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BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk persists in chronic hepatitis B (CHB) patients despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain. METHODS: This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2,000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable. RESULTS: In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared to those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk. CONCLUSION: Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic CHB patients. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in CHB patients.
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BACKGROUND AND AIMS: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. APPROACH AND RESULTS: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). CONCLUSIONS: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.
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Antivirais , Carcinoma Hepatocelular , Antígenos E da Hepatite B , Hepatite B Crônica , Neoplasias Hepáticas , Carga Viral , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Masculino , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Feminino , Pessoa de Meia-Idade , Antígenos E da Hepatite B/sangue , Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Adulto , Taiwan/epidemiologia , Vírus da Hepatite B , Hong Kong/epidemiologia , República da Coreia/epidemiologia , Estudos de Coortes , Tenofovir/uso terapêutico , Guanina/análogos & derivados , Guanina/uso terapêutico , DNA Viral/sangue , Incidência , Fatores de RiscoRESUMO
Backgound and Objectives: The treatments of choice for patients with early-stage hepatocellular carcinoma (HCC) are surgical resection, local ablation therapy, and liver transplantation; however, transarterial chemoembolization (TACE) is commonly performed due to variations among patients and liver diseases. This study aimed to assess the efficacy of TACE in patients with early-stage HCC. Materials and Methods: A retrospective analysis was performed of all TACE procedures performed at Kyung Hee University Hospital at Gangdong over a 15-year period (July 2006 to November 2021). The study included a total of 97 eligible patients with early-stage HCC ≤ 5 cm initially treated with TACE. The mean participant age was 63.47 ± 11.02 years; 69 were men (71.1%). The number of Child-Pugh class A patients was the highest (74 patients [76.3%]), followed by Child-Pugh class B (19 patients [19.6%]) and Child-Pugh class C (4 patients [4.12%]). Results: A complete response was achieved in 84 (86.6%) patients after the first TACE procedure, with 1-, 2-, and 3-year survival rates of 91.8%, 87.3%, and 75.4%, respectively. In the multivariate analysis, the patients with a low initial alpha-fetoprotein (AFP) ≤ 20 ng/mL (p = 0.02) and a complete response after the first TACE (p = 0.03) were associated with favorable overall survival. Conclusions: TACE can be used to treat patients with early-stage HCC who are unsuitable for ablation or surgery. If patients are well selected, TACE may be an alternative treatment for patients with low AFP levels who respond well to the initial TACE procedure.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas , Estudos Retrospectivos , Resultado do Tratamento , Estadiamento de Neoplasias , Quimioembolização Terapêutica/efeitos adversos , Resposta Patológica CompletaRESUMO
Endoscopic resection (ER) is an effective treatment for early gastric cancer (EGC) without metastases. Existing endoscopic mucosal resection (EMR) is easy to perform, has few complications, and can be applied when the lesion size is small. However, en bloc and complete resection rates vary depending on the size and severity of the lesion. EMR using the cap-mounted panendoscopic method and EMR after circumferential preamputation of the lesion are useful in the treatment of EGC. However, completely oversized lesions (≥2 cm) and lesions associated with ulcers or submucosal fibrosis are more likely to fail resection. Endoscopic submucosal dissection has been widely used to resect tumors larger than 2 cm in diameter and has a higher acceptable complication rate and en bloc and complete resection rates than EMR. ER for EGC is superior to surgical resection in terms of improving patient quality of life. Additionally, compared to surgery, emergency rooms have a lower rate of treatment-related complications, shorter hospital stays, and lower costs. Accordingly, the indications for ER are expanding in the field of therapeutic endoscopy. Long-term outcomes regarding recurrence are excellent in both absolute and extended criteria for ER in EGC. Close surveillance should be performed after ER to detect early metachronous gastric cancer and precancerous lesions that can be treated with ER. Follow-up gastroscopy and abdominopelvic computed tomography scans every 6 to 12 months are recommended for patients who undergo curative ER for EGC on absolute or extended criteria.
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Hepatite C Crônica , Hepatite C , Humanos , Sofosbuvir/uso terapêutico , Lactamas Macrocíclicas/uso terapêutico , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Antivirais/efeitos adversos , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepacivirus/genética , Genótipo , Resultado do Tratamento , Quimioterapia CombinadaRESUMO
INTRODUCTION: Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) for the prevention of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B; however, it has distinct long-term renal and bone toxicities. This study aimed to develop and validate a machine learning model (designated as Prediction of Liver cancer using Artificial intelligence-driven model for Network-antiviral Selection for hepatitis B [PLAN-S]) to predict an individualized risk of HCC during ETV or TDF therapy. METHODS: This multinational study included 13,970 patients with chronic hepatitis B. The derivation (n = 6,790), Korean validation (n = 4,543), and Hong Kong-Taiwan validation cohorts (n = 2,637) were established. Patients were classified as the TDF-superior group when a PLAN-S-predicted HCC risk under ETV treatment is greater than under TDF treatment, and the others were defined as the TDF-nonsuperior group. RESULTS: The PLAN-S model was derived using 8 variables and generated a c-index between 0.67 and 0.78 for each cohort. The TDF-superior group included a higher proportion of male patients and patients with cirrhosis than the TDF-nonsuperior group. In the derivation, Korean validation, and Hong Kong-Taiwan validation cohorts, 65.3%, 63.5%, and 76.4% of patients were classified as the TDF-superior group, respectively. In the TDF-superior group of each cohort, TDF was associated with a significantly lower risk of HCC than ETV (hazard ratio = 0.60-0.73, all P < 0.05). In the TDF-nonsuperior group, however, there was no significant difference between the 2 drugs (hazard ratio = 1.16-1.29, all P > 0.1). DISCUSSION: Considering the individual HCC risk predicted by PLAN-S and the potential TDF-related toxicities, TDF and ETV treatment may be recommended for the TDF-superior and TDF-nonsuperior groups, respectively.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Masculino , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/complicações , Inteligência Artificial , Neoplasias Hepáticas/complicações , Resultado do Tratamento , Tenofovir/uso terapêutico , Aprendizado de Máquina , Vírus da Hepatite B , Estudos RetrospectivosRESUMO
Background and Objectives: The risk of bleeding after endoscopic procedures in patients with liver cirrhosis remains unclear because of secondary blood coagulation disorders. In this study, we used various indices to evaluate the risk of bleeding in patients with cirrhosis. Materials and Methods: Patients with liver cirrhosis aged ≥18 years who underwent endoscopic interventions at Kyung Hee University Hospital at Gangdong between February 2007 and September 2021 were included. Clinical information, including demographic data, laboratory results, the presence of cirrhosis complications, and the degree of fibrosis, was checked and evaluated based on medical records. Results: A total of 101 patients with cirrhosis were analyzed. A total of 16 of the 101 patients (15.8%) experienced bleeding after the endoscopic procedure. One patient (0.99%) presented with spurting, while the others presented with mild oozing. All patients underwent hemostatic procedures using hemoclips. The presence of a varix significantly increased post-endoscopic bleeding (p = 0.03). Patients with FIB > 3.25 showed a statistically significant bleeding tendency (p = 0.00). Conclusions: There was no significant difference in bleeding risk according to the platelet count, prothrombin time, Child−Pugh score, and model for end-stage liver disease (MELD). Considering the degree of liver fibrosis and the invasiveness of the planned procedure, most endoscopic procedures can be performed safely but should be further evaluated in a cohort with a larger sample size.
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Doença Hepática Terminal , Humanos , Adolescente , Adulto , Estudos Retrospectivos , Doença Hepática Terminal/complicações , Hemorragia Gastrointestinal/etiologia , Índice de Gravidade de Doença , Cirrose Hepática/complicações , EndoscopiaRESUMO
BACKGROUND & AIMS: The comparative risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) receiving tenofovir disoproxil fumarate (TDF) vs. entecavir (ETV) remains controversial. In this individual patient data (IPD) meta-analysis, we aimed to compare HCC risk between the two drugs and identify subgroups who may benefit more from one treatment than the other. METHODS: Published meta-analyses, electronic databases and congress proceedings were searched to identify eligible studies through January 2021. We compared HCC risk between the two drugs using a multivariable Cox proportional hazards model with anonymised IPD from treatment-naïve patients with CHB receiving TDF or ETV for ≥1 year. Treatment effect consistency was explored in propensity score matching (PSM), weighting (PSW) and subgroup analyses for age, sex, hepatitis B e-antigen (HBeAg) positivity, cirrhosis and diabetes status. RESULTS: We included 11 studies from Korea, Taiwan and Hong Kong involving 42,939 patients receiving TDF (n = 6,979) or ETV (n = 35,960) monotherapy. Patients receiving TDF had significantly lower HCC risk (adjusted hazard ratio [HR] 0.77; 95% CI 0.61-0.98; p = 0.03). Lower HCC risk with TDF was consistently observed in PSM (HR 0.73; 95% CI 0.59-0.88; p <0.01) and PSW (HR 0.83; 95% CI 0.67-1.03; p = 0.10) analyses and in all subgroups, with statistical significance in the ≥50 years of age (HR 0.76; 95% CI 0.58-1.00; p <0.05), male (HR 0.74; 95% CI 0.58-0.96; p = 0.02), HBeAg-positive (HR 0.69; 95% CI 0.49-0.97; p = 0.03) and non-diabetic (HR 0.79; 95% CI 0.63-1.00; p <0.05) subgroups. CONCLUSION: TDF was associated with significantly lower HCC risk than ETV in patients with CHB, particularly those with HBeAg positivity. Longer follow-up may be needed to better define incidence differences between the treatments in various subgroups. IMPACT AND IMPLICATIONS: Previous aggregate data meta-analyses have reported inconsistent conclusions on the relative effectiveness of tenofovir disoproxil fumarate and entecavir in reducing hepatocellular carcinoma risk in patients with chronic hepatitis B (CHB). This individual patient data meta-analysis on 11 studies involving 42,939 patients from Korea, Taiwan and Hong Kong suggested that tenofovir disoproxil fumarate-treated patients have a significantly lower hepatocellular carcinoma risk than entecavir-treated patients, which was observed in all subgroups of clinical interest and by different analytical methodologies. These findings should be taken into account by healthcare providers when determining the optimal course of treatment for patients with CHB and may be considered in ensuring that treatment guidelines for CHB remain pertinent.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Masculino , Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Antígenos E da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Estudos Retrospectivos , Tenofovir/uso terapêutico , Resultado do Tratamento , Feminino , Pessoa de Meia-IdadeRESUMO
Introduction: In spite of the high frequency of recurrence of hepatocellular carcinoma (HCC) after resection, little evidence exists to directly help to plan a reasonable schedule for the frequency and intensity of postoperative surveillance for recurrence. Methods: 1,918 consecutive patients with Child-Turcott-Pugh class A who had T1- or T2-staged HCCs detected by active surveillance and underwent curative resection for their tumors at 3 teaching hospitals in Korea, followed by recurrence screening at 6-monthly or shorter intervals. To set an evidence-based timetable for postoperative surveillance, we investigated the annual hazard rate of recurrence through postoperative year 10 in patients undergoing hepatectomy for HCC, and the clinical and morphological phenotypes associated with early versus late recurrence. Results: The estimated hazard rate for recurrence peaked during year 0-1 (21.7%), with a subsequent gradual decrease through 5 years, followed by stabilization at <7.0% until year 10, except in the case of cirrhotics, who had a rate of 10.5% during year 4-5. Multivariate time-to-recurrence analysis by recurrence period revealed that serum alpha-fetoprotein ≥200 ng/mL, larger size of tumor, tumor multiplicity, microvascular invasion, capsular invasion, and higher METAVIR fibrosis stage were significantly related to disease recurrence within 5 years after resection, while cirrhosis (METAVIR F4) alone was related to disease recurrence beyond 5 years (Ps < 0.05). Post-relapse overall survival was better in the latter group (p = 0.033). Conclusions: Our chronological and morphological insights into recurrence after resection of primary HCCs may help implement an optimal intensity of surveillance for recurrence.
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INTRODUCTION: Chronic hepatitis B (CHB) is a major cause of chronic liver diseases and tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV) are recommended as primary treatments. This study aimed to evaluate the efficacy and safety of ETV, TDF, and TAF in a real-world clinical setting. METHODS: In this retrospective cohort study, a total of 363 CHB patients who were treated with ETV (n = 163), TDF (n = 154), or TAF (n = 46) from July 2007 to September 2019 were enrolled. RESULTS: Median patient age was 51 years and 66.4% of patients were male. Median duration of treatment with ETV, TDF, or TAF was 49.0 months (interquartile range, 27.0-74.0 months). In terms of safety, cholesterol was mildly increased in the ETV and TAF groups and significantly lowered in the TDF group than baseline (p < 0.001). There was no significant difference in liver cirrhosis-related complications among the 3 groups at 48 weeks (p = 0.235). Hepatitis B e antigen seroconversion, complete virological response, and alanine aminotransferase normalization at 48 weeks as measures of treatment efficacy were not significantly different among the 3 groups (p = 0.142, 0.538, and 0.520, respectively). There was also no significant difference in cumulative incidence rate of hepatocellular carcinoma (HCC) between the ETV and TDF groups (p = 0.894). CONCLUSIONS: ETV, TDF, and TAF were safe antiviral agents and showed similar antiviral effect for CHB at 48 weeks. Cirrhosis-related complications and annual HCC incidence rates did not differ significantly between the ETV and TDF groups over the 48 week follow-up period.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Alanina , Antivirais/efeitos adversos , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tenofovir/efeitos adversos , Tenofovir/análogos & derivados , Resultado do TratamentoRESUMO
Background/Aims: The coronavirus disease 2019 (COVID-19) outbreak caused numerous social and cultural changes, but few studies focused on their effects on gastroenterology (GI) fellowship training. This study evaluated the impact of COVID-19 on GI fellowship training. Methods: A web-based questionnaire was sent out to GI fellows in Korea between 15 February and 15 March 2021. The questionnaire included questions regarding the characteristics of GI fellows, perception of COVID-19 outbreak, impact of COVID-19 outbreak, and telemedicine on the education of a GI fellowship. Results: Among 111 answers, 94 respondents were analyzed. The GI fellows were provided with sufficient information about the COVID-19 outbreak (74.7%), well educated, and provided with personal protective equipment use (74.7% and 83.9%, respectively). On the other hand, outpatient schedule and volume decreased in 25.5% and 37.8% of respondents, respectively. Moreover, endoscopy sessions and volume decreased in 51.1% and 65.6% of respondents, respectively. As a result, 78.9% of respondents were concerned that the COVID-19 outbreak adversely affected their education. Telemedicine utilization was introduced during the COVID-19 outbreak, but only 20.0% and 10.6% of respondents agreed that telemedicine has benefits from the patient's and doctor's perspectives, respectively. In addition, only 25.9% of respondents were willing to continue telemedicine if adequately reimbursed, and 68.2% of respondents were concerned that it adversely affected their education. Conclusions: The COVID-19 outbreak has adversely affected GI fellowship training in Korea for outpatient clinics, gastrointestinal endoscopy, educational conferences, and telemedicine. This study highlights that GI fellowship training needs more attention in the COVID-19 outbreak.
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COVID-19/patologia , Educação Médica/estatística & dados numéricos , Gastroenterologia/educação , Médicos/psicologia , Adulto , COVID-19/epidemiologia , COVID-19/virologia , Bolsas de Estudo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , SARS-CoV-2/isolamento & purificação , Inquéritos e Questionários , TelemedicinaRESUMO
BACKGROUND: Identification of a simplified prediction model for lymph node metastasis (LNM) for patients with early colorectal cancer (CRC) is urgently needed to determine treatment and follow-up strategies. Therefore, in this study, we aimed to develop an accurate predictive model for LNM in early CRC. METHODS: We analyzed data from the 2004-2016 Surveillance Epidemiology and End Results database to develop and validate prediction models for LNM. Seven models, namely, logistic regression, XGBoost, k-nearest neighbors, classification and regression trees model, support vector machines, neural network, and random forest (RF) models, were used. RESULTS: A total of 26,733 patients with a diagnosis of early CRC (T1) were analyzed. The models included 8 independent prognostic variables; age at diagnosis, sex, race, primary site, histologic type, tumor grade, and, tumor size. LNM was significantly more frequent in patients with larger tumors, women, younger patients, and patients with more poorly differentiated tumor. The RF model showed the best predictive performance in comparison to the other method, achieving an accuracy of 96.0%, a sensitivity of 99.7%, a specificity of 92.9%, and an area under the curve of 0.991. Tumor size is the most important features in predicting LNM in early CRC. CONCLUSION: We established a simplified reproducible predictive model for LNM in early CRC that could be used to guide treatment decisions. These findings warrant further confirmation in large prospective clinical trials.
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The recent incidence and management patterns of alcohol-related liver disease (ARLD) are not well defined in Korea. We sought to evaluate the epidemiology of ARLD with regard to disease severity and alcohol cessation management after diagnosis. We performed an observational cohort study of standardized Common Data Model data from the Health Insurance Review and Assessment-National Patient Samples database between 2012 and 2016. The incidence and demographic properties of ARLD were extracted and divided into non-cirrhotic alcoholic liver disease (ALD) and alcoholic liver cirrhosis (ALC). ALC was compared with non-alcoholic cirrhosis by severity at diagnosis. The management patterns were captured by the initiation of pharmaco- and behavioral therapy for alcohol cessation. We analyzed data from 72,556 ALD to 7295 ALC patients. The ALD incidence was stable from 990 to 1025 per 100,000 people. In ALD, the proportion of patients who were ≥ 65 years old, the proportion of female patients, and the comorbidity index increased significantly during the study period (all P values < 0.001). ALC accounted for > 20% of all cirrhosis, with decompensation occurring twice as often as in non-alcoholic cirrhosis. The initiation of alcoholism management was stationary in ARLD, remaining at < 10% for both pharmacotherapy and behavioral therapy, regardless of severity or the site of diagnosis. The incidence of ARLD did not decrease during the study period. Moreover, an increasing trend in the proportion of people vulnerable to drinking was observed. Unfortunately, management for the cessation of alcohol use remains very low. The best way to manage ARLD should be evaluated in further study.
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Hepatopatias Alcoólicas/epidemiologia , Adulto , Idoso , Estudos de Coortes , Terapia Combinada , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Cirrose Hepática Alcoólica/diagnóstico , Cirrose Hepática Alcoólica/epidemiologia , Cirrose Hepática Alcoólica/etiologia , Cirrose Hepática Alcoólica/terapia , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/terapia , Masculino , Pessoa de Meia-Idade , Vigilância da População , República da Coreia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Recently, new direct-acting antivirals (DAAs) are known to eradicate chronic hepatitis C (CHC) virus infection and prevent the progression of liver fibrosis. Liver fibrosis may predispose to liver cirrhosis or hepatocellular carcinoma. We investigated the effect of DAAs on liver fibrosis using non-invasive methods, and evaluated the correlations of these methods. METHODS: We retrospectively analyzed 68 patients with CHC who were treated with DAAs and reached sustained virologic response at 12 weeks post-treatment from January 2016 to October 2018. The degree of liver fibrosis was assessed using serum biomarkers, such as AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. Liver stiffness was assessed using two-dimensional shear-wave elastography (2 D-SWE). The pre- and post-treatment serum biomarker levels and SWE findings were evaluated and compared. RESULTS: A total of 68 patients with CHC were enrolled. The median age was 58 years (52.3-73 years) and 37 patients (54.4%) were female. After treatment, the median APRI was decreased from 0.701 to 0.328 (P < 0.0001), and the median FIB-4 was decreased from 2.355 to 1.860 (P < 0.0001). The median kPa in 2 D-SWE significantly reduced from 6.85 to 5.66 (P = 0.013). APRI and FIB-4 were significantly correlated pre- and post-treatment; however, the correlation between the serum biomarkers and 2 D-SWE was partially significant. CONCLUSION: The serum fibrosis biomarkers and liver stiffness on 2 D-SWE were shown to be improved after the treatment with DAAs. Further research including larger number of patients is needed to compare the efficacy of each evaluating method.
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Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Idoso , Antivirais , Biomarcadores/sangue , Feminino , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 µL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8â¯mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.
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Agonistas do Receptor A2 de Adenosina/administração & dosagem , Tetracloreto de Carbono/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Polidesoxirribonucleotídeos/administração & dosagem , Agonistas do Receptor A2 de Adenosina/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Polidesoxirribonucleotídeos/farmacologia , Resultado do TratamentoRESUMO
Biologicals like anti-tumor necrosis factor (TNF) therapy for Crohn's disease (CD) are safe and effective but there is a significant rate of primary and secondary nonresponse in the patients. In this study, we applied a computational approach to discover novel drug therapies for anti-TNF refractory CD in silico. We use a transcriptome dataset (GSE100833) for the anti-TNF refractory CD patients from NCBI GEO. After co-expression analysis, we specifically investigated the extent of protein-protein interactions among genes in clusters based on a protein-protein interaction database, STRING. Pathway analysis was performed using the clEnrich function based on KEGG gene sets. Co-expressed genes in cluster 1, 2, 3, 4, up or down-regulated genes and all differentially expressed genes are highly connected. Among them, cluster 1, which is highly enriched for chemokine signaling, also showed enrichment for cytokine-cytokine receptor interaction and identifies several drugs including cyclosporin with known efficacy in CD. Vorinostat, histone deacetylase inhibitors, and piperlongumine, which is known to have inhibitory effect on activity of NF-κB, were also identified. Some alkaloids were also selected as potential therapeutic drugs. These finding suggest that they might serve as a novel therapeutic option for anti-TNF refractory CD and support the use of public molecular data and computational approaches to discover novel therapeutic options for CD.
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Biologia Computacional/métodos , Doença de Crohn/tratamento farmacológico , Descoberta de Drogas/métodos , Reposicionamento de Medicamentos/métodos , Anticorpos Monoclonais/farmacologia , Ciclosporinas/farmacologia , Dioxolanos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Família Multigênica/genética , Mapas de Interação de Proteínas , Transcriptoma/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vorinostat/farmacologiaRESUMO
The human gut microbiota is an important component in the pathogenesis of Crohn's disease (CD), promoting host-microbe imbalances and disturbing intestinal and immune homeostasis. We aimed to assess the potential clinical usefulness of the colonic tissue microbiome for obtaining biomarkers for upper gastrointestinal (UGI) tract involvement in CD. We analyzed colonic tissue samples from 26 CD patients (13 with and 13 without UGI involvement at diagnosis) from the Inflammatory Bowel Disease Multi-Omics Database. QIIME1, DiTaxa, linear discriminant analysis effect size (LEfSe), and PICRUSt2 methods were used to examine microbial dysbiosis. Linear support vector machine (SVM) and random forest classifier (RF) algorithms were used to identify the UGI tract involvement-associated biomarkers. There were no statistically significant differences in community richness, phylogenetic diversity, and phylogenetic distance between the two groups of CD patients. DiTaxa analysis predicted significant association of the species Ruminococcus torques with UGI involvement, which was confirmed by the LEfSe analysis (P = 0.025). For the feature ranking method in both linear SVM and RF models, the species R. torques and age at diagnosis contributed to the combined models. The L-methionine biosynthesis III (P = 0.038) and palmitate biosynthesis II (P = 0.050) were under-represented in CD with UGI involvement. These findings suggest that R. torques might serve as a novel potential biomarker for UGI involvement in CD and its correlations, in addition to a range of bacterial species. The mechanisms of interaction between hosts and R. torques should be further investigated.
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The area of endoscopic application has been continuously expanded since its introduction in the last century and the frequency of its use also increased stiffly in the last decades. Because gastrointestinal endoscopy is naturally exposed to diseased internal organs and contact with pathogenic materials, endoscopy mediated infection or disease transmission becomes a major concern in this field. Gastrointestinal endoscopy is not for single use and the proper reprocessing process is a critical factor for safe and reliable endoscopy procedures. What needed in these circumstances is a practical guideline for reprocessing the endoscope and its accessories which is feasible in the real clinical field to guarantee acceptable prevention of pathogen transmission. This guideline contains principles and instructions of the reprocessing procedure according to the step by step. And it newly includes general information and updated knowledge about endoscopy-mediated infection and disinfection. Multiple societies and working groups participated to revise; Korean Association for the Study of the Liver, the Korean Society of Infectious Diseases, Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Society of Gastroenterology, Korean Society of Gastrointestinal Cancer, Korean Association for the Study of Intestinal Diseases, Korean Pancreatobiliary Association, the Korean Society of Gastrointestinal Endoscopy Nurses and Associates and Korean Society of Gastrointestinal Endoscopy. Through this cooperation, we enhanced communication and established a better concordance. We still need more researches in this field and fill up the unproven area. And our guidelines will be renewed accordingly.
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BACKGROUND: Lactobacillus paracasei and Glycyrrhiza glabra have been reported as having beneficial effects on Helicobacter pylori infection. We aimed to assess the efficacy and safety of fermented milk containing L paracasei HP7 and G glabra in patients with H pylori infection. METHODS: This multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted in 2 hospitals from April to December 2017. Patients with H pylori infection were randomized into either the treatment group (fermented milk with L paracasei HP7 and G glabra) or placebo group (fermented milk only) once daily for 8 weeks. The primary endpoint was the gastric load of H pylori measured by C-urea breath test (UBT). Secondary endpoints were histologic and clinical improvement. RESULTS: A total of 142 patients were randomly allocated to the treatment (nâ=â71) or placebo groups (nâ=â71). Compared to baseline data, the quantitative value of C-UBT at 8 weeks was significantly reduced in the treatment group (from 20.8â±â13.2% to 16.9â±â10.8%, Pâ=â.035), but not in the placebo group (Pâ=â.130). Chronic inflammation improved significantly only in the treatment group (Pâ=â.013), whereas the neutrophil activity deteriorated significantly only in the placebo group (Pâ=â.003). Moreover, the treatment group had significant improvement in gastrointestinal symptoms (Pâ=â.049) and quality of life (Pâ=â.029). No serious adverse events were observed. CONCLUSION: The combination of fermented milk containing L paracasei and G glabra reduced H pylori density and improved histologic inflammation. However, their mechanisms of action should be elucidated in further studies.
Assuntos
Glycyrrhiza/fisiologia , Infecções por Helicobacter/tratamento farmacológico , Lacticaseibacillus paracasei/fisiologia , Leite/microbiologia , Probióticos/administração & dosagem , Adulto , Idoso , Animais , Testes Respiratórios , Método Duplo-Cego , Feminino , Fermentação , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Probióticos/efeitos adversos , Estudos Prospectivos , Qualidade de Vida/psicologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND/AIMS: Little is known for the capacity and quality of colonoscopy, and adherence to colonoscopy surveillance guidelines in Korea. This study aimed to investigate the present and potential colonoscopic capacity, colonoscopic quality, and adherence to colonoscopy surveillance guidelines in Korea. METHODS: We surveyed representative endoscopists of 72 endoscopy units from June to August 2015, using a 36-item questionnaire regarding colonoscopic capacity, quality, and adherence to colonoscopy surveillance guidelines of each hospitals. RESULTS: Among the 62 respondents who answered the questionnaire, 51 respondents were analyzed after exclusion of 11 incomplete answers. Only 1 of 3 of endoscopy units can afford to perform additional colonoscopies in addition to current practice, and the potential maximum number of colonoscopies per week was only 42. The quality of colonoscopy was variable as reporting of quality indicators of colonoscopy were considerably variable (29.4%-94.1%) between endoscopy units. Furthermore, there are substantial gaps in the adherence to colonoscopy surveillance guidelines, as concordance rate for guideline recommendation was less than 50% in most scenarios. CONCLUSIONS: The potential capacity and quality of colonoscopy in Korea was suboptimal. Considering suboptimal reporting of colonoscopic quality indicators and low adherence rate for colonoscopy surveillance guidelines, quality improvement of colonoscopy should be underlined in Korea.