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Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma

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World Journal of Gastroenterology 2013年第16期19卷 2449-2455页

作者： Lydia Giannitrapani Maurizio Soresi Daniele Balasus Anna Licata Giuseppe Montalto Unit of internal medicine Biomedical Department of Internal Medicine and Specialties DiBiMIS University of Palermo

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellu-lar carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV coinfected patients show a higher prevalence of the lowproducer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.

关键词： Single nucleotide polymorphisms Interleukin-6 Chronic hepatitis Liver cirrhosis Hepatocellular carcinoma

Food allergy in irritable bowel syndrome:The case of non-celiac wheat sensitivity

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World Journal of Gastroenterology 2015年第23期21卷 7089-7109页

作者： Pasquale Mansueto Alberto D'Alcamo Aurelio Seidita Antonio Carroccio biomedical department of internal medicine and specialist University Hospital of Palermo internal medicine department Hospital of Sciacca (Agrigento)

Irritable bowel syndrome(IBS) is one of the most common gastrointestinal disorders, having a prevalence of 12%-30% in the general population. Most patientswith IBS attribute their symptoms to adverse food reactions. We review the role of diet in the pathogenesis of IBS and the importance of dietary factors in the management of these patients. The MEDLINE electronic database(1966 to Jan 2015) was searched using the following keywords: "food", "diet", "food allergy", "food hypersensitivity", "food intolerance", "IBS", "epidemiology", "pathogenesis", "pathophysiology", "diagnosis", "treatment". We found 153 eligible papers; 80 were excluded because: not written in English, exclusive biochemical and experimental research, case reports, reviews, and research otherwise not relevant to our specific interest. We selected 73 papers: 43 original papers, 26 reviews and 4 letters to the editor. These papers focused on IBS pathogenesis, the association between IBS and atopy, and between IBS and food allergy, the relationship between IBS and non-celiac wheat sensitivity, the role of diet in IBS. Pending further scientific evidence, a cautious approach is advisable but the concept of food allergy should be included as a possible cause of IBS, and a dietary approach may have a place in the routine clinical management of IBS.

关键词： Irritable bowel syndrome Food allergy Food intolerance Non-celiac wheat sensitivity Atopy Asthma Elimination diet

Safety of pegylated interferon and ribavirin therapy for chronic hepatitis C in patients with sickle cell anemia

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World Journal of Hepatology 2010年第5期2卷 180-184页

作者： Hussain Issa Division of Gastroenterology Department of Internal MedicineKing Fahad Specialist Hospital

AIM:To evaluate the safety and efficacy of combined pegylated interferon and ribavirin for the treatment of chronic hepatitis C(HCV)in patients with sickle cell anemia(SCA). METHODS:Fifty-two patients with SCA and HCV were treated over a period of 7 years from June 2002 to July *** medical records were reviewed for:age at treatment,sex,body mass index,Hb level at the start of therapy and on follow-up,hemoglobin electrophoresis,liver function tests,G6PD level,LDH, bilirubin,HCV-RNA viral load,HCV genotype,liver biopsy,duration of treatment,and side *** were treated with pegylated interferon and a standard dose of *** treatment was continued for 24 wk for those with genotype 2 and 3 and for 48 wk for those with genotype 1 and 4. RESULTS:Fifty-two patients(30 females and 22 males) were *** mean age was 29.5 years(range 15-54 years).HCV genotype was determined in 48 and 15 had liver *** mean pre-treatment HCV-RNA viral load was 986330 IU/mL(range 12762-3329282 IU/mL).The liver biopsy showed gradeⅠin 6 and gradeⅡin 9 and stageⅠin 13 and stageⅡin *** 8 were receiving hydroxyurea at the time of *** tolerated the treatment well and none experienced a decrease in their Hb which required blood transfusion pre,during or after *** were no hematological side effects attributable to ribavirin at the usual recommended ***-seven(71.2%)achieved SVR at 6 mo after the end of *** remaining 15 were *** of them showed an ETR but had a *** remaining 13 had a relatively significant HCV-RNA viral load with a mean HCV-RNA viral load of 1829741.2 IU/mL(900000-3329282 IU/mL) and eight of them had HCV genotype 1,four had HCV genotype 4,and one had HCV genotype 5. CONCLUSION:Patients with SCA and HCV can be treated with pegylated interferon and ribavirin at the usual recommended *** is even so in those who are not receiving *** treatment is safe and effective and the resp

关键词： Sickle cell anemia Chronic hepatitis C Treatment

Acute distal common bile duct angle is risk factor for postendoscopic retrograde cholangiopancreatography pancreatitis in beginner endoscopist

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World Journal of Clinical Cases 2020年第1期8卷 20-28页

作者： Sung Yong Han Dong Uk Kim Moon Won Lee Young Joo Park Dong Hoon Baek Gwang Ha Kim Geun Am Song Division of Gastroenterology Department of Internal Medicine and Biomedical Research Institute Pusan National University Hospital

BACKGROUND Post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP)is a critical and poorly managed complication of ERCP. Endoscopists need to understand the risk factors for PEP. However, the majority of studies investigating ERCP-related risk factors have included well-trained endoscopists,with the issue of endoscopist experience on PEP incidence not having been systematically *** To explore the risk factors for PEP in beginner endoscopists without *** We performed a retrospective analysis of 293 patients, with na?ve papilla and no history of pancreatitis, treated using bile duct cannulation. Patients were classified according to the endoscopist’s experience(beginner vs expert). The angle of the distal common bile duct(CBD) was measured as the angle between the lower wall of the bile duct and a vertical line extending to the lower wall of the bile duct on coronal view computed *** After propensity matching, there were no differences between patients treated by the expert and beginner endoscopist with regard to age, sex, mean bile duct dilatation, and ratio of benign disease. The distal CBD angle was classified as acute(> 30o) or obtuse(≤ 30o), based on the mean angle of 29.9o for the group. An acute distal CBD angle was a significant risk factor for PEP for beginner(P =0.049), but not *** For beginner endoscopists first performing unsupervised ERCP, cases with an obtuse distal CBD angle may be more appropriate to lower the risk of PEP.

关键词： Common bile duct angle Endoscopic retrograde cholangiopancreatography Novice learner Pancreatitis Risk factor Begginer endoscopist

New magnifying endoscopic classification for superficial esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2017年第24期23卷 4416-4421页

作者： Su Jin Kim Gwang Ha Kim Moon Won Lee Hye Kyung Jeon Dong Hoon Baek Bong Eun Lee Geun Am Song department of internal medicine Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and TechnologyPusan National University Yangsan Hospital department of internal medicine Pusan National University School of Medicine and Biomedical Research InstitutePusan National University Hospital

To assess the accuracy of a new magnifying endoscopy (ME) classification for predicting depth of invasion of superficial esophageal squamous cell carcinoma (SESCC). METHODSThis study included a total of 70 lesions in 69 patients with SESCC who underwent ME with narrow-band imaging (ME-NBI) before resection from August 2010 to July 2016. Accuracy of ME-NBI for predicting depth of invasion of SESCC was analyzed by using a new ME classification proposed by the Japan Esophageal Society (JES), and interobserver agreement was assessed. RESULTSOverall accuracy of ME-NBI for estimating depth of invasion of SESCC was 78.6%. Sensitivity and specificity of type B1 for tumors limited to the epithelial layer (m1) or invading into the lamina propria (m2) were 71.4% and 100%, respectively. Sensitivity and specificity of type B2 for tumors invading into the muscularis mucosa (m3) or superficial submucosa (≤ 200 μm, sm1) were 94.4% and 73.1%, respectively, while those of type B3 for tumors invading into the deep submucosa (> 200 μm, sm2) were 75.0% and 97.8%, respectively. Interobserver agreement was excellent (κ = 0.86, 95%CI: 0.76-0.95). CONCLUSIONThe recently developed JES ME classification is useful for predicting depth of invasion of SESCC, with reliable interobserver agreement.

关键词： Narrow-band imaging Esophageal cancer Squamous cell carcinoma Magnifying endoscopy

Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2018年第36期24卷 4104-4118页

作者： Jorge-Luis Torres Ignacio Novo-Veleiro Laura Manzanedo Lucía Alvela-Suárez Ronald Macías Francisco-Javier Laso Miguel Marcos department of internal medicine University Hospital of SalamancaInstitute of Biomedical Research of Salamanca-IBSAL Spanish Working Group on Alcohol and Alcoholism Spanish Society of Internal Medicine department of internal medicine University Hospital of Santiago de Compostela department of internal medicine HM Rosaleda HospitalSantiago de Compostela department of medicine Faculty of MedicineUniversity of Salamanca

MicroRNAs(miRNAs) are small non-coding RNAs that regulate multiple physiological and pathological functions through the modulation of gene expression at the post-transcriptional level. Accumulating evidence has established a role for miRNAs in the development and pathogenesis of liver disease. Specifically, a large number of studies have assessed the role of miRNAsin alcoholic liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD), two diseases that share common underlying mechanisms and pathological characteristics. The purpose of the current review is to summarize and update the body of literature investigating the role of miRNAs in liver disease. In addition, the potential use of miRNAs as biomarkers and/or therapeutic targets is discussed. Among all miRNAs analyzed, miR-34 a, miR-122 and miR-155 are most involved in the pathogenesis of NAFLD. Of note, these three miRNAs have also been implicated in ALD, reinforcing a common disease mechanism between these two entities and the pleiotropic effects of specific miRNAs. Currently, no single miRNA or panel of miRNAs has been identified for the detection of, or staging of ALD or NAFLD. While promising results have been shown in murine models, no therapeutic based-miRNA agents have been developed for use in humans with liver disease.

关键词： Alcohol use disorder Alcoholic liver disease Non-alcoholic fatty liver disease Steatosis Obesity miRNA Biomarkers

Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis

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World Journal of Gastroenterology 2018年第40期24卷 4606-4614页

作者： Young-Cheol Ju Dae-Won Jun Jun Choi Waqar Khalid Saeed Hyo-Young Lee Hyun-Woo Oh department of Translational medicine Graduate school of Biomedical Science and Engineering Hanyang University department of internal medicine School of Medicine Hanyang University department of Industrial Management Engineering Korea University

AIM To investigate survival rate and incidence of hepatocellular carcinoma(HCC) in patients with decompensated cirrhosis in the antiviral *** We used the Korean Health Insurance Review and Assessment. Korea's health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance ***, 48365 antiviral treatment-na?ve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1 st decompensated chronic hepatitis B(CHB) and treatment-na?ve patients(n = 7166). RESULTS The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1^(st) decompensated CHB treatment-na?ve subjects. But the annual mortality rates sharply decreased to 3.4%(2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5%(1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-na?ve patients was 3.4%(2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-na?ve *** Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.

关键词： Hepatitis B Antiviral agent Decompensated cirrhosis Mortality Hepatocellular carcinoma

Incidence, prevalence and risk of stroke in patients with Takayasu arteritis: a nationwide population-based study in South Korea

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Stroke & Vascular Neurology 2022年第2期7卷 149-157页

作者： Sung Soo Ahn Minkyung Han Yong-Beom Park Inkyung Jung Sang-Won Lee department of internal medicine Yongin Severance HospitalYonsei University College of MedicineYonginSouth Korea Biostatistics Collaboration Unit Department of Biomedical Systems InformaticsYonsei University College of MedicineSeoulSouth Korea Division of Rheumatology Department of Internal MedicineYonsei University College of MedicineSeoulSouth Korea Institute for Immunology and Immunological Diseases Yonsei University College of MedicineSeoulSouth Korea Division of Biostatistics Department of Biomedical Systems InformaticsYonsei University College of MedicineSeoulSouth Korea

Background Takayasu arteritis(TAK)is a disease associated with increased risk of cardiovascular *** aimed to evaluate the incidence,prevalence and risk of stroke in patients with *** Data from 1065 patients were obtained from a national database(2010–2018).The annual incidence and prevalence per 100000 persons were estimated using the registration population in the midst of every year,and the standardised incidence ratio(SIR)of stroke was compared with the general population based on the data from the 2006 national report for cardiovascular and cerebrovascular ***-adjusted incidence rate ratio(IRR)of stroke based on the time interval after diagnosis was also calculated.A time-dependent Cox regression was conducted to investigate predictive factors of *** The overall incidence rate of TAK ranged between 0.2 and 0.3/100000 person-years annually;the prevalence of TAK gradually increased,reaching 3.25/100000 person-years in ***-three(6.9%)patients experienced stroke during follow-up,and the risk of developing stroke was higher than the general population(overall SIR 7.39,95%CI 5.79 to 9.29;men:SIR 5.70,95%CI 2.84 to 10.20;women:SIR 7.06,95%CI 5.41 to 9.05).Most stroke events(90.9%)were cerebral infarction for men,whereas the proportion of cerebral infarction was lower(62.9%)in *** half of stroke events occurred within 6 months after diagnosis,and stroke was more common within 6 months of diagnosis compared with after 3 years in women(IRR 13.46,95%CI 6.86 to 26.40).In Cox regression analysis,age was the sole predictor of stroke(adjusted HR 1.02,95%CI 1.00 to 1.04,p=0.043).Conclusions The annual incidence of TAK was similar to the previous studies from Asia,and the risk of stroke increased in *** patterns of subtype and incidence of stroke were found according to sex,although age was the only predictor.

关键词： prevalence patients diagnosis

Naturally occurring mutations in the reverse transcriptase region of hepatitis B virus polymerase from treatment-na?ve Korean patients infected with genotype C2

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World Journal of Gastroenterology 2017年第23期23卷 4222-4232页

作者： Ji-Eun Kim So-Young Lee Hong Kim Ki-Jeong Kim Won-Hyeok Choe Bum-Joon Kim department of biomedical Sciences Microbiology and Immunologyand Liver Research InstituteSeoul National University College of Medicine department of Microbiology School of MedicineJoong-Ang University department of internal medicine Konkuk University School of Medicine

AIM To report naturally occurring mutations in the reverse transcriptase region(RT) of hepatitis B virus(HBV) polymerase from treatment na?ve Korean chronic patients infected with genotype *** Here, full-length HBV reverse transcriptase RT sequences were amplified and sequenced from 131 treatment na?ve 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) at42 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 na?ve 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.

关键词： Hepatitis B virus Polymerase Reverse transcriptase Potential nucleos(t)ide analog resistance Chronic hepatitis Hepatocellular carcinoma