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liver stiffness measurements in patients with HBV vs HCV chronic hepatitis:A comparative study

World Journal of Gastroenterology 2010年第38期16卷 4832-4837页

作者： Ioan Sporea Roxana Sirli Alexandra Deleanu Adriana Tudora Alina Popescu Manuela Curescu Simona Bota Department of Gastroenterology and Hepatology University of Medicine and Pharmacy(Timisoara) Department of Infectious Diseases University of Medicine and Pharmacy(Timisoara)

AIM:To assess the values of liver stiffness (LS) in pa-tients with hepatitis B virus (HBV) chronic hepatitis and to compare them with those in patients with hepatitis C virus (HCV) chronic hepatitis. METHODS: The study included 140 patients with HBV chronic hepatitis, and 317 patients with HCV chronic hepatitis, in which LS was measured (FibroScan-Echo-sens) and liver biopsy was performed in the same session (assessed according to the Metavir score). RESULTS:According to the Metavir score of the 140 HBV patients: one had F0,32 had F1, 67 had F2,33 had F3 and 7 had F4. Of the 317 HCV patients:5 had F0, 34 had F1, 146 had F2, 93 had F3 and 39 had F4. For the same severity of fibrosis, the mean values of LS in HBV patients were similar to those in HCV patients:F1,6.5±1.9 kPa vs 5.8±2.1 kPa (P=0.0889); F2,7.1±2 kPa vs 6.9±2.5 kPa (P = 0.3369); F3,9.1±3.6 kPa vs 9.9±5 kPa (P=0.7038); F4,19.8± 8.6 kPa vs 17.3±6.1 kPa (P=0.6574). A signif icant direct correlation between LS measurements and fibrosis was found in HCV patients (Spearman’s r=0.578, P<0.0001), as well as in HBV patients (r=0.408, P<0.0001). The correlation was more signif icant in HCV than in HBV patients (Fisher’s Z-test,Z= 2.210,P=0.0271). CONCLUSION:In our group, the mean values of LS in patients with chronic B hepatitis were similar to those in patients with chronic HCV hepatitis, for the same stage of f ibrosis. Also, LS was correlated with the severity of fibrosis both in HBV and HCV chronic hepatitis patients.

关键词： Chronic B hepatitis Chronic C hepatitis Fibrosis Transient elastography liver biopsy

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Complementary and Alternative Medicine-related Drug-induced liver Injury in Asia

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Journal of Clinical and Translational Hepatology 2019年第3期7卷 263-274页

作者： Cyriac Abby Philips Philip Augustine Sasidharan Rajesh Praveen Kumar Y Deepak Madhu The liver Unit and Monarch liver Lab Cochin Gastroenterology GroupErnakulam Medical CentreKochiKeralaIndia Gastroenterology Cochin Gastroenterology GroupErnakulam Medical CentreKochiKeralaIndia Interventional Radiology Cochin Gastroenterology GroupErnakulam Medical CentreKochiKeralaIndia Gastroenterology Government Medical CollegeThrissurKeralaIndia Gastroenterology Aster MIMSCalicutKeralaIndia

The use of complementary and alternative medicines(CAMs)for treatment of acute and chronic diseases is on the rise world over,especially in Asian countries,and mostly in China and India.Drug-induced liver injury(DILI)due to CAM is increasingly reported in the literature from multiple centers all around the world and with large-number patient series published from the West,mostly based on nation-wide DILI networks and multicenter collaboration.Comprehensive DILI networks are lacking among major Asian countries with high incidence of CAM practices.Chinese medical societies dealing with drug toxicity,CAM practice and hepatobiliary disease have adopted an integrated approach to establishing identification,diagnosis and treatment of CAM-related DILI,representing a systematic approach that could be iterated by other countries for improving patient outcomes.In this exhaustive review,we provide published data on CAM-related DILI in Asia,with detail on incidences along with analysis of patient population and their clinical outcomes.Concise and clear discussion on commonly implicated CAM agents in major Asian countries and associated chemical and toxicology analyses as well as descriptions of liver biopsy findings are discussed with future directions.

关键词： CAM Herbals Ayurveda Chinese DILI Hepatitis Cirrhosis ACLF liver biopsy

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Regression of liver fibrosis: evidence and challenges

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Chinese Medical Journal 2020年第14期133卷 1696-1702页

作者： Ya-Meng Sun Shu-Yan Chen Hong You liver Research Center Beijing Friendship HospitalCapital Medical UniversityBeijing Key Laboratory of Translational Medicine on Liver CirrhosisNational Clinical Research Center of Digestive DiseasesBeijing 100050China

It has been reported that liver fibrosis could be reversed after eliminating liver injuries.This article systematically summarizes the evidence of fibrosis regression based on histology,liver stiffness,and serum biomarkers,and discusses several clinically relevant challenges.Evidence from liver biopsy has been regarded as the gold standard in the assessment of fibrosis regression.Semiquantitative staging and grading systems are traditionally and routinely used to define regression.Recently,the predominantly regressive,indeterminate,and predominantly progressive score was proposed,based on the regressive features from“hepatic repair complex”,to provide additional information regarding the quality of fibrosis.For non-invasive assessment,although liver stiffness and serum biomarkers could be applied to reflect the dynamic changes of liver fibrosis,other confounding factors such as liver inflammation have to be considered.In conclusion,both histology and non-invasive methods can provide evidence regarding fibrosis regression.The predictive value of fibrosis regression in long-term prognosis warrants further investigation.

关键词： liver fibrosis Regression Reversal liver biopsy liver stiffness Serum biomarker

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Primary malignant liver mesenchymal tumor: A case report

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World Journal of Gastroenterology 2010年第41期16卷 5263-5266页

作者： Jing Chen Ya-Ju Du Ji-Tao Song Bing-Rong Liu Lin-Ning E Department of Gastroenterology Second Af��liated Hospital of Harbin Medical UniversityHarbin 150086Heilongjiang ProvinceChina Lin-Ning EDepartment of RadiologyFirst Hospital of Shanxi MedicalUniversityTaiyuan 030001Shanxi ProvinceChina

Primary malignant liver mesenchymal tumor is a rare condition defined as a tumor with vascular, fibrous, adi-pose, and other mesenchymal tissue differentiation. We report a case of primary malignant liver mesenchymal tumor in a 51-year-old male with anemia, weight loss and hepatomegaly. Finally unconventional liver biopsy and histological manifestation led to the definitive diag-nosis.

关键词： Hepatic mesenchymal tumor liver biopsy Hepatic leiomyosarcoma Hepatic schwannoma

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Clinical and pathological analysis of acute rejection following orthotopic liver transplantation

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Chinese Medical Journal 2009年第12期122卷 1400-1403页

作者： MA Yi WANG Guo-dong HE Xiao-shun LI Jun-liang ZHU Xiao-feng HU Rui-de Organ Transplantation First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510080 China Department of Pathology First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510080 China

Background Acute rejection is one of the most important factors for prognosis following liver transplantation. With the use of potent immunosuppressants, acute rejection does not always present typical manifestations. Moreover, other complications often occur concomitantly after liver transplantation, which makes early diagnosis of acute rejection more difficult. Acute rejection is best diagnosed by liver biopsy. Differentiation of clinical manifestations and pathological features plays an important role in achieving individualized immunosuppressive treatment and prolonging long term survival of patients given orthotopic liver transplants. Methods From January 2004 to December 2006, 516 orthotopic liver transplantations were performed at the First Affiliated Hospital, Sun Yat-sen University. For patients who suffered acute rejection, clinical manifestations, histopathological features, diagnosis and anti-rejection treatment were summarized and analyzed. Results In 86 cases （16.7%）, of the 516 recipients, 106 episodes of acute rejection occurred, which included 9 with histopathological borderline changes, 36 Banff I rejections, 48 Banff II and 13 Banff III. Among these, 36 were cured by adjusting the dose of immunosuppressant and 65 were reversed by methylprednisolone pulse treatment. Five were methylprednisolone resistant, 3 of whom were given OKT3 treatment and 2 underwent liver retransplantation. Conclusions Due to potent immunosuppressive agents, acute rejection following an orthotopic liver transplantation lacks typical clinical manifestations and pathological features. Acute rejection is best diagnosed by liver biopsy. Designing rational individualized immunosuppressive regimen based on clinical and pathological features of acute rejection plays an important role in prolonging long term survival of patients.

关键词： liver transplantation acute rejection liver biopsy treatment

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Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?

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World Journal of Gastroenterology 2010年第29期16卷 3704-3708页

作者： Rosilene G Badiani Vitória Becker Renata M Perez Carla AL Matos Lara B Lemos Valéria P Lanzoni Luis Eduardo C Andrade Alessandra Dellavance Antonio Eduardo B Silva Maria Lucia G Ferraz Division of Gastroenterology Federal University of Sao Paulo04023-900Sao PauloBrazil Department of Internal Medicine Federal University of Rio de Janeiro21941-913Rio de JaneiroBrazil Department of Pathology Immunology Group Fleury Medicine and Health 不详

AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate and presence of rosettes).RESULTS:Among patients with hepatitis C and intense interface hepatitis there was a low prevalence of autoantibodies(ANA=12%,SMA=5%,LKM-1=0%) and the median γ-globulin level was within the normal range.Typical histological findings of autoimmune disease were observed in only two cases(2%).After applying the score for diagnosis of autoimmune hepatitis,only one patient was classified with a definitive diagnosis of autoimmune hepatitis.Since overlap with autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis C we sought to identify the variables associated with this finding.The presence of intense interface hepatitis was associated with more advanced age,both at the time of infection and at the time of the biopsy,and higher prevalence of blood transfusion and alcohol abuse.CONCLUSION:Although possible,overlap with autoimmune hepatitis is a very rare association in HCV-infected patients with intense interface hepatitis,an unusual presentation which seems to be related to other host variables.

关键词： Hepatitis C liver biopsy Antinuclear antibody Autoimmune hepatitis Interface hepatitis

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Metabolic and hepatic effects of liraglutide,obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2018年第2期24卷 179-194页

作者： Kirstine S Tolbol Maria NB Kristiansen Henrik H Hansen Sanne S Veidal Kristoffer TG Rigbolt Matthew P Gillum Jacob Jelsing Niels Vrang Michael Feigh Gubra Aps Horsholm DK-2970Denmark Department of Biomedical Sciences Faculty of Health SciencesUniversity of CopenhagenCopenhagen DK-2200Denmark Section for Metabolic Imaging and liver Metabolism The Novo Nordisk Foundation Center for Basic Metabolic ResearchFaculty of Health SciencesUniversity of CopenhagenCopenhagen DK-2200Denmark Department of Chemistry Faculty of ScienceUniversity of CopenhagenCopenhagen DK-2200Denmark

AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis(NASH) in obese mouse models of biopsy-confirmedNASH.METHODS Male wild-type C57 BL/6 J mice(DIO-NASH) and Lep^(ob/ob)(ob/ob-NASH) mice were fed a diet high in trans-fat(40%), fructose(20%) and cholesterol(2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score(NAS) and fibrosis staging system. The mice were kept on the diet and received vehicle, liraglutide(0.2 mg/kg, SC, BID), obeticholic acid(OCA, 30 mg/kg PO, QD), or elafibranor(30 mg/kg PO, QD) for eight weeks. Within-subject comparisons were performed on changes in steatosis, inflammation, ballooning degeneration, and fibrosis scores. In addition, compound effects were evaluated by quantitative liver histology, including percent fractional area of liver fat, galectin-3, and collagen 1 a1.RESULTS Liraglutide and elafibranor, but not OCA, reduced body weight in both models. Liraglutide improved steatosis scores in DIO-NASH mice only. Elafibranor and OCA reduced histopathological scores of hepatic steatosis and inflammation in both models, but only elafibranor reduced fibrosis severity. Liraglutide and OCA reduced total liver fat, collagen 1 a1, and galectin-3 content, driven by significant reductions in liver weight. The individual drug effects on NASH histological endpoints were supported by global gene expression(RNA sequencing) and liver lipid biochemistry.CONCLUSION DIO-NASH and ob/ob-NASH mouse models show distinct treatment effects of liraglutide, OCA, and elafibranor, being in general agreement with corresponding findings in clinical trials for NASH. The present data therefore further supports the clinical translatability and utility of DIO-NASH and ob/ob-NASH mouse models of NASH for probing the therapeutic efficacy of compounds in preclinical drug development for NASH.

关键词： Nonalcoholic steatohepatitis Disease models Pathology Fibrosis liver biopsy Transcriptomics Pharmacodynamics Glucagon-like peptide-1 receptor Peroxisome proliferator-activated receptor Farnesoid X receptor

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Congenital hepatic fibrosis in a young boy with congenital hypothyroidism:A case report

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World Journal of Clinical Cases 2021年第6期9卷 1475-1482页

作者： Fang-Fei Xiao Yi-Zhong Wang Fang Dong Xiao-Lu Li Ting Zhang Department of Gastroenterology Hepatology and NutritionShanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200062China

BACKGROUND Congenital hepatic fibrosis(CHF)is a rare autosomal recessive disorder characterized by variable degrees of periportal fibrosis and malformation of bile ducts.CHF is generally accompanied by a variety of conditions or syndromes with other organ involvement.CASE SUMMARY We report a 5-year-4-month-old Chinese boy with congenital hypothyroidism(CH)diagnosed with CHF.The patient was diagnosed with CH by a newborn screening test and has since been taking levothyroxine.He has developed normally without neurocognitive deficits.Abnormal liver function was observed in the patient at the age of 4 years and 11 mo,and elevated levels of liver function indices were persistent for 5 mo.Radiological imaging indicated hepatosplenomegaly without narrowing of the portal vein but dilated splenic vein.A liver biopsy confirmed the pathological features of CHF.Genetic testing revealed two novel homozygous mutations,namely,c.2141-3T>C variant in PKHD1 related to CHF and c.2921G>A(p.R974H)in DUOX2 related to CH.The patient was treated with compound glycyrrhizin tablet,ursodeoxycholic acid,and levothyroxine after diagnosis.The patient achieved a favorable clinical outcome during a follow-up period of over 2 years.CONCLUSION Herein,we report the first case of a Chinese boy with comorbidity of CHF and CH,carrying both PKHD1 gene and DUOX2 gene novel mutations.liver biopsy and genetic testing should be considered for the diagnosis of coexistent liver disease in CH patients with unexplained abnormal liver function.

关键词： Congenital hepatic fibrosis Congenital hypothyroidism liver biopsy PKHD1 DUOX2 Case report Genetic testing

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Atypical adult-onset Still’s disease with an initial and sole manifestation of liver injury: A case report and review of literature

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World Journal of Clinical Cases 2021年第1期9卷 224-231页

作者： Fan Yu Shao-You Qin Chang-Yu Zhou Lu Zhao Yan Xu Er-Na Jia Jiang-Bin Wang Department of Gastroenterology and Hepatology China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Digestive Heze Municipal HospitalHeze 274000Shandong ProvinceChina

BACKGROUND Adult-onset Still's disease(AOSD)typically presents with a high spiking fever,polyarthritis,transient maculopapular rash,neutrophilic leukocytosis,and hepatosplenomegaly.It has a wide spectrum of clinical symptoms ranging from mild to severe,with extensive involvement of almost every organ.Although liver involvement in the form of increased hepatic enzymes and bilirubin is common,no AOSD case with liver involvement as the initial manifestation of AOSD has been reported.CASE SUMMARY A 35-year-old woman presented to the hepatology department with progressively worsening jaundice for one week.liver chemistry tests revealed a significantly increased liver enzymes and bilirubin level.Given that the clinical examination was unremarkable,liver biopsy was considered because the patient had a history of AOSD 6 years ago.liver histopathology revealed that most hepatic lobules were still recognizable.Fusional necrosis was observed around most central veins.A few bridging necrotic zones were also found.Infiltration of multiple plasma cells were observed in the necrotic zone,and the reticular scaffold was still expanded.Additionally,no obvious fibrosis was observed in the portal area.Mild mixed inflammatory cell infiltration was noted in the interstitium of the portal area.Further examination was unremarkable except for a remarkably high level of ferritin.Collectively,a presumptive diagnosis of liver injury secondary to AOSD was made.The hepatic involvement responded well to glucocorticoid treatment.CONCLUSION This case highlights that hepatic involvement as an initial and sole manifestation could be a pattern of relapsed AOSD.The diagnosis of AOSD should be considered in the case of nonresolving liver injury after the exclusion of common etiologies for liver diseases.A liver biopsy can be useful for the differential diagnosis of liver injury associated with AOSD.

关键词： Adult-onset Still's disease liver injury liver biopsy Histopathology Glucocorticoid treatment Case report

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Serum hepatitis B core-related antigen as a surrogate marker of hepatitis B e antigen seroconversion in chronic hepatitis B

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World Journal of Gastroenterology 2021年第40期27卷 6927-6938页

作者： Xiu-Mei Chi Xiao-Mei Wang Zhong-Feng Wang Rui-Hong Wu Xiu-Zhu Gao Hong-Qin Xu Yan-Hua Ding Jun-Qi Niu Department of Hepatology Key Laboratory of Zoonosis ResearchMinistry EducationThe First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina Phase I Clinical Trials Unit The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina

BACKGROUND Quantitative hepatitis B core-related antigen(qHBcrAg)has a better correlation with intrahepatic hepatitis B virus(HBV)covalently closed circular DNA(cccDNA)than HBV DNA or hepatitis B e antigen(HBeAg),but data are still lacking for its clinical application.AIM The aim was to investigate serum qHBcrAg levels in patients with chronic hepatitis B and assess the correlation of serum qHBcrAg with pregenomic RNA(pgRNA),cccDNA,and HBeAg seroconversion.METHODS This study was a secondary analysis of patients who underwent percutaneous liver biopsy between July 2014 and June 2019 in two multicenter randomized controlled clinical trials of peginterferon vs nucleos(t)ide analog(NUC)-based therapy(NCT03509688 and NCT03546530).Serum qHBcrAg,pgRNA,HBV DNA,hepatitis B core antigen,HBeAg,liver cccDNA,and HBV DNA were measured.The correlations of serum qHBcrAg with other biomarkers were analyzed.RESULTS A total of 139 patients were included.The mean qHBcrAg levels were 5.32±1.18 log10 U/mL at baseline and decreased during treatment(all P<0.0001).Serum qHBcrAg levels were positively correlated with pgRNA(r=0.597,P<0.0001)and cccDNA(r=0.527,P<0.0001)levels.The correlation of serum qHBcrAg level and intrahepatic HBV DNA levels at baseline was weak but significant(r=0.399,P<0.0001).HBcrAg predicted HBeAg seroconversion,with areas under the receiver operating characteristics curve of 0.788 at 24 wk and 0.825 at 48 wk.Log HBcrAg at wk 24 and 48 was independently associated with HBeAg seroconversion[odds ratio(OR)=2.402,95%confidence interval(CI):1.314-4.391,P=0.004;OR=3.587,95%CI:1.315-9.784,P=0.013].CONCLUSION Serum HBcrAg levels were correlated with HBV virological markers and could be used to predict HBeAg seroconversion.

关键词： Hepatitis B virus Hepatitis B core antigen Hepatitis B virus DNA Detection liver biopsy Pregenomic RNA Quantitative hepatitis B core-related antigen Receiver operating characteristic Seroconversion Correlation

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