J. M. Henderson

Distal splenorenal shunt versus endoscopic sclerotherapy for long-term management of variceal bleeding. Preliminary report of a prospective, randomized trial.

This paper reports the preliminary results of a prospective randomized trial comparing endoscopic variceal sclerosis and distal splenorenal shunt (DSRS) in the management of patients with cirrhosis and variceal bleeding. Seventy-one patients have been entered; 36 have received sclerosis and 35 DSRS. Randomization of the study population was stratified on Childs A/B (56%) and Childs C (44%). Sixty-one per cent had alcoholic and 39% nonalcoholic cirrhosis. No patients have been lost to follow-up, which currently stands at a median of 26 months. Rebleeding occurred significantly (p < 0.05) more frequently in patients in the sclerosis group (19 of 36: 53%) compared to DSRS (1 of 35: 3%), but only 11 of 36 (31%) were not controlled by further sclerosis and failed that therapy. Patients in whom sclerosis failed underwent surgery. Survival was significantly (p < 0.01) improved in the sclerosis group (+ surgery in 31%), with an 84% 2-year survival compared to a 59% 2-year survival in the DSRS group. Portal perfusion was significantly (p < 0.05) better maintained in the sclerosis (95%) compared to the DSRS (53%) group. Galactose elimination capacity improved significantly (p < 0.05) in 21 patients successfully managed by sclerosis at 1 year and was significantly (p < 0.01) better maintained in the sclerosis compared to DSRS group. The authors conclude that endoscopic sclerosis: (1) has a higher rebleeding rate than DSRS, with one third of patients failing therapy from rebleeding; (2) allows significant improvement in liver function when successful; and (3) gives significantly improved survival in the management of variceal bleeding when backed up by surgical therapy for patients with uncontrolled rebleeding.

The Emory prospective randomized trial: selective versus nonselective shunt to control variceal bleeding. Ten year follow-up.

From 1971 to 1975, 55 patients with variceal bleeding secondary to cirrhosis were entered into a prospective randomized trial comparing distal splenorenal (selective) and H-graft interposition (nonselective) shunt. This 10-year follow-up documents that selective shunt is better (p less than 0.05) in four of the five variables monitored. Control of bleeding: selective shunt prevented variceal bleeding better than interposition shunt due to the higher (0.05 less than p less than 0.1) occlusion rate (30%) of interposition shunt. Selective shunt maintained postoperative portal perfusion better (p less than 0.01) than patent interposition shunt. Seventy-five per cent of selective shunt survivors have portal perfusion at 10 years: no patient with a patent nonselective shunt perfuses the liver. Quantitative liver function was better preserved (p less than 0.01) 10 years after selective shunt than nonselective shunt. Postoperative encephalopathy occurred in fewer (p less than 0.01) selective (27%) than nonselective (75%) shunt patients over the 10 years. Survival: in the randomized population, the improved survival in the selective shunt subgroup did not reach statistical significance. However, improved survival was confirmed in nonalcoholics. Five of eight nonalcoholics operated with selective shunt are alive at 10 years with patent shunts. No nonalcoholic, of seven total, operated with nonselective shunt survived 10 years with a patent shunt. These data show that selective shunt was superior to nonselective shunt. There was less rebleeding and encephalopathy after distal splenorenal shunt; postoperative portal perfusion and hepatic function were maintained.

First-Order Clearance of Plasma Galactose: The Effect of Liver Disease

Galactose clearance kinetics at plasma concentrations of 0.01-0.1 mg/ml were studied during continuous infusion of 25-100 mg D-galactose per minute. In 10 subjects, plasma galactose vs. time curves during 140-min infusion, and 60 min thereafter, showed the data to fit a single-compartment model and attain 95% of plasma steady state by 80 min. Doubling the infusion rate in 14 subjects resulted in an 8% reduction in clearance at the higher rate. Hepatic extraction in normal subjects was 94%, while in cirrhotics it was 79%. Day-to-day reproducibility in 11 subjects gave a coefficient of variation of 4.5%. Extrahepatic clearance showed 2% of the total to occur in the urine, and 2.3% to occur by erythrocyte metabolism. The overall mean (+/-SD) clearance in the normal subjects of 1378 +/- 218 ml/min was significantly (p less than 0.05) greater than for the stable cirrhotics at 918 +/- 279 ml/min, but not significantly different from patients with acute hepatocellular damage at 1186 +/- 300 ml/min. This index gives flow-dependent hepatic clearance, and provides a noninvasive measure of effective liver blood flow.

Hemodynamic Differences Between Alcoholic and Nonalcoholic Cirrhotics Following Distal Splenorenal Shunt—effect on Survival?

The distal splenorenal shunt significantly improves 5-year survival from variceal bleeding in nonalcoholic (70%) compared to alcoholic (45%) cirrhosis patients. This study quantitates hemodynamic differences occurring in the first year after DSRS in 16 alcoholic compared to eight nonalcoholic patients. Portal venous perfusion was retained significantly better (p less than .01) by the nonalcoholic (seven of eight) than by the alcoholic (four of sixteen) patients. Mean liver blood flow (p less than 0.07), flow/unit liver volume (p less than .05), and flow required to perform a specific hepatocyte function (p less than 0.05) all increased significantly in the alcoholic compared to nonalcoholic group. Cardiac output increased significantly in the alcoholic patients (p less than 0.05), but was unchanged in the nonalcoholic patients. The alcoholic patients divided into two subsets, 11 who showed increase in flow (1082 +/- 260 to 1496 +/- 388 ml/min) and five who did not (1246 +/- 269 to 994 +/- 159 ml/min). The former had significantly (p less than 0.05) poorer hepatocyte function and had a significant (p less than 0.05) increase in flow/unit volume and flow/unit function at 1 year, which may have helped to maintain hepatocyte integrity. The latter, in parallel with the nonalcoholic patients, showed no significant change in these parameters and maintained a good functional hepatocyte mass. These data lead us to hypothesize that: 1) alcoholic liver injury has an increased risk of leading to loss of portal perfusion after DSRS, 2) as hepatocyte function falls, there is initial increase in hepatic arterial flow in alcoholic patients, triggered by increase in cardiac output, and 3) progressive injury and/or failure of the compensatory hemodynamic mechanism leads to earlier mortality in alcoholic patients. In contrast, the nonalcoholic cirrhosis patients preserve portal perfusion and maintain liver blood flow, both quantitatively and qualitatively, with retained hepatocyte function and improved survival.

Management of variceal bleeding in patients with noncirrhotic portal vein thrombosis

Since 1971, 70 patients have been seen at Emory University Hospital with gastroesophageal varices secondary to extrahepatic portal vein thrombosis (PVT). Thirty-seven of these patients had had prior major operative therapy. In only three patients (8%) was shunt surgery successful, and there was a high incidence of rebleeding, other morbidity, and mortality. Of especial note are the serious consequences of simple splenectomy; splenomegaly and thrombycytopenia should rarely, if ever, be used as indication for splenectomy in portal hypertension. In 1977, the use of selective distal splenorenal shunt (DSRS) was begun at Emory in this population and a selective shunt has been possible in 24 of 29 patients (83%) who had had no prior operative therapy. Results have been excellent with a greater than 90% patency rate, long-term portal perfusion in all, no encephalopathy, and late rebleeding in one patient. Quantitative studies at 3–6 years show stability of liver function, significant decrease in spleen size, and rise in platelet count. However, long-term follow-up (>15 years) is required in PVT patients before definitive assessment can be obtained. A specific problem of the PVT patient is late shunt stenosis which requires close observation; dilatation of the shunt was performed in six of the 24 patients with a patent shunt. Poor results with non-shunt operative procedures in PVT were again documented. The proper role of endoscopie variceal sclerotherapy is not yet clear, but appears to be an excellent addition to the therapeutic options. In conclusion, for patients with a patent splenic vein, initial therapy should be a selective shunt; for patients without a patent splenic venous system, endoscopie sclerotherapy is the procedure of choice.

Splenopancreatic disconnection. Improved selectivity of distal splenorenal shunt.

Distal splenorenal shunt (DSRS) improves survival from variceal bleeding in nonalcoholic cirrhotics but not in alcoholic subjects. The metabolic response after DSRS is also different in alcoholic and nonalcoholic cirrhotics. Portal perfusion, quality of blood perfusing the liver, cardiac output, and liver blood flow do not change in nonalcoholics. In alcoholics, portal perfusion is frequently lost (60%), quality of blood perfusing the liver decreases, and cardiac output and liver blood flow increase. It is proposed that portal flow is lost in alcoholics via pancreatic and colonic collaterals after surgery. Elimination of this sump by adding complete dissection of the splenic vein and division of the splenocolic ligament to DSRS (splenopancreatic disconnection, SPD) could preserve portal perfusion, decrease shunt loss of hepatotrophic factor, and improve survival in alcoholic cirrhotics. This report compares data 1 year after surgery in two groups of cirrhotics: group I (8 nonalcoholic; 16 alcoholic) had DSRS without SPD; group II (17 nonalcoholic; 11 alcoholic) received DSRS + SPD. Methods: Portal perfusion grade, cardiac output (CO), liver blood flow (f), hepatic function (GEC), and hepatic volume (vol) were measured before and 1 year after surgery. Shunt loss of hepatotrophic factor was estimated by insulin response (change in plasma concentration over 10 minutes: AUC) after arginine stimulation. Results: Groups I and II were similar before surgery. Metabolically, nonalcoholics remained stable after both DSRS and DSRS + SPD. After standard DSRS, alcoholics lost portal perfusion (75%, p < 0.05), CO, and f increased (p < 0.05), and quality of blood perfusing the liver was decreased (GEC/f: p < 0.05). DSRS + SPD preserved portal perfusion better (p < 0.05) in alcoholic cirrhotics than did DSRS alone. After DSRS + SPD, the metabolic response in alcoholics resembled that of nonalcoholics. CO, f, and GEC/f remained stable. These data show: (1) DSRS + SPD preserves postoperative portal perfusion in alcoholic cirrhotics better than DSRS alone. (2) Metabolic response to DSRS + SPD is similar in alcoholic and nonalcoholic cirrhotics. (3) Because portal perfusion and metabolic integrity.

Selective variceal decompression after splenectomy or splenic vein thrombosis. With a note on splenopancreatic disconnection

Eight patients have had selective variceal decompression after a splenectomy or splenic vein thrombosis with successful control of bleeding. The principle veins utilized in these patients, either alone or in combination, were: (a) the splenic remnant, (b) the coronary, (c) the gastroepiploic, and (d) an inferior mesenteric that joined the splenic. High quality preoperative angiography is essential but operative exploration is often required to assess fully the possible shunt options. Simple splenectomy for thrombocytopenia in portal hypertension is rarely justifiable and creates far more problems than it solves. Complete splenopancreatic disconnection extends the selective shunt concept.

Noncirrhotic portal vein thrombosis. Physiology before and after shunts.

Controversy exists concerning the proper therapy for bleeding gastroesophageal varices secondary to noncirrhotic portal vein thrombosis. Disparity of opinion exists regarding the significance of hepatic portal blood flow and the consequences of total portal-systemic shunts in this condition. One patient is presented who developed severe, crippling encephalopathy 20 years after a central splenorenal shunt. This was associated with loss of portal flow to the liver and marked nitrogen intolerance. Closure of the shunt resulted in restoration of hepatic portal flow via collateral veins (HPI 0.36), clearance of encephalopathy and return to near normal protein tolerance. An additional patient was studied with hyperammonemia and early suggestive signs of encephalopathy eight years following a mesocaval shunt. Four patients were evaluated before and after selective distal splenorenal shunts. All had “cavernous transformation” of the portal vein with angiographic evidence of portal flow to the liver. Postoperative angiograms revealed continued hepatic portal perfusion and a patent shunt in each patient. Radionuclide imaging postoperatively gave an estimated portal fraction of total hepatic blood flow (HPI) of .39 and .60 in two of the four patients. We conclude that 1) there is significant hepatic portal perfusion in noncirrhotic portal vein thrombosis (cavernous transformation), 2) loss of this hepatic portal flow following total shunts can lead to severe encephalopathy, 3) the selective distal splenorenal shunt maintains hepatic portal perfusion and is the procedure of choice when there is a patent splenic vein and surgical intervention is indicated.

Distal splenorenal shunt with splenopancreatic disconnection -A 4 year assessment-

The aims of distal splenorenal shunt with splenopancreatic disconnection (DSRS-SPD) were to improve maintenance of portal flow and prevent siphoning of hepatotrophic factors from the pancreas, as occurs after standard DSRS. The main patient population targeted for improvement were alcoholic cirrhotics, who have poorer survival than nonalcoholic cirrhotics and greater loss of portal flow (60%) after standard DSRS. Seventy-eight patients had DSRS-SPD during the study period 1983 to 1987: thirty-two patients were Childs A, 25 were Childs B, and 21 were Childs C. The 35 patients with alcoholic cirrhosis were a significantly poorer risk group by Childs class and galactose elimination capacity (GEC) than the 39 patients with nonalcoholic cirrhosis. Four patients had portal vein thrombosis. At 4-year follow-up, portal perfusion is maintained in 84% alcoholic and 90% nonalcoholic patients, with hepatic and systemic hemodynamics showing identical patterns for both groups. Hepatic function measured by GEC was maintained in alcoholic patients (290 +/- 68 mg/min to 303 +/- 74 mg/min) and nonalcoholics patients (342 +/- 92 to 320 +/- 118 mg/min). Gastric variceal rebleeding occurred in 10 patients--4 early (less than 2 months) and 6 late (18 to 54 months), leading to operation in 4 and transhepatic embolization in 4 patients: 2 of these patients died from this complication. Survival data show an operative mortality rate of 6.4% and overall mortality rate of 30%, with no significant difference between alcoholic and nonalcoholic cirrhotics. DSRS-SPD has significantly improved maintenance of portal perfusion and survival in patients with alcoholic cirrhosis requiring selective shunt for variceal bleeding when compared to standard DSRS. In this population DSRS-SPD is the operation of choice. In patients with nonalcoholic cirrhosis, the current data have not shown DSRS-SPD to have advantage over standard DSRS.

Change in hepatic function, hemodynamics, and morphology after liver transplant. Physiological effect of therapy.

Orthotopic liver transplantation (OLT) has become standard therapy for patients with acute hepatic necrosis and end-stage liver disease. This study measured change in hepatic function (galactose elimination capacity [GEC]), liver blood flow (low dose galactose clearance: flow), hepatic volume (CT scan; volume) and morphology after OLT. The aim was to measure the physiologic response after OLT and compare this response with that after selective shunt (SS) and sclerotherapy (ES) to determine which patients should receive specific therapy. Between January 1987 and November 1988, 37 patients underwent OLT. Operative mortality was 18%, which was similar to that of SS in Childs C cirrhotics. GEC and volume were less in transplant patients than in cirrhotics treated with SS or ES. GEC, flow, and volume normalized after OLT; GEC was preserved after ES and SS, but volume decreased. Three preoperative patterns were observed that can aid in selection of OLT candidates. Patients with chronic cirrhosis (chronic active hepatitis; cryptogenic) need OLT when GEC is less than or equal to 225 mg/min and volume is less than or equal to 50% normal. Patients with Budd-Chiari Syndrome require OLT if cirrhosis has evolved. Patients with sclerosing cholangitis and primary biliary cirrhosis qualify for transplants when complications of the portal hypertensive syndrome develop. The studies can also direct therapy for ES failures. Selective shunt is indicated in those patients with stable disease whose GEC is greater than or equal to 300 mg/min and liver volume is greater than 75% normal; OLT is indicated for cirrhotics with GEC that is less than 225 mg/min and liver volume that is less than 50% predicted normal.