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Hepatitis B core-related antigen (HBcrAg) is a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Studies on anti-viral therapy have shown that the use of NUC therapy in HBV patients could reduce the incidence of HCC. However, the incidence of HCC continues to increase after long-term anti-viral therapy. The relationship between HBcrAg and HCC development in CHB-related liver cirrhosis (LC) patients undergoing long-term anti-viral therapy is still unclear. This study enrolled 1108 treatment-naïve CHB patients diagnosed with HBV-related LC receiving NUC therapy from April 1999 to February 2015. The baseline biomarkers, disease history, and following results were collected by the hospital. Among the 1108 patients, 219 developed HCC within a median follow-up period of 6.85 years. A multivariable Cox regression model was used, with adjustment for age, gender, FIB-4, DM, and HBsAg-HQ. The adjusted hazard ratios for the HBcrAg tertile levels were 1.70 (95%CI: 1.21, 2.39) and 2.14 (95%CI: 1.50, 3.05) for levels 3.4-4.9 and >4.9 logU/mL, respectively, compared with levels ≤3.4. The effect of the HBcrAg level on HCC incidence was found to be significantly modified by HBsAg-HQ, where lower HBsAg-HQ (≤ 3) values were associated with a significantly higher risk, but HBsAg-HQ levels >3 were not. Our results highlight that, after adjustment for potential confounding factors, patients with CHB-related LC and higher HBcrAg levels are at significant risk for HCC development, even while undergoing long-term effective anti-viral therapy. The HBcrAg level is therefore an independent risk factor for HCC development, especially for patients with HBsAg-HQ levels <3.
Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/diagnóstico , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Antivirais/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Biomarcadores , Cirrose Hepática/tratamento farmacológico , DNA ViralRESUMO
Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a novel marker for evaluating fibrosis and predicting the development of hepatocellular carcinoma (HCC). However, the role of WFA+-M2BP in the prognosis of HCC patients after curative surgery remains unknown. In this study, we aimed to evaluate the prognostic role of serum WFA+-M2BP in HCC patients after curative resection and liver transplantation. We enrolled 460 HCC patients (357 resection and 103 transplantation) to analyze the risk factors for HCC recurrence and patient's survival. We employed time-to-event models using univariate and multivariable Cox proportional hazards regression analyses and calculated the hazard ratios (HRs) and adjusted HRs with their corresponding 95% confidence intervals (CIs). The levels of WFA+-M2BP were 0.19-14.51 COI (median 1.08) in patients of hepatectomy and 0.47-19.90 COI (median 6.0) in transplant patients. The levels of WFA+-M2BP in liver transplant patients is much higher than that of hepatectomy patients. Overall, liver fibrotic stage was positively correlated to WFA+-M2BP levels (P<0.0001). This study demonstrated that elevated WFA+-M2BP level (COI ≥0.75) was associated with a higher HCC recurrence rate in the resection group (P<0.001). Survival analysis showed that an elevated WFA+-M2BP level (COI ≥1.43) is associated with a higher mortality risk after surgical resection (P=0.0088) in the univariate analysis only. In liver transplant patients, WFA+-M2BP level (COI ≥3.81) did not predict HCC recurrence at all, but was associated poor survival after transplantation, with a borderline significance (P=0.0943). Serum WFA+-M2BP is a reliable marker for liver fibrosis in the present study. It is also reliable marker to predict prognosis of HCC after surgical resection. However, the prognostic role of WFA+-M2BP in HCC related transplants is equivocal, which is different from that of surgical resection.
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BACKGROUND: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC. AIMS: The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy. METHODS: From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (n = 146) or TDF (n = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups. RESULT: After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027-2.770, p = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763-12.558, p = 0.002), but not in early recurrence. CONCLUSIONS: TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.
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BACKGROUND: Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC. METHODS: We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. RESULTS: During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.
Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus , Neoplasias Hepáticas , Fígado , Metformina/administração & dosagem , Recidiva Local de Neoplasia , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/cirurgia , Feminino , Seguimentos , Humanos , Fígado/metabolismo , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND/PURPOSE: Effective antiviral-therapy can reduce the risk of liver cirrhosis related hepatocellular carcinoma in patients with chronic hepatitis B and hepatitis C. Yet, the difference of hepatocellular carcinoma development in chronic hepatitis B and hepatitis C patients with cirrhosis after effective antiviral therapy treatment is unknown. In this study, We comprehensive explored the difference among them. METHODS: 1363 patients with cirrhosis and hepatitis B virus treated with nucleos(t)ide analogues (NUCs) with completely suppressed virus, and patients with cirrhosis and hepatitis C virus treated with pegylated interferon (peg-IFN)/ribavirin (RBV) combination therapy who achieved sustained virologic response were enrolled. RESULTS: Total 261 developed hepatocellular carcinoma within a median follow-up of 4.25 years. Univariate analysis, patients developed hepatocellular carcinoma tended to be of older age, and had lower platelet counts, were chronic hepatitis B carriers, and had higher serum alfa-fetoprotein (AFP) (≥20 ng/mL), FIB-4 index and APRI scores. Subsequent multivariate analysis revealed older age, lower platelet counts, high AFP levels and chronic hepatitis B carriers were independent risk factors of hepatocellular carcinoma. CONCLUSION: Our findings identify that chronic hepatitis B patients were with a higher risk of hepatocellular carcinoma compared to chronic hepatitis C patients after achieving virological response. Special attention should be paid to those patients.
Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Quimioterapia Combinada , Hepacivirus , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologiaRESUMO
BACKGROUND AND AIM: Tenofovir disoproxil fumarate (TDF) and entecavir are effective antiviral medications that are recommended as first-line monotherapies for the treatment of chronic hepatitis B (CHB) infection, including decompensated liver cirrhosis with ascites. Acute kidney injury (AKI) commonly occurs in patients with cirrhosis and ascites. The aim of this study was to compare the development of AKI during TDF and entecavir treatment of CHB patients with cirrhotic refractory ascites. METHODS: From January 2011 to April 2017, we identified patients who were diagnosed with cirrhosis with refractory ascites and received TDF or entecavir treatments at Kaohsiung Chang Gung Memorial Hospital. AKI was defined as an increase in serum creatinine of more than 0.3 mg/dL or 1.5-fold from baseline. All episodes of AKI were recorded and compared between those who received TDF and entecavir. RESULTS: A total of 111 patients were enrolled in this retrospective study, of which 22 patients were treated with TDF and 89 were treated with entecavir. Patients with AKI episodes had a higher proportion of TDF treatment (P = 0.01), male (P = 0.023), hepatocellular carcinoma (P = 0.007), admission (P = 0.045), and mortality (P = 0.018). Logistic regression analysis illustrated that TDF treatment of patients with comorbidity was an independent risk factor for the development of AKI [odds ratio (OR), 3.756; 95% confidence interval (CI), 1.293-10.912; P = 0.015] and hepatorenal syndrome (OR, 7.651; 95% CI, 1.697-34.508; P = 0.008). CONCLUSIONS: TDF treatment is a risk factor for AKI and HRS development in cirrhotic patients with refractory ascites in comparison with entecavir treatment, especially in patients with comorbidity.
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Injúria Renal Aguda , Hepatite B Crônica , Neoplasias Hepáticas , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Antivirais/efeitos adversos , Ascite/diagnóstico , Ascite/epidemiologia , Ascite/etiologia , Guanina/análogos & derivados , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Estudos Retrospectivos , Tenofovir/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Non-invasive techniques for liver fibrosis diagnosis are very important for clinician especially in high-risk patients for liver biopsy. We further explored the diagnostic accuracy of FibroScan, FIB-4 and aminotransferase-to-platelet ratio index (APRI) in identifying liver fibrosis and assess their predictive role for oesophageal varices in patients with hepatocellular carcinoma (HCC). METHODS: In total, 380 patients who underwent surgery for HCC were included based on retrospective study design. Liver fibrosis was pathologically diagnosed using the Ishak scoring system. Liver stiffness parameters were measured using FibroScan. APRI and FIB-4 were calculated. Among those, 121 patients who received oesophagogastroduodenoscopic examination underwent variceal evaluation. RESULTS: For liver cirrhosis diagnosis with FibroScan, the optimal cut-off values for the patients with HCC overall, left HCC and right HCC were 8.85, 11.75 and 8.70 kPa (the accuracy were 78.7%, 78.4% and 79.2%, respectively). They had high areas under the receiver operating characteristic curve of 0.84, 0.84 and 0.85. The combined FibroScan, APRI and FIB-4 had very high specificity (more than 92%) for cirrhosis diagnosis. The optimal cut-off liver stiffness values for the diagnosis of varices were all 11.2 kPa. For predicting varices, the optimal cut-off values of FIB-4 and APRI were 2.64 and 0.71, their accuracy were 64.3%-78.4%, 69.4% and 72.7%, respectively. CONCLUSIONS: FibroScan, FIB-4 and APRI have moderate accuracy for liver fibrosis diagnosis and oesophageal varices prediction in patients with hepatoma. This is a study of these non-invasive techniques applied in specific hepatoma patients and with inevitable limitations and need future more studies for validation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Aspartato Aminotransferases , Biomarcadores , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Comparative long-term efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) for prevention of disease progression to hepatocellular carcinoma (HCC) among high-risk patients with chronic hepatitis B (CHB)-related compensated cirrhosis is controversial. AIMS: To compare the long-term efficacy of ETV and TDF in HCC prevention in patients with CHB-related cirrhosis, and to evaluate predictive risk factors for HCC development. METHODS: From January 2008 to March 2018, 894 treatment-naïve patients with CHB-related compensated cirrhosis on ETV or TDF were enrolled based on the longitudinal cohort study. Data were originally collected for 7.3 years of follow-up or after the launch of TDF in 2011. Only the 5-year cumulative incidence and risk factors of HCC were assessed. RESULT: Total 678 and 216 patients received ETV and TDF, respectively. The cumulative risk of HCC at 1, 3 and 5 years of follow-up was 1.6%, 11.3% and 18.7%, respectively, in the ETV group; and 0.9%, 6.7% and 10.7%, respectively, in the TDF group (P = 0.0305). Univariate and adjusted-multivariable models revealed that platelet count, alpha-fetoprotein (AFP) levels and upper gastrointestinal (UGI) varices were independent risk factors for HCC development. TDF resulted in risk of HCC development compared to ETV with adjusted hazard ratios (aHRs) of 0.66 (95% confidence interval [CI]:0.40, 1.08; P = 0.0971), 0.69 (95% CI: 0.42, 1.14; P = 0.1488) and 0.66 (95% CI: 0.38, 1.14; P = 0.1407) under stepwise selection, propensity score adjustment, and propensity score matching multivariable models, respectively. CONCLUSIONS: For treatment-naïve patients with CHB-related compensated cirrhosis with 5-year follow-up, after variable adjustments, propensity score approaches and subgroup analyses, TDF showed a lower rate of HCC development that did not reach statistical significance, compared to the ETV.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Humanos , Cirrose Hepática/tratamento farmacológico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan , Tenofovir/uso terapêutico , alfa-Fetoproteínas/metabolismoRESUMO
Chibby is an antagonist of ß-catenin and is considered a potential tumor suppressor protein, but the role of Chibby in hepatocellular carcinoma (HCC) has not been characterized. The expression patterns of Chibby and ß-catenin in HCC specimens and paired adjacent noncancerous tissues were measured by Western blotting and immunohistochemistry. The correlations between Chibby expression and clinicopathological parameters were analyzed. Then the biological functions of Chibby were analyzed in vitro. The Chibby protein was significantly downexpressed in human primary HCC tissues compared to that in matched adjacent normal liver tissue and is a risk factor for HCC recurrence and shorter survival. Furthermore, we found that in HCC tissues the high expression of ß-catenin with low expression of Chibby in the nuclei was an independent predictor for disease-free survival (DFS) (p = 0.012) and overall survival (OS) (p = 0.005). Subsequent genetic manipulation in vitro studies revealed that Chibby knockdown induced the expression of ß-catenin and C-myc, cyclin D1 protein, which promoted cell proliferation and invasiveness. In contrast, overexpression of Chibby decreased ß-catenin expression and inhibited the cell proliferation and invasiveness. Our results suggest that low expression of Chibby was associated with advanced tumor-node-metastasis (TNM) stage and poor differentiation. Furthermore, the combination of Chibby and ß-catenin can predict poor prognosis in patients with HCC. Chibby inhibited HCC progression by blocking ß-catenin signaling in vitro. Chibby is a biomarker and may be a potential therapeutic target for HCC.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Proteínas de Transporte/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Proteínas Nucleares/metabolismo , beta Catenina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/genética , Proliferação de Células , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Proteínas Nucleares/genética , Prognóstico , Transdução de Sinais , Adulto Jovem , beta Catenina/genéticaRESUMO
BACKGROUND: Urokinase plasminogen activator (uPA) is an extracellular matrix-degrading protease that is involved in the invasiveness and progression of cancer. There is good evidence that uPA expression is a clinically relevant biomarker in some solid tumors, but its role in hepatocellulcar carcinoma (HCC) is uncertain. We evaluated the prognostic value of serum uPA before surgery in HCC patients receiving curative resection. METHODS: Serum uPA levels were determined by enzyme-linked immunosorbent assay in 282 HCC patients who received complete liver resections at Kaohsiung Chang Gung Memorial Hospital. Overall survival (OS) curves were constructed using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional -hazards regression model was used to identify independent prognostic factors. The median follow-up time was 52 months. RESULTS: Patients with higher pretreatment serum uPA (≥1 ng/ml) had significantly shorter OS (p = 0.002). Patients with liver cirrhosis, hypoalbuminemia, and thrombocytopenia were significantly more likely to present with elevated uPA levels. Multivariate Cox regression analyses indicated that high pretreatment serum uPA [hazard ratio (HR), 1.848, p = 0.006], vascular invasion (HR, 2.940, p < 0.001), and pathology stage III/IV (HR, 3.517, p < 0.001) were independent prognostic factors for OS. In further stratified analyses, the combination of serum uPA and AFP had more capacity to predict OS. CONCLUSIONS: We conclude that uPA is a clinically relevant biomarker in HCC patients receiving curative resection, with higher expression of uPA being associated with higher mortality. This also highlights the potential utility of uPA as a therapeutic target for improved treatment strategies.
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Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Proteínas de Membrana/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Análise de Sobrevida , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND: The first-line eradication rate of standard triple therapy for Helicobacter pylori infection has declined to <80%, and alternative therapies with >90% success rates are needed. Inconsistent eradication rates were reported for proton pump inhibitor- and amoxicillin-containing high-dose dual therapy. OBJECTIVES: We performed a prospective, randomized controlled study to assess the efficacy of esomeprazole- and amoxicillin-containing high-dose dual therapy and investigated the influencing clinical factors. PATIENTS AND METHODS: We recruited 240/278 eligible H. pylori-infected patients after exclusion. They were randomly assigned to 14 day high-dose dual therapy (esomeprazole 40 mg three times daily and amoxicillin 750 mg four times daily for 14 days; EA group) or 7 day non-bismuth quadruple therapy (esomeprazole 40 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily for 7 days; EACM group). Urea breath tests were followed up 8 weeks later. RESULTS: The eradication rates for the EA and EACM groups were 91.7% (95% CI = 85.3%-96.0%) and 86.7% (95% CI = 79.3%-92.2%) (P = 0.21) in ITT analysis; and 95.7% (95% CI = 90.2%-98.6%) and 92.0% (95% CI = 85.4%-96.3%) (P = 0.26) in PP analysis. The adverse event rates were 9.6% versus 23.0% in the two groups (P = 0.01). The H. pylori culture positivity rate was 91.8%. The antibiotic resistance rates were amoxicillin, 0%; clarithromycin, 14.6%; and metronidazole, 33.7%. CONCLUSIONS: A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy achieves a high eradication rate as first-line anti-H. pylori therapy, comparable to that with 7 day non-bismuth quadruple therapy but with fewer adverse events.
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Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Esquema de Medicação , Farmacorresistência Bacteriana , Quimioterapia Combinada , Esomeprazol/efeitos adversos , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Projetos de Pesquisa , TaiwanRESUMO
BACKGROUND: Hepatitis C virus (HCV)-infected patients who achieved sustained virologic response (SVR) may still develop hepatocellular carcinoma (HCC). The characteristic of HCC and the prognosis between SVR and non-SVR patients were not well known. METHODS: Among 1884 HCV-infected patients who were treated with pegylated IFN plus ribavirin therapies, 122 patients developed HCC during follow-up were enrolled in this study. Laboratory data were collected before and at least 1 year after IFN-based therapy, as well as the latest follow-up. RESULTS: Both SVR and non-SVR patients had similar risk factors to develop HCC, but with a little difference. Liver cirrhosis plays a key role in HCC occurrence in both groups. Among the patients who developed HCC, non-SVR patients had significantly higher total bilirubin, higher FIB-4, lower pre-treatment platelet count, higher pre-treatment AFP levels and higher proportion of cirrhosis than SVR patients before occurrence of HCC. After curative treatment, SVR patients had lower recurrence and longer overall survival than non-SVR patients by Kaplan-Meier analysis. Multivariate analysis revealed that APRI ≥0.7 was the independent risk factor for HCC recurrence; and AFP ≥20 ng/ml post IFN therapy, as well as HCC recurrence were the independent risk factors of mortality. CONCLUSION: Liver cirrhosis plays a key role in HCC occurrence after antiviral therapies. SVR patients may have lower HCC recurrence and longer survival rates than non-SVR patients. Only APRI was associated with HCC recurrence; and post-IFN AFP and HCC recurrence were predictive of subsequent mortality independently.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/complicações , Neoplasias Hepáticas/mortalidade , Idoso , Quimioterapia Combinada , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Humanos , Interferon-alfa/uso terapêutico , Estimativa de Kaplan-Meier , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Ribavirina/uso terapêutico , Fatores de Risco , Taxa de Sobrevida , Resposta Viral Sustentada , TaiwanRESUMO
BACKGROUND/PURPOSE: Prdevious meta-analyses assess whether or not patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409 C > G) was associated with increased risk of hepatocellular carcinoma (HCC) in Caucasians patients with hepatitis C virus (HCV)-related cirrhosis, these meta-analyses did not provide firm conclusions. Only one cross-sectional study involving Asian patients has previously been conducted to explore this issue. We aim to investigate this in a longitudinal cohort of Asian chronic hepatitis C (CHC) patients. METHODS: We consecutively enrolled 1011 CHC patients who underwent liver biopsy before initiating interferon-based therapy. These patients were followed-up and screened for HCC up to a median of 6.9 years. The influence of rs738409 (GG) genotype on the occurrence of HCC was assessed using the Kaplan-Meier method, then according to the multivariate Cox model. RESULTS: During follow-up, 143 (14.1%) patients developed HCC. rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.634). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.12). Among 261 patients with liver cirrhosis, rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.737). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.72). CONCLUSION: In this longitudinal study with liver biopsy to stage liver fibrosis, we affirm there is no influence of the rs738409 (GG) genotype on the occurrence of HCC in Asian CHC patients, including cirrhotic patients.
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Carcinoma Hepatocelular/genética , Hepatite C Crônica/complicações , Lipase/genética , Cirrose Hepática/complicações , Neoplasias Hepáticas/genética , Proteínas de Membrana/genética , Adulto , Idoso , Carcinoma Hepatocelular/epidemiologia , Estudos Transversais , Feminino , Predisposição Genética para Doença , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/patologia , Neoplasias Hepáticas/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Taiwan/epidemiologiaRESUMO
BACKGROUND/PURPOSE: Metabolic risk factors are associated with liver fibrosis. Whether or not metabolic risk factors affect the severity of liver fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), or risk factors associated with non-alcoholic fatty liver disease (NAFLD) remains unclear. We aimed to investigate this by transient elastography. METHODS: In this cross-sectional study, we enrolled 1513 patients who presented with chronic liver disease (CLD) at a tertiary hospital. Liver stiffness measurement (LSM) >13 kPa was used as a cutoff suggesting possible liver cirrhosis (LC). RESULTS: Possible LC was noted in 7.8% of the CHB patients, 19.9% of the CHC patients, and 11.9% of the patients with risk factors associated with NAFLD. After adjustments for biochemical and virological factors were made, BMI (per 1 kg/m2 increase) (OR: 1.17, 95% CI: 1.06-1.29, P = 0.002) was found to be an independent factor associated with possible LC in CHB patients; BMI (per 1 kg/m2 increase) (OR: 1.15, 95% CI: 1.07-1.24, P < 0.001) and diabetes mellitus (DM) (OR: 2.32, 95% CI: 1.25-4.30, P = 0.008) were found to be independent factors associated with possible LC in CHC patients; and BMI (per 1 kg/m2 increase) (OR: 1.19, 95% CI: 1.07-1.32, P = 0.002) and DM (OR: 10.35, 95% CI: 2.95-36.32, P < 0.001) were found to be independent factors associated with possible LC in patients with risk factors associated with NAFLD. CONCLUSION: Elevated BMI was an independent risk factor associated with possible LC across the three different etiologies of CLD. As such, weight loss may be beneficial in these patients.
Assuntos
Índice de Massa Corporal , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/etiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND & AIMS: Diabetes mellitus (DM) has been found to be strongly associated with an increased risk of hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients. Several studies have also found an association between metabolic steatosis and the risk of HCC in CHC patients, whether this latter association has been accounted for by the known relationship between DM and HCC is still unknown. METHODS: A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC and treated with interferon and ribavirin was studied. Cumulative incidence and HCC risk were analysed using the Kaplan-Meier method and Cox proportional hazard analysis. RESULTS: Hepatocellular carcinoma developed in 140 subjects over a median follow-up period of 97.3 months, while 699 patients achieved sustained virological response (SVR). According to multivariate analyses, age ≥ 60 years, advanced fibrosis and genotype 1 were identified as independent factors significantly associated with HCC development in SVR patients. Furthermore, using the absence of steatosis and absence of DM as references, the presence of steatosis without DM (HR = 2.09, 95% CI = 1.12-3.9, P = .021), the presence of DM without steatosis (HR = 2.78, 95% CI = 1.3-5.92, P = .008) and the combined presence of steatosis and DM (HR = 3.25, 95% CI = 1.44-7.33, P = .004) were identified as independent factors significantly associated with HCC development in the SVR patients. In contrast, steatosis alone, DM alone and the combined presence of steatosis and DM were not associated with HCC development in non-SVR patients. CONCLUSIONS: Steatosis and DM may be associated with HCC development in non-genotype 3 CHC patients with SVR.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/complicações , Complicações do Diabetes/virologia , Fígado Gorduroso/complicações , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Adulto , Carcinoma Hepatocelular/virologia , Diabetes Mellitus/virologia , Fígado Gorduroso/virologia , Feminino , Genótipo , Hepatite C Crônica/complicações , Humanos , Interferons/uso terapêutico , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Ribavirina/uso terapêutico , Fatores de Risco , Resposta Viral Sustentada , Taiwan/epidemiologiaRESUMO
BACKGROUND/PURPOSE: Although antiviral therapy reduces development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC), HCC often develops in patients with non-sustained virologic response (non-SVR). We aimed to evaluate risk factors for HCC in HCV patients with non-SVR. METHODS: From March 2002 to December 2013, 800 patients with CHC who had received combined pegylated interferon (peg-IFN)/ribavirin (RBV) therapy without achieving SVR were enrolled. Main outcome measure was HCC development. Variables were cirrhosis, platelet count, α-fetoprotein (AFP) levels, aspartate aminotransferase (AST) to platelet ratio index (APRI), and IL28B polymorphism (CT + TT). RESULTS: One-hundred of 800 non-SVR patients developed HCC within a median 53.5-months follow-up. Cumulative incidence of HCC for all patients was 1.4%, 5.6% and 12.3%, respectively, at 1st, 3rd and 5th years of follow-up. In univariate analysis, patients who developed HCC tended to have LC (p< 0.001), lower platelet counts (<150 × 109/l, p < 0.001), higher AFP levels (≥20 ng/ml, p < 0.001), higher Fib-4 levels (p < 0.001), higher APRI levels (p < 0.001), IL 28B polymorphism (CT + TT) (p < 0.001) and higher incidence of diabetes mellitus (DM) (p = 0.019). Multivariate analysis in overall patients revealed that cirrhosis (HR: 2.94, 95% CI: 1.81-4.77, p < 0.001), IL28B rs12979860 (CT + TT) polymorphisms (HR: 3.22, 95% CI: 2.17-4.78, p < 0.001), and high APRI levels (≥2.57) (HR: 2.32, 95% CI: 1.47-3.67, p < 0.001) were independent risk factors for HCC. CONCLUSION: Liver cirrhosis, high APRI levels, and IL28B rs12979860 at baseline are independent risk factors for HCC development in patients without SVR after peg-IFN combination therapy.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/complicações , Neoplasias Hepáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspartato Aminotransferases/sangue , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Humanos , Interferon-alfa/uso terapêutico , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , Análise de Regressão , Estudos Retrospectivos , Ribavirina/uso terapêutico , Fatores de Risco , Resposta Viral Sustentada , Taiwan/epidemiologia , Tomografia Computadorizada por Raios X , Falha de TratamentoRESUMO
Some patients with hepatitis C virus (HCV) infections who fail to achieve sustained virological responses (SVRs) after interferon (IFN) therapy do not develop hepatocellular carcinoma (HCC). Risk stratification of these patients may help identify those who would benefit most from treatment with direct-acting antivirals (DAAs).A total of 552 HCV-infected patients with non-SVR status were enrolled. Laboratory data before and after IFN treatment were analyzed to determine the relationship of changes in serum markers with development of HCC during the 7-year study period.HCC developed in 93 patients. The risk factors for HCC were pre-existing liver cirrhosis, low hemoglobin level at baseline, low pretreatment platelet count, high post-treatment alpha-fetoprotein (AFP) level (≥15âng/mL), and high post-treatment Fibrosis 4 (FIB4) index (>3.25). For patients without pre-existing cirrhosis, those with high post-treatment AFP level and FIB4 index had the highest risk of HCC (1 year: 6.7%; 3 years: 10.9%; 5 years: 29.7%), followed by those with high post-treatment AFP level and low post-treatment FIB4 index (5 years: 25%), and those with low post-treatment AFP level and high post-treatment FIB4 index (1 year: 3.7%; 3 years: 5.2%; 5 years: 10.6%). The risk was even lower for patients with low post-treatment AFP level and FIB4 index (1 year: 0%; 3 years: 0.4%; 5 years: 2.5%). None of the patients with FIB4 indexes consistently below 1.45 developed HCC.The combined use of post-treatment AFP level and FIB4 index was useful for risk stratification of HCV-infected patients with non-SVR status after IFN therapy. These data may help clinicians to identify patients who most urgently need DAA treatment.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Interferons/uso terapêutico , Neoplasias Hepáticas/etiologia , Resposta Viral Sustentada , Biomarcadores/sangue , Estudos de Coortes , Feminino , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND/PURPOSE: Controlled attenuation parameter (CAP) is a method for measuring steatosis based on FibroScan. Despite observer dependency, ultrasound (US) robustly diagnoses moderate and severe steatosis. Here, we aimed to evaluate the correlation of CAP with US-identified steatosis in real-world clinical practice. METHODS: CAP and US were performed for 1554 chronic liver disease (CLD) patients. CAP was performed by two technicians, and US was performed by 30 hepatologists. The performance of the CAP as compared with the US results was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: 532 (34.2%) of the patients had hepatitis C virus (HCV) infection, 723 (46.5%) of the patients had hepatitis B virus (HBV) infection, and the rest were patients with metabolic risk factors. CAP values were significantly correlated with the steatosis grades identified by US for all the patients (ρ = 0.497, P < 0.001), for the HBV-infected patients (ρ = 0.495, P < 0.001), for the HCV-infected patients (ρ = 0.343, P < 0.001), and for the patients with metabolic risk factors (ρ = 0.515, P < 0.001). Using CAP, the AUROC values were 0.759, 0.795, 0.715, and 0.716 for ≥moderate steatosis identified by US in, respectively, all the patients, the HBV-infected patients, the HCV-infected patients, and the patients with metabolic risk factors. The AUROC values were 0.791, 0.868, 0.807 and 0.701 for severe steatosis identified by US in, respectively, all the patients, the HBV-infected patients, the HCV-infected patients, and the patients with metabolic risk factors. CONCLUSION: CAP values were well correlated with the steatosis grades assessed by US in real-world clinical practice.
Assuntos
Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico por imagem , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Fígado/patologia , Adulto , Idoso , Área Sob a Curva , Feminino , Humanos , Modelos Lineares , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Taiwan/epidemiologia , UltrassonografiaRESUMO
BACKGROUND AND AIMS: A recent meta-analysis revealed that the genotype PNPLA3 rs738409 GG is associated with a higher risk of hepatic steatosis (HS) in Caucasian patients with chronic hepatitis C (CHC). However, controversial results were found regarding Asian populations. Furthermore, previous studies have shown a negative association between interferon lambda 3 (IFNL3) rs12979860 CC and HS in Caucasian CHC patients, but there have been no reports indicating any such association in Asian populations. In this study, then, we investigated the association of PNPLA3 and IFNL3 polymorphisms with HS in Asian CHC patients. METHODS: We enrolled consecutive CHC patients who underwent liver biopsy prior to antiviral therapy. We excluded those patients with decompensated liver disease, any co-existing chronic liver disease, or HIV or HBV co-infection. RESULTS: 1080 CHC patients were enrolled, and HS was found in 453 (41.9%) patients. The frequency distribution of the G allele was significantly associated with HS (P<0.001), and this conferred a higher risk to G allele homozygotes (OR: 2.06, 95% CI: 1.46-2.88, P <0.001) than to G allele carriers (OR: 1.98, 95% CI: 1.52-2.58, P<0.001). There was a borderline significant difference in the prevalence of HS in rs12979860 CC versus non-CC (40.8% versus 49.3%, P = 0.059). After adjustment for age, sex, body mass index, diabetes, and excessive alcohol intake, the rs738409 G allele homozygote carriers still carried a higher risk for HS (OR: 1.93, 95% CI: 1.35-2.77, P = 0.003). CONCLUSION: The PNPLA3 rs738409 GG genotype is positively associated with HS, while the IFNL3 rs 12979860 CC genotype may be negatively associated with HS, in Asian CHC patients.