Rolling review: the treatment of major complications of cirrhosis.
Explore the source record for details and available documents.
Adrenergic beta-Antagonists↗
Biomedical subjects
J Rodés
Publications and source records attributed to J Rodés.
Effects of continued NO inhibition on portal hypertensive syndrome after portal vein stenosis in rat.
The present study investigated whether chronic nitric oxide (NO) inhibition prevents the hyperdynamic circulatory syndrome that appears in rats after partial portal vein ligation (PPVL). N omega-nitro-L-arginine methyl ester (L-NAME; 30 micrograms.kg-1.min-1, n = 17), a NO biosynthesis inhibitor, or vehicle (n = 17) was infused continuously from PPVL through subcutaneously osmotic pumps. Studies were performed, in ketamine-anesthetized Sprague-Dawley rats, in one-half of the animals at 4 days and in the remaining one-half at 8 days from PPVL. At 4 days, PPVL rats treated with L-NAME had higher mean arterial pressure (MAP), systemic vascular resistance (SVR), and splanchnic arteriolar resistance (SAR) and lower cardiac output and portal venous inflow (PVI) than PPVL rats treated with vehicle (P < 0.05). Similarly, at 8 days PPVL rats treated with L-NAME had higher MAP and SVR and lower cardiac output (P < 0.05) than PPVL rats treated with vehicle. In contrast, PVI and SAR were similar. At 4 days plasma volume and mesenteric-systemic shunting were lower, although nonsignificantly, in PPVL rats treated with L-NAME. This trend completely disappeared at 8 days. L-NAME did not change portal pressure at either 4 or 8 days. After 4 days of continuous treatment with L-NAME, nonportal hypertensive control rats had a significantly higher MAP, lower cardiac index and PVI, and higher SVR and SAR than nonportal hypertensive rats treated with vehicle. Contrary to PPVL rats, these effects were maintained after 8 days of treatment. The present study shows that NO contributes to the systemic disturbances of portal hypertension. However, NO inhibition delayed but did not prevent the splanchnic vasodilation that appears after PPVL, suggesting that other factors could also be involved.
Animals↗
Effect of chronic ethanol feeding on glutathione and functional integrity of mitochondria in periportal and perivenous rat hepatocytes.
Chronic ethanol feeding selectively impairs the translocation of cytosol GSH into the mitochondrial matrix. Since ethanol-induced liver cell injury is preferentially localized in the centrilobular area, we examined the hepatic acinar distribution of mitochondrial GSH transport in ethanol-fed rats. Enriched periportal (PP) and perivenous (PV) hepatocytes from pair- and ethanol-fed rats were prepared as well as mitochondria from these cells. The mitochondrial pool size of GSH was decreased in both PP and PV cells from ethanol-fed rats either as expressed per 10(6) cells or per microliter of mitochondrial matrix volume. The rate of reaccumulation of mitochondrial GSH and the linear relationship of mitochondrial to cytosol GSH from ethanol-fed mitochondria were lower for both PP and PV cells, effects observed more prominently in the PV cells. Mitochondrial functional integrity was lower in both PP and PV ethanol-fed rats, which was associated with decreased cellular ATP levels and mitochondrial membrane potential, effects which were greater in the PV cells. Mitochondrial GSH depletion by ethanol feeding preceded the onset of functional changes in mitochondria, suggesting that mitochondrial GSH is critical in maintaining a functionally competent organelle and that the greater depletion of mitochondrial GSH by ethanol feeding in PV cells could contribute to the pathogenesis of alcoholic liver disease.
Animals↗
Predictive factors of in-hospital CNS complications following liver transplantation.
We prospectively evaluated 84 consecutive adult patients with chronic liver disease before and after liver transplantation to define the type and frequency of post-transplant neurologic complications, and to assess possible pretransplant and operative variables associated with in-hospital CNS complications. There were 25 patients (30%) who presented 23 neurologic complications of the central and six of the peripheral nervous system. Seventy-five percent of the complications occurred in the first month post-transplant. The most frequent CNS complications included anoxic (six patients) and septic (five) encephalopathy, as well as brain hemorrhage (five). Patients who presented CNS complications had a higher mortality rate than those who did not (55% versus 17%, p = 0.002). Multiple logistic regression analysis showed abnormal pretransplant neurologic examination suggestive of chronic hepatic encephalopathy (p = 0.007) and noncholestatic liver disease (p = 0.012) to be independently associated with in-hospital CNS complications. These data indicate that CNS neurologic complications following liver transplant are common in patients with noncholestatic liver disease and are associated with increased mortality. The pretransplant neurologic examination is an important predictor of CNS complications that occur in the immediate post-transplant period.
Adult↗
Genetic polymorphism of liver alcohol dehydrogenase in Spanish subjects: significance of alcohol consumption and liver disease.
Class I alcohol dehydrogenase (ADH) phenotypes have been studied by starch gel electrophoresis and activity analysis in liver tissue obtained at necropsy from 61 non-alcoholic subjects with normal liver (controls), and in biopsies from 60 chronic alcoholics with liver disease and from 24 subjects with non-alcoholic liver disease. Twenty-three per cent of controls exhibited the ADH2 phenotype, which represents the highest frequency for atypical ADH found in a Caucasian population. Both alcoholic and non-alcoholic patients with liver disease showed a lower frequency of the atypical phenotype (6.6% and 8.8%, respectively). No differences in the ADH2 locus were detected among groups of patients with different severity of alcoholic and non-alcoholic liver disease. The allele frequencies of the ADH3 locus for the controls (ADH3 = 0.63, ADH3 = 0.37) are common to those of other Caucasian populations. Similar ADH3 allele frequencies were observed in patients with alcoholic and non-alcoholic liver disease. Discrepancies between the various phenotyping and genotyping studies now known for several populations suggest that local differences may exist in the distribution of the ADH polymorphism in even geographically close regions, and that the effect of ADH polymorphism on vulnerability towards alcohol may not be identical in different populations.
Alcohol Dehydrogenase↗
Effect of bolus injection and continuous infusion of somatostatin on gastric perfusion in cirrhotic patients with portal-hypertensive gastropathy.
Gastric perfusion has been found to be increased in cirrhotic patients with portal-hypertensive gastropathy. This phenomenon may contribute to gastric bleeding from these lesions. Therefore drugs reducing gastric mucosal perfusion may be beneficial in the treatment of bleeding portal-hypertensive gastropathy. In this study, gastric mucosal perfusion was assessed, by means of laser-Doppler flowmetry and reflectance spectrophotometry, in 36 cirrhotic patients with portal-hypertensive gastropathy in basal conditions and after double-blind administration of placebo or somatostatin. Intravenous bolus injection of 250 micrograms somatostatin induced a rapid, marked decrease in gastric perfusion (-31.6% +/- 7.9%, p < 0.05), as assessed on laser-Doppler flowmetry, that lasted for only 6 min. Changes in the hemoglobin content of the gastric mucosa paralleled those of laser-Doppler signal. The oxygen content of the gastric mucosa was mildly reduced (-6.9% +/- 1.1%, p < 0.05). When the bolus injection was followed by a continuous infusion of somatostatin, the reduction in gastric perfusion, as assessed by means of laser-Doppler flowmetry, was maintained, although the magnitude of the reduction (-17% +/- 7%) was significantly lower than that observed immediately after the bolus (p < 0.05); the hemoglobin content of the gastric mucosa was also significantly reduced (-8% +/- 1%), but no changes were observed in the oxygen content. Placebo administration had no effect on any of these parameters. We conclude that the increased gastric perfusion in cirrhotic patients with portal-hypertensive gastropathy can be effectively decreased by somatostatin administration.
Double-Blind Method↗
Endoscopic sclerotherapy in upper gastrointestinal bleeding due to the Mallory-Weiss syndrome.
OBJECTIVES: Therapeutic endoscopic techniques have changed the need for emergency surgery in gastrointestinal bleeding episodes. However, there is only little information about endoscopic therapies in severe gastrointestinal bleeding due to the Mallory-Weiss syndrome. The aim of this clinical study was to assess the usefulness of early endoscopic examination and sclerotherapy for severe or recurrent bleeding due to the Mallory-Weiss syndrome. METHODS: We studied all 50 cases of gastrointestinal bleeding secondary to the Mallory-Weiss syndrome seen in 2175 consecutive emergency endoscopic examinations performed in a University Hospital over a 3-year period. Endoscopic sclerotherapy (1/10000 adrenaline + 1% polidocanol) was performed in all patients with active bleeding or visible vessel at endoscopic examination. The remaining patients were medically treated. RESULTS: Active bleeding or a visible vessel were found in 13 patients; definitive hemostasis was obtained in all cases with sclerotherapy. The remaining 37 patients were successfully treated by conservative therapy. On admission, the severity of the hemorrhagic episodes was significantly higher in patients treated with sclerotherapy than in those who did not require this procedure. An esophageal perforation, successfully managed by conservative means, was the only complication recorded in the subset of patients undergoing sclerotherapy. CONCLUSIONS: Severe bleeding due to Mallory-Weiss syndrome can be successfully treated by sclerotherapy. Early endoscopic examination is an accurate procedure in identifying patients who do not require sclerotherapy.
Adult↗
[Screening for excessive alcohol consumption].
Explore the source record for details and available documents.
Alcohol Drinking↗
Impaired function of pancreatic islets from rats with portal hypertension resulting from cirrhosis and partial portal vein ligation.
Increased circulating insulin and glucagon levels are a common observation in patients with cirrhosis, as well as in portal hypertensive models. Hyperinsulinemia and hyperglucagonemia may be caused either by increased beta- and alpha-cell secretion or by defective hepatic clearance of these hormones. To elucidate whether an abnormal endocrine pancreatic function might contribute to the hyperinsulinism or to the hyperglucagonism observed in chronic portal hypertension, insulin and glucagon secretion were measured in vitro in isolated pancreatic islets from rats with partial portal vein ligated and rats with cirrhosis caused by carbon tetrachloride poisoning. Both rats with partial portal vein ligation and rats with cirrhosis caused by carbon tetrachloride poisoning exhibited hyperinsulinism and hyperglucagonism as compared with control rats. Isolated pancreatic islets from both experimental portal hypertensive models showed an impaired insulin secretion after glucose stimulation. On the contrary, glucagon secretion was significantly increased, and there was a markedly enhanced response to arginine. This increased in vitro glucagon production could not be corrected, even in the presence of high glucose concentrations in the incubation medium. Therefore our data show that although hyperglucagonism in rats with partial portal vein ligation and in rats with cirrhosis caused by carbon tetrachloride poisoning is promoted by an enhanced alpha-cell secretion, hyperinsulinism is associated with impaired beta-cell secretion.
Animals↗
c-met mRNA overexpression in human hepatocellular carcinoma.
This study was aimed at assessing the presence of c-met overexpression in human hepatocellular carcinoma and at determining whether this feature is associated with a definite clinical or pathological characteristic. Expression of c-met was determined by Northern-blot hybridization of a specific probe (human met proto-oncogene) in 18 tumoral and nontumoral liver samples obtained in 18 cirrhotic patients with hepatocellular carcinoma submitted to surgical treatment. Eight of the 18 hepatocellular carcinomas exhibited c-met overexpression, with an increase ranging between 2-fold and 10-fold when compared by densitometry with the surrounding liver. By contrast, in the remaining 10 cases c-met expression was almost identical to that of the surrounding nontumoral liver tissue. Overexpression of c-met was not related to either the age, sex, etiology or functional status of the underlying liver disease, or to the size of the tumor, to its differentiation degree or to the presence of pseudocapsule invasion and existence of additional neoplastic nodules. These data indicate that almost half of the human hepatocellular carcinomas exhibit c-met overexpression. Nevertheless, the biological relevance of this characteristic is not known.
Blotting, Northern↗
[Thrombocytopenic purpura and acute nephropathy associated with circulating immune complexes in hepatitis A virus infection].
Explore the source record for details and available documents.
Acute Disease↗
Is hepatitis C virus infection a trigger of porphyria cutanea tarda?
The causes of liver disease, ranging from fatty changes to cirrhosis and hepatocellular carcinoma, in porphyria cutanea tarda (PCT) remain unclear. We tested 100 consecutive PCT patients for antibodies to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay and a recombinant immunoblot assay. 75 (79%) patients with sporadic PCT but none of 5 with familial PCT were positive. HCV RNA was found in serum of all 18 anti-HCV-positive patients tested. There were no significant differences in the prevalence of anti-HCV between treated and untreated patients or between those with and without various HCV risk factors. The frequency of anti-HCV increased with the severity of liver histology. These findings implicate HCV in the aetiology of PCT-associated liver disease.
Enzyme-Linked Immunosorbent Assay↗
Effects of propranolol on gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy.
This study investigated the effects of the short-term administration of propranolol on gastric blood perfusion in cirrhotic patients with portal hypertensive gastropathy. Portal hypertensive gastropathy is a common cause of nonvariceal bleeding in cirrhosis, which is associated with increased gastric mucosal perfusion and is favorably influenced by propranolol therapy. Gastric mucosal perfusion was evaluated with laser-Doppler flowmetry and reflectance spectrophotometry. Measurements were performed under basal conditions and after the double-blind administration of propranolol (0.15 mg/kg intravenously) or placebo. Propranolol administration significantly reduced (p < 0.001) the laser-Doppler signal (2.93 +/- 0.23 vs. 2.25 +/- 0.22 V) and the hemoglobin content of the gastric mucosa (99.2 +/- 3.8 vs. 89.3 +/- 3.1 arbitrary units), whereas the oxygen content remained unchanged (37.4 +/- 1.2 vs. 36.9 +/- 1.0 arbitrary units). Placebo administration had no effect in any of these parameters. Changes in gastric perfusion after propranolol administration were associated with a significant decrease in hepatic venous pressure gradient and azygos blood flow. We conclude that short-term propranolol administration, in addition to lowering portal pressure, reduces the increased gastric blood perfusion in cirrhotic patients with portal hypertensive gastropathy, an effect that may contribute to prevention of bleeding from these lesions.
Female↗
Clinical manifestations and therapy of hepatic encephalopathy.
Explore the source record for details and available documents.
Acute Disease↗
Propranolol versus sclerotherapy in preventing variceal rebleeding: a randomized controlled trial.
BACKGROUND: Sclerotherapy has been widely recommended as initial treatment for prevention of variceal rebleeding. The present study was aimed at comparing the efficacy of endoscopic sclerotherapy and long-term administration of propranolol in the prevention of rebleeding and long-term survival in patients who had bled from varices. METHODS: One hundred sixteen consecutive cirrhotic patients admitted because of variceal bleeding were randomly allocated to either continuous administration of propranolol to reduce the resting heart rate by 25% (58 patients) or weekly intravariceal sclerotherapy sessions using 5% ethanolamide oleate until varices disappeared (58 patients). Results were analyzed on an intention-to-treat basis. RESULTS: Rebleeding occurred in 37 patients of the propranolol group and in 26 patients of the sclerotherapy group (RR = 1.45; 95% CI, 1.03-2.03). The actuarial probability of rebleeding was lower in the sclerotherapy group (P = 0.02). No differences were found in rebleeding index, hospitalization requirements, survival, and causes of death. Complications were significantly more frequent and severe in the sclerotherapy group. CONCLUSIONS: Despite the higher efficacy of sclerotherapy decreasing the probability of rebleeding when compared with propranolol, no beneficial effects were observed on other parameters also reflecting the efficacy of therapy. Moreover, complications of sclerotherapy were more frequent and severe than those of propranolol, which probably shall restrict the use of long-term elective sclerotherapy.
Aged↗
Circulating levels of endothelin in cirrhosis.
BACKGROUND: Current information concerning endothelin in cirrhosis is conflicting. Plasma endothelin concentration has been found to be increased in some studies and normal or reduced in others. The present study was aimed to investigate the plasma levels of endothelin in cirrhosis and to assess whether it is involved in the renal and hemodynamic disturbances and neurohumoral changes present in this condition. METHODS: Renal function, plasma renin activity, and plasma concentration of aldosterone, norepinephrine, antidiuretic hormone, atrial natriuretic factor, and endothelin were measured in 9 healthy subjects, 7 compensated cirrhotics, and 25 cirrhotics with ascites (10 with functional renal failure). RESULTS: Cirrhotics with ascites with and without functional renal failure showed higher endothelin levels (15.6 +/- 6.4 and 15.7 +/- 4.6 pg/mL, respectively; mean +/- SD) than compensated cirrhotics (6.4 +/- 1.8 pg/mL) and healthy subjects (3.4 +/- 1.0 pg/mL) (analysis of variance, F = 21.84; P < 0.001). These patients also showed higher plasma levels of renin, aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic factor, although plasma endothelin levels only correlated significantly with plasma atrial natriuretic factor (r = 0.73, P < 0.001) and antidiuretic hormone concentrations (r = 0.59, P < 0.001). In 7 additional nonazotemic cirrhotics with ascites, plasma renin activity and the plasma concentration of aldosterone and endothelin were measured before and 24 hours after the intravenous administration of a saline solution of human serum albumin. Volume expansion markedly suppressed renin and aldosterone but not endothelin (21.03 +/- 7.34 vs. 23.97 +/- 14.29 pg/mL). CONCLUSIONS: Circulating plasma levels of endothelin are elevated in cirrhosis with ascites and do not decrease following plasma volume expansion.
Adult↗
Liver transplantation for acute liver failure: analysis of applicability.
BACKGROUND: Liver transplantation has emerged as the most important advance in the therapy of acute liver failure. To assess the applicability of liver transplantation in this setting, the outcome of 62 patients with acute liver failure consecutively admitted to hospital was analyzed. METHODS: Criteria for indicating liver transplantation were grade III-IV hepatic encephalopathy or progression of encephalopathy following a transient improvement. In subfulminant cases, liver transplantation was also indicated when no improvement was observed after a 3-day period of conservative treatment. RESULTS: Thirteen (21%) of the 62 patients never met criteria for transplant indication; all of them were discharged after receiving conventional therapy. Twenty-one (34%) patients with criteria for indicating liver transplantation could not receive the transplant because of either contraindications (17 patients; only 1 being discharged from hospital) or death before donor organ availability (4 patients). Finally, 28 (45%) patients received a liver transplant and 22 were discharged from hospital. CONCLUSIONS: The applicability of liver transplantation in acute liver failure is relatively low. Considering the high survival rate (79%) obtained in the patients with transplantations and the poor survival rate (6%) observed in those who could not be transplanted, efforts should be made to increase liver transplant applicability to improve the prognosis in acute liver failure.
Adolescent↗
Hemodynamic effects of acute changes in intra-abdominal pressure in patients with cirrhosis.
BACKGROUND: Changes in intra-abdominal pressure (IAP) have significant circulatory effects. However, whether this may influence the gastroesophageal collateral blood flow in patients with cirrhosis has not been studied. METHODS: In 14 portal hypertensive cirrhotics, serial hemodynamic measurements were obtained in baseline conditions 30 minutes after the mechanical increase of IAP by 10 mm Hg and 30 minutes after returning IAP to baseline levels. RESULTS: Increasing IAP caused similar increases in free and wedged hepatic venous pressures (+10.3 mm Hg and +11.0 mm Hg, respectively; P < 0.005), without changing the hepatic venous pressure gradient (HVPG). However, there were significant decreases in cardiac output (-18%; P < 0.005) and hepatic blood flow (-20%; P < 0.05), whereas azygos blood flow, an index of gastroesophageal collateral blood flow, increased markedly (+23%; P < 0.005). The opposite occurred after releasing the high IAP. CONCLUSION: In portal hypertensive cirrhotics, acute changes in IAP did not change HVPG but markedly modified splanchnic and systemic hemodynamics. Brief elevations of IAP may have deletereous effects, as shown by the increase in azygos blood flow and the decrease in cardiac output and hepatic blood flow, whereas reduction of a high IAP causes the opposite changes and may be beneficial.
Abdomen↗