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Disease dependent qualitative and quantitative differences in the inflammatory response to ascites occurring in cirrhotics

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World Journal of Hepatology 2014年第2期6卷 85-91页

作者： Bashar M Attar Magdalena George Nicolae Ion-Nedelcu guilliano ramadori David H Van Thiel Division of Gastroenterology and Hepatology John H Stroger Hospital of Cook County Rush University Medical Center Victor Babes Infectious and Tropical Disease Clinic Department of Gastroenterology and Endocrinology August Georg University

AIM:To assess differing patterns and levels of ascitic fluid cyctokine and growth factors exist between those with a high risk and low risk of spontaneous bacterial peritonitis(SBP). METHODS: A total of 57 consecutive patients with ascites requiring a large volume paracentesis were studied. Their age, gender, specific underlying disease conditions were recorded after a review of their clinical records. Each underwent a routine assessment prior to their paracentesis consisting of a complete blood count, complete metabolic profile and prothrombin time/international normalized ratio(INR) determination. The ascitic fluid was cultured and a complete cellcount and albumin determination was obtained on the fluid. In addition, blood and ascitic fluid was assessed for the levels of interleukin interleukin(IL)-1A, IL-1B, IL-2, IL-4, IL-8, IL-10, monocyte chemotactic protein(MCP)-1, tumor necrosis factor(TNF)-α, interferon(IFN)-γ, vascular endothelial growth factor(VEGF) and epidermal growth factor(EGF) utilizing the Randox Biochip platforms(Boston, MA). A serum-ascites gradient, for each cytokine and growth factor was calculated. The results are reported as mean ± SEM between disease groups with statistical analysis consisting of the student t-test(two tailed) with a P value of 0.05 defining significance. RESULTS: No clinically important demographic or biochemical differences between the 4 groups studied were evident. In contrast, marked difference in the cytokine and growth factors levels and pattern were evident between the 4 disease groups. Individuals with alcoholic cirrhosis had the highest levels of IL-1A, IL-1B, IL-4, IFNγ. Those with malignant disease had the highest levels of IL-2. Those with hepatitis C virus(HCV) associated cirrhosis had the highest value for IL-6, IL-8, IL-10, MCP-1 and VEGF. Those with cardiac disease had the highest level of TNF-α and EGF. The calculated serum- ascites gradients for the cardiac and malignant disease groups had a greater frequenc

关键词： Ascites Cirrhosis Growth factors Inflammation Procalcitonin

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Hypoalbuminemia: an underestimated, vital characteristic of hospitalized COVID-19 positive patients?

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Hepatoma Research 2020年第6期6卷 1-10页

作者： Giuliano ramadori Clinic for Gastroenterology and Endocrinology University Medical Center GöttingenGöttingen 37075Germany

The COVID-19 pandemic has led to the greatest worldwide health crisis in *** number of infected patients with severe SARS-CoV-2(COVID-19)disease has overwhelmed the capacity of almost all health care systems around *** has now been reported in patients with severe disease seeking help in the emergency room because of COVID-19 *** the past,hypoalbuminemia was considered to be a negative prognostic marker,not only in patients with chronic liver disease,but also in patients with SARS and MERS *** is the major serum protein synthesized by the liver.A low serum albumin level is an ominous clinical *** of amino acids to a patient's diet is of fundamental importance to hepatic albumin synthesis in different clinical *** highlights the importance of nutritional support during the early phases of ***,albumin synthesis in the hepatocyte is downregulated at a pretranslational level by the direct interaction of the major acute-phase cytokines which are released into the circulation during the cytokine"storm"induced by the viral effects on the *** mechanisms contribute to severe hypoalbuminemia which,combined with massive fluid losses due to the fever,is responsible for severe hypovolemia and shock commonly observed in patients with COVID-19 in critical care settings.

关键词： Severe acute respiratory syndrome cornonavirus 2 SARS-CoV-2 COVID-19 albumin synthesis nutrition acute-phase reaction cytokines liver extrahepatic organs

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Endotoxin receptor CD14 gene variants and histological features in chronic HCV infection

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World Journal of Gastroenterology 2009年第31期15卷 3884-3890页

作者： Eva Askar Giuliano ramadori Sabine Mihm Department of Gastroenterology and Endocrinology University Medical CenterGeorg-August-University

AIM:To analyze the correlation between CD14 rs2569190/C-159T single nucleotide polymorphism (SNP) and disease progression in chronic hepatitis ***: Liver biopsy specimens from a total of 137 and 349 patients with chronic hepatitis C were separately evaluated with respect to necroinflammatory activity (grading) and architectural changes (staging). In one group, further histological lesions characteristic for hepatitis C, hepatitis C virus subtypes, and biochemical parameters of liver disease were also investigated. Samples of genomic DNA were genotyped for the respective SNP by 5'-nuclease assays using fluorescent dye-labeled allele-specif ic ***: Genotype distribution did not deviate from the Hardy-Weinberg equilibrium. In the first group, patients homozygous for the variant allele T were found to be younger than C allele carriers (39.6±12.5 vs 45.7±11.5, P=0.008). Among the histological lesions studied, portal lymphoid aggregates were more frequently observed among TT homozygotes than among C carriers (21/37 vs 32/100, P=0.008). The presence of portal lymphoid aggregates was closely correlated with hepatic inflammation (P=0.003) and with bile duct damage (P<0.001). The degree of fibrosis, in contrast, was not found to be related to the CD14 gene C-159T ***: The data suggest a possible relationship between CD14 C-159T polymorphism and the formation of portal lymphoid aggregates, but not liver fibrosis progression in chronic hepatitis C.

关键词： CD14 Endotoxins Hepatitis C virus Inflammation Lipopolysaccharides Liver fibrosis Portal system Single nucleotide polymorphism

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Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy

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World Journal of Gastroenterology 2001年第2期7卷 222-227页

作者： Perdita Wietzke-Braun Volker Meier Felix Braun Giuliano ramadori Abteilung für Gastroenterologie und Endokrinologie Georg-August-UniversitatGottingenGermany

AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon *** Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as *** Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete *** Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/*** prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be p

关键词： hepatitis C, chronic/drug therapy interferon alpha-2a/therapeutic use interferon alpha-2a/administration & dosage ribavirin/administration & dosage ribavirin/therapeutic use

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HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV-infection: does it really mean viral replication?

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World Journal of Gastroenterology 2001年第2期7卷 228-234页

作者： Volker Meier Sabine Mihm Perdita Wietzke-Braun Guliano ramadori Georg-August-Universitat gottingen Zentrum innere medizinAbteilung Für Gastroenterologie Und EndokrinologieRobert-Koch-Straβe 4037075 GottingenGermany

AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.

关键词： Adult Aged Antiviral Agents Female Hepacivirus Hepatitis C, Chronic Humans Interferon-alpha Leukocytes, Mononuclear Male Middle Aged RNA, Viral Research Support, Non-U.S. Gov't Reverse Transcriptase Polymerase Chain Reaction Viral Load Virus Replication

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Is laparoscopy an advantage in the diagnosis of cirrhosis in chronic hepatitis C virus infection?

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World Journal of Gastroenterology 2003年第4期9卷 745-750页

作者： Perdita Wietzke-Braun Felix Braun Peter Schott Giuliano ramadori Department of Internal Medicine Division of Gastroenterology and EndocrinologyUniversity of GoettingenGermany

AIM:To evaluate the potential of laparoscopy in the diagnosis of cirrhosis and outcome of interferon treatment in HCV-infected patients. METHODS:In this retrospective study,diagnostic laparoscopy with laparoscopic liver biopsy was performed in 72 consecutive patients with chronic HCV *** presence or absence of drrhosis was analyzed macroscopically by laparoscopy and microscopically by liver biopsy *** and laboratory data and outcome of interferon-alfa treatment were compared between cirrhotic and noncirrhotic patients. RESULTS:Laparoscopically,cirrhosis was seen in 29.2 % (21/72)and non-cirrhosis in 70.8 %(51/72)of patients. Cirrhotic patients were significantly older with a significant longer duration of HCV infection than noncirrhotic patients. Laboratory parameters(AST,y-GT,y-globulin fraction)were measured significantly higher as well as significantly lower (prothrombin index,platelet count)in cirrhotic patients than in non-cirrhotic ***,cirrhosis was confirmed in 11.1%(8/72)and non cirrhosis in 88.9 %(64/72).Patients with macroscopically confirmed cirrhosis(n=21)showed histologically cirrhosis in 38.2 %(8/21)and histologically non- cirrhosis in 61.9 %(13/21).In contrast,patients with macroscopically non-cirrhosis(n=51)showed histologically non cirrhosis in all cases(51/51).Thirty-nine of 72 patients were treated with interferon-alfa,resulting in 35.9 %(14/39) patients with sustained response and 64.1%(25/39)with non ***-responders showed significantly more macroscopically cirrhosis than sustained *** contrast,there were no significant histological differences between non-responders and sustained responders. CONCLUSION:Diagnostic laparoscopy is more accurate than liver biopsy in recognizing cirrhosis in patients with chronic HCV *** biopsy is the best way to assess inflammatory grade and fibrotic *** invasive marker for staging,prognosis and management,and treatment outcome of chro

关键词： Adult Biopsy Comparative Study Female Genotype Hepacivirus purification Hepatitis C, Chronic Humans Interferon-alpha Laparoscopy Liver Cirrhosis Male Middle Aged RNA, Viral Reproducibility of Results Retrospective Studies Treatment Outcome

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Reabsorption of iron into acutely damaged rat liver:A role for ferritins

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World Journal of Gastroenterology 2017年第41期23卷 7347-7358页

作者： Ihtzaz Ahmed Malik Jorg Wilting Giuliano ramadori Naila Naz Institute of Anatomy and Cell Biology University Medical Center Department of Gastroenterology and Endocrinology University Medical Center Faculty of Life Sciences The University of Manchester

AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and *** Rats received intraperitoneal injection of the hepatotoxin thioacetamide(TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain(FTL), and ferritin heavy chain(FTH)was investigated in the liver by q RT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron *** After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase(aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72 h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ(1 h) and IL-1β(3 h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter(96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH an

关键词： Iron metabolism Ferritin Liver Cytokines Acute liver damage

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Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis c virus related cirrhosis

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World Journal of Gastroenterology 2004年第15期10卷 2213-2217页

作者： Perdita Wietzke-Braun Felix Braun Burckhart Sattler Giuliano ramadori Burckhardt Ringe Abteilung for Gastroenterologie und Endokrinologie Georg-August-Universitt37075 GttingenGermany Georg-August-Universitt 37075 GttingenGermany Zentrum Pathologie Georg-August-Universitt37075 GttingenGermany

AIM:Steroids can increase hepatitis C virus(HCV) *** liver transplantation(LTx),steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid *** can worsen the outcome of recurrent HCV ***, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. METHODS:Thirty patients undergoing LTx received initial steroid-free *** for LTx included 7 patients with HCV related *** immunosuppression consisted of tacrolimus 2×0.05mg/kg.d po and mycophenolate mofetil(MMF)2×15mg/kg.d *** tacrolimus dosage was adjusted to trough levels in the target range of 10-15μg/L during the first 3 mo and 5-10μg/L *** of acute rejection were verified histologically. RESULTS:Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 *** rejection occurred in 8/30 patients, including 1 HCV infected *** HCV-infected patients had HCV genotype Ⅱ(lb).HCV seropositivity occurred within the first 4 mo after *** virus load was not remarkably increased during the first year after ***,grafts had no severe recurrent hepatitis. CONCLUSION:From our experience,initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver ***,none of the HCV infected patients developed serious chronic liver *** suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.

关键词： Liver Transplantation Adult Drug Therapy, Combination Female Hepatitis C Humans Immunosuppressive Agents Liver Cirrhosis Male Middle Aged Mycophenolic Acid derivatives Postoperative Care Tacrolimus

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Adult-to-adult right lobe living donor liver transplantation:Comparison of endoscopic retrograde cholangiography with standard T2-weighted magnetic resonance cholangiography for evaluation of donor biliary anatomy

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World Journal of Gastroenterology 2006年第36期12卷 5820-5825页

作者： Perdita Wietzke-Braun Felix Braun Dieter Müller Thomas Lorf Burckhardt Ringe Giuliano ramadori Abteilung für Gastroenterologie und Endokrinologie Georg-August-Universitt Gttingen Germany Klinik für Allgemeine Chirurgie und Thorax-chirurgie Universitt Schleswig-Holstein Campus Kiel Germany Abteilung für Diagnostische Radiologie Georg-August-Universitt Gttingen Germany Klinik für Allgemeine Chirurgie Georg-August-Universitt Gttingen Germany Center for Liver Pancreas and Biliary Disease Drexel University College of Medicine Philadelphia United States

AIM: To compare the value of endoscopic retrograde cholangiography (ERC) and standard T2-weighted magnetic resonance cholangiography (MRC) in the evaluation process as adult-to-adult right lobe living donor liver transplantation (LDLTx) demands a successful outcome, and exact knowledge of the biliary tree is implicated to avoid biliary complications, ***: After starting the LDLTx program, 18 liver transplant candidates were selected for LDLTx by a stepwise evaluation process. ERC and standard T2-weighted MRC were performed to evaluate the biliary system of the donor liver. The anatomical findings of ERC and MRC mapping were compared using the Ohkubo classification. RESULTS: ERC allowed mapping of the whole biliary system in 15/15 (100%) cases, including 14/15 (93.3%) with biliary variants while routine MRC was only accurate in 2/13 (15.4%) cases. MRC was limited in depicting the biliary system proximal of the hepatic bifurcation. Postoperative biliary complications occurred in 2 donors and 8 recipients. Biliary complications were associated with Ohkubo type C, E or G in 6/8 recipients, and 2/3 recipients with biliary leak received a graft with multiple (≥2) bile ducts. CONCLUSION: Pretransplant ERC is safe and superior over standard MRC for detection of biliary variations that occur with a high frequency. However, precise knowledge of biliary variants did not reduce the incidence of postoperative biliary complications.

关键词： Living donor liver transplantation Donors biliary tree Endoscopic retrograde cholangiography Magnetic resonance cholangiography

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Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

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World Journal of Gastroenterology 2005年第39期11卷 6188-6192页

作者： Perdita Wietzke-Braun Volker Meier Katrin Neubauer-Saile Sabine Mihm Giuliano ramadori Abteilung für Gastroenterologie und Endokrinologie Georg-August-Universitt Gttingen Germany

AIM： Before pegylated interferon alpha （IFN） was introduced for the therapy of chronic hepatitis C virus （HCV）-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time, higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C. METHODS： Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 （n = 12） were treated for 24 wk, and patients with genotypes other than 2 or 3 （n = 34） for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment （EOT）. Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received low-dose ribavirin （10 mg（kg·d）） additionally. RESULTS： During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients （n = 9） infected with genotype 2 or 3 showed an initial virological response rate of 100%. Six patients （66.7%） were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed （33.3%）. In comparison, patients infected with genotypes other than 2 or 3 （n = 34） showed an initial virological response rate of only 23.5% （n = 8）, and even in combination with ribavirin a sustained virological response （SVR） rate of only 11.8% （n = 4） could be achieved. CONCLUSION： In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expe

关键词： Chronic hepatitis C virus infection Genotype 2 and 3 Alpha interferon Daily dose interferon therapy

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