Seventeen cirrhotics with refractory ascites were treated with transjugular intrahepatic portosys... more Seventeen cirrhotics with refractory ascites were treated with transjugular intrahepatic portosystemic shunt (TIPS) and followed for 15.5 +/- 3.4 months. Five patients died, four within 3 months after TIPS (hepatocellular failure) and one after 22 months (cholangiocarcinoma). Six patients received transplants 1 to 10 months after the procedure. Actuarial survival at 6, 12, and 24 months was 75%, 75%, and 63%, respectively. Portosystemic venous pressure gradient decreased by 46% at 1 month and by 38% at 7 to 12 months. Eight patients presented 18 stenoses 1 to 18 months after TIPS. Twelve stenoses required balloon dilatation. Tense ascites was present before TIPS in 100% of the patients, whereas it was mild or absent in 56% at 1 month, in 66% at 3 to 6 months, in 57% at 7 to 12 months, and in 100% at 24 months after TIPS. Requirements for diuretics and paracentesis decreased after TIPS (P < .001, both). One month after TIPS, urinary and fractional sodium excretion increased (P < .001, both), plasma renin activity, plasma aldosterone (P < .005, both), and plasma norepinephrine (P < .05) decreased and cardiac output (P < .01) increased, systemic vascular resistances (P < .005) decreased, and arterial pressure did not change. Acute hepatic encephalopathy was frequent early after TIPS but was responsive to treatment and caused no long-term disability. In conclusion, TIPS is useful in the treatment of refractory ascites through lowering portal pressure and improving renal sodium excretion. This effect could be attributable to an increase in effective blood volume causing deactivation of vasopressor systems.
Seventy-two patients with chronic hepatitis C were included in a randomised trial of lymphoblasto... more Seventy-two patients with chronic hepatitis C were included in a randomised trial of lymphoblastoid interferon versus no treatment. Thirty-six patients entered each group. Interferon was given in a step-down schedule for 12 months. Aminotransferase activities ...
For the 30-50% of patients with chronic hepatitis C who do not respond to alpha-interferon therap... more For the 30-50% of patients with chronic hepatitis C who do not respond to alpha-interferon therapy there is no alternative treatment. Some previously untreated patients have shown a biochemical response to ribavirin, but the antiviral effects of this substance on alpha-interferon-resistant cases is largely unknown. Twelve patients with chronic hepatitis C who had not responded to a 6-12 month course of alpha-interferon were included in this study. Oral ribavirin was administered at a dose of 16 mg/kg per day for 6 or 9 months. Aminotransferase levels had not significantly changed during interferon therapy but decreased significantly during ribavirin treatment (mean alanine aminotransferase at baseline, 102 +/- 18 IU/l vs. 55 +/- 14 IU/l at 6 months; P = 0.0001). Aminotransferase levels became normal in 6 cases (50%), significantly decreased in 3 patients (25%), and did not significantly change in the remaining 3 cases (25%). All patients with normalized aminotransferase values relapsed after ribavirin was discontinued and aminotransferase activity returned to pretreatment levels. Before therapy serum hepatitis C virus RNA was detected by polymerase chain reaction in 10 cases. None of them had cleared viral RNA when tested following 3, 6 and 9 months of ribavirin therapy. Side-effects were mild and reversible. In conclusion, about half of the patients with chronic hepatitis C who are unresponsive to alpha-interferon show a clear-cut biochemical response after 6-9 months of ribavirin administration. However, ribavirin does not clear circulating hepatitis C virus RNA and relapses occur after withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
Tumor necrosis factor α (TNF-α) is a cytokine with pleiotropic properties that is induced in a va... more Tumor necrosis factor α (TNF-α) is a cytokine with pleiotropic properties that is induced in a variety of pathological situations including viral infections. In this work, we analyzed the expression of TNF-α gene in patients with chronic hepatitis C. Serum TNF-α levels were found to be elevated in all chronic hepatitis C patients including those cases presenting sustained biochemical remission of the disease after interferon therapy. Untreated patients with chronic hepatitis C showed increased TNF-α messenger RNA (mRNA) levels in the liver and mononuclear cells as compared with healthy controls. After completion of treatment with interferon, patients experiencing sustained complete response showed values of TNF-α mRNA, both in the liver and in peripheral mononuclear cells, within the normal range, significantly lower than patients who did not respond to interferon and than those with complete response who relapsed after interferon withdrawal. Pretreatment values of TNF-α mRNA were lower in long-term responders to interferon than in cases who failed to respond to the treatment. Values of TNF-α mRNA in the liver or in mononuclear cells were higher in specimens with positive hepatitis C virus (HCV) RNA than in those samples where the virus was undetectable. Neither the intensity of the liver damage nor the amount of HCV RNA in serum or in cells showed correlation with the levels of TNF-α transcripts in peripheral mononuclear cells but it was found that high TNF-α values were associated with genotype 1b. In conclusion, there is an enhanced expression of TNF-α in HCV infection. High levels of this cytokine may play a role in the resistance to interferon therapy.
Antiphospholipid antibodies are a type of autoantibodies that have been implicated in the occurre... more Antiphospholipid antibodies are a type of autoantibodies that have been implicated in the occurrence of thrombocytopenia and thrombotic events and have been described in autoimmune disorders and diverse viral diseases. In this study anticardiolipin antibodies (immunoglobulin G [IgG] isotype) were determined in serum from 100 patients with chronic hepatitis C and 52 healthy controls. In addition, hepatitis C virus (HCV) markers (anti-HCV and HCV RNA) were investigated in 73 patients with thrombotic disorders and no clinical evidence of liver disease; of these patients 37 cases tested negatively for anticardiolipin antibodies and 36 positively. Anticardiolipin test was positive more frequently (22%) in the group of patients with chronic hepatitis C than in healthy controls (1.9%; P < .001). Using conditional logistic-regression analysis we found that in hepatitis C patients the presence of thrombocytopenia, portal hypertension and the existence of prior thrombotic episodes were significantly related to positivity for anticardiolipin antibodies (P < .05 in all cases). In patients with no evidence of liver disease and a history of thrombotic events, hepatitis C markers were absent in all cases who tested negatively for anticardiolipin antibodies (n = 37), but were present in 16.7% of those positive for anticardiolipin (n = 36) (P = .01). In conclusion, anticardiolipin antibodies are frequently found in patients with chronic hepatitis C and in these patients they may be implicated in the occurrence of thrombosis and in the development of thrombocytopenia. Occult HCV infection is present in a significant proportion of patients with thrombotic disorders and positive for anticardiolipin (the antiphospholipid syndrome).
Seventeen cirrhotics with refractory ascites were treated with transjugular intrahepatic portosys... more Seventeen cirrhotics with refractory ascites were treated with transjugular intrahepatic portosystemic shunt (TIPS) and followed for 15.5 +/- 3.4 months. Five patients died, four within 3 months after TIPS (hepatocellular failure) and one after 22 months (cholangiocarcinoma). Six patients received transplants 1 to 10 months after the procedure. Actuarial survival at 6, 12, and 24 months was 75%, 75%, and 63%, respectively. Portosystemic venous pressure gradient decreased by 46% at 1 month and by 38% at 7 to 12 months. Eight patients presented 18 stenoses 1 to 18 months after TIPS. Twelve stenoses required balloon dilatation. Tense ascites was present before TIPS in 100% of the patients, whereas it was mild or absent in 56% at 1 month, in 66% at 3 to 6 months, in 57% at 7 to 12 months, and in 100% at 24 months after TIPS. Requirements for diuretics and paracentesis decreased after TIPS (P &amp;amp;lt; .001, both). One month after TIPS, urinary and fractional sodium excretion increased (P &amp;amp;lt; .001, both), plasma renin activity, plasma aldosterone (P &amp;amp;lt; .005, both), and plasma norepinephrine (P &amp;amp;lt; .05) decreased and cardiac output (P &amp;amp;lt; .01) increased, systemic vascular resistances (P &amp;amp;lt; .005) decreased, and arterial pressure did not change. Acute hepatic encephalopathy was frequent early after TIPS but was responsive to treatment and caused no long-term disability. In conclusion, TIPS is useful in the treatment of refractory ascites through lowering portal pressure and improving renal sodium excretion. This effect could be attributable to an increase in effective blood volume causing deactivation of vasopressor systems.
Seventy-two patients with chronic hepatitis C were included in a randomised trial of lymphoblasto... more Seventy-two patients with chronic hepatitis C were included in a randomised trial of lymphoblastoid interferon versus no treatment. Thirty-six patients entered each group. Interferon was given in a step-down schedule for 12 months. Aminotransferase activities ...
For the 30-50% of patients with chronic hepatitis C who do not respond to alpha-interferon therap... more For the 30-50% of patients with chronic hepatitis C who do not respond to alpha-interferon therapy there is no alternative treatment. Some previously untreated patients have shown a biochemical response to ribavirin, but the antiviral effects of this substance on alpha-interferon-resistant cases is largely unknown. Twelve patients with chronic hepatitis C who had not responded to a 6-12 month course of alpha-interferon were included in this study. Oral ribavirin was administered at a dose of 16 mg/kg per day for 6 or 9 months. Aminotransferase levels had not significantly changed during interferon therapy but decreased significantly during ribavirin treatment (mean alanine aminotransferase at baseline, 102 +/- 18 IU/l vs. 55 +/- 14 IU/l at 6 months; P = 0.0001). Aminotransferase levels became normal in 6 cases (50%), significantly decreased in 3 patients (25%), and did not significantly change in the remaining 3 cases (25%). All patients with normalized aminotransferase values relapsed after ribavirin was discontinued and aminotransferase activity returned to pretreatment levels. Before therapy serum hepatitis C virus RNA was detected by polymerase chain reaction in 10 cases. None of them had cleared viral RNA when tested following 3, 6 and 9 months of ribavirin therapy. Side-effects were mild and reversible. In conclusion, about half of the patients with chronic hepatitis C who are unresponsive to alpha-interferon show a clear-cut biochemical response after 6-9 months of ribavirin administration. However, ribavirin does not clear circulating hepatitis C virus RNA and relapses occur after withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
Tumor necrosis factor α (TNF-α) is a cytokine with pleiotropic properties that is induced in a va... more Tumor necrosis factor α (TNF-α) is a cytokine with pleiotropic properties that is induced in a variety of pathological situations including viral infections. In this work, we analyzed the expression of TNF-α gene in patients with chronic hepatitis C. Serum TNF-α levels were found to be elevated in all chronic hepatitis C patients including those cases presenting sustained biochemical remission of the disease after interferon therapy. Untreated patients with chronic hepatitis C showed increased TNF-α messenger RNA (mRNA) levels in the liver and mononuclear cells as compared with healthy controls. After completion of treatment with interferon, patients experiencing sustained complete response showed values of TNF-α mRNA, both in the liver and in peripheral mononuclear cells, within the normal range, significantly lower than patients who did not respond to interferon and than those with complete response who relapsed after interferon withdrawal. Pretreatment values of TNF-α mRNA were lower in long-term responders to interferon than in cases who failed to respond to the treatment. Values of TNF-α mRNA in the liver or in mononuclear cells were higher in specimens with positive hepatitis C virus (HCV) RNA than in those samples where the virus was undetectable. Neither the intensity of the liver damage nor the amount of HCV RNA in serum or in cells showed correlation with the levels of TNF-α transcripts in peripheral mononuclear cells but it was found that high TNF-α values were associated with genotype 1b. In conclusion, there is an enhanced expression of TNF-α in HCV infection. High levels of this cytokine may play a role in the resistance to interferon therapy.
Antiphospholipid antibodies are a type of autoantibodies that have been implicated in the occurre... more Antiphospholipid antibodies are a type of autoantibodies that have been implicated in the occurrence of thrombocytopenia and thrombotic events and have been described in autoimmune disorders and diverse viral diseases. In this study anticardiolipin antibodies (immunoglobulin G [IgG] isotype) were determined in serum from 100 patients with chronic hepatitis C and 52 healthy controls. In addition, hepatitis C virus (HCV) markers (anti-HCV and HCV RNA) were investigated in 73 patients with thrombotic disorders and no clinical evidence of liver disease; of these patients 37 cases tested negatively for anticardiolipin antibodies and 36 positively. Anticardiolipin test was positive more frequently (22%) in the group of patients with chronic hepatitis C than in healthy controls (1.9%; P < .001). Using conditional logistic-regression analysis we found that in hepatitis C patients the presence of thrombocytopenia, portal hypertension and the existence of prior thrombotic episodes were significantly related to positivity for anticardiolipin antibodies (P < .05 in all cases). In patients with no evidence of liver disease and a history of thrombotic events, hepatitis C markers were absent in all cases who tested negatively for anticardiolipin antibodies (n = 37), but were present in 16.7% of those positive for anticardiolipin (n = 36) (P = .01). In conclusion, anticardiolipin antibodies are frequently found in patients with chronic hepatitis C and in these patients they may be implicated in the occurrence of thrombosis and in the development of thrombocytopenia. Occult HCV infection is present in a significant proportion of patients with thrombotic disorders and positive for anticardiolipin (the antiphospholipid syndrome).
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