Chronic Portosystemic Encephalopathy Research Articles

Massive spontaneous portosystemic shunt is a solid, easily identifiable prognostic factor in patients with cirrhosis.

Spontaneous portosystemic shunts (SPSSs) are associated with complications and death in cirrhosis. We evaluated chronic portosystemic encephalopathy (CPSE) and survival in cirrhotic patients with massive (>10 mm diameter) SPSS (MSPSS). We have retrospectively compared 77 cirrhotic patients with MSPSS and 77 paired-matched patients without SPSS. More patients with MSPSS presented with CPSE (40.3% vs. 20.8%, P = 0.010) or died (33.8% vs. 18.2%, P = 0.039). Model for Endstage Liver Disease (MELD) score [hazard ratio (HR) 1.146, 95% confidence interval (CI) 1.099-1.195], follow-up (FU) ascites (HR 5.128, 95% CI 2.396-10.973) and age (HR 1.048, 95% CI 1.017-1.080) were associated with CPSE; and MELD score (HR 1.082, 95% CI 1.035-1.131), FU renal failure (HR 9.319, 95% CI 3.595-24.158), and FU ascites (HR 4.320, 95% CI 1.615-11.555) were associated with death. Liver function worsened faster in the MSPSS group. Among patients with better liver function (MELD < 11.5), MSPSS patients presented worse survival (P = 0.048, Breslow test). Comparing patients by the Child-Pugh group, we did not find differences in survival; in patients from Child-Pugh group B + C, the MSPSS group presented less time free of CPSE (P < 0.05, log-rank test). Patients with splenorenal MSPSS presented better survival (P = 0.04, log-rank test), and patients with umbilical MSPSS had shorter time free of CPSE (P < 0.016, log-rank test). MSPSS increased CPSE and death risks during long FU. Even with better liver function (MELD < 11.5), MSPSS was associated with lower survival. Splenorenal MSPSS presented better survival and the umbilical type was associated with shorter time free of CPSE.

Neurologic manifestations of gastrointestinal and liver diseases.

Hepatic and gastrointestinal disorders can produce a wide spectrum of neurologic complications both affecting the central nervous system (CNS) and the peripheral nervous system. These manifestations range in severity from coma in acute liver failure and acute pancreatitis, to minor cognitive changes in chronic portosystemic encephalopathy and hepatitis C. Cerebrovascular diseases can complicate hepatitis C infection and inflammatory bowel disease. Demyelinating disorders may co-exist with inflammatory bowel disease. Anti-tumor necrosis factor alpha drugs may induce demyelination. Ataxia may occur in malabsorption syndromes and in gluten related disorders. Characteristic movement disorders are key features of acquired hepatocerebral degeneration and of Whipple disease. Multiple types of neuropathy can be found in association with hepatitis, inflammatory bowel disease and gluten related disorders.

Treatment of chronic portosystemic encephalopathy in cirrhotic patients by embolization of portosystemic shunts

AIMS/BACKGROUNDS: Large spontaneous portal-systemic shunts can occasionally be the cause of chronic and disabling encephalopathy in cirrhotic patients. Shunt embolization has been proposed, however the clinical relevance of this technique remains uncertain. We report our results in seven patients treated by shunt embolization. Although the procedure was achieved and technically successful in all patients, the clinical results were poor as long-term improvement was obtained in only one patient. Three patients died within 3 months after the procedure from cirrhoses' end stage complications. We believe that optimal management of these patients with chronic spontaneous encephalopathy is liver transplantation.

Laparoscopic Disconnection of a Huge Paraumbilical Vein Shunt for Portosystemic Encephalopathy

Chronic portosystemic encephalopathy (CPSE) resulting from portosystemic shunts (PSS) is a devastating clinical problem. When CPSE is refractory to medical treatment, occlusion of the PSS should be considered. We report a case of CPSE due to a huge paraumbilical vein shunt that was successfully treated with laparoscopic disconnection. A 54-year-old woman diagnosed with liver cirrhosis was referred to our department for treatment of hepatic encephalopathy. She had repeatedly experienced episodes of disturbance of consciousness, and had hyperammoniemia refractory to medical treatment. Computed tomography showed a huge patent paraumbilical vein connected to the systemic circulation through the round ligament. Laparoscopic disconnection of the paraumbilical vein shunt was performed. The postoperative course was uncomplicated and there has been no recurrence of hepatic encephalopathy in the 2 years since, nor has there been a need for further medical treatment. We believe this is the first case report of CPSE treated laparoscopically, and it demonstrates that laparoscopic disconnection of PSS, especially paraumbilical vein shunts, can be a safe and effective procedure to treat CPSE.

Transhepatic splenic vein embolization during temporary balloon occlusion of a spontaneous portosystemic shunt for chronic portosystemic encephalopathy

A 69-year-old woman undergoing medical treatment for liver cirrhosis with chronic hepatic encephalopathy developed consciousness disturbance. Emergency blood analysis revealed hyperammonemia, and abdominal CT demonstrated a large splenorenal shunt as the cause of her symptoms. The splenic vein was embolized at the portal side of the shunt entrance via the percutaneous transhepatic route, while preserving the splenorenal shunt and preventing retrograde flow to the splenorenal shunt from the superior mesenteric vein. The temporary balloon occlusion of the outflow pathway of the shunt allowed safe and accurate embolization with detachable coils under the flow control of the shunt. After the interventional procedure, her blood NH 3 level decreased markedly, and the hepatic encephalopathy immediately disappeared. Postprocedural elevation of portal blood pressure was slight.

Reversal of Portosystemic Encephalopathy after Endoscopic Embolization of Recurrent Gastroesophageal Varices

Abstract:Chronic portosystemic encephalopathy (CPSE) due to a shunt via gastroesophageal varices is uncommon. We were able to control a case of CPSE due to recurrent gastroesophageal varices using endoscopic embolization (EE). A 68‐year‐old man presented at our hospital in a confused, apathetic and tremulous state. He had undergone devascularization, proximal gastric transection and splenectomy for esopha‐geal varices due to liver cirrhosis 16 years previously. The patient had hyperammone‐mia (228 µg/dl), and endoscopic examination revealed nodular cardiac varices and large recurrent esophageal varices. Superior mesenteric arterial portography revealed that a large volume of superior mesenteric venous blood drained into the cardiac and esophageal varices through the remnant left gastric vein. The plasma ammonia level in the esophageal varices taken at the time of EE was 419 pg/dl, which was a much higher level than that of peripheral vessels, the superior vena cava and azygos vein, and suggested that the encephalopathy was due to the portosystemic shunt via the gastroesophageal varices. EE was performed using 5% ethanolamine oleate with iopamidol under fluoroscopy. The esophageal and cardiac varices were successfully embolized, the CPSE disappeared, and the plasma ammonia level decreased to 27 pg/dl. No complications were observed, and the patient was discharged on day 37 after EE. We conclude that EE is an effective and safe treatment for CPSE due to gastroesophageal varices.

PREVENTION OF VARICEAL REBLEEDING

Recurrent variceal hemorrhage occurs in 50% to 80% of cirrhotic patients who survive a variceal bleeding episode. The aim of preventing rebleeding is to improve survival by reducing the mortality associated with rebleeding; however, although shunt surgery is the most effective treatment to prevent recurrent bleeding, it does not increase survival and is associated with an increased incidence of chronic portosystemic encephalopathy. The distal splenorenal shunt is associated with a reduced incidence of encephalopathy, compared with nonselective shunts, but the true magnitude and longevity of this effect is still controversial. beta-Blockers reduce the incidence of rebleeding, but the effect is modest, and there is little or no effect on mortality when compared with no treatment. Injection sclerotherapy reduces the incidence of rebleeding and improves survival when a schedule of both emergency and long-term injection is compared with no sclerotherapy. No technical variation of injection sclerotherapy has been shown to be superior to another. Endoscopic variceal banding may result in fewer complications but the efficacy is similar to that of injection sclerotherapy. Trials of long-term sclerotherapy versus beta-blockers show very similar mortality and rebleeding rates. Addition of beta-blockade to sclerotherapy does not confer any advantages when compared with sclerotherapy alone. Improvements in pharmacologic therapy, such as the addition of isosorbide mononitrate to propranolol, may in the future make drug therapy the first treatment option to prevent rebleeding. Shunt surgery is superior to sclerotherapy in preventing rebleeding and has a similar mortality; however, liver transplantation is technically more difficult in shunted patients, but shunts do not adversely affect overall survival after transplantation. There are few data to allow optimal selection of a particular therapy or sequence of therapies to prevent variceal rebleeding for any individual patient. This will need to be studied in large trials and is a major issue in the current clinical management of cirrhotics who have bled from varices.

Treatment of post-shunt portal systemic encephalopathy by embolization of the shunt.

Operative ligation of portosystemic shunts is effective in controlling chronic portosystemic encephalopathy (CPSE) but is associated with significant mortality. Review of the records of five patients with CPSE treated with radiologic occlusion procedures showed that these are suitable alternatives to surgery. Three patients had alcoholic cirrhosis, one had hepatic fibrosis from schistosomiasis, and one had post-necrotic cirrhosis. All had CPSE with progressive, severe cerebral impairment refractory to clinical treatment. Four patients had a spontaneous splenorenal shunt, and one had a surgically created mesocaval shunt (MCS). Partial splenic embolization was performed in two patients, direct shunt embolization was performed via percutaneous transhepatic portography in two other patients, and an MCS embolization was performed in one patient through the inferior vena cava. In four patients embolization controlled the CPSE. In the remaining patient it could not be evaluated because of his premature death from intraabdominal bleeding, a late complication of the procedure. Interventional radiologic procedures are effective in the control of CPSE in selected patients.

Chronic portosystemic encephalopathy: embolization of portosystemic shunts.

Operative ligation of portosystemic shunts is effective in controlling chronic portosystemic encephalopathy (CPSE) but is associated with significant mortality. Review of the records of five patients with CPSE treated with radiologic occlusion procedures showed that these are suitable alternatives to surgery. Three patients had alcoholic cirrhosis, one had hepatic fibrosis from schistosomiasis, and one had post-necrotic cirrhosis. All had CPSE with progressive, severe cerebral impairment refractory to clinical treatment. Four patients had a spontaneous splenorenal shunt, and one had a surgically created mesocaval shunt (MCS). Partial splenic embolization was performed in two patients, direct shunt embolization was performed via percutaneous transhepatic portography in two other patients, and an MCS embolization was performed in one patient through the inferior vena cava. In four patients embolization controlled the CPSE. In the remaining patient it could not be evaluated because of his premature death from intraabdominal bleeding, a late complication of the procedure. Interventional radiologic procedures are effective in the control of CPSE in selected patients.

Cerebrospinal fluid gamma-aminobutyric acid levels in dogs with chronic portosystemic encephalopathy.

Cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) levels were measured in a dog model of spontaneous chronic portosystemic encephalopathy. Dogs with congenital portacaval shunts (intra- or extra-hepatic) develop neurological features of abnormal psychomotor behaviour and depressed consciousness that are consistent with the symptoms of chronic portosystemic encephalopathy in humans. In the five dogs studied, plasma ammonia was elevated, as was CSF tryptophan, both usual biochemical abnormalities in portosystemic encephalopathy. CSF levels of GABA in five dogs with portosystemic encephalopathy (100 +/- 13 pmol/ml) were not significantly different from those in five control dogs (96 +/- 14 pmol/ml). CSF levels of GABA were not altered after ammonia infusion. If enhanced GABA-ergic neurotransmission, due to influx of gut-derived GABA into the brain, is responsible for the pathophysiology of chronic portosystemic encephalopathy in this model, it is not reflected by increased levels of GABA in CSF.

Effect of lactulose on cerebral metabolism in patients with chronic portosystemic encephalopathy.

Cerebral blood flow and cerebral metabolism were studied in six patients with moderately severe portosystemic encephalopathy before and after a 10-day course of lactulose. As a result of therapy there was a mean increase in cerebral oxygen utilization but no changes in either mean glucose consumption or in mean cerebral blood flow. It appears therefore that the abnormalities in cerebral metabolism that have been previously described in patients with hepatic encephalopathy can be improved by the oral administration of lactulose.

EFFECT OF INDUCED METABOLIC ALKALOSIS IN HEPATIC ENCEPHALOPATHY

500 ml. of 5% sodium bicarbonate given to five patients in hepatic coma caused a striking improvement in their clinical condition and increases in their cerebral blood-flow, cerebral oxygen consumption, and oxygen/glucose index. Similar changes were noted in flow and oxygen consumption in five patients with chronic porto-systemic encephalopathy.