Biliary adverse events in acromegaly during somatostatin receptor ligands: predictors of onset and response to ursodeoxycholic acid treatment.

PURPOSE: Somatostatin receptor ligands (SRL) are the first-line medical treatment for acromegaly. Gallbladder alterations are one of most important SRL side effect, but according to some authors growth hormone hypersecretion itself is a risk factor for gallstones. This single center, longitudinal retrospective study evaluated the incidence and the predictors of biliary adverse events (BAE) in acromegaly during SRL therapy and their response to ursodeoxycholic acid (UDCA). METHODS: 91 acromegaly patients with indication to SRL were enrolled. Evaluations of acromegaly activity (GH, IGF-I, IGF-I/ULN) and metabolic profile were collected before starting treatment, yearly during follow-up and at BAE onset. In patients developing BAE we searched for predictors of UDCA effectiveness. RESULTS: 61.5% of patients developed BAE (58.9% cholelithiasis; 41.1% only sludge). IGF-I and IGF-I/ULN proved to be positive predictor of BAE, which occur about 5 years after SRL starting. None of metabolic markers proved to be associated with BAE. Only five patients (5.5%) underwent cholecystectomy for symptomatic cholelithiasis. 71% of patients started UDCA treatment, achieving regression of BAE in 60% of cases (88% in patients developing only sludge and 30% in patients affected by cholelithiasis, p < 0.001). BMI and obesity were negative predictors of UDCA efficacy. In 50% of the subjects BAE resolved after 36 months of therapy with a lower rate if cholelithiasis was present. CONCLUSION: Biliary stone disease is a frequent SRL adverse event, although it is often symptomless. Ultrasound follow-up mainly in the first 5 years of therapy, early UDCA starting and proper lifestyle represent a valid strategy in their detection and management.

HLA-DR5 antigen. A genetic factor influencing the outcome of hepatitis C virus infection?

BACKGROUND: Prognosis may be quite different among individuals infected with hepatitis C virus (HCV): a chronic liver disease is believed to occur in half the patients while in the other half there are no signs of histologic progression of liver damage. The host immune response might play an important role in such different outcomes. A relationship has been shown between HLA genes and immune response to viral hepatitis B, but to our knowledge, no evidence of an association with HCV has been reported so far. We investigated whether HLA class II alleles might influence the outcome of HCV infection. METHODS: Eighty-seven individuals, positive for anti-HCV by second-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay tests, enrolled from May 1, 1991, to June 31, 1992, were evaluated. Thirty-six were symptom-free subjects found to have HCV antibodies when screened for blood donation: they all had normal results of liver function tests, normal results of physical examination, and normal hepatobiliary ultrasonography. Fifty-one were patients diagnosed as having a chronic liver disease by percutaneous liver biopsy specimen; histologic assessment was chronic persistent hepatitis in 15, chronic active hepatitis in 28, and liver cirrhosis in eight. A group of 231 donors of platelets and bone marrow, negative for anti-HCV, was used as a control population. All participants were typed for HLA class II antigens (DR and DQ) using National Institutes of Health recommended microlymphocytotoxicity test and were followed up by means of alanine aminotransferase and HCV testing for at least 1 year. RESULTS: Frequency of HLA-DR5 antigen was higher in symptom-free anti-HCV-positive individuals (52.8%) than among HCV-related patients with chronic liver disease (13.7%). The difference was statistically significant (corrected P value = .005; 95% confidence interval, 19.6% to 58.6%); between DR5 and long-term evolution of hepatitis C, there was a negative association (relative risk = 0.142). Moreover, frequency of HLA-DR5-positive subjects appeared to be inversely proportional to severity of liver disease (52.8% in symptom-free patients, 26.6% in patients with chronic persistent hepatitis, 10.7% in patients with chronic active hepatitis, and 0% in patients with liver cirrhosis, P < .001). CONCLUSIONS: Our results point to a strict relationship between HLA haplotype and ability of immune response to influence the outcome of HCV infection. Presence of HLA-DR5 antigen appears as a protective factor against a severe outcome of chronic infection, being correlated with a benign evolution of the infection, often asymptomatic, or a less severe chronic liver disease.

Prevalence of HCV antibodies in a uraemic population undergoing maintenance dialysis therapy and in the staff members of the dialysis unit.

We studied, by both 1st and 2nd generation assay, the prevalence rate of HCVAb in a population of 141 dialysis patients, 37 transplanted patients and 55 staff members. From this study emerges a higher sensitivity of the 2nd generation HCVAb test (15.38 versus 36.79% of positive responses, respectively), and a significant positive correlation between lengths of dialysis period. We have not found a significant difference between HCVAb-positive and -negative patients in relation to the blood transfusions. None of the 21 CAPD patients (home dialysis) resulted positive, even if transfused. Two nurses were positive. In our experience, the environmental factor seems more important. Since the isolation of the positive patients is an effective but not feasible measure, it is necessary to improve the operating management of the hemodialysis sessions, avoiding any contact between patients via material (instrumentation, monitors) and teaching the staff members to use severe preventive standards with all hemodialysis patients.