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2.
Ann Lab Med ; 42(2): 249-257, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635616

RESUMO

BACKGROUND: Non-invasive clinical algorithms for the detection of liver fibrosis (LF) can reduce the need for liver biopsy (LB). We explored the implementation of two serum biomarkers, enhanced liver fibrosis (ELF) and Mac-2 binding protein glycosylation isomer (M2BPGi), in clinical algorithms for LF in chronic hepatitis B (CHB) patients. METHODS: Two clinical algorithms were applied to 152 CHB patients: (1) transient elastography (TE) followed by biomarkers (TE/ELF and TE/M2GPGi); (2) biomarker test followed by TE (ELF/TE and M2BPGi/TE). Using the cut-off value or index for the detection of advanced LF (TE≥F3; 9.8 in ELF and 3.0 in M2BPGi), LB was expected to be performed in cases with discordant TE and biomarker results. RESULTS: In both algorithms, the expected number of LBs was lower when using M2BPGi than when using ELF (TE/ELF or ELF/TE, 13.2% [N=20]; TE/M2BPGi or M2BPGi/TE, 9.9% [N=15]), although there was no statistical difference (P=0.398). In the TE low-risk group (TE≤F2), the discordance rate was significantly lower in the TE/M2BPGi approach than in the TE/ELF approach (1.5% [2/136] vs. 11.0% [15/136], P=0.002). In the biomarker low-risk group, there was no significant difference between the ELF/TE and M2BPGi/TE approaches (3.9% [5/126] vs. 8.8% [13/147], P=0.118). CONCLUSIONS: Both ELF and M2BPGi can be implemented in non-invasive clinical algorithms for assessing LF in CHB patients. Given the lowest possibility of losing advanced LF cases in the low-risk group when using the TE/M2BPGi approach, this combination seems useful in clinical practice.


Assuntos
Hepatite B Crônica , Algoritmos , Biópsia , Glicosilação , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Humanos , Cirrose Hepática/diagnóstico
3.
Korean J Intern Med ; 36(2): 292-304, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32241083

RESUMO

BACKGROUND/AIMS: Chronic hepatitis C (CHC) treatment has dramatically improved since direct-acting antiviral (DAA) therapy was introduced. However, the use of DAA therapy in CHC patients with hepatocellular carcinoma (HCC) remains controversial. We investigated the DAA treatment response in CHC patients with HCC. METHODS: We retrospectively analyzed CHC patients treated with DAA from 2016 to 2018. Patients were divided into two groups based on their HCC-history before DAA therapy. Baseline characteristics, sustained virologic response at 12 weeks (SVR 12), and HCC recurrence after DAA therapy were evaluated. We also used propensity score matching (PSM) in a 2:1 ratio to reduce confounding variables. RESULTS: A total of 192 patients were enrolled; 78.1% were treatment-naïve, and 34.9% had liver cirrhosis (LC). Among these patients, 168 did not have HCC, and 24 had HCC. The HCC group was older (57.0 years vs. 72.0 years, p < 0.001), had a higher incidence of LC (26.2% vs. 95.8%, p < 0.001), fibrosis-4 index (2.6 vs. 9.2, p < 0.001), liver stiffness measurement (7.0 kPa vs. 17.4 kPa, p = 0.012), and α-fetoprotein (4.4 ng/mL vs. 8.2 ng/mL, p ≤ 0.001). The SVR 12 rate was 97.0% in the non- HCC group and 91.7% in the HCC group (p = 0.213). HCC recurrence was observed in 14 patients (58.3%) in the HCC group. CONCLUSION: DAA treatment efficacy in CHC patients with or those without HCC were not significantly different, and HCC recurrence was relatively common.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Retrospectivos
4.
J Liver Cancer ; 21(2): 155-162, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37383082

RESUMO

Background/Aims: Because hepatitis B virus (HBV) replication has been known to play an important role in cancer recurrence after curative treatment of HBV-related hepatocellular carcinoma (HCC), we examined whether treatment based on nucleos(t)ide analogues (NAs) might decrease the recurrence rate and improve patient survival. Methods: The retrospective cohort study enrolled 73 patients with chronic hepatitis B who were treated with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) with curative intent for HCC. Among those, 30 and 43 patients were treated with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), respectively. Results: Of the 73 patients, 51 experienced HCC recurrence, and 14 patients were dead during a follow-up of 73±34 months. Multivariate analyses showed that tumor size (hazard ratio [HR], 1.590; 95% confidence-interval [CI], 1.106-2.285; P=0.012) and Child-Pugh class B (vs. class A/non cirrhosis; HR, 5.794; 95% CI, 2.311-14.523; P=0.001) was significantly associated with HCC recurrence, and Child-Pugh class B (HR, 7.357; 95% CI, 2.100-25.777; P=0.002) was an independent unfavorable prognostic factor for survival. During NAs therapy, TDF was superior to ETV for complete viral response at 1 year after the date of combination of TACE and RFA (P=0.016). However, the risks of HCC recurrence and survival were not significantly different between those treated with TDF versus ETV. Conclusions: TDF was superior to ETV for achieving complete viral response. However, the recurrence and mortality after TACE and RFA for HBV-related HCC were not significantly different between patients treated with TDF versus ETV.

5.
Gut ; 69(12): 2214-2222, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32209606

RESUMO

OBJECTIVE: Direct comparison of the clinical outcomes between nucleos(t)ide analogue (NA) discontinuation versus NA continuation has not been performed in patients with chronic hepatitis B who achieved HBsAg-seroclearance. Whether NA discontinuation was as safe as NA continuation after NA-induced surface antigen of HBV (HBsAg) seroclearance was investigated in the present study. DESIGNS: This multicentre study included 276 patients from 16 hospitals in Korea who achieved NA-induced HBsAg seroclearance: 131 (47.5%) discontinued NA treatment within 6 months after HBsAg seroclearance (NA discontinuation group) and 145 (52.5%) continued NA treatment (NA continuation group). Primary endpoint was HBsAg reversion and secondary endpoints included serum HBV DNA redetection and development of hepatocellular carcinoma (HCC). RESULTS: During follow-up (median=26.9 months, IQR=12.2-49.2 months), 10 patients (3.6%) experienced HBsAg reversion, 6 (2.2%) showed HBV DNA redetection and 8 (2.9%) developed HCC. Compared with NA continuation, NA discontinuation was not associated with HBsAg reversion in both univariable (HR=0.45, 95% CI=0.12 to 1.76, log-rank p=0.24) and multivariable analyses (adjusted HR=0.65, 95% CI=0.16 to 2.59, p=0.54). The cumulative probabilities of HBsAg reversion at 1, 3 and 5 years were 0.8%, 2.3% and 5.0% in the NA discontinuation group, and 1.5%, 6.3% and 8.4% in the NA continuation group, respectively. NA discontinuation was not associated with higher risk of either HBV redetection (HR=0.83, 95% CI=0.16 to 4.16, log-rank p=0.82) or HCC development (HR=0.53, 95% CI=0.12 to 2.23, log-rank p=0.38). CONCLUSION: The discontinuation of NA was not associated with a higher risk of either HBsAg reversion, serum HBV DNA redetection or HCC development compared with NA continuation among patients who achieved HBsAg seroclearance with NA.


Assuntos
Antivirais/administração & dosagem , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Resposta Viral Sustentada , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Feminino , Seguimentos , Guanina/administração & dosagem , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Humanos , Lamivudina/administração & dosagem , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Tenofovir/administração & dosagem
6.
Korean J Gastroenterol ; 75(3): 147-156, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32209803

RESUMO

Background/Aims: A switch to systemic therapy, such as sorafenib, should be considered for hepatocellular carcinoma (HCC) patients refractory to transarterial chemoembolization (TACE). On the other hand, treatment changes are difficult if the liver function worsens to Child-Pugh B or C. Therefore, predicting the risk factors for non-responsiveness to TACE and deteriorating liver function may be helpful. Methods: Newly diagnosed Child-Pugh A HCC patients who underwent TACE from January 2012 to June 2018 were included. After 1 year, this study evaluated whether there was a treatment response to TACE and whether the Child-Pugh class had worsened. Results: Among 121 patients, 65 were refractory and 56 responded to TACE. In multivariable logistic regression analysis, the tumor size, tumor number, and albumin at the time of the diagnosis of HCC were significant prognostic factors for the treatment response to TACE. Among 65 patients who presented TACE-refractoriness, 27 showed liver function deterioration from Child-Pugh class A to class B or C after TACE. In multivariable logistic regression analysis, bilirubin at the diagnosis of HCC was a significant prognostic factor for liver function deterioration. A predictive algorithm based on the regression equations revealed a sensitivity, specificity, positive predictive value, and negative predictive value of 74.1%, 74.5%, 45.5%, and 90.9%, respectively, for TACE-refractoriness and liver function deterioration. Conclusions: The prognostic model incorporating the tumor size, tumor number, albumin, and bilirubin at the diagnosis of HCC may help identify patients who show a poor response to TACE and aggravation of liver function after TACE, who may benefit from early switching into systemic therapy before liver function aggravation.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Neoplasias Hepáticas/terapia , Fígado/fisiopatologia , Idoso , Área Sob a Curva , Bilirrubina/análise , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Fatores de Risco , Resultado do Tratamento
7.
Korean J Intern Med ; 35(3): 566-573, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31916422

RESUMO

BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy, arising from the peripheral intrahepatic bile duct epithelium. Hepatitis B virus (HBV) or hepatitis C virus (HCV) may be involved in the development of ICC. We explored the prognostic value of hepatitis virus infection, as well as other prognostic factors affecting survival in patients with ICC. METHODS: A retrospective chart review was performed for patients diagnosed with ICC between August 2005 and December 2018 at Konkuk University Medical Center. We identified a total of 131 patients with ICC. Overall survival rates of patients with and without hepatitis were determined. Univariate and multivariate analyses were used to estimate factors influencing survival outcomes. RESULTS: A total of 17.6% (23/131) of patients were positive for HBV or HCV. Hepatitis B positive ICC patients were significantly younger with higher albumin and higher α-fetoprotein than those without hepatitis viral infections. The median survival of hepatitis-positive and hepatitis-negative groups was 280 and 213 days, respectively. Survival rates were not significantly different between the two groups (p = 0.279). Multivariate analyses indicated that lower serum carbohydrate antigen 19-9 (CA 19-9) (p < 0.001), lower T stage (p = 0.042), the absence of lymph-node metastasis (p = 0.043), and receiving curative surgery (p = 0.033) were independent predictors of better outcomes. CONCLUSION: While hepatitis influenced a number of clinical features in ICC patients, it did not affect survival rate. Prognostic factors influencing survival outcomes with ICC were CA 19-9 level, T stage, the presence of lymph node metastasis, and curative surgery.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hepatite B , Neoplasias Hepáticas , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Hepatite B/diagnóstico , Humanos , Prognóstico , Estudos Retrospectivos
9.
World J Gastroenterol ; 25(33): 4985-4998, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31543688

RESUMO

BACKGROUND: Hepatitis B virus (HBV) DNA polymerase mutations usually occur to long term use of nucleos(t)ide analogues (NAs), but they can occur spontaneously in treatment-naïve chronic hepatitis B (CHB) patients. The naturally occurring HBV DNA polymerase mutations might complicate antiviral therapy with NAs, leading to the generation of drug-resistant viral mutants and disease progression. The most common substitutions are known to be YMDD-motif mutations, but their prevalence and the influence on antiviral therapy is unclear. AIM: To investigate prevalence of the naturally occurring rtM204I mutations in treatment-naïve CHB genotype C2 patients and their influence on antiviral therapy. METHODS: A total of 410 treatment-naïve CHB patients infected with HBV genotype C2 strains were enrolled in this retrospective study. Among the 410 patients, 232 were treated with NAs for at least 12 mo. Significant fibrosis was defined as fibrosis-4 index > 3.25 or aspartate aminotransferase to platelet ratio index > 1.5. Complete viral response (CVR) during NAs was defined as undetectable serum HBV DNA (< 24 IU/mL). The rtM204I variants were analyzed by a newly developed locked nucleotide probe (LNA probe) based real-time PCR (LNA-RT-PCR) method. RESULTS: The LNA-RT-PCR could discriminate rtM204I mutant-type (17 patients, 4.2%) from rtM204 wild-type (386 patients, 95.8%) in 403 of 410 patients (98.3% sensitivity). Multivariate analysis showed that naturally occurring rtM204I variants were more frequently detected in patients with significant fibrosis [odd-ratio (OR) 3.397, 95% confidence-interval (CI) 1.119-10.319, P = 0.031]. Of 232 patients receiving NAs, multivariate analysis revealed that achievement of CVR was reversely associated with naturally occurring rtM204I variants prior to NAs treatment (OR 0.014, 95%CI 0.002-0.096, P < 0.001). Almost patients receiving tenofovir achieved CVR at 12 mo of tenofovir, irrespective of pre-existence of naturally occurring rtM204I mutations (CVR rates: patients with rtM204I, 100%; patients without rtM204I, 96.6%), whereas, pre-existence of naturally-occurring rtM204I-mutations prior to NAs significantly affects CVR rates in patients receiving entecavir (at 12 mo: Patients with rtM204I, 16.7%; patients without rtM204I, 95.6%, P < 0.001). CONCLUSION: The newly developed LNA-RT-PCR method could detect naturally occurring rtM204I mutations with high-sensitivity. Theses mutations were more frequent in patients with liver fibrosis. Tenofovir is a more suitable treatment than entecavir for CHB patients carrying the naturally occurring rtM204I mutations.


Assuntos
Produtos do Gene pol/genética , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Análise Mutacional de DNA/métodos , Sondas de DNA/genética , DNA Viral/isolamento & purificação , Farmacorresistência Viral/genética , Estudos de Viabilidade , Feminino , Guanina/farmacologia , Guanina/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Oligonucleotídeos/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Tenofovir/farmacologia
10.
Front Immunol ; 10: 1735, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31402915

RESUMO

Hepatitis B virus infection is a serious global health problem and causes life-threatening liver disease. In particular, genotype C shows high prevalence and severe liver disease compared with other genotypes. However, the underlying mechanisms regarding virological traits still remain unclear. This study investigated the clinical factors and capacity to modulate Type I interferon (IFN-I) between two HBV polymerase polymorphisms rt269L and rt269I in genotype C. This report compared clinical factors between rt269L and rt269I in 220 Korean chronic patients with genotype C infections. The prevalence of preC mutations between rt269L and rt269I was compared using this study's cohort and the GenBank database. For in vitro and in vivo experiments, transient transfection using HBV genome plasmid and HBV virion infection using HepG2-hNTCP-C4 and HepaRG systems and hydrodynamic injection of HBV genome into mice tails were conducted, respectively. This report's clinical data indicated that rt269I vs. rt269L was more significantly related to HBV e antigen (HBeAg) negative serostatus, lower levels of HBV DNA and HBsAg, and disease progression. Our epidemiological study showed HBeAg negative infections of rt269I infections were attributed to a higher frequency of preC mutations at 1896 (G to A). Our in vitro and in vivo studies also found that rt269I could lead to mitochondrial stress mediated STING dependent IFN-I production, resulting in decreasing HBV replication via the induction of heme-oxygenase-1. In addition, we also found that rt269I could lead to enhanced iNOS mediated NO production in an IFN-I dependent manner. These data demonstrated that rt269I can contribute to HBeAg negative infections and liver disease progression in chronic patients with genotype C infections via mitochondrial stress mediated IFN-I production.


Assuntos
Genótipo , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , Interferon Tipo I/imunologia , Mitocôndrias Hepáticas , Estresse Fisiológico/imunologia , Adulto , Animais , Progressão da Doença , Feminino , Células Hep G2 , Antígenos E da Hepatite B/genética , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Mitocôndrias Hepáticas/imunologia , Mitocôndrias Hepáticas/patologia
11.
World J Gastroenterol ; 25(25): 3256-3267, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31333316

RESUMO

BACKGROUND: Accurate detection of significant fibrosis (fibrosis stage 2 or higher on the METAVIR scale) is important especially for chronic hepatitis B (CHB) patients with high viral loads but with normal or mildly elevated alanine aminotransferase (ALT) levels because the presence of significant fibrosis is accepted as the indication for antiviral treatment. Liver biopsy is the reference standard for diagnosing significant fibrosis, but it is an invasive procedure. Consequently, noninvasive imaging-based measurements, such as magnetic resonance elastography (MRE) or two-dimensional shear-wave elastography (2D-SWE), have been proposed for the quantitative assessment of liver fibrosis. AIM: To explore MRE and 2D-SWE to identify fibrosis stage, and to compare their performance with that of serum-based indices. METHODS: The study enrolled 63 treatment-naïve CHB patients with high viral loads but with normal or mildly elevated ALT levels who underwent liver biopsy before a decision was made to initiate antiviral therapy. MRE and 2D-SWE were performed, and serum-based indices, such as FIB-4 and aspartate transaminase to platelet ratio index (APRI), were calculated. The diagnostic performances of MRE, 2D-SWE, FIB-4, and APRI for assessing significant fibrosis (≥ F2) and cirrhosis (F4) were evaluated with liver histology as the reference standard, using receiver operating characteristic analyses. RESULTS: The liver fibrosis stage was F0/F1 in 19, F2 in 14, F3 in 14, and F4 in 16 patients, respectively. MRE significantly discriminated F2 from F0/1 (P = 0.022), whereas 2D-SWE showed a broad overlap in distinguishing those stages. MRE showed a higher correlation coefficient value with fibrosis stage than 2D-SWE with fibrosis stage (0.869 vs 0.649, Spearman test; P < 0.001). Multivariate linear regression analyses showed that fibrosis stage was the only factor affecting the values of MRE (P < 0.001), whereas body mass index (P = 0.042) and fibrosis stage (P < 0.001) were independent factors affecting 2D-SWE values. MRE performance for diagnosing significant fibrosis was better [area under the curve (AUC) = 0.906, positive predictive value (PPV) 97.3%, negative predictive value (NPV) 69.2%] than that of FIB-4 (AUC = 0.697, P = 0.002) and APRI (AUC = 0.717, P = 0.010), whereas the performance of 2D-SWE (AUC = 0.843, PPV 86%, NPV 65%) was not significantly different from that of FIB-4 or APRI. CONCLUSION: Compared to SWE, MRE might be more precise non-invasive assessment for depicting significant fibrosis and for making-decision to initiate antiviral-therapy in treatment-naïve CHB patients with normal or mildly-elevated ALT levels.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite B Crônica/patologia , Cirrose Hepática/diagnóstico , Fígado/diagnóstico por imagem , Adulto , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Aspartato Aminotransferases/sangue , Biópsia , Tomada de Decisão Clínica/métodos , Progressão da Doença , Feminino , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Projetos Piloto , Curva ROC , Carga Viral
12.
Korean J Gastroenterol ; 73(3): 167-176, 2019 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-31013560

RESUMO

Background/Aims: Surgical resection or ablation is recommended for the treatment of early hepatocellular carcinoma (HCC), whereas transarterial chemoembolization (TACE) is frequently used in early HCC ineligible for curative resection. We evaluated the clinical effects and safety of radiofrequency ablation (RFA) shortly after TACE in patients with Barcelona clinic liver cancer (BCLC) stage A HCC. Methods: Sixty-seven BCLC stage A HCC patients who failed to achieve complete response to TACE as either a first line treatment and who subsequently received RFA at the Konkuk University Medical Center from January 2005 to December 2017 were included. Evaluation indices included treatment response, overall survival rate, recurrence-free survival, prognostic factors, and procedure-related complications. Results: Median follow-up was 46.9 months. Fifty-four (80.6%) patients were of Child-Pugh class A, and 13 (19.4%) were of class B. Modified UICC stages were I in 10 (14.9%), II in 46 (68.7%), and III in 11 (16.4%) patients. In the 67 study subjects, cumulative recurrence-free survival rates were 86.8%, 55.9% and 29.7% at 1, 3, and 5 years, respectively, and overall survival rates were 100%, 93.4%, and 83.5% at 1, 3, and 5 years, respectively. Tumor size significantly predicted recurrence. No treatment-related death occurred. Conclusions: Combination of RFA was an efficient and safe treatment for BCLC stage A HCC patients that failed to achieve complete response to initial TACE. We suggest TACE plus RFA be considered as a curative option for early HCC patients ineligible for curative resection of RFA.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ablação por Radiofrequência , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
13.
J Korean Med Sci ; 33(52): e335, 2018 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-30584413

RESUMO

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious infectious complication in patients with liver cirrhosis. However, information about prognosis of SBP in hepatocellular carcinoma (HCC) patients is limited. We investigated the clinical course of SBP in HCC patients. METHODS: This study enrolled patients diagnosed with SBP between 2005 and 2017. Medical records of patients were reviewed and clinical course was compared between the non-HCC and HCC groups. RESULTS: In total, 123 SBP cases including 49 HCC cases were enrolled. Men were predominant (48/74, 64.9% vs. 34/49, 69.4%; P = 0.697); median age was 58 years in both non-HCC and HCC groups (P = 0.887). The most common etiology was alcohol (32/74, 43.2%) in non-HCC group and hepatitis B (30/49, 61.2%) in HCC group (P = 0.009). Antibiotic resistance rate was higher in non-HCC than in HCC group (29.7% vs. 12.2%; P = 0.028); in-hospital mortality did not differ between the groups (25/74, 33.8% vs. 13/49, 26.5%; P = 0.431). Development rate of hepatorenal syndrome did not differ between non-HCC and HCC group (14/74, 18.9% vs. 10/49, 20.4%; P = 1.000), but hepatic encephalopathy was less common in HCC group (26/74, 35.2% vs. 9/49, 18.3%; P = 0.008). The most important predictor of in-hospital mortality in patients with HCC was white blood cell count above 11,570 cells/mm3 (odds ratio, 6.629; 95% confidence interval, 1.652-26.590; P = 0.008). CONCLUSION: Prognosis of SBP in HCC patients is relatively less severe. This result may be related with reduced antibiotics resistance and lower development rates of other complications, such as hepatic encephalopathy. Degree of systemic inflammation may be the most important factor for in-hospital mortality.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Peritonite/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Antibacterianos/uso terapêutico , Área Sob a Curva , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Hepatite B/complicações , Mortalidade Hospitalar , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Peritonite/complicações , Peritonite/tratamento farmacológico , Prognóstico , Curva ROC , Recidiva , Estudos Retrospectivos
14.
Korean J Gastroenterol ; 72(4): 197-204, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30419644

RESUMO

BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has been shown to achieve a high rate of sustained virologic response (SVR) and favorable outcomes in chronic hepatitis C (CHC) patients. We investigated the virologic response and its clinical impact in CHC patients. METHODS: CHC patients with compensated liver function treated with DAAs between 2016 and 2017 were included for retrospective analysis. We analyzed baseline characteristics and virologic and biochemical responses at on-treatment 4 weeks, end of treatment, and post-treatment 12 weeks. Fibrosis was measured as liver stiffness measurement by transient elastography (FibroScan). Adverse events were monitored during the treatment period. RESULTS: A total of 135 patients (61.5% with genotype [GT] 1b and 38.5% with GT 2a) were enrolled 47.4% were male, 79.3% were treatment naive, and 30.4% had cirrhosis. SVR 12 was observed in 97.6% (81/83) in the GT 1b and 98.1% (51/52) in the GT 2a; treatment with daclatasvir+asunaprevir was the most commonly used in GT 1b (55/83), and sofosbuvir+ribavirin was the most commonly used in GT 2a (49/52). The median change of liver stiffness measurement at two time points using the signed rank test was -3.2 kPa in patients who underwent transient elastography before treatment and at SVR 12 (n=25). The most common adverse events were anemia, dyspepsia, and insomnia. One GT 2a patient treated with sofosbuvir+ribavirin stopped the treatment at 8 weeks due to symptomatic bradyarrhythmia; however, he recovered spontaneously and achieved SVR 12. CONCLUSIONS: DAA treatment of chronic hepatitis C genotype 1b and 2a resulted in a high rate of sustained virologic response and improvement of liver fibrosis score.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Antivirais/efeitos adversos , Esquema de Medicação , Dispepsia/etiologia , Técnicas de Imagem por Elasticidade , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento
15.
Ann Lab Med ; 38(4): 331-337, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29611383

RESUMO

BACKGROUND: Liver biopsies have been partially replaced by noninvasive methods for assessing liver fibrosis. We explored the usefulness of four novel biomarkers, enhanced liver fibrosis (ELF), glycosylation isomer of Mac-2 binding protein (M2BPGi), galectin-3, and soluble suppression of tumorigenicity 2 (sST2), in association with liver fibrosis. METHODS: ELF, M2BPGi, galectin-3, and sST2 were assayed in 173 patients with chronic liver diseases. The results were analyzed according to fibrosis grade (F0/1, F2, and F3/4) by transient elastography (TE). RESULTS: ELF, M2BPGi, galectin-3, and sST2 values differed significantly according to TE grade; ELF and M2BPGi values were higher in F2 and F3/4 than in F0/1 (P≤0.001, all), sST2 values were higher in F3/4 than in F0/1 and F2 (P<0.05), and galectin-3 values were higher in F3/4 than in F0/1 (P=0.0036). ELF and M2BPGi showed good TE fibrosis detection performance (area under the curves [AUC], 0.841 and 0.833 for ≥F2; and 0.837 and 0.808 for ≥F3). The sensitivity and specificity for predicting TE grade F≥2 were 84.1% and 76.7% for ELF and 63.6% and 91.5% for M2BPGi. CONCLUSIONS: This is the first study to compare the liver fibrosis assessment of four novel biomarkers: ELF, M2BPGi, galectin-3, and sST2. The biomarkers varied significantly according to TE grade, and each biomarker showed a different trend. ELF and M2BPGi seem to have comparable good performance for detecting liver fibrosis.


Assuntos
Antígenos de Neoplasias/metabolismo , Galectina 3/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Cirrose Hepática/diagnóstico , Hepatopatias/diagnóstico , Glicoproteínas de Membrana/metabolismo , Adulto , Idoso , Área Sob a Curva , Biomarcadores/metabolismo , Proteínas Sanguíneas , Doença Crônica , Técnicas de Imagem por Elasticidade , Feminino , Galectinas , Glicosilação , Humanos , Cirrose Hepática/patologia , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença
16.
Dig Dis Sci ; 63(2): 466-473, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29282635

RESUMO

BACKGROUND AND OBJECTIVES: Endoscopic submucosal dissection (ESD) has become widely accepted method for treating early gastric cancer (EGC), but little is known about its role in patients with liver cirrhosis (LC). The aims of this study were to evaluate the outcomes of ESD in treating EGC in patients with LC. METHODS: The multicenter retrospective study identified 43 patients with chronic hepatitis B (CHB)-related cirrhosis undergoing ESD for treating EGC. The patients (LC group) were subdivided into two groups based on their Child-Pugh classification (CP-class): 32 with CP-class A (LC-A) and 11 with CP-class B (LC-B). The patients were compared to 47 non-cirrhotic CHB patients who underwent ESD (CHB group). Eight patients had a past history of hepatocellular carcinoma (HCC) prior to ESD, but no patients had viable HCC when ESD was performed. RESULTS: Procedural outcomes (en bloc, lateral/basal margins resection) and post-procedural complications (bleeding or perforation) did not differ significantly between the LC and CHB groups or between the LC-A and LC-B groups. No patients experienced worsening of the Child-Pugh score 1 month after ESD compared with the baseline score. During a median observation period of 66 months, the recurrence rates of gastric cancers were similar between the LC and CHB groups (5-year recurrence rates: 2.4 vs. 2.3%, p = 0.925), and all recurrent gastric cancers were completely resected by additional ESD. The overall mortality rate was increased in the LC group (5-year mortality rates: 17.9 vs. 5.7%, p = 0.034), and 8 of 10 deaths were attributed to liver-related diseases (such as HCC, complications of portal hypertension, hepatic failure). CONCLUSIONS: ESD is feasible in patients with EGC and comorbid LC, even those with CP-class B cirrhosis. Their prognosis depends on LC-related diseases and not recurrent EGC.


Assuntos
Endoscopia Gastrointestinal , Cirrose Hepática/complicações , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
17.
J Infect Dis ; 216(11): 1407-1414, 2017 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-29029102

RESUMO

Background: Antiviral treatment for hepatitis B virus (HBV) e antigen (HBeAg)-positive chronic HBV infection is still controversial. We assessed whether antiviral treatment reduces the risk of liver disease progression in these patients. Methods: This study included consecutive patients in 8 large-volume hospitals in Korea who tested positive for HBeAg and had an HBV DNA level of >20000 IU/mL, an alanine aminotransferase (ALT) level of <40 IU/L, and no evidence of cirrhosis. The primary end point was the development of hepatocellular carcinoma (HCC), and the secondary end point was the development of cirrhosis. Results: A total of 484 patients were included: 87 were in the antiviral treatment group, and 397 were in the control group. Baseline liver function was significantly more favorable for the control group. After matching for propensity score to overcome those differences, the antiviral treatment group had a significantly reduced risk for HCC (hazard ratio [HR], 0.234; log-rank P = .046) and cirrhosis (HR, 0.235; log-rank P = .015), compared with the control group. After balancing the baseline characteristics by using inverse probability weighting, antiviral therapy significantly decreased the risk of HCC (HR, 0.189; log-rank P = .004) and cirrhosis (HR, 0.347; log-rank P = .036). Conclusion: Antiviral therapy for patients with HBeAg-positive chronic HBV infection and have a high HBV load reduces the risk of HCC, even if the ALT level is below the upper limit of normal.


Assuntos
Antivirais/uso terapêutico , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Adulto , Alanina Transaminase/sangue , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Feminino , Genótipo , Antígenos E da Hepatite B/sangue , Humanos , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Farmacogenômicos , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
18.
World J Gastroenterol ; 23(23): 4222-4232, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28694662

RESUMO

AIM: To report naturally occurring mutations in the reverse transcriptase region (RT) of hepatitis B virus (HBV) polymerase from treatment naïve Korean chronic patients infected with genotype C2. METHODS: Here, full-length HBV reverse transcriptase RT sequences were amplified and sequenced from 131 treatment naïve Korean patients chronically infected with hepatitis B genotype C2. The patients had two distinct clinical statuses: 59 patients with chronic hepatitis (CH) and 72 patients with hepatocellular carcinoma (HCC). The deduced amino acids (AAs) at 42 previously reported potential nucleos(t)ide analog resistance (NAr) mutation positions in the RT region were analyzed. RESULTS: Potential NAr mutations involving 24 positions were found in 79 of the 131 patients (60.3%). Notably, AA substitutions at 2 positions (rt184 and rt204) involved in primary drug resistance and at 2 positions (rt80 and rt180) that functioned as secondary/compensatory mutations were detected in 10 patients (1 CH patient and 9 HCC patients) and 7 patients (1 CH and 6 HCC patients), respectively. The overall mutation frequencies in the HCC patients (3.17%, 96/3024 mutations) were significantly higher than the frequencies in the CH patients (2.09%, 52/2478 mutations) (P = 0.003). In addition, a total of 3 NAr positions, rt80, rt139 and rt204 were found to be significantly related to HCC from treatment naïve Korean patients. CONCLUSION: Our data showed that naturally occurring NAr mutations in South Korea might contribute to liver disease progression (particularly HCC generation) in chronic patients with genotype C2 infections.


Assuntos
Genótipo , Vírus da Hepatite B/enzimologia , Mutação , DNA Polimerase Dirigida por RNA/genética , Adulto , Idoso , Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Análise Mutacional de DNA , DNA Viral/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Farmacorresistência Viral/genética , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , República da Coreia
19.
J Clin Gastroenterol ; 50(10): 882-888, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27322532

RESUMO

GOALS: To evaluate the degree of liver fibrosis as a predictor of mortality and hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B. BACKGROUND: The level of fibrosis predicts mortality and liver-related complications. STUDY: A total of 542 patients over 18 years old with chronic hepatitis B who visited the Konkuk University Hospital between the years 2005 and 2006 were enrolled. We performed noninvasive tests of fibrosis (APRI, FIB-4) and hepatitis B virus (HBV) DNA levels. The data on mortality and newly developed HCC collected during a 5-year follow-up were analyzed. RESULTS: In 5 years, 40 patients died and 68 patients developed HCC. The area under the receiver operator characteristic (AUROC) curve of APRI, FIB-4, and HBV DNA levels for mortality was 0.760, 0.789, and 0.463, with cut-off points at 0.766, 2.671, and 3.150, respectively. The AUROC curve of APRI, FIB-4, and HBV DNA levels for HCC was 0.731, 0.803, and 0.523, with cut-off points at 0.766, 2.225, and 4.245, respectively. APRI and FIB-4 were predictors of mortality and HCC development, where patients with APRI over 0.766 had a greater risk of death [odds ratio (OR)=3.214, 95% confidence interval (CI), 1.009-10.238] and HCC development (OR=4.245, 95% CI, 1.723-10.456). Patients with FIB-4>2.671 had a higher risk of death (OR=4.431, 95% CI, 1.512-12.986) and those over 2.225 had a greater risk of developing HCC (OR=3.607, 95% CI, 1.622-8.021). CONCLUSIONS: APRI and FIB-4 may be more useful than HBV DNA level in predicting 5-year mortality and development of HCC.


Assuntos
Carcinoma Hepatocelular/mortalidade , Hepatite B Crônica , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Adulto , Área Sob a Curva , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia , Índice de Gravidade de Doença , Análise de Sobrevida
20.
J Clin Gastroenterol ; 50(8): 676-85, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27203430

RESUMO

BACKGROUND AND AIMS: This study evaluated the clinical significance of subclinical ascites in patients with hepatitis B virus-related cirrhosis treated with lamivudine (LMV) or entecavir (ETV). METHODS: This multicenter retrospective study involved 8 hospitals. Patients were classified by degree of ascites: (1) no ascites (no ascites on imaging, no diuretics), (2) subclinical ascites (small amount of ascites on imaging, no diuretics), and (3) clinical ascites (moderate to severe ascites or diuretics). RESULTS: Out of 501 patients, 336 (68%), 51 (10%), and 114 (23%) patients were classified as no-ascites, subclinical ascites, and clinical ascites, respectively. In all, 100 (20%) and 401 (80%) were treated with LMV and ETV, respectively. Over 58±24 months of follow-up, 105 patients (21%) developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma did not differ between LMV-treated and ETV-treated patients (P=0.61); it was higher in the clinical-ascites group than the no-ascites (P=0.054) and subclinical-ascites (P=0.03) groups, but it was comparable between the latter 2 (P=0.225). Forty-five patients (9%) died during follow-up. Survival was significantly shorter in the clinical-ascites group than the other 2 (both P<0.005), but it was comparable between no-ascites and subclinical-ascites groups (P=0.444). Multivariate analysis showed that mortality was significantly associated with prothrombin time [hazard ratio (HR)=2.42; 95% confidence interval (CI), 1.59-3.70], serum albumin (HR=0.54; 95% CI, 0.29-0.99), and presence of clinical ascites (HR=3.58; 95% CI, 1.54-8.30). CONCLUSIONS: Subclinical ascites did not affect prognosis in patients with hepatitis B virus-related cirrhosis receiving antiviral treatment.


Assuntos
Antivirais/uso terapêutico , Ascite/etiologia , Hepatite B Crônica/complicações , Cirrose Hepática/complicações , Adulto , Ascite/epidemiologia , Ascite/patologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Feminino , Seguimentos , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/mortalidade , Humanos , Incidência , Lamivudina/uso terapêutico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Tempo de Protrombina , Estudos Retrospectivos , Albumina Sérica/metabolismo
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