-year follow-up with an annual incidence of 0.2% and a 10-year cumulative risk of 1.9%. Anti-HBV treatment-experienced subjects had a significantly higher risk of HBsAg seroreversion than anti-HBV treatment-naive subjects (83/310 [26.8%] vs 1/7320 [0.01%], P < 0.001). Lower rates of positive anti-HBs and anti-HCV were observed in anti-HBV treatment-experienced subjects who developed HBsAg seroreversion. Both positive anti-HBs (hazard ratio/95% confidence interval: 0.56/0.348-0.903, P = 0.017) and positive anti-HCV (hazard ratio/95% confidence interval: 0.08/0.030-0.234, P < 0.001) were independent factors of HBsAg seroreversion in anti-HBV treatment-experienced subjects. Less than 5% of the HBsAg seroreverters had clinical hepatitis flare at HBsAg seroreversion. The HBsAg titer was low, and only transient reappeared in most of the HBsAg seroreverters. CONCLUSIONS: Subjects with resolved HBV infection were at a minimal risk of HBsAg seroreversion, unless with prior anti-HBV treatment experience. Fortunately, even with a reappearance of HBsAg, it was transient and clinically non-relevant.

13.
J Chin Med Assoc ; 84(8): 757-765, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074934

RESUMO

BACKGROUND: The association between hepatitis C virus (HCV) infection and chronic kidney disease (CKD) still remains controversial. We aimed to investigate whether HCV really affects renal function, and to analyze the association between clinical effects of CHC and decreased kidney function (assessed by glomerular filtration rate (eGFR) level). METHODS: An estimated 3360 patients with HCV infection and 3360 age- and sex-matched community-based control individuals without HCV were enrolled (1:1, case and control ratio) in this study between 2004 and 2016. We used the modification of diet in renal diseases to calculate eGFR. Demographic and laboratory parameters were assessed, and appropriate statistical methods were performed for the analysis. RESULTS: Multivariate logistic regression analysis revealed that serum alanine aminotransferase level (odds ratio [OR] 0.998; 95% confidence interval [CI] 0.997-0.999; P = 0.001), platelet count (OR 0.997; 95% CI 0.995-0.999; p = 0.002), and hypertension (OR 1.31; 95% CI 1.03-1.66; P = 0.027) were significantly associated with HCV infection and serum triglyceride levels (OR 1.001; 95% CI 1.00-1.002; p = 0.005), platelet count (OR 0.996; 95% CI 0.995-0.997; p < 0.001), body mass index (BMI) >25 (OR 1.43; 95% CI 1.23-1.67; p < 0.001), hypertension (OR 1.69; 95% CI 1.42-1.99; p < 0.001), hyperlipidemia (OR 1.32; 95% CI 1.02-1.71; p = 0.035), and diabetes (OR 1.33; 95% CI 1.03-1.71; p = 0.032) were significantly associated with a low eGFR (<90 mL/min/m3) in control subjects. The BMI >25 kg/m2, hypertension, and diabetes were found to be associated with low eGFR interaction with the HCV infection, via a multivariate analysis. CONCLUSION: Our study found that the patients with HCV infection are associated with a low eGFR compared with non-HCV-infected patients. This association is consistent in obese, diabetic, and hypertensive patients.

14.
Kaohsiung J Med Sci ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34166564

RESUMO

Viral hepatitis is a devastating disease with the risk for cirrhosis and carcinogenicity. Regulatory T cells (Tregs) play important roles in the disease course of viral hepatitis via maintaining the balance between overt-immune responses and viral replications. We hypothesized that genetic polymorphisms of Treg-related genes, such as interleukin-2, transforming growth factor-ß 1 (TGF-ß1), forkhead box P3 (FOXP3), and adenylyl cyclase type 9 modulate the hosts' immune regulation under circumstances of viral hepatitis. We examined the effect of five single nucleotide polymorphisms (SNPs) of Treg-related genes on the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), alanine aminotransferase, and non-invasive hepatic fibrosis marker (Fibrosis-4 index) in a total of 138 participants with viral hepatitis. The rs1800469 (a TGF-ß1 SNP) GG genotype is associated with higher serum CRP levels, and the rs3761547 (a FOXP3 SNP) C allele in the females is associated with higher ESR levels. Besides, female participants carrying the rs3761547 C allele had a significantly higher Fibrosis-4 (FIB-4) index than the females carrying the TT genotype, while the rs3761547 C allele had the opposite effect in males. With linear-regression moderation analysis, we found that sex moderated the impact of the FOXP3 SNP on the levels of FIB-4, whereas the FOXP3 SNP caused the opposite effect between males and females on the severity of hepatic fibrosis. These results provide evidence for the participation of TGF-ß1 and FOXP3 in the inflammatory responses associated with viral hepatitis, where FOXP3 function may be moderated by sex.

15.
J Gastroenterol Hepatol ; 36(10): 2884-2892, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33963615

RESUMO

BACKGROUND AND AIM: It is currently unknown how hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PR) therapy affects the incidence of new-onset liver cirrhosis (LC) in patients without cirrhosis and the incidence of decompensated liver disease (DLD) or hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS: Taiwanese chronic hepatitis C cohort (T-COACH) is a nationwide HCV registry cohort from 23 hospitals in Taiwan recruited between 2003 and 2015. This study enrolled 10 693 patients with chronic hepatitis C (CHC), linked to the Taiwan National Health Insurance Research Database, receiving PR therapy for at least 4 weeks for new-onset LC and liver-related complications (DLD or HCC). RESULTS: Of the 10 693 patients, 1372 (12.8%) patients had LC, and the mean age was 54.0 ± 11.4 years. The mean follow-up duration was 4.38 ± 2.79 years, with overall 46 798 person-years. The 10-year cumulative incidence rates of new-onset LC were 5.0% (95% confidence interval [CI]: 3.2-7.7) in patients without cirrhosis with a sustained virologic response (SVR) and 21.9% (95% CI: 13.4-32.4) in those without SVR (hazard ratio [HR]: 0.22, P < 0.001). The 10-year cumulative incidence rates of liver-related complications were 21.4% (95% CI: 11.1-37.2) in patients with cirrhosis with SVR and 47.0% (95% CI: 11.1-86.0) in those without SVR after adjustment for age, sex, and competing mortality (HR: 0.52, P < 0.001). CONCLUSIONS: Hepatitis C virus eradication with PR therapy decreased the incidence of new-onset LC in noncirrhotic patients and the incidence of liver-related complications in cirrhotic patients with CHC.

16.
Hepatol Int ; 15(4): 946-956, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34008091

RESUMO

BACKGROUND: Patients with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma (HCC) can be markedly heterogeneous with varying prognosis. This study aims to establish a new subclassification system for BCLC-C HCC to better predict overall survival (OS) and to tailor therapy. METHODS: We retrospectively studied 1856 BCLC-C HCC patients between 2006 and 2017 from E-Da Hospital, Taiwan (n = 622, training cohort), Kaohsiung Medical University Hospital, Taiwan (n = 774, Taiwan validation cohort), and Stanford University Medical Center and Mayo Clinic (United States), Hanyang University Hospital (South Korea), and Ogaki Municipal Hospital (Japan) to make up the international validation cohort (n = 460). RESULTS: In the training cohort, significant factors associated with OS were largest tumor size ≥ 10 cm, extrahepatic spread, macrovascular invasion, and Child-Pugh class, which provided the basis, together with aged ≥ 75 years, for the substaging, through C0 to C4, of BCLC-C HCC patients. The median OS for substages C0, C1, C2, C3, and C4 were 43.8 months (95% confidence interval [CI] 32.2-53.7), 20.6 months (CI 14.1-25.9), 11.5 months (CI 8.02-14.1), 5.7 months (CI 4.02-5.98), and 3.2 months (CI 2.41-3.59), respectively, (p < 0.05). OS remained distinct among the proposed substages in the Taiwan validation cohort as well as the international validation cohort. The distinction between the substages persisted in subgroup analysis by substage combined with treatment modality. In substage C0-C3, patients receiving HCC curative therapy had a significantly better median OS than those receiving sorafenib or palliative therapy. CONCLUSION: Our new substaging system provides more precise prognosis to better tailor therapy for BCLC-C HCC patients.

17.
J Infect Dis ; 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33999179

RESUMO

BACKGROUND: Long-term incidences and baseline determinants of functional cure (HBsAg seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood. METHODS: This is an international multicenter cohort study of treatment-naïve chronic hepatitis B (CHB) patients who initiated on ETV or TDF without baseline malignancy. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression. RESULTS: The analysis included 4,769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26,614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% CI, 1.54 -- 2.88%) and an annual rate of 0.22% (95% CI, 0.17--0.28%). Baseline predictors included low-level viremia with HBV DNA <2,000 IU/mL (adjusted sub-distribution HR [aSHR], 3.14; 95% CI, 1.80--5.49), elevated serum alanine aminotransferase (ALT) >200 U/L (aSHR, 3.68; 95% CI, 2.07--6.53), serum bilirubin (aSHR, 1.11 per mg/dL; 95% CI, 1.06--1.17), and fatty liver (aSHR, 1.84; 95% CI, 1.03--3.29). CONCLUSION: HBsAg seroclearance rarely occurs in CHB patients treated with ETV or TDF and is associated with low-level viremia, ALT flare, bilirubin level, and fatty liver.

18.
Sci Rep ; 11(1): 8184, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854160

RESUMO

Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11-19.46, P < 0.001), followed by HDV RNA positivity (HR/ CI 5.73/1.35-24.29, P = 0.02), age > 50 years old (HR/CI 3.64/2.03-6.54, P < 0.001), male gender (HR/CI 2.69/1.29-5.60, P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03-1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04-19.09, P = 0.04) and BMI (HR/CI 1.11/1.03-1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.

19.
Sci Rep ; 11(1): 8554, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879825

RESUMO

The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10-0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13-0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04-40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.

20.
J Gastroenterol Hepatol ; 36(8): 2261-2269, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33651428

RESUMO

BACKGROUND AND AIM: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS: A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS: Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities. CONCLUSIONS: Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did.

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