Prokinetics reduce bacterial translocation in cirrhosis: will sweeping the gut keep the fluid clean?
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Biomedical subjects
Publications and source records attributed to G García-Tsao.
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BACKGROUND & AIMS: Nonselective beta-blockers are effective in reducing portal pressure in cirrhotic patients. However, this beneficial effect is highly variable and may depend on the extent of portal system collateralization. The aim of this study was to compare portal pressure response with timolol, a nonselective beta-blocker, in cirrhotic patients with and without varices. METHODS: Portal and systemic hemodynamics were measured before and after a single oral dose of 10 mg of timolol in 50 patients with cirrhosis and portal hypertension, 15 with and 35 without esophageal varices. RESULTS: Timolol significantly decreased portal pressure in all patients (mean reduction, 20% +/- 13%; P < 0.0001). The reduction in hepatic venous pressure gradient was greater in patients without varices (-24% +/- 14%) than in those with varices (-12% +/- 8%) (P < 0.01). A decrease in the hepatic venous pressure gradient of <12 mm Hg was achieved in 7 of 12 (58%) patients without varices and a baseline pressure gradient of <12 mm Hg, but only in 3 of 15 patients with varices (20%) (P < 0.01). CONCLUSIONS: Timolol is effective in reducing portal pressure in cirrhotic patients, more so in patients without varices, suggesting that nonselective beta-blockers will be more effective in the treatment of portal hypertension when administered at early stages, before the development of varices.
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In the early 1970s, we began to perform selective shunts on a regular basis for the treatment of portal hypertension. In a 15-year period, 177 patients (155 with liver cirrhosis) were treated with 3 kinds of selective shunts: the Warren shunt (128 patients) the end-to-end splenorenal shunt (29 patients), and the splenocaval shunt (20 patients). One hundred sixty-seven of the procedures were elective. Operative mortality was 14%, and survival for the Child's class A group was 75% at 1 year, 69% at 5 years, and 65% at 15 years. Incapacitating encephalopathy was observed in 7% of the patients, rebleeding in 6%, and shunt thrombosis in 6%. Postoperative portal vein alterations included reduced venous diameter (13%) and thrombosis (21%). Experience with the Warren shunt in schistosomiasis, a disease in which normal liver function is the rule in Latin American countries, is discussed. We believe that, when feasible, the selective shunts are the treatment of choice for portal hypertension in Latin American countries.
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The aim of this study was to evaluate, using a double-blind technique, the efficacy of the association of transdermal nitroglycerin to vasopressin infusion for the treatment of variceal bleeding. Sixty-nine cirrhotic patients with active variceal bleeding were randomly allocated to receive vasopressin (0.4 to 0.8 unit per min until variceal bleeding has been controlled for 12 hr) associated with nitroglycerin administered transdermically in a slow-release preparation (10 mg in 24 hr) or placebo. An initial control of variceal hemorrhage was achieved in 83% of the patients receiving vasopressin-nitroglycerin and in 74% in the vasopressin-placebo group. Owing to a lower frequency of recurrent bleeding during therapy (18 vs. 42%, p = 0.11), vasopressin-nitroglycerin achieved a definitive control of bleeding in a higher proportion of patients than vasopressin-placebo (73 vs. 54%, p = 0.13). The group treated with the drug combination showed favorable results in relation to transfusion requirements (2.9 +/- 0.4 vs. 4.2 +/- 0.5 units, p = 0.05), total dose of vasopressin required (453 +/- 47 vs. 587 +/- 50 units, p less than 0.05), need of balloon tamponade (6 vs. 15, p less than 0.05) and requirement for emergency surgery (0 vs. 4, p = 0.07). There were no significant differences in the undesirable effects associated with treatment, observed in 37 and 49% of cases, respectively. Hospital mortality was similar (33 vs. 25%). This study demonstrates that transdermal nitroglycerin improves the effectiveness of vasopressin for controlling variceal hemorrhage.
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Patients with portal hypertension without a demonstrable cause have been reported in the literature under several different terms, such as tropical splenomegaly, phlebosclerosis, obliterative portal venopathy of the liver, hepatoportal sclerosis, noncirrhotic portal fibrosis and idiopathic portal hypertension (IPH). Such patients have been described worldwide, with a greater frequency in India and Japan. The etiology of IPH is still unknown, although some of the theories that have been proposed are: exposure to toxic substances or drugs, relationship with the hepatitis-B virus, immunologic abnormalities, systemic or intra-abdominal infections and clotting abnormalities. The main histopathologic findings are periportal fibrosis, obliteration of small portal veins and sclerosis of the interhepatic portal system. Although these abnormalities could be secondary to portal hypertension, it has been proposed that the vascular changes are the primary event that leads to portal hypertension. The site of increased resistance in IPH is found at the presinusoidal level with some component at the sinusoidal and postsinusoidal level. The main symptoms and signs in IPH are upper gastrointestinal tract bleeding secondary to esophago-gastric varices, symptoms related to anemia, and splenomegaly. The long-term prognosis for patients with IPH is better than for cirrhotic patients, with a 77% survival at ten years. Variceal bleeding is the main cause of death, and some treatment to prevent bleeding or its recurrence is warranted. Although no comparative trial has been performed in IPH patients, the surgical management could be the first choice for elective treatment in these patient without liver failure, because of the high re-bleeding rates with chronic sclerotherapy. Pharmacologic management could be considered for prophylactic treatment of these patients.
The Sugiura Procedure (SP) was performed in 27 patients with hemorrhagic portal hypertension secondary to extrahepatic portal vein thrombosis without associated liver disease (EPVT). There were fourteen females and 13 males. Mean age was 28 +/- 14 years. The causes of EPVT were: protein C deficiency-2 cases, antithrombin III deficiency-1 case, omphalitis history-2 cases, pancreatitis history-1 case and idiopathic-21 cases. The SP was completed with two surgical stages in 14 patients and with one operation in nine. There was one operative death. One patient developed mild postoperative encephalopathy, and two patients re-bled at long-term. Actuarial survival was 82% at five and ten years. It is concluded that the SP is a good alternative for the management of hemorrhagic portal hypertension secondary to EPVT.
Since the usefulness of liver biopsy in the diagnosis of fever of unknown origin is still controversial, we analyzed the charts of 54 patients with fever of unknown origin in whom histological and microbiological studies of a liver biopsy were performed. The cause of fever was established in 43 (80%) patients and it was most frequently of an infectious origin (52%). Histological analysis of liver biopsy was useful in determining the final diagnosis in 26 patients (48%) and was the main/only diagnostic method in a third of them. It was useful even in patients with no evidence of hepatic disfunction. Microbiological analysis of liver biopsy was positive in 7 cases (25% of infectious causes). We consider that liver biopsy should be performed early in the work-up of patients with fever of unknown origin.
We analyzed 82 cases of hepatobiliary fibropolycystic disease (FPD) that were seen at the Instituto Nacional de la Nutrición "Salvador Zubirán" in Mexico City in the thirty-year period comprised from 1956 to 1986. The different entities that compose FPD were distributed as follows: 61 (74%) cases of polycystic liver disease, 13 (16%) cases of choledochal cyst, and 8 (10%) cases of congenital hepatic fibrosis; there were 5 (6%) cases of Caroli's disease, 3 associated with congenital hepatic fibrosis and 2 with choledochal cyst. Polycystic liver disease predominated in females (67%) and presented at 54 +/- 12 years (mean +/- SEM) with pain, a mass, symptoms related to renal insufficiency or incidentally; polycystic kidneys were present in 61%. Liver function tests were normal in 94%. Choledochal cyst also predominated in females and presented at a mean age of 19 years with cholangitis. Liver function tests were abnormal in 69%. Congenital hepatic fibrosis (50% male) presented with variceal hemorrhage or cholangitis (in 3 patients associated with Caroli's disease). Polycystic kidneys were present in five patients. Four of the five patients with Caroli's disease were female and presented at a mean age of 19 years with cholangitis. It never presented as an isolated disease, but was associated more frequently to congenital hepatic fibrosis. The diseases that are part of the hepatobiliary polycystic disease vary in severity and thus the prognosis in an individual patient is determined by the type of fibropolycystic disease present. This is the largest series of this disease published in our country.
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