BACKGROUND:Cirrhosis is associated with several extrahepatic manifestations including portopulmonary hypertension (PPHT).Recent data suggest that endothelins (ETs) are related to the pathophysiology of PPHT.The study ...BACKGROUND:Cirrhosis is associated with several extrahepatic manifestations including portopulmonary hypertension (PPHT).Recent data suggest that endothelins (ETs) are related to the pathophysiology of PPHT.The study aimed to measure serum ET levels in hospitalized cirrhotic patients and to determine their association with PPHT and patient outcome.METHODS:Fifty-seven cirrhotic patients [43 males;median age 58 (28-87) years] underwent Doppler echocardiography.Patients with systolic pulmonary arterial pressure ≥40 mmHg and pulmonary acceleration time <100 ms were deemed to have PPHT.ET-1,2,and 3 serum levels were measured with an ELISA assay.All-cause mortality was recorded over a median period of 24 months.RESULTS:Nine out of 57 patients (15.8%) had PPHT.Among various clinical variables,only autoimmune hepatitis was associated with PPHT (OR=11.5;95% CI,1.58-83.4;P=0.01).ET-1 levels [9.1 (1.6-20.7) vs 2.5 (1.4-9.2) pg/mL,P=0.02] and the ET-1/ET-3 ratio [4.73 (0.9-22.4) vs 1.6 (0.3-10.7),P=0.02] were significantly higher in patients with PPHT than in those without.ET-2 and ET-3 levels did not differ between the two groups.There was no difference in survival between the two groups,although ET-1 levels were associated with an adverse outcome in Cox regression analysis (HR=1.11;95% CI,1.02-1.22;P=0.02 per unit increase in ET-1).CONCLUSION:Our data suggest that ET-1 and the ET-1/ET-3 ratio are elevated in patients with PPHT and that ET-1 is associated with a poor outcome irrespective of PPHT.展开更多
BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in ...BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in patients with chronic HCV infection and investigate its possible association with anemia.METHODS: Ninety-three consecutive patients(62 males and 31 females) with chronic HCV infection, who had never received antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load measurement and genotype sequencing were also performed.RESULTS: Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia(19.4% vs 5.3%, P=0.040) compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia(70.0% vs 34.9%, P=0.030), lower EPO concentrations(median 16.35 vs 30.65 m U/m L, P=0.005), and higher HCV RNA viral load(median 891.5×103 vs 367.5×103 IU/m L, P=0.016). In multivariate regression analysis the presence of anti-EPO remained an independent predictor of anemia(adjusted OR: 14.303, 95% CI: 1.417-36.580, P=0.024). EPO response to anemia was less prominent among anti-EPO positive patients(P=0.001).CONCLUSIONS: Circulating anti-EPO are detected in a significant proportion of treatment-na?ve HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.展开更多
基金supported by a grant from the Special Account for Research Funds(ELKE)of the National and Kapodistrian University of Athens,Greece(7493)
文摘BACKGROUND:Cirrhosis is associated with several extrahepatic manifestations including portopulmonary hypertension (PPHT).Recent data suggest that endothelins (ETs) are related to the pathophysiology of PPHT.The study aimed to measure serum ET levels in hospitalized cirrhotic patients and to determine their association with PPHT and patient outcome.METHODS:Fifty-seven cirrhotic patients [43 males;median age 58 (28-87) years] underwent Doppler echocardiography.Patients with systolic pulmonary arterial pressure ≥40 mmHg and pulmonary acceleration time <100 ms were deemed to have PPHT.ET-1,2,and 3 serum levels were measured with an ELISA assay.All-cause mortality was recorded over a median period of 24 months.RESULTS:Nine out of 57 patients (15.8%) had PPHT.Among various clinical variables,only autoimmune hepatitis was associated with PPHT (OR=11.5;95% CI,1.58-83.4;P=0.01).ET-1 levels [9.1 (1.6-20.7) vs 2.5 (1.4-9.2) pg/mL,P=0.02] and the ET-1/ET-3 ratio [4.73 (0.9-22.4) vs 1.6 (0.3-10.7),P=0.02] were significantly higher in patients with PPHT than in those without.ET-2 and ET-3 levels did not differ between the two groups.There was no difference in survival between the two groups,although ET-1 levels were associated with an adverse outcome in Cox regression analysis (HR=1.11;95% CI,1.02-1.22;P=0.02 per unit increase in ET-1).CONCLUSION:Our data suggest that ET-1 and the ET-1/ET-3 ratio are elevated in patients with PPHT and that ET-1 is associated with a poor outcome irrespective of PPHT.
基金supported by a grant from the Special Account for Research Grants(ELKE)of the National and Kapodistrian University of Athens(No.70/3/7247)
文摘BACKGROUND: Chronic hepatitis C virus(HCV) infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin(anti-EPO) have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in patients with chronic HCV infection and investigate its possible association with anemia.METHODS: Ninety-three consecutive patients(62 males and 31 females) with chronic HCV infection, who had never received antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCV RNA viral load measurement and genotype sequencing were also performed.RESULTS: Circulating anti-EPO were detected in 10.8% of HCV-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia(19.4% vs 5.3%, P=0.040) compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia(70.0% vs 34.9%, P=0.030), lower EPO concentrations(median 16.35 vs 30.65 m U/m L, P=0.005), and higher HCV RNA viral load(median 891.5×103 vs 367.5×103 IU/m L, P=0.016). In multivariate regression analysis the presence of anti-EPO remained an independent predictor of anemia(adjusted OR: 14.303, 95% CI: 1.417-36.580, P=0.024). EPO response to anemia was less prominent among anti-EPO positive patients(P=0.001).CONCLUSIONS: Circulating anti-EPO are detected in a significant proportion of treatment-na?ve HCV-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCV-related anemia.
