Cerebral magnetic resonance imaging reveals marked abnormalities of brain tissue density in patients with cirrhosis without overt hepatic encephalopathy.

BACKGROUND & AIMS: We applied advanced magnetic resonance imaging and Voxed based Morphometry analysis to assess brain tissue density in patients with cirrhosis. METHODS: Forty eight patients with cirrhosis without overt hepatic encephalopathy (17 Child A, 13 Child B, and 18 Child C) and 51 healthy subjects were matched for age and sex. Seventeen patients had history of overt hepatic encephalopathy, eight of them had minimal hepatic encephalopathy at inclusion, 10 other patients had minimal hepatic encephalopathy at inclusion but without history of previous overt hepatic encephalopathy, and 21 patients had none of these features. RESULTS: Patients with cirrhosis presented decreased brain density in many areas of the grey and white matter. The extension and size of the affected areas were greater in patients with alcoholic cirrhosis than in those with post-hepatitic cirrhosis and correlated directly with the degree of liver failure and cerebral dysfunction (as estimated by neuropsychological tests and the antecedent of overt hepatic encephalopathy). Twelve additional patients with cirrhosis who underwent liver transplantation were explored after a median time of 11months (7-50months) after liver transplant. At the time of liver transplantation, three patients belonged to class A of the Child-Pugh classification, five to class B and four to class C. Compared to healthy subjects, liver transplant patients showed areas of reduced brain density in both grey and white matter. CONCLUSIONS: These results indicate that loss of brain tissue density is common in cirrhosis, progresses during the course of the disease, is greater in patients with history of hepatic encephalopathy, and persists after liver transplantation. The significance, physiopathology, and clinical relevance of this abnormality cannot be ascertained from the current study.

Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration.

Hyponatraemia is common in patients with advanced cirrhosis and is associated with remarkable changes in brain cells, particularly a reduction in myoinositol and other intracellular organic osmolytes related to the hypo-osmolality of the extracellular fluid. It has been recently suggested that hyponatraemia may be an important factor associated with the development of overt hepatic encephalopathy (HE). To test this hypothesis, we retrospectively analysed the incidence and predictive factors of overt HE using a database of 70 patients with cirrhosis included in a prospective study comparing transjugular intrahepatic portosystemic shunts (TIPS) vs large-volume paracentesis in the management of refractory of ascites. Variables used in the analysis included age, sex, previous history of HE, treatment assignment (TIPS vs large volume paracentesis plus albumin), treatment with diuretics, serum bilirubin, serum creatinine and serum sodium concentration. Laboratory parameters were measured at entry, at 1 month and every 3 months during follow-up and at the time of development of HE in patients who developed this complication. During a mean follow-up of 10 months, 50 patients (71%) developed 117 episodes of HE. In the whole population of patients, the occurrence of HE was independently associated with serum hyponatraemia, serum bilirubin and serum creatinine. In conclusion, in patients with refractory ascites, the occurrence of HE is related to the impairment of liver and renal function and presence of hyponatraemia.

[Hepatorenal syndrome]. / Síndrome hepatorrenal.

Hepatorenal syndrome (HRS) is a severe complication in patients with cirrhosis and ascites. Renal insufficiency is functional and is caused by renal vasoconstriction. HRS occurs in 10% of patients with advanced cirrhosis. Diagnosis of HRS is based on ruling out other causes of renal insufficiency. There are two types of HRS: type 1 has rapid onset and progressive course and a mean survival of 15 days without treatment, while type 2 is less severe and progressive, with a mean survival of 6 months. Definitive treatment of HRS is liver transplantation. However, in the last few years administration of vasoconstrictive drugs or placement of portosystemic shunts have been shown to be effective in reversing HRS. Therefore, these measures may be used as a bridge before liver transplantation is performed. Finally, the risk of developing HRS in the context of spontaneous bacterial peritonitis can be prevented by administering albumin together with the corresponding antibiotics. In cases of severe acute alcoholic hepatitis, pentoxifylline can be administered.

Síndrome hepatorrenal / Hepatorenal syndrome

El síndrome hepatorrenal (SHR) es una complicación grave que presentan los pacientes con cirrosis y ascitis. La insuficiencia renal es de carácter funcional y está causada por vasoconstricción renal. El SHR ocurre en el 10% de los pacientes con cirrosis avanzada. El diagnóstico de SHR se basa en la exclusión de otras etiologías de insuficiencia renal. Hay dos tipos de SHR: el tipo 1, que es de inicio rápido y evolución progresiva, con una supervivencia media de 15 días sin tratamiento, y el tipo 2, que es menos grave y progresivo, con una supervivencia media de 6 meses. El tratamiento definitivo del SHR es el trasplante hepático. Sin embargo, en los últimos años se ha demostrado que la administración de vasoconstrictores o la colocación de derivaciones portosistémicas son eficaces para revertir el SHR. Por ello, pueden utilizarse como puente para el trasplante hepático. Finalmente, el riesgo de desarrollar SHR en el contexto de una peritonitis bacteriana espontánea puede prevenirse administrando albúmina junto con los antibióticos correspondientes y, en los casos de hepatitis alcohólica aguda grave, administrando pentoxifilina

Hepatorenal syndrome (HRS) is a severe complication in patients with cirrhosis and ascites. Renal insufficiency is functional and is caused by renal vasoconstriction. HRS occurs in 10% of patients with advanced cirrhosis. Diagnosis of HRS is based on ruling out other causes of renal insufficiency. There are two types of HRS: type 1 has rapid onset and progressive course and a mean survival of 15 days without treatment, while type 2 is less severe and progressive, with a mean survival of 6 months. Definitive treatment of HRS is liver transplantation. However, in the last few years administration of vasoconstrictive drugs or placement of portosystemic shunts have been shown to be effective in reversing HRS. Therefore, these measures may be used as a bridge before liver transplantation is performed. Finally, the risk of developing HRS in the context of spontaneous bacterial peritonitis can be prevented by administering albumin together with the corresponding antibiotics. In cases of severe acute alcoholic hepatitis, pentoxifylline can be administered

Aquaporin-1 and aquaporin-2 urinary excretion in cirrhosis: Relationship with ascites and hepatorenal syndrome.

Several experimental models of cirrhosis have shown dysregulation of renal aquaporins in different phases of liver disease. We investigated the urinary excretion of both aquaporin-1 and aquaporin-2 in patients with cirrhosis at different stages of the disease. Twenty-four-hour urine was collected from 11 healthy volunteers, 13 patients with compensated cirrhosis (without ascites), and 20 patients with decompensated cirrhosis (11 with ascites without renal failure and 9 with hepatorenal syndrome). Aquaporin-1 and aquaporin-2 excretion was analyzed by immunoblotting. Urinary aquaporin-2 excretion was reduced in patients with cirrhosis compared to healthy subjects. A progressive decrease in urinary aquaporin-2 excretion was observed as the severity of cirrhosis increased, from compensated cirrhosis to cirrhosis with ascites and hepatorenal syndrome. Patients with hyponatremia had lower urinary aquaporin-2 excretion than patients without hyponatremia. Vasopressin plasma level did not correlate with aquaporin-2 excretion. There were no differences between healthy subjects and patients with cirrhosis with or without ascites in urinary excretion of aquaporin-1, but urinary aquaporin-1 excretion of those with hepatorenal syndrome was extremely low. In conclusion, patients with cirrhosis appear to exhibit a decreased abundance of renal aquaporin-2 and therefore lower water permeability in the collecting tubules. This may represent an adaptive renal response to sodium retention, with expansion of extracellular fluid volume and dilutional hyponatremia observed in those who have cirrhosis with ascites. Finally, aquaporin-1 does not appear to play a role in the progressive dysregulation of extracellular fluid volume in cirrhosis.

Renal failure in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis: value of MELD score.

BACKGROUND & AIMS: Although renal failure is a common complication of sepsis and patients with cirrhosis frequently develop sepsis, there have been no studies specifically assessing renal function in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis. The aim of this study was to investigate prospectively the frequency, characteristics, and outcome of renal failure in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis. METHODS: One hundred six consecutive patients with cirrhosis and sepsis were studied prospectively. Patients with spontaneous bacterial peritonitis were excluded. RESULTS: Twenty-nine out of 106 patients (27%) with cirrhosis and sepsis developed acute renal failure as compared with only 8 of 100 patients (8%) from a control group of cirrhotic patients without infection (P < .0001). Renal failure in the sepsis group was reversible in 22 (76%; 21% of all patients) patients and nonreversible in 7 (24%; 6% of all patients) patients. Renal failure was associated with impairment of effective arterial blood volume, without evidence of tubular damage. The occurrence and type of renal failure correlated strongly with mortality (mortality at 3 months: nonreversible renal failure, 100%; reversible renal failure, 55%; no renal failure, 13%). Among variables obtained at diagnosis of sepsis, the Model for End-Stage Liver Disease (MELD) score was the only independent predictive factor of mortality. CONCLUSIONS: Renal failure is common in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis and is associated with arterial underfilling and renal vasoconstriction. Outcome is poor, even in the setting of reversible renal failure. The MELD score is the best prognostic marker of patients with cirrhosis and sepsis.