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Prognoses of patients with acute-on-chronic hepatitis B liver failure are closely associated with altered SOCS1 mRNA expression and cytokine production following glucocorticoid treatment

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Cellular & Molecular Immunology 2014年第4期11卷 396-404页

作者： Jian-Jun Zhang Yu-Chen Fan Ze-Hua Zhao Yang Yang Cheng-Yun DOU Shuai Gao Kai Wang Department of hepatology Qilu Hospital of Shandong University Ji'nan China Institute of hepatology Shandong University Ji'nan China

Suppressor of cytokine signaling （SOCS） 1 plays a crucial role in the immune response and might contribute to the prognoses of liver failure treated with glucocorticoid. We recruited 47 acute-on-chronic hepatitis B liver failure （ACHBLF） patients receiving glucocorticoid treatment and 30 healthy controls to determine the potential effects of glucocorticoid on the transcriptional level of SOCS1 in peripheral blood mononuclear cells. On the third and twenty-eighth days of glucocorticoid treatment, SOCS1 expression was negatively correlated with model for end-stage liver disease （MELD） score. Interleukin-6 （IL-6） and tumor-necrosis factor-a （＇I＇NF-a） levels were statistically lower, while the SOCS1 transcription level was higher in survivors than non-survivors both in pre- and post-treatment ACHBLF patients. The methylation rate of the SOCS1 promoter in ACHBLF patients was higher than in healthy control patients as determined by methylation-specific polymerase chain reaction. The mRNA level of SOCS1 in methylated promoters was significantly lower than from patients with unmethylated SOCS1 promoters, interferon （IFN）-y-responsive and STATl-dependent gene expression was higher in survivors and was dramatically decreased with rising expression of SOCS1 after glucocorticoid treatment. Mortality rates were significantly higher in methylated patients than for those without methylation at the end of a 90-day follow-up. Furthermore, we found that five in six surviving patients displayed demethylated SOCS1 on the twenty-eighth day after treatment, while that number was 3 in 10 in the non-survivors. These findings suggested that ACHBLF patients without SOCS1 methylation may have a favorable response to corticosteroid treatment.

关键词： acute-on-chronic hepatitis B liver failure cytokine glucocorticoid treatment methylation SOCS

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Indicators of sorafenib efficacy in patients with advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第35期20卷 12581-12587页

作者： Masayoshi Yada Akihide Masumoto Kenta Motomura Hirotaka Tajiri Yusuke Morita Hideo Suzuki Takeshi Senju Toshimasa Koyanagi Department of hepatology Iizuka Hospital

AIM: To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma (HCC).

关键词： Hand-foot syndrome Hepatocellular carcinoma Indicator of efficacy Sorafenib Time to progression

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Stem cells for liver tissue repair:Current knowledge and perspectives

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World Journal of Gastroenterology 2008年第6期14卷 864-875页

作者： Philippe A Lysy David Campard Fran oise Smets Mustapha Najimi Etienne M Sokal Université Catholique de Louvain & Cliniques Universitaires Saint Luc HPED Department Unit PEDI Laboratory of Pediatric Hepatology and Cell Therapy Brussels 1200 Belgium

Stem cells from extra-or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being increasingly considered for future applications in liver cell therapy. In that field, liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation, while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures. However, the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype, both in vitro and in vivo. Furthermore, the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures. The present review focuses on the current knowledge of the stem cell potential for liver therapy. We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo. We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.

关键词： Stem cells Hepatocyte differentiation Liver regeneration Cell therapy

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Hepatocellular carcinoma or interferon-based therapy history attenuates sofosbuvir/ribavirin for Japanese genotype 2 hepatitis C virus

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World Journal of Gastroenterology 2018年第13期24卷 1478-1485页

作者： Masayoshi Yada Masayuki Miyazaki Kosuke Tanaka Akihide Masumoto Kenta Motomura Department of hepatology Iizuka Hospital

AIM To investigate the real-world efficacy and safety of sofosbuvir/ribavirin(SOF/RBV) therapy for Japanese patients with genotype 2 hepatitis C virus(GT2-HCV).METHODS A total of 182 patients with GT2-HCV infection who received SOF/RBV therapy for 12 wk at our hospital were enrolled. The patients comprised 122 men and 60 women(age range: 17-84 years; mean age ± SD: 60.1 ± 12.1 years). Relationships between virological response and clinical data were examined by logistic regression analyses. RESULTS The proportions of patients with liver cirrhosis and history of hepatocellular carcinoma(HCC) were 29.0% and 17.3%, respectively. The proportion of patients with prior interferon(IFN)-based therapy was 25.6%. SOF/RBV therapy rapidly decreased HCV RNA levels. Several patients required RBV dose reduction because of anemia or fatigue. Four patients discontinued the therapy. The rates of sustained virological response at 12 wk after the end of treatment were 87.9%(intention to treat: 160/182) and 94.1%(per protocol: 159/169). Multivariate analyses showed that history of HCC or IFN-based therapy independently reduced the efficacy of SOF/RBV therapy. CONCLUSION SOF/RBV therapy for GT2-HCV is safe, highly tolerated, and effective. History of HCC or IFN-based therapy independently reduces the efficacy of this treatment.

关键词： Sofosbuvir Ribavirin Genotype 2 Hepatitis C virus Interferon-based therapy Hepatocellular carcinoma

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Bile-acid-induced cell injury and protection

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World Journal of Gastroenterology 2009年第14期15卷 1677-1689页

作者： Maria J Perez Oscar Briz Research unit University Hospital of Salamanca Laboratory of Experimental hepatology and Drug Targeting CIBERehd University of Salamanca E.D. 129 37007 Salamanca Spain

Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids （BAs） in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyI-N- methylglycine or pharmacological properties. cholylsarcosine, interest owing have also aroused to their protective

关键词： Apoptosis Cholestasis Liver Necrosis Oxidative stress Ursodeoxycholic acid

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How good is endoscopic ultrasound for TNM staging of gastric cancers? A meta-analysis and systematic review

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World Journal of Gastroenterology 2008年第25期14卷 4011-4019页

作者： Srinivas Reddy Puli Jyotsna Batapati Krishna Reddy Matthew L Bechtold Mainor R Antillon Jamal A Ibdah Division of Gastroenterology and hepatology University of Missouri-Columbia

AIM: To evaluate the accuracy of endoscopic ultrasound (EUS) for staging of gastric cancers. METHODS: Only EUS studies confirmed by surgery were selected. Only studies from which a 2 × 2 table could be constructed for true positive, false negative, false positive and true negative values were included. Articles were searched in Medline, Pubmed, Ovid journals, Cumulative index for nursing & allied health literature, International pharmaceutical abstracts, old Medline, Medline nonindexed citations, and Cochrane control trial registry. Two reviewers independently searched and extracted data. The differences were resolved by mutual agreement. 2 × 2 tables were constructed with the data extracted from each study. Meta-analysis for the accuracy of EUS was analyzed by calculating pooled estimates of sensitivity, specifi city, likelihood ratios, and diagnostic odds ratio. Pooling was conducted by both the Mantel-Haenszel method (fi xed effects model) and DerSimonian Laird method (random effects model). The heterogeneity of studies was tested using Cochran's Q test based upon inverse variance weights. RESULTS: Initial search identified 1620 reference articles and of these, 376 relevant articles were selected and reviewed. Twenty-two studies (n = 1896) which met the inclusion criteria were included in this analysis. Pooled sensitivity of T1 was 88.1% (95% CI: 84.5-91.1) and T2 was 82.3% (95% CI: 78.2-86.0). For T3, pooled sensitivity was 89.7% (95% CI: 87.1-92.0). T4 hada pooled sensitivity of 99.2% (95% CI: 97.1-99.9). For nodal staging, the pooled sensitivity for N1 was 58.2% (95% CI: 53.5-62.8) and N2 was 64.9% (95% CI: 60.8-68.8). Pooled sensitivity to diagnose distant metastasis was 73.2% (95% CI: 63.2-81.7). The P for chi-squared heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION: EUS results are more accurate with advanced disease than early disease. If EUS diagnoses advanced disease, such as T4 disease, the patient is 500 times more likely to h

关键词： Gastric cancer Staging Meta-analysis Endoscopic ultrasound

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Current Evidence Concerning Effects of Ketogenic Diet and Intermittent Fasting in Patients with Nonalcoholic Fatty Liver

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Journal of Clinical and Translational hepatology 2022年第4期10卷 730-739页

作者： Pimsiri Sripongpun Chaitong Churuangsuk Chalermrat Bunchorntavakul Gastroenterology and hepatology unit Division of Internal MedicineFaculty of MedicinePrince of Songkla UniversityHat YaiThailand Nutrition and Obesity Management unit Division of Internal MedicineFaculty of MedicinePrince of Songkla UniversityHat YaiThailand Division of Gastroenterology and hepatology Department of MedicineRajavithi HospitalRangsit UniversityBangkokThailand

Nonalcoholic fatty liver disease (NAFLD) is emerging globally, while no therapeutic medication has been approved as an effective treatment to date, lifestyle intervention through dietary modification and physical exercise plays a critical role in NAFLD management. In terms of dietary modification, Mediterranean diet is the most studied dietary pattern and is recommended in many guidelines, however, it may not be feasible and affordable for many patients. Recently, a ketogenic diet and intermittent fasting have gained public attention and have been studied in the role of weight management. This article reviews specifically whether these trendy dietary patterns have an effect on NAFLD outcomes regarding intrahepatic fat content, fibrosis, and liver enzymes, the scientific rationales behind these particular dietary patterns, as well as the safety concerns in some certain patient groups.

关键词： Nonalcoholic fatty liver disease Ketogenic diet,Intermittent fasting Lifestyle modification Weight reduction

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Arterial-phase contrast-enhanced ultrasonography for evaluating anti-angiogenesis treatment: A pilot study

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World Journal of Gastroenterology 2011年第8期17卷 1045-1050页

作者： Keiko Yoshida Tomihiko Hirokawa Fuminori Moriyasu Masahiko Yamada Yasuharu Imai Department of Gastroenterology and hepatology Tokyo Medical University

AIM:To verify whether arterial-phase contrast-enhanced ultrasonography(CEUS) of tumor parenchymal tissue is useful for evaluation of anti-angiogenesis ***:Rabbits with liver tumor were subjected to CEUS,and images of the nodular maximal diameter in vascular phase were *** analysis was performed to plot the time intensity curve(TIC) at the tumor parenchyma,which set the diameter of the region of interest of intensity *** TIC was calculated to obtain the time to peak intensity(TPI) and the magnitude of *** were randomly assigned to a treatment group with sorafenib and a control *** weeks later,the same ultrasound examination was repeated followed by pathological testing to assess the effect of sorafenib on the liver ***:In four rabbits in the treatment group,the rate of change of tumor size was decreased comparedwith that of the control(the rate 2.3 vs 7.9,P = 0.02).The TPI of the treatment group elongated significantly(the rate 3.1 vs 1.1,P = 0.07 for SonoVue,2.0 vs 0.88,P = 0.09 for Sonazoid).The magnitude of PI showed no significant *** pathological examination,capillary diameters in the treatment group were significantly smaller than those in the control group(26.4 vs 42.8 μm,P = 0.013).CONCLUSION:Analysis of the TIC in the arterial phase of tumor tissue could evaluate the efficacy of antiangiogenesis drug treatment in liver tumor.

关键词： Liver tumor Ultrasound agent Contrast-enhanced ultrasonography Sorafenib Animal model

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Emerging Therapeutic Strategies in The Fight Against Primary Biliary Cholangitis

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Journal of Clinical and Translational hepatology 2023年第4期11卷 949-957页

作者： Abigail Medford Jonathan Childs Ashleigh Little Sanjukta Chakraborty Leonardo Baiocchi Gianfranco Alpini Shannon Glaser Department of Medical Physiology Texas A&M University School of MedicineBryanTXUSA hepatology unit University of Tor VergataRomeItaly Division of Gastroenterology and hepatology Department of MedicineIndiana University School of MedicineIndianapolisINUSA

The liver has a vital role in many metabolic and regulatory processes in the *** biliary cholangitis(PBC),previously known as primary biliary cirrhosis,is a chronic cholestatic autoimmune disease of the intrahepatic bile ducts associated with loss of tolerance to mitochondrial *** this time there is no definitive cure for PBC;however,ursodeoxycholic acid(UDCA)has been shown to reduce injury when administered as the first line of *** therapeutics can be given concurrently or as an alternative to UDCA to manage the symptoms and further curb disease ***,a liver transplant is the only potentially curative option when the patient has developed end-stage liver disease or intractable *** review aims to delineate the pathogenesis of primary biliary cholangitis and shed light on current therapeutic strategies in the treatment of PBC.

关键词： Cholestatic liver disease Therapeutic approaches Biliary epithelia ursodeoxycholic acid

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Appropriateness of colonoscopy: Diagnostic yield and safety in guidelines

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World Journal of Gastroenterology 2007年第12期13卷 1816-1819页

作者： Mario Grassini Carlo Verna Paolo Niola Monica Navino Edda Battaglia Gabrio Bassotti Gastroenterology and Endoscopy unit Cardinal Massaja Hospital Asti Italy Gastroenterology and hepatology Section Department of Clinical and Experimental Medicine University of Perugia Perugia Italy

AIM: To evaluate if the guidelines for the appro-priateness of performing colonoscopy by American Society for Gastrointestinal Endoscopy (AGSE) and Italian Society of Digestive Endoscopy (SIED) yield a good diagnostic efficacy and do not present risks of missing important colonic pathologies in an Italian population ***: A total of 1017 consecutive patients (560 men and 457 women; mean age 64.4 ± 16 years) referred to an open-access endoscopy unit for colonoscopy from July 2004 to May 2006 were evaluated according to ASGE and SIED guidelines for appropriateness of performing the procedure. Diagnostic yield was defined as the percentage of relevant colonic pathologies of the total number of colonoscopies ***: About 85.2% patients underwent colono-scopy that was considered appropriate based on at least one ASGE or SIED criterion, while it was considered inappropriate for 14.8% of patients. The diagnostic yield of colonoscopy was significantly higher for appropriate colonoscopies (26.94% vs 10.6%, P < 0.001) than for inappropriate colonoscopies (5.3%). There was no missed colorectal cancer following the ASGE/SIED ***: ASGE/SIED guidelines have shown a good diagnostic yield and the rate of missing relevant colonic pathologies seems very low. Unfortunately, the percentage of inappropriate referrals for colonoscopy in an open-access endoscopy system is still high, despite the number of papers published on the issue and the definition of international guidelines. Further steps are required to update and standardize the guidelines to increase their diffusion and to promote educational programs for general practitioners.

关键词： Colon Colonoscopy Endoscopy Guidelines

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