RESUMEN
Animal models of liver cirrhosis (LC) display a reduced hypothalamic somatostatinergic tone. To test whether a similar mechanism could explain the enhanced Growth Hormone (GH) secretory response to GH-Releasing Hormone (GHRH), which is seen in human LC, we studied the effect of the cholinesterase inhibitor pyridostigmine (PD), which is able to reduce the release of hypothalamic somatostatin (SS), on the GHRH-stimulated GH secretion. We considered that if PD were unable to increase GH secretion, this would constitute evidence of an already inhibited endogenous somatostatinergic tone. If proved, this in turn could explain the enhanced GH response to GHRH seen in LC. Ten LC patients and nine controls were given GHRH (100 microg, intravenously), or PD (120 mg, orally) plus GHRH. After GHRH alone, the GH peak was four times higher in LC than in controls (40.85+/-15.7 ng/ml in LC and 9.35+/-2.5 ng/ml in controls). In LC, PD administration markedly increased the GH response to GHRH (GH peak: 98.0+/-19.7 ng/ml; +240% vs. GHRH alone). The ability of PD to increase the GH response in patients with LC suggests that in this condition the enhanced GH response to GHRH is not due to a completely inhibited endogenous somatostatinergic tone. SS appears instead to maintain its modulator role on GH secretion in human LC, in contrast with what observed in animal models.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona de Crecimiento Humana/metabolismo , Hipotálamo/fisiología , Cirrosis Hepática/patología , Somatostatina/fisiología , Hepatitis B/patología , Hepatitis C/patología , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Masculino , Placebos , Método Simple CiegoAsunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Ribavirina/uso terapéutico , Femenino , Humanos , Interferones/administración & dosificación , Masculino , Persona de Mediana Edad , Retratamiento , Ribavirina/administración & dosificaciónRESUMEN
We evaluated the agreement between wedged hepatic vein pressure (WHVP), portal vein pressure (PVP), and its relationship with portal hemodynamics in 21 patients with HCV-related cirrhosis with esophageal varices. Direct measurements of the portohepatic gradient (HVPG) were obtained by ultrasound-guided fine needle puncture of the right hepatic and the portal veins. In five cases PVP was 6.4-10.4 mm Hg higher than WHVP. In 12 cases measurements were similar (WHVP - PVP < or = 3 mm Hg). In the remaining four cases WHVP was 3.6-9.6 mm Hg higher than PVP. WHVP and PVP agreement was not related to HVPG mean value, Child-Pugh score, or grading of esophageal varices. By contrast, the difference between WHVP and PVP was inversely related to the portal flow velocity (P = 0.053) and directly related to the portal vascular resistance (P = 0.02). Whereas the portal branches were visualized in patients with WHVP lower or similar to PVP, a predominant left portosystemic collateral flow was observed in patients with WHVP > PVP. Our data point out that, in patients with cirrhosis due to hepatitis C virus infection, discrepant HVPG values reflect true hemodynamic differences.
Asunto(s)
Hemodinámica/fisiología , Venas Hepáticas/fisiopatología , Hepatitis C/complicaciones , Cirrosis Hepática/etiología , Cirrosis Hepática/fisiopatología , Sistema Porta/fisiopatología , Vena Porta/fisiopatología , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Circulación Colateral , Várices Esofágicas y Gástricas/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resistencia Vascular , Presión Venosa/fisiologíaRESUMEN
OBJECTIVE: The liver is the major site of apolipoprotein(a) synthesis, and an inverse correlation between the size of apolipoprotein(a) isoforms and its serum levels have been described. We evaluated the Apo(a) serum levels and its isoforms in patients with liver cirrhosis at different stages of the disease (Childe Turcotte classification), and during the characteristic phase of liver synthesis decline. METHODS: We studied 84 patients with liver cirrhosis and 185 control subjects with normal liver function. RESULTS: Apo(a) serum levels were significantly lower (p < 0.01) in cirrhotic patients and, after 24 months, six patients showing a change from class A to class B had a statistically significant decrease in Apo(a) concentrations (p = 0.0313). Moreover, our data showed an inversion of the small/large isoforms ratio in patient with cirrhosis in spite of the reduction in plasma concentration. CONCLUSION: We showed a reduction of Apo(a) serum concentrations in a large number of patients with cirrhosis and, for the first time, during the characteristic phase of liver synthesis decline, confirming the liver as the major site of Apolipoprotein(a) synthesis. Moreover we showed in the cirrhotic patients that the normal correlation between Apo(a) isoforms and Apo(a) concentrations is not conserved and the low levels are not dependent upon a high prevalence of large isoforms.
Asunto(s)
Apolipoproteínas A/sangre , Apolipoproteínas A/clasificación , Cirrosis Hepática/sangre , Apolipoproteínas A/metabolismo , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Hígado/metabolismo , Pruebas de Función Hepática , Masculino , Persona de Mediana EdadRESUMEN
It was our aim to evaluate whether the baseline activity of 2-5 oligoadenylate synthetase (2-5 OAS) in serum and changes induced by the treatment with interferon are relevant factors in remission of chronic hepatitis C. Seventeen out of 30 adult patients with chronic hepatitis C were randomized to receive recombinant alpha-2b interferon at the dosage of 3 MU three times weekly. By the end of the third month, nine patients had normalized transaminase levels and continued to receive 3 MU of interferon for an additional 3 months, whereas in eight non-responders the dosage was increased to 6 MU for the same period of time. A single patient responded to the increased dosage. Baseline 2-5 OAS serum activity was significantly higher in patients with chronic hepatitis when compared with normal controls. Follow-up on the 13 untreated cases showed that 2-5 OAS elevation was stable and unrelated to concomitant infections. Comparison of responders and non-responders showed that the latter had higher baseline 2-5 OAS activity, tended to have an earlier and higher peak in the enzyme during the first 4 weeks of treatment, and maintained higher levels during the first 3 months of therapy. The increased dosage of interferon in this group led to an additional, although temporary, increase in 2-5 OAS. Our data suggest that HCV infection by itself induces elevated 2-5 OAS levels. The paradoxical increase in non-responders indicates that monitoring of the enzyme in serum does not predict the response to interferon. The role of the 2-5 OAS pathway in inducing the antiviral state in HCV infection should be further evaluated at tissue level.