[Interferon, ribavirin and amantadine in prior nonresponders to interferon and ribavirin therapy with chronic hepatitis C (genotype 1)]. / Interferón, ribavirina y amantadina en pacientes con hepatitis C crónica (genotipo 1) sin respuesta al tratamiento previo con interferón y ribavirina.

OBJECTIVE: Despite advances in the treatment of chronic hepatitis C virus (HCV), the disease persists after treatment with interferon and ribavirin in a large percentage of patients and other therapeutic options are lacking. We investigated the efficacy of retreatment with antiviral therapy including amantadine. EXPERIMENTAL DESIGN: prospective and open pilot study. PATIENTS: Thirty-nine patients with chronic HCV, genotype 1, who were nonresponders to interferon and ribavirin were included. The patients were given repeat treatment with interferon-alpha 2A (9 MU/week), ribavirin (1,000-1,200 mg/day) and amantadine (200 mg/day) for 48 weeks. RESULTS: HCV-RNA was undetectable in 5 patients in week 48 (12.8%) and in only 2 patients after 24 weeks of follow-up (5.1% of sustained responses). In patients with basal viremia of < 8 105 U/ml the probability of response at the end of treatment and of sustained response was 26.3 and 10.5%, respectively; in patients with elevated viremias response was 0%. CONCLUSIONS: In patients with chronic HCV genotype 1 without response to interferon and ribavirin, triple antiviral therapy with interferon, ribavirin and amantadine is not useful.

Time course of serum hepatitis C virus-RNA during chronic hepatitis C treatment accurately predicts the type of response.

AIM: To establish the value of alanine aminotransferase normalization and hepatitis C virus-RNA clearance as predictors of sustained virological response in naïve and relapser chronic hepatitis C patients on mono or combination therapy. METHODS: A total of 282 hepatitis C patients were studied: 98 naïves on interferon, and 64 naïves and 75 relapsers on interferon plus oral ribavirin; 45 patients were excluded. Drugs were administered at standard doses for 12 months. Alanine aminotransferase and hepatitis C virus-RNA were determined at baseline and at weeks 4, 12, 24, 48, and at 72 and 96 weeks after completion of therapy. RESULTS: The rate of sustained response was greater (P < 0.05) in naïves and relapsers on combination therapy (33% and 48%, respectively) than in naïves on interferon alone (16%). Hepatitis C virus-RNA significantly decreased from baseline by week 4 in naïves on interferon and relapsers on combination therapy and by week 12 in naïves on combination therapy. Alanine aminotransferase levels paralleled viremic load in naïves on interferon, yet in patients on combination therapy, alanine aminotransferase normalized independently of the virological response. During treatment, the main factor associated with sustained response was hepatitis C virus-RNA clearance by week 4 in naïves on interferon and relapsers on combination therapy, and by week 24 in naïves on combination therapy. CONCLUSION: Clearance of viraemia constitutes the best predictor of a sustained response to therapy, but needs to be measured at patient-specific times.

Sustained response to interferon-alpha or to interferon-alpha plus ribavirin in hepatitis C virus-associated symptomatic mixed cryoglobulinaemia.

BACKGROUND: Hepatitis C virus (HCV) infection has been associated with mixed cryoglobulinaemia. AIM: To investigate the efficacy of anti-viral therapy on the eradication of HCV and its clinical manifestations in patients with HCV-associated symptomatic mixed cryoglobulinaemia. PATIENTS AND METHODS: 18 out of 32 patients with symptomatic mixed cryoglobulinaemia (MC group) received a 12-month course of interferon (3 MU three times a week, subcutaneously). Nonresponders or relapsers to this therapy were treated with interferon plus ribavirin (1200 mg/day, orally) for 12-months. 226 patients with HCV infection and without cryoglobulins were studied in comparison (Hepatitis C group). Serial quantification of serum HCV-RNA and cryoglobulins were performed. RESULTS: In the MC group, 10 out of 18 patients (55%) receiving interferon showed an end of treatment response, but at the end of follow-up, only five (28%) patients had a sustained response. In the hepatitis C group, 91 patients (47%) showed an end of treatment response but only 42 (20%) a sustained response. In the MC group alanine transaminase, cryocrit and rheumatoid factor decreased significantly in responders, with an improvement or disappearance of the MC-associated clinical manifestations. Alanine transaminase, cryocrit and rheumatoid factor increased in the relapsers and the clinical manifestations reappeared. Nonresponders and relapsers to interferon in the MC group were retreated with interferon plus ribavirin. Five out of eight nonresponders showed a end of treatment response but it was sustained in three of them. In the relapsers, treatment with combined therapy achieved a sustained response in four out of the five patients (80%). CONCLUSIONS: Interferon as monotherapy or combined with ribavirin is a safe and effective treatment in patients with HCV-associated MC. The presence of cryoglobulins does not affect the response to anti-viral treatment in patients with HCV infection. The eradication of HCV is associated with an improvement or disappearance of MC-associated clinical manifestations.

Improvement in liver fibrosis, functionality and hemodynamics in CCI4-cirrhotic rats after injection of the Liver Growth Factor.

BACKGROUND/AIMS: Most substances used in experimental models of cirrhosis are chosen either as protectors of lipid peroxidation, as antifibrogenic agents or as vitamins, among others. In this report, we analyze the improvement produced, in established cirrhosis (CCl4 plus phenobarbital) in rats, by intraperitoneal injection of Liver Growth Factor, a hepatic mitogen with activity both in vivo and in vitro. METHODS: Following confirmation of CCl4-induced cirrhosis, Liver Growth Factor (4.5 microg per ratx2 injections/week for 3 weeks) was administered to one group of rats (Cirr+LGF). The remaining rats (Cirr) received saline. The groups were compared in terms of serum enzymes, tissue damage, total liver collagen, collagenase activity, microsomal enzyme activities, splanchnic and systemic hemodynamics and portosystemic shunting. RESULTS: Treatment of rats presenting CCl4-induced cirrhosis with Liver Growth Factor decreased serum aminotransferase levels and increased levels of serum albumin and total protein. The Liver collagen content was lower in rats treated with Liver Growth Factor (2.96 vs. 4.32 mg/g liver, p<0.01). Microscopic studies revealed that the livers of rats receiving Liver Growth Factor showed decreases in fibrosis, necrosis and inflammatory infiltration, as well as a recovery of architectural integrity. Liver function was improved after treatment with Liver Growth Factor, as indicated by the rate constant for elimination of aminopyrine, which increased from 0.0063 to 0.0170 (p<0.05). This increase was accompanied by a higher total amount of cytochrome P-450 as well as of certain P-450 isoenzymes, especially those that are hormone-dependent, such as P-450 3A. The improved liver histology and function observed in Cirr+LGF rats was associated with decreases in portal pressure (14.4 vs. 9.4 mm Hg, p<0.01) and portosystemic shunting (55.8 vs. 11.5%, p<0.01), as well as increases in mean arterial pressure and systemic vascular resistance, and a reduction in ascites. CONCLUSIONS: Administration of the hepatic mitogen, Liver Growth Factor, to CCl4-cirrhotic rats decreased liver collagen and reorganized the hepatic extracellular matrix, resulting in an improvement in liver function, reduced portal pressure and amelioration of ascites.

Propranolol plus prazosin compared with propranolol plus isosorbide-5-mononitrate in the treatment of portal hypertension.

BACKGROUND & AIMS: The association of prazosin to propranolol enhances the decrease in portal pressure but may cause hypotension and sodium retention. The aim of this study was to compare the portal pressure reduction and safety of the combination of propranolol plus prazosin with that of propranolol plus isosorbide-5-mononitrate (ISMN). METHODS: Fifty-six portal-hypertensive cirrhotics received randomly propranolol plus prazosin (n = 28) or propranolol plus ISMN (n = 28) orally for 3 months. Hemodynamics and liver and renal function were assessed at baseline and after 3 months. RESULTS: Propranolol plus prazosin caused a greater reduction in hepatic venous pressure gradient (HVPG) than propranolol plus ISMN (-24.2% +/- 11% vs. -16.1% +/- 11%; P < 0.01). A reduction in HVPG of > 20% was significantly more frequent in the propranolol plus prazosin group than in the propranolol plus ISMN group (85% vs. 53%; P < 0.05). Neither treatment modified hepatic blood flow, quantitative liver function test results, glomerular filtration rate, plasma renin activity, or plasma aldosterone level. Side effects occurred in 13 patients receiving propranolol plus prazosin compared with 7 receiving propranolol plus ISMN (P = 0.16). CONCLUSIONS: Propranolol plus prazosin has a greater portal pressure-lowering effect than propranolol plus ISMN. Both therapies were safe for liver and renal function. However, the combination of propranolol plus prazosin caused a greater decrease in arterial pressure and was less well tolerated than propranolol plus ISMN.

Selective impairment of endothelium-mediated vasodilation in liver transplant recipients with cyclosporin A-induced hypertension.

Arterial hypertension is commonly observed in orthotopic liver transplantation (OLT) recipients receiving cyclosporin A (CsA), but the precise pathogenetic mechanisms remain partially unknown. The aim of this study was to investigate endothelium-dependent and -independent dilation and adrenergic constriction of resistance vessels of OLT recipients treated with CsA. Vascular reactivity was examined in 22 OLT patients, 10 with and 12 without arterial hypertension, and in 10 control subjects by assessing the forearm blood flow response to the brachial artery infusion of increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine. In 10 OLT patients, the response to methacholine was also examined after acetylsalicylate. The ratio of serum nitrite and nitrate to serum creatinine was lower (P < .05) in OLT patients with hypertension than in nonhypertensive patients and controls. Basal forearm flow was similar in the three groups. Methacholine vasodilation was impaired in the hypertensive patients as shown by a lower maximum forearm vasodilator response and a shift in the dose response curve to methacholine to the right compared with the nonhypertensive OLT patients and the controls. The response to methacholine was not modified after salicylate. Forearm flow response to nitroprusside was similar in the three groups. No differences between the patients and the controls were found in the maximum forearm flow contraction in response to phenylephrine. An impairment in endothelium-dependent vasodilation could mediate arterial hypertension in OLT patients immunosuppressed with CsA.

Accuracy of portal and forearm blood flow measurements in the assessment of the portal pressure response to propranolol.

BACKGROUND/AIMS: The portal pressure response to propranolol varies significantly in individual patients with cirrhosis. At present, propranolol responders can be identified only by measuring the hepatic venous pressure gradient. The aims of this study were: 1) to investigate whether the noninvasive monitoring of portal blood flow by pulsed Doppler ultrasound and forearm blood flow by strain-gauge plethysmography can predict the hepatic venous pressure gradient response to propranolol in patients with cirrhosis, and 2) to analyze the factors that may influence this response. METHODS: Hemodynamic measurements were undertaken in 80 patients with cirrhosis before and after receiving propranolol (0.15 mg/kg i.v., n = 60) or placebo (n = 20). RESULTS: No changes were observed in the placebo group. Propranolol lowered (p < 0.01) hepatic venous pressure gradient from 17.6 +/- 3.8 to 14.7 +/- 3.8 mmHg, portal blood flow from 1122 +/- 363 to 897 +/- 332 ml/min and forearm blood flow from 7.52 +/- 3.1 to 6.12 +/- 2.3 ml/min%. Changes in hepatic venous pressure gradient were correlated (p < 0.01) with those of portal blood flow (r = 0.82) and forearm blood flow (r = 0.54). The reduction in hepatic venous pressure gradient was > 20% in 23 patients ("responders"). The accuracy of portal Doppler flowmetry in identifying responders was higher than that of forearm plethysmography (88.3 vs. 68.3%, p < 0.05). Multivariate analysis proved that previous variceal bleeding was the only factor independently associated with a lack of response to propranolol (relative risk 3.42, 95% CI 1.5-7.4, p < 0.01). Hepatic venous pressure gradient reduction by propranolol was higher in non-bleeders than in bleeders (-19.9 +/- 9.4 vs. -11.3 +/- 8.6%, p < 0.01). CONCLUSIONS: Portal Doppler ultrasound can be used as a reliable surrogate indicator of the hepatic venous pressure gradient response to acute propranolol administration. In addition, our study indicates that this response is mainly influenced by previous variceal hemorrhage.

Changes in gastrin and serum pepsinogens in monitoring of Helicobacter pylori response to therapy.

The aims of this study in 50 patients with H. pylori infection and duodenal ulcer were to examine the effect of eradication therapy on the serum levels of gastrin, pepsinogen I, and pepsinogen II and to investigate whether monitoring of the serum changes in these peptides after treatment could predict patient outcome. H. pylori status was assessed at entry and one and six months after therapy by culturing and microscopic analysis of the gastric mucosa and by [14C]urea breath test. Significant decreases were observed in the serum levels of gastrin (-11.4 +/- 3%), pepsinogen I (-28.9 +/- 4%), and pepsinogen II (-40.4 +/- 3%) in the 45 patients whose infection was eradicated, but not in the patients without eradication. Serum values of these peptides were unchanged in an additional group of 10 patients that only received omeprazol, none of whom had H. pylori eradicated. The best cutoff point of the percentage of each peptide to predict patient outcome was 10% for gastrin and pepsinogen I, and 15% for pepsinogen II. A pepsinogen II decrease > 15% resulted in the best marker of H. pylori clearance, accurately identifying patient outcome 86.6% of the time, whereas the diagnostic accuracy of gastrin and pepsinogen I was 61.7% and 76.6%, respectively. Significant correlations were found between the bacterial load assessed by histology with the serum concentrations of pepsinogen I and II and with the urease activity as measured by the amount of 14CO2 excreted. In conclusion, eradication of H. pylori infection is followed by a significant drop in serum levels of gastrin, pepsinogen I, and pepsinogen II. Changes in the latter are the most uniform and may be used as an indirect tool to predict treatment outcome.

Arterioportal fistula and hemobilia with associated acute cholecystitis: a complication of percutaneous liver biopsy.

Complications attributable to percutaneous liver biopsy, including hemobilia and arterioportal fistula, are uncommon. In this report, we present the case of a patient who underwent percutaneous liver biopsy and, as a consequence of this procedure, developed an arterioportal fistula and hemobilia with associated acute cholecystitis. The diagnosis of hemobilia was possible with abdominal ultrasound and upper endoscopy, but the patient required cholecystectomy. Hepatic angiography was performed, demonstrating the arterioportal fistula and hemobilia. Transcatheter embolization occluded the fistula, resolving the hemobilia. We recommend ultrasound and upper endoscopy as initial diagnostic procedures, but angiography and selective embolization must not be delayed if arterioportal fistula and/or hemobilia is suspected since these measures may help to prevent further complications.

Interferon and prednisone therapy in chronic hepatitis C with non-organ-specific antibodies.

BACKGROUND/AIMS: The relationship between hepatitis C virus and autoimmunity is controversial. The issue is particularly relevant in those patients with hepatitis C virus infection and serum autoantibodies in whom steroids can exacerbate viral replication and interferon can lead to decompensated liver disease. The aim of this study was to evaluate the response to a course of prednisone or interferon-alpha 2b. METHODS/RESULTS: The 12 study patients had biopsy-proven chronic hepatitis, serum HCV-RNA (by nested polymerase chain reaction) and non-organ-specific antibodies (eight with liver and kidney microsomal antibodies and four with antinuclear antibodies). Eight of these 12 patients received a 4-month course of prednisone (0.5 mg/kg per day), which increased alanine aminotransferase (mean +/- SE) (174 +/- 31 vs 252 +/- 18 U/l, p < 0.05) and bilirubin levels (0.96 +/- 0.17 vs 1.42 +/- 0.18 mg/dl, p = 0.09), without changing liver histology (Knodell index, 13.6 +/- 0.4 vs 13.1 +/- 0.3). Subsequent treatment with interferon in the 12 patients reduced serum alanine aminotransferase levels (170 +/- 20 vs 41 +/- 7 U/l, p < 0.0001) and portal and lobular inflammation (Knodell index, 13.8 +/- 0.5 vs 8.4 +/- 0.2, p < 0.001). A complete response to interferon was observed in ten of these patients (83%), eight of whom had previously been treated with prednisone. Serum HCV-RNA level decreased in interferon responders. A sustained response 1 year after withdrawal of interferon was seen in only five patients (41%). CONCLUSIONS: Patients with chronic hepatitis C and autoantibodies show a favorable response to interferon, but not to prednisone. The latter regimen can exacerbate liver necrosis in these subjects. The presence of autoantibodies in hepatitis C patients does not modify the response to interferon.

Continuous prazosin administration in cirrhotic patients: effects on portal hemodynamics and on liver and renal function.

BACKGROUND & AIMS: Hepatic vascular resistance is influenced by alpha-adrenergic tone. The aim of this study was to investigate the effects of continuous blockade of alpha-adrenoceptors with prazosin on hemodynamics, liver function, and renal function and whether the association of propranolol or furosemide enhances the portal pressure lowering effect of prazosin. METHODS: Cirrhotic patients with portal hypertension were studied at baseline and after a 3-month course of prazosin (n = 18) or placebo (n = 10). RESULTS: No changes were observed in the placebo group. Prazosin decreased the hepatic venous pressure gradient (HVPG) while increasing hepatic blood flow. Liver function improved as shown by an increase in hepatic and intrinsic hepatic clearances of indocyanine green and galactose elimination capacity. A significant reduction in mean arterial pressure and systemic vascular resistance was associated with increases in plasma renin activity and aldosterone concentration and a decrease in glomerular filtration rate. The plasma volume increased significantly, and 6 patients developed edema. The association of propranolol (n = 8) but not furosemide (n = 7) to prazosin increased the reduction in HVPG and attenuated the increase in plasma renin activity. CONCLUSIONS: In cirrhotic patients, continuous prazosin administration reduces portal pressure and improves liver perfusion and function but favors sodium and water retention. The association of propranolol enhances the decrease in portal pressure, suggesting a potential benefit from this combined therapy.

Enhanced endothelium-dependent vasodilation in patients with cirrhosis.

Experimental evidence indicates that an increased production of nitric oxide could play a role in the peripheral vasodilation of portal hypertension. To test this hypothesis in humans, we studied basal serum NO(2-) + NO3- levels and the response of forearm resistance vessels to increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine infused into the brachial artery of 12 cirrhotic patients and 10 controls. Forearm vascular resistance (FVR) was calculated from mean arterial pressure and forearm blood flow (FBF). Cirrhotics showed higher NO(2-) + NO3- levels (P < 0.05), higher FBF (P < 0.01), and lower FVR (P < 0.01) than controls. The reduction of FVR in response to every dose of methacholine was greater in cirrhotics than in controls; this was significant (P < 0.05) at the 3 and 10 micrograms/min doses. This response to methacholine was not modified by blockade of vascular prostacyclin. The response to nitroprusside was similar in both groups. The increase in FVR in response to every dose of phenylephrine was significantly (P < 0.01) lower in cirrhotics than in controls. In cirrhotics, a significant correlation (r = -0.81, P < 0.01) was found between the FVR response to the highest doses of methacholine and phenylephrine. In conclusion, cirrhotic patients show an enhanced endothelium-mediated vasodilation, which suggests an increased synthesis of nitric oxide. This defect may mediate the peripheral vasodilation and hyporeactivity to vasopressors of these patients.

Hepatic growth induced by injection of the liver growth factor into normal rats.

Normal Wistar rats injected with the liver growth factor (LGF), a mitogen specific for liver cells, experienced hepatic growth. LGF shows two peaks of activity in vivo, both of them mitogenic. Rats injected either with 6.8 ng or 3.9 micrograms LGF/rat every 3-4 days experienced liver growth showing a see-saw profile. Dry liver weight usually peaked at day 2 (microgram doses) or at day 3 (ng doses) after each injection, with increases of about 30% over controls. Liver DNA synthesis, measured by [3H]-thymidine incorporation, peaked 24 h after LGF injection at both doses. Liver protein synthesis, measured by [14]C-leucine incorporation, usually peaked 24 h after DNA synthesis maximums. Mitogen-stimulated cells were also assessed by immunohistochemical staining for proliferating cell nuclear antigen in livers of LGF-injected rats. Rats injected with rat serum albumin purified from normal rats to serve as controls showed a 6% increase in dry liver weight, but when serum albumin from 3-day fasted rats was injected instead, the increase was not statistically significant. The mild effect of rat serum albumin could be due to the lipid content of the solutions injected, but the level of lipids/mg protein in LGF solutions was half that determined with serum albumin from 3-day fasted rats. From the microscopic and ultramicroscopic studies carried out in rat livers injected with LGF at each dose, we observed: (1) an increase in the number of hepatocytes undergoing mitosis; (2) transient increases in lipid and glycogen contents, as occur after liver resection; (3) no signs of degeneration, such as the appearance of amyloids or fibrosis; (4) no increase in lysosome number, as in hepatotoxicity; (5) no alterations in endothelial or Kupffer cells; and (6) no ultrastructural signs of degeneration either in cytoplasmic organelles (rough endoplasmic reticulum, mitochondria) or in nuclei. One year after LGF injection, rat liver, pancreas, kidneys and spleen were normal, with no signs of degeneration or onset of fibrosis.

Hemodynamic effects of alpha-adrenergic blockade with prazosin in cirrhotic patients with portal hypertension.

This study was aimed at investigating whether the blockade of alpha 1-adrenergic receptors could reduce portal pressure in cirrhosis. Splanchnic and systemic hemodynamics were measured in 12 cirrhotic patients with esophageal varices at baseline and 1 hr after oral administration of 2 mg of prazosin (acute study). Measurements were repeated in 10 of these 12 patients after a 3-mo course of 5 mg/12 hr of prazosin (long-term study). Short-term prazosin significantly lowered the hepatic venous pressure gradient from 20.1 +/- 1.3 to 14.4 +/- 0.9 mm Hg (-25.7%) (p < 0.01), and chronic prazosin reduced it to 16.5 +/- 1.3 mm Hg (-19.1%) (p < 0.01). Hepatic blood flow was increased, thus changes in the hepatic venous pressure gradient resulted from a reduction in the estimated hepatic vascular resistance. Reductions in hepatic venous pressure gradient achieved after short-term and long-term prazosin were not significantly different. Reductions in mean arterial pressure and systemic vascular resistance were significantly greater after short-term than after long-term prazosin. Long-term prazosin was associated with significant increases in hepatic and intrinsic hepatic clearances of indocyanine green. This therapy also led to an increase in pulmonary capillary pressure (+ 28.6%, p < 0.05) and body weight (+ 3.06%, p < 0.01) and a decrease in hematocrit (-6.1%, p < 0.05) and urinary sodium excretion (-22.6%, p < 0.05). In contrast, there were no hemodynamic changes in a group of six cirrhotic patients receiving placebo. In cirrhotic patients, short-term prazosin lowers portal pressure by decreasing hepatic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Octreotide prevents postprandial splanchnic hyperemia in patients with portal hypertension.

An increase in splanchnic blood flow is a physiological response to food intake. In patients with cirrhosis whose hepatic vascular resistance is already high, this increase in flow leads to marked increases in portal pressure. This study investigates whether octreotide prevents the increases in hepatic flow and portal pressure that follow the ingestion of a meal in patients with cirrhosis. Twenty-two patients with cirrhosis and portal hypertension were randomized to receive a mixed liquid meal (520 kcal) plus a single subcutaneous injection of either placebo or octreotide (200 micrograms). In the placebo group the ingestion of a meal was followed by an increase in the hepatic venous pressure gradient (+ 19.4 +/- 4.3%, p < 0.01) and hepatic blood flow (+ 38.2 +/- 14.6%, p < 0.05) at 30 min. In contrast, in the octreotide group eating caused no significant change in the hepatic venous pressure gradient (-2.8 +/- 3.6%, NS), while hepatic flow was decreased (-6.08 +/- 5.4%, p < 0.05). Octreotide blunted the postprandial increase in serum insulin and glucagon levels observed in the placebo group. In conclusion, in patients with cirrhosis and portal hypertension, octreotide prevents the postprandial increase in hepatic blood flow, and consequently also in portal pressure. These findings suggest that this drug could play a role in the long-term management of portal hypertension.

Oral administration of clonidine in patients with alcoholic cirrhosis. Hemodynamic and liver function effects.

The effects of long-term oral clonidine treatment on hepatic and systemic hemodynamics and on quantitative liver function tests were investigated in 15 patients with alcoholic cirrhosis. Clonidine was administered at a mean dose of 0.33 +/- 0.1 mg/day (mean +/- SD) for a mean period of 64 +/- 10 days. Oral clonidine induced a significant reduction in the hepatic venous pressure gradient from 18.8 +/- 3.0 mm Hg to 15.9 +/- 3.4 mm Hg (P less than 0.001), which was the result of an increase in the free hepatic venous pressure from 5.1 +/- 4.2 mm Hg to 8.7 +/- 3.8 mm Hg (P less than 0.05). In 10 of the 15 patients (67%), the reduction in the hepatic venous pressure gradient was greater than 10% of baseline values. Hepatic blood flow did not change significantly after clonidine treatment. Additionally, treatment with clonidine decreased mean arterial pressure by 15.5% +/- 6% (P less than 0.001), heart rate by 17.7% +/- 7% (P less than 0.001), and cardiac output by 14.6% +/- 7% (P less than 0.001). However, systemic vascular resistance did not change significantly. There were no adverse effects on liver function, as shown by the nonsignificant changes in galactose-elimination capacity (149 +/- 59 vs. 170 +/- 58 mg/min), hepatic clearance of indocyanine green (0.19 +/- 0.10 vs. 0.17 +/- 0.07 L/min), and hepatic intrinsic clearance of indocyanine green (0.23 +/- 0.14 vs. 0.21 +/- 0.1 L/min) before and after clonidine treatment, respectively. In none of the patients was the drug withdrawn because of side effects, although 12 subjects complained of dry mouths. This study suggests that in patients with alcoholic cirrhosis, long-term oral clonidine administration achieves a reduction in the hepatic venous pressure gradient without adverse effects on hepatic blood flow and liver function.

Trauma in cirrhosis: an indicator of the pattern of alcohol abuse in different societies.

While some morbidities associated with the excessive use of alcohol are related to the total amount of alcohol consumed--cirrhosis being an example--other pathologies, such as trauma and those of psycho-social origin, are mainly related to the frequency of acute alcoholic intoxication rather than to the total amount consumed. The balance between these two types of alcohol-associated morbidities can provide an indication of the relative frequency of intoxication, and thus of the pattern of alcohol abuse in a population. Since trauma is highly associated with acute alcoholic intoxication, the prevalence of bone fractures was determined in cirrhotics in nine countries. The prevalence of rib and vertebral fractures on routine chest x-rays showed a 17-fold variation in the different countries, from 2% and 6% in Spain and Italy to 30% and 34% in Canada and the USA, suggesting marked differences in the pattern of alcohol abuse to intoxication. Conversely, the prevalence of cirrhosis is twice as high in Spain and Italy than in Canada and the USA. A strong positive correlation between per capita consumption and cirrhosis mortality (r = 0.86; p less than 0.01) exists among the nine countries studied, while the correlation between per capita alcohol consumption and the prevalence of trauma is not statistically significant (r = 0.40). Supporting a strong association between trauma and alcoholic intoxication, the prevalence of trauma was found to be highly correlated: r = 0.88, p less than 0.002, with the degree of concern for the psycho-social consequences of alcohol abuse in the different countries. Data indicate that trauma can be used as an objective indicator to assess the pattern of alcohol abuse in a population.

The use of the Dornier MPL-9000 lithotripter in the treatment of gallbladder and renal stones. Early experience.

The experience of two units (Gastroenterology and Urology) of Clínica La Luz, Madrid, in the treatment of gallbladder and renal lithiasis using the Dornier MPL-9000 lithotripter is reported herein. This lithotriptor has been utilized in the treatment of all cases of gallbladder calculi for which it is indicated and renal calculi localized high up (kidney), and in those cases that are difficult to treat with other lithotriptors such as patients with kyphoscoliosis, radiolucent calculi, elderly patients, children, etc.). During the first year the gallstone lithotripsy unit was utilized, 401 patients were referred for treatment. Of these, 180 met the criteria for patient selection. (Over 360 have been treated to date.) Sixty of these 180 patients had a single gallstone of up to 2.5 cm. These 60 patients were selected for the study since they comprised a group where the best results could be expected. The aim of studying this patient group was to evaluate the results achieved by lithotripsy and the short and medium-term outcome in this ideal group of patients. Concerning renal lithiasis, these are the first 100 cases treated with the MPL-9000 (currently over 420 have been treated). Eighty cases had a single calculus (60 caliceal and 20 pyelic), 15 had multiple calculi, and 5 had a staghorn stone. Treatment for gallbladder and renal lithiasis was exclusively by shock waves; i.e., as monotherapy with no other auxiliary procedure. The average number of shock waves used was 2,350 with a mean kV of 18 for gallbladder lithiasis.(ABSTRACT TRUNCATED AT 250 WORDS)