Biomedical subjects

Tilman Sauerbruch

Publications and source records attributed to Tilman Sauerbruch.

At least 91 records · Page 5Linked to original sources

PubMed2003

The tandem-repeat polymorphism of the DC-SIGNR gene does not affect the susceptibility to HIV infection and the progression to AIDS.

DC-SIGNR is a C-type lectin that functions as a transreceptor for HIV-1. The exon 4 of the DC-SIGNR gene comprises a variable number of 69-bp tandem repeats, encoding for parts of the extracellular protein domain. Here, we analyzed the relevance of this gene polymorphism for the interindividual transmission of HIV-1 and the progression to AIDS. A cross-sectional comparison between HIV-1-infected patients (n = 391) and healthy volunteers (n = 134) did not reveal significant differences with regard to the DC-SIGNR allele distribution. Moreover, DC-SIGNR allele frequencies were similar in slowly progressing HIV patients (n = 31) and patients who rapidly progressed to AIDS (n = 46). Additionally, in a cohort of 149 newly HIV-infected patients, no relationship was found between HIV set point viremia and DC-SIGNR genotypes. Thus, the DC-SIGNR tandem-repeat polymorphism in exon 4 does not have a significant impact on the host's susceptibility to HIV and the clinical progression to AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Pharmacokinetics and pharmacodynamic action of budesonide in early- and late-stage primary biliary cirrhosis.

Budesonide has been discussed as a potential treatment option in primary biliary cirrhosis (PBC). Therefore, we studied the pharmacokinetics and pharmacodynamics of budesonide in patients with PBC stage I/II and stage IV. Twelve patients with early PBC stage I/II and 7 patients with PBC stage IV under continuous treatment with ursodeoxycholic acid (UDCA) were enrolled in an exploratory trial. Each patient received oral budesonide for 3 weeks at weekly increasing dosages of 3 mg once to thrice per day. Budesonide and cortisol plasma levels, urinary cortisol excretion, serum liver tests, and immunoglobulins were determined on days 1, 7, and 21 of the study. Patients with PBC stage IV showed significantly higher peak plasma concentrations (4.9 +/- 3.5 vs. 1.5 +/- 0.4 ng/mL; P <.05) and areas under the plasma concentration-time curves (AUC) (23.2 +/- 16.8 vs. 5.1 +/- 1.4 hours. ng/mL, P <.01, total AUC extrapolated to infinity [AUC(0- infinity )]) after a single dose of 3 mg budesonide when compared with patients with PBC stage I/II. Equally, AUC of budesonide were significantly increased under a multiple dose regimen on day 21 (14.0 +/- 11.6 vs. 5.0 +/- 1.9 hours. ng/mL, P <.01, AUC at steady state from dosing time to 8 hours [AUC(ss,0-8 h)]). Higher levels of budesonide were related to a significant decrease in plasma cortisol and reduction of urinary cortisol excretion in patients with stage IV disease. Two patients with stage IV disease developed portal vein thrombosis (PVT). In conclusion, administration of budesonide leads to markedly elevated plasma levels in cirrhotic patients with PBC associated with serious adverse drug reactions. Thus, further evaluation of combined treatment with UDCA may be considered in early-stage PBC but not in cirrhotic patients with PBC.

Adult↗

PubMed2003

An independent evaluation of modern prognostic scores in a central European cohort of 120 patients with hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is a common cancer worldwide. As prognosis of HCC patients depends not only on tumour extension but also on liver function, TNM staging of HCC is of limited value. The Okuda score incorporating the variables of liver function and tumour extension is used widely. However, among patients with an intermediate Okuda score, survival varies considerably. Several newer scores promise to perform better than the Okuda score in stratifying HCC patients. We therefore tested the ability of several newer scores to predict survival in comparison to the Okuda score in a European cohort of HCC patients. PATIENTS AND METHODS: A total of 120 patients with sufficient follow-up data were identified retrospectively among the 130 patients with HCC first seen between 1997 and 2000 in our department. Child-Pugh score, Okuda score, Vienna survival model for HCC (VISUM-HCC) score, Chevret score, Barcelona clinic liver cancer (BCLC) classification and cancer of the liver Italian programme (CLIP) score were calculated. Survival analysis was performed for all eligible patients stratified according to each scoring system. Receiver operating characteristics analysis was performed using six months survival as the outcome measure. Univariate and stepwise logistic regression analyses were performed to identify prognostic factors. RESULTS: Survival times of HCC patients grouped according to all scores were significantly different. All scores performed similarly to the Okuda score in the receiver operating characteristic analysis. Prognostic factors for survival were albumin concentration and the presence of portal obstruction. CONCLUSION: In our central European cohort, there was no advantage of using the newer scores instead of the Okuda score.

Adult↗

PubMed2003

Reference range for gastrointestinal oxalate absorption measured with a standardized [13C2]oxalate absorption test.

PURPOSE: Hyperoxaluria is a prominent risk factor for calcium oxalate urinary stones. Oxalate in urine is synthesized in the body or absorbed from food in the gastrointestinal tract. The amount of oxalate absorbed by patients with calcium oxalate stones may vary from a few percent to 50% of the dietary intake. Reference values for oxalate absorption measured under a standardized diet have never been attained in sufficient numbers from healthy individuals. Therefore, to our knowledge we collected for the first time the values required to interpret test results in patients with recurrent urinary stones. MATERIALS AND METHODS: A total of 120 healthy volunteers, including 60 females and 60 males, received an identical standard diet on 2 consecutive days. On the morning of day 2 a capsule containing 0.37 mmol. sodium [13C2]oxalate (not radioactive) was ingested with water. Urinary oxalate was measured by gas chromatography-mass spectrometry. Absorption at a fixed 800 mg. daily Ca input is expressed as a percent of the labeled oxalate dose. RESULTS: For the standardized [13C2]oxalate absorption test the reference range in 95% of the 120 volunteers was 2.2% to 18.5% (mean +/- SD 7.9% +/- 4.0%). The repeatability of the standardized test was determined in 26 of the 120 volunteers by repeating the test twice. The mean intra-individual SD was 3.39% +/- 1.68%. CONCLUSIONS: We assessed reference values of intestinal oxalate absorption using a standardized diet. Interindividual and intra-individual variance was high.

Absorption↗

PubMed2003

Comparison of MELD, Child-Pugh, and Emory model for the prediction of survival in patients undergoing transjugular intrahepatic portosystemic shunting.

OBJECTIVES: Recently, new prognostic models (Model for End-Stage Liver Disease [MELD model] and Emory score) were proposed for the prediction of survival in transjugular intrahepatic portosystemic shunt (TIPS) patients. Although the MELD model is considered to be superior and has consecutively been applied to priority listing for liver transplantation, these models have never been directly compared in terms of long-term prognosis. We therefore compared the prognostic accuracy of the different models, including the Child-Pugh score, in an unselected cohort of TIPS patients followed long-term. METHODS: Baseline risk scores for 162 unselected consecutive TIPS patients followed until death (n = 81), liver transplantation, or end of observation (n = 81) (mean follow-up 30.7 +/- 26.4 months) were calculated, and respective concordance- (c-)statistics for the predictive accuracy of 3-, 12-, and 36-month survival for the three models were compared statistically. RESULTS: All three models predicted short-term (3-month) survival with similar accuracy. The MELD model generated the best c-statistics for both 12-month (c-statistic 0.73, 95% CI = 0.64-0.82) and 36-month survival (c-statistic 0.74, 95% CI = 0.64-0.84). The predictive accuracy of the Emory score was significantly lower (c-statistic for 12-month survival: 0.60, 95% CI = 0.52-0.68, p = 0.012 vs MELD). In the statistical comparison of the MELD and the Child-Pugh model, only a trend favoring MELD for the prediction of 1-yr survival in patients with intestinal bleeding could be observed (MELD: c-statistic 0.78, 95% CI = 0.67-0.89; Child-Pugh: c-statistic 0.67, 95% CI = 0.55-0.80, p = 0.059). CONCLUSIONS: The MELD model is superior to the Emory score but only slightly superior to the Child-Pugh classification for the prediction of long-term survival in TIPS patients.

Evaluation Studies as Topic↗

PubMed2003

Acenocoumarol is not a safe alternative for anticoagulation in phenprocoumon-induced hepatic failure. Report of two cases.

Acenocoumarol has been proposed repeatedly as a safe alternative drug regimen for oral anticoagulation in patients who have suffered phenprocoumon-induced fulminant hepatic failure. The current report describes 2 patients with phenprocoumon-induced hepatic failure, necessitating liver transplantation in 1 case, who showed recurrence of liver damage when oral anticoagulation with acenocoumarol was attempted. Thus, acenocoumarol may not be a safe therapeutic alternative for patients who survived severe phenprocoumon-induced hepatotoxicity.

Acenocoumarol↗

PubMed2003

Bleeding complications after percutaneous liver biopsy. An analysis of risk factors.

BACKGROUND AND AIMS: To assess the risk of bleeding after percutaneous liver biopsy, we retrospectively analyzed 629 procedures with particular respect to patients with an increased a priori bleeding risk. METHODS: Factors possibly related to the risk of bleeding were analyzed by univariate analysis. Those variables which were significant in the univariate analysis were then entered into a forward conditional logistic regression model. RESULTS: Biopsy-related bleeding events defined as clinically overt complication (n = 10; 1.6%), an otherwise unexplained drop in serum hemoglobin concentration of greater than 2 g/dl (n = 45; 7.1%) or intra- or extrahepatic hematoma assessed by ultrasound (n = 17; 2.7%) were identified in 72 patients. 58% of the bleeding events occurred in patients with particular risk factors for bleeding. Biopsy-related mortality in the study cohort was 0.48%. Logistic regression analysis indicated mycobacterial infection [odds ratio (OR) 24.0], pre-biopsy prophylactic platelet substitution (OR 9.9), acute liver failure (OR 9.1), heparin administration on the day of biopsy (OR 8.7), advanced liver cirrhosis (OR 5.1), therapy with corticosteroids (OR 3.5) or metamizole (OR 2.8) and leukemia or lymphoma (OR 2.8) as significant (p < or = 0.05) independent risk factors. Delayed bleeding (>24 h after biopsy) was identified in 70% of the bleeding events. CONCLUSIONS: In our study cohort which comprised a high proportion of patients with particular risk factors for bleeding, biopsy-related bleeding occurred more frequently and later than commonly observed and was associated with only a few prognostic factors. Considering these predictors before liver biopsy will aid to reduce the rate of bleeding complications.

Adolescent↗

PubMed2003

Prognostic impact of renal impairment and sodium imbalance in patients undergoing transjugular intrahepatic portosystemic shunting for the prevention of variceal rebleeding.

BACKGROUND/AIM: Kidney function and portal pressure have prognostic relevance in nonshunted patients with cirrhosis. Since insertion of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal pressure and may improve the renal function, the aim of the present study was to investigate the prognostic role of renal impairment and portal hemodynamics in patients with compensated cirrhosis electively shunted due to recurrent variceal hemorrhages. METHODS: Data of 101 consecutive and prospectively followed patients with compensated cirrhosis (bilirubin <5 mg/dl) undergoing elective TIPS due to recurrent variceal bleeding (45 died, and 8 were transplanted during the follow-up period) were evaluated in a multivariate Cox model. RESULTS: Creatinine and sodium were identified as the only independent predictors of survival in this model. The 90th percentile of creatinine (>1.7 mg/dl) defined a subgroup with a similar poor prognosis as the 90th percentile of the model for end-stage liver disease (MELD) score. Neither baseline nor post-TIPS portal pressure correlated with the long-term outcome. CONCLUSIONS: In compensated patients undergoing TIPS due to variceal bleeding, renal impairment indicates a poor prognosis. Portal hemodynamic parameters are not predictive of survival in TIPS patients.

Cohort Studies↗

PubMed2002

Cell activation by synthetic lipopeptides of the hepatitis C virus (HCV)--core protein is mediated by toll like receptors (TLRs) 2 and 4.

T cell epitopes coupled to a lipid moiety (lipopeptides) may be superior immunostimulants compared to peptide antigens and are currently studied as potential vaccines. The cause of enhanced immunogenicity of lipopeptides is largely unknown but members of the novel family of Toll like receptors (TLR) such as TLR2 and TLR4 have been shown to mediate activation of cells in response to bacterial lipopolysaccharide (LPS) and other lipidated bacterial or viral components. We studied TLR-mediated activation by 14 synthetic lipopeptides corresponding to T cell epitopes on hepatitis C virus (HCV) core in human embryonic kidney cells (HEK293) transiently over-expressing TLR2 and in Ba/F3 mouse bone marrow cells stably transfected with TLR4 and the adaptor molecule MD-2. Stimulation of transfected HEK293 or Ba/F3 cells was measured via luciferase activity as a reporter of nuclear factor kappaB activation. Free peptides, a non-HCV-related lipopeptide as well as LPS and the lipopeptide SK4 were used as controls. Ten of the 14 HCV core lipopeptides stimulated luciferase activity in TLR2-transfected HEK293 cells but not in mock-transfected control cells. Nine of the 14 lipopeptides also stimulated luciferase activity in the TLR4/MD-2 double-transfected Ba/F3 cells but not Ba/F3 control cells. Overall, there was a close statistical correlation between TLR2 and TLR4/MD-2-mediated cell activation by the lipopeptides. In contrast, the corresponding free peptides had no stimulatory effect on TLR2 nor on TLR4/MD-2 transfected cells. Thus, lipopeptides but not their corresponding free peptides can activate cells via TLRs 2 and 4. This activation is apparently affected by the amino acid sequence of the peptide moiety.

Amino Acid Sequence↗

PubMed2002

Therapeutic vaccination against metastatic renal cell carcinoma by autologous dendritic cells: preclinical results and outcome of a first clinical phase I/II trial.

In this study we have presented in vitro data and results of a preliminary clinical trial using dendritic cells (DC) in patients with progressive metastatic renal cell carcinoma. DC precursor cells were obtained from peripheral blood mononuclear cells (PBMC). DC were pulsed with autologous tumor cell lysate if available. In total, 15 patients were treated with a median of 3.95 x 10(6) DC administered and ultrasound-guided into a lymph node or into adjacent tissue. Seven patients remained with progressive disease (PD), 7 patients showed stable disease (SD), and one patient displayed a partial response (PR). Most interestingly, the patient who was treated with the highest number of DC (14.4 x 10(6) DC/vaccine) displayed a PR. Delayed-type hypersensitivity (DTH) reaction using autologous tumor lysate was positive in 3 out of 13 patients, including the patient with PR. Two out of 3 patients receiving additional treatment with keyhole limpet hemocyanin (KLH) showed reactivity to KLH after vaccination. CD3+CD4+ and CD3+CD28+ cells as well as the proliferation rate of peripheral blood lymphocytes (PBL) increased significantly in the blood of patients during therapy. In conclusion, our observations confirm the capability of tumor-lysate pulsed autologous DC vaccines to stimulate an immune response in patients with metastatic renal cell carcinoma even in the presence of a large tumor burden. The lack of adverse effects together with immunologic effects support further investigation of this novel therapeutic approach. Further studies are necessary to demonstrate clinical effectiveness in cancer patients, in particular in patients with less advanced disease.

Adult↗

PubMed2002

Keeping central venous lines open: a prospective comparison of heparin, vitamin C and sodium chloride sealing solutions in medical patients.

OBJECTIVE: To prevent catheter occlusion, intermittently used central venous catheters are frequently sealed with vitamin C solution or heparin solution between use. The present study was designed to test the effectiveness of this approach and to compare the efficiency of sealing solutions. DESIGN AND SETTING: Prospective randomized study performed on a 9-bed medical ICU and on medical wards of an academic tertiary care center. PARTICIPANTS. Ninety-nine central venous line placements were prospectively included in the study and randomized into three treatment groups: sodium chloride 0.9%, vitamin C (200 mg/ml) and heparin (5000 IU/ml) sealing solutions. INTERVENTIONS AND MEASUREMENTS: Catheters were filled with the respective sealing solution and patency was tested once every 2 days using a standardized routine. Catheter patency was compared among the three groups using Kaplan-Meier statistics and log-rank testing. RESULTS: There was a significant difference in catheter patency between the three groups (p<0.03, log-rank test). A comparison of catheter survival between the catheters filled with heparin and those filled with sodium chloride, but not between those filled with vitamin C solution and with sodium chloride solution, exhibited significant differences in catheter patency (p<0.04, log-rank test). CONCLUSIONS: Local anticoagulation of intermittently used central venous catheters prolongs catheter patency. High-dose (5000 IU/ml) heparin solution is a useful anticoagulant for this purpose, while vitamin C solution does not prolong catheter patency.

Academic Medical Centers↗

PubMed2002

Reduced CC chemokine receptor (CCR) 1 and CCR5 surface expression on peripheral blood T lymphocytes from patients with chronic hepatitis C infection.

T cell recruitment to the infected liver is an essential step for the efficient elimination of hepatitis viruses. The surface expression of CC chemokine receptor (CCR) 1, CCR4, and CCR5 on peripheral blood T lymphocytes and their responsiveness to the chemokines macrophage inflammatory proteins (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation, normally T cell-expressed and secreted) was analyzed in patients with chronic hepatitis C and hepatitis B infection and compared with healthy subjects. Although CCR4 surface expression was not altered, hepatitis C virus (HCV)-infected patients had lower proportions of CD8 T cells with CCR1 and CCR5 surface expression (P<.05). Migration of CD8 T cells in response to MIP-1alpha, MIP-1beta, and RANTES was significantly reduced in HCV-infected patients (P<.05). Intracellular CCR1 and CCR5 protein and messenger RNA levels in peripheral blood T cells did not indicate reduced chemokine receptor biosynthesis in hepatitis C infection. Thus, chronic hepatitis C, but not hepatitis B, infection alters surface expression of distinct CCRs, resulting in lower CC chemokine responsiveness.

Adult↗

PubMed2002

Inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expression in fulminant hepatic failure.

BACKGROUND/AIMS: Inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) have important functions in inflammation and vasoregulation but their role in fulminant hepatic failure (FHF) is not well understood. METHODS: Intrahepatic in situ staining and semi-quantification of iNOS and eNOS by immunohistochemistry in 25 patients with FHF, in 40 patients with chronic liver diseases (CLD) and in ten normal controls (NC). RESULTS: Expression patterns of iNOS and eNOS differed. While in NC only faint iNOS expression was found in some Kupffer cells/macrophages and hepatocytes, eNOS was expressed constitutively in sinusoidal and vascular endothelial cells. In CLD, iNOS expression was induced in Kupffer cells/macrophages and hepatocytes, representing the main iNOS expressing cell types. Additionally, bile ducts, vascular endothelial cells and lymphocytes also expressed iNOS (P = 0.001). In contrast, no differences were found between eNOS expression in CLD and NC (P = 0.64). The same cell types expressed eNOS and iNOS in FHF but numbers of both were significantly enhanced, exceeding the levels seen in CLD (P < 0.001, P = 0.017). CONCLUSIONS: Our data demonstrate that iNOS and eNOS are differently regulated in physiologic conditions and in liver disease. While eNOS seems to be involved in the physiological regulation of hepatic perfusion, strong upregulation of iNOS might contribute to inflammatory processes in FHF.

Bile Ducts↗

PubMed2002

Increased urotensin II plasma levels in patients with cirrhosis and portal hypertension.

BACKGROUND/AIMS: Vasodilatation--despite activation of endogenous vasoconstrictors--is pronounced in portal hypertension. We therefore investigated the role of Urotensin II (U II), a newly described peptide reported to be a vasoconstrictor in the central arterial compartment and a vasodilator in the splanchnic vasculature. METHODS: U II immunoreactivity was measured in 50 patients with cirrhosis and in 15 healthy controls. U II levels were compared in portal venous and central venous blood of 30 patients immediately before transjugular intrahepatic porto-systemic stent shunt implantation. RESULTS: U II levels (median, range, ng/ml) were significantly increased in cirrhotics (12.3, 1.6-41.4) compared to controls (3.6, 0.1-12.0; P<0.001). In patients with cirrhosis, U II levels were significantly higher in central venous (12.9, 2.5-41.4) than in portal venous blood (11.0, 0.6-31.9; P<0.005). U II levels were higher in ascitic than in non-ascitic patients (P<0.02). They correlated positively with the wedged hepatic venous pressure gradient (rho=0.34, P<0.005) and negatively with the mean arterial pressure (rho=-0.41; P<0.001). CONCLUSIONS: Urotensin II formation is upregulated in patients with cirrhosis and portal hypertension. The transhepatic gradient suggests a hepatic production of this peptide.

Adult↗

PubMed2002

DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP-expressing tumors and does not interfere with liver regeneration in mice.

The oncofetal alpha-fetoprotein (AFP) is reexpressed in the majority of hepatocellular carcinomas and may be used as a target molecule for an immunotherapy or prophylaxis against this tumor. We investigated the potential of DNA vaccination with AFP-expressing plasmid DNA to induce an immune response against AFP-expressing tumor cells in DBA/2 mice. 62.5% of mice vaccinated with AFP-expressing plasmid DNA, rejected subcutaneous syngeneic AFP-expressing P815 tumors, whereas only 16.7% of mice vaccinated with control plasmid rejected these tumor cells (P=.03). Mean survival of mice after challenge with subcutaneous AFP-expressing tumor cells was prolonged for 8 days in mice vaccinated with AFP-expressing DNA (35 days) compared to mice vaccinated with control plasmid (27 days). To rule out possible autoimmune reactions against regenerating liver, which also reexpresses AFP, we evaluated the influence of AFP-specific DNA vaccination on liver regeneration in DBA/2 mice. Histologic quantification of proliferating hepatocytes and of the amount of necrotic liver tissue in carbon tetrachloride-damaged liver did not reveal statistically significant differences in mice vaccinated with AFP-expressing plasmid compared to control mice. These data suggest that AFP-specific DNA vaccination represents a useful tool to inhibit growth of AFP-expressing tumors in mice that does not affect liver regeneration.

Animals↗

PubMed2002

Abdominal infections in patients with acute leukaemia: a prospective study applying ultrasonography and microbiology.

A prospective study of 62 chemotherapy-induced neutropenic episodes in patients with acute leukaemia was conducted to determine the incidence and causes of abdominal infections, and to assess the diagnostic value of the combined use of ultrasonography (US) and microbiology. Each patient underwent US of liver, gallbladder and complete bowel before chemotherapy, on days 2-4 after the end of chemotherapy and in cases of fever, diarrhoea or abdominal pain. US was combined with a standardized clinical examination and a broad spectrum of microbiological investigations. From January to August 2001, 243 US examinations were performed. The overall incidence of abdominal infectious diseases was 17.7% (11 out of 62, 95% confidence interval (CI): 9-29%). Four patients (6.5%) developed neutropenic enterocolitis; two of them died, two survived. Bowel wall thickening (BWT) > 4 mm in these four patients ranged from 5.8 to 23.6 mm and was detected only in one patient with mucositis. In three other patients (4.8%) Clostridium difficile, and in one patient (1.6%) Campylobacter jejuni, caused enterocolitis without BWT. Cholecystitis was diagnosed in three patients (4.8%) and hepatic candidiasis was strongly suspected in one patient. Abdominal infections caused by gastroenteritis viruses, cytomegalovirus (CMV) or Cryptosporidium were not observed. We conclude that in neutropenic patients with acute leukaemia receiving chemotherapy: (i) BWT is not a feature of chemotherapy-induced mucositis and should therefore be considered as sign of infectious enterocolitis; (ii) viruses, classic bacterial enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Aeromonas, Vibrio subsp., enterohaemorrhagic Escherichia coli) and Cryptosporidium have a very low incidence; and (iii) abdominal infections may be underestimated when US is not used in every patient with abdominal pain.

Abdominal Pain↗

PubMed2002

Differential expansion of T-cell receptor variable beta subsets after antigenic stimulation in patients with different outcomes of hepatitis C infection.

Persistent antigenic stimulation during chronic hepatitis C may alter the T-cell receptor variable chain beta (TCR BV) repertoire as well as the cytokine responses of hepatitis C virus (HCV)-specific T lymphocytes. We analysed the distribution of the TCR BV subsets 2.1, 3.1, 5.1, 6.1, 8, 13.1, 13.6, 14.1, 17.1, 21.3 in relation to intracytoplasmic expression of interleukin-2, interferon-gamma, interleukin-4 and interleukin-10. Using flow cytometry, CD45RO+ memory T cells of 27 patients with chronic hepatitis C, eight patients with resolved HCV infection and 16 non-HCV-related controls were studied with and without stimulation by the HCV core, NS3, NS4, NS5a and NS5b proteins. Patients with chronic and resolved hepatitis C differed by larger basal TCR BV2.1+, BV6.1+, BV17.1+ and BV21.3+ subsets in chronic hepatitis C, which were correlated to the numbers of T cells with spontaneous interleukin-2 and interferon-gamma production (r=0.51-0.73, P<0.05). Upon HCV-specific stimulation these subsets did not expand, whereas a marked in vitro expansion of TCR BV8+ T cells in response to all HCV proteins was selectively noted in chronic hepatitis C (P<0.05). This expansion of TCR BV8+ memory T cells was significantly correlated to HCV-induced interleukin-10 expression (r=0.58-0.98, P<0.01). Thus, differential involvement of selected TCR BV subsets may be related to the outcome of HCV infection.

Adolescent↗

PubMed2002

Frequency of the HIV-protective CC chemokine receptor 5-Delta32/Delta32 genotype is increased in hepatitis C.

BACKGROUND & AIMS: A homozygous 32-base pair deletion in the CCR5 gene (CCR5-Delta32) protects against human immunodeficiency virus infection (HIV). However, the role of this mutation in other infections, such as hepatitis C virus (HCV) infection, has not been defined. METHODS: We determined the frequency of the CCR5-Delta32 mutation by polymerase chain reaction in anti-HCV(+) (n = 153), anti-HIV(+) (n = 102), and anti-HCV(+)/HIV(+) (n = 130) white patients as well as in 102 healthy blood donors. Then, HIV and HCV loads, aminotransferases, and CD4 and CD8 cell counts were compared between the resulting subsets of CCR5-Delta32/wild-type heterozygotes, CCR5-Delta32, and wild-type homozygotes, respectively. RESULTS: Twelve of 153 (7.8%) anti-HCV-seropositive patients and 1 of 102 (1.0%) healthy blood donors were CCR5-Delta32 homozygous, whereas CCR5-Delta32 homozygosity was absent in anti-HIV(+) and anti-HCV(+)/HIV(+) patients (P < 0.001). The frequency of the CCR5-Delta32 allele was higher in the anti-HCV(+) (16.0%, P < 0.05) and anti-HCV(+)/HIV(+) (12.7%, NS) patients than in healthy blood donors (8.3%) and anti-HIV(+) patients (9.3%), respectively. Anti-HCV(+) CCR5-Delta32 homozygotes occurred 3 times more frequently than expected from the Hardy-Weinberg equation (P < 0.0001) and had significantly higher HCV loads than wild-type patients (P = 0.045). CONCLUSIONS: The increased prevalence of CCR5-Delta32 homozygosity associated with increased viral loads in patients with chronic hepatitis C suggests that the CCR5-Delta32 mutation may be an adverse host factor in hepatitis C.

Adolescent↗