Survival after liver transplantation for hepatitis C is unchanged over two decades in Canada.

Allograft failure secondary to recurrence of hepatitis C virus (HCV) infection is the most common cause of death and retransplantation among recipients with HCV infection. It has been suggested that patients transplanted for HCV have had worse outcomes in more recent years than in previous years (the 'era effect'). A Canadian transplantation registry database was analyzed to determine the outcomes of patients transplanted over the years for HCV. The results of the present analysis of 1002 patients show that the 'era effect' was not seen in liver transplantation recipients with HCV in Canada, because no survival difference was noted based on the year of transplantation. All groups had overall two-year and five-year survival rates of 76% to 83% and 69% to 72%, respectively. The present study's national results prove continued benefit to transplantation of HCV patients.

Transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic variceal ligation in the prevention of variceal rebleeding in patients with cirrhosis: a randomised trial.

BACKGROUND AND AIMS: The transjugular intrahepatic portosystemic shunt (TIPS) is a new therapeutic modality for variceal bleeding. In this study we compared the two year survival and rebleeding rates in cirrhotic patients treated by either variceal band ligation or TIPS for variceal bleeding. METHODS: Eighty cirrhotic patients (Pugh score 7-12) with variceal bleeding were randomly allocated to TIPS (n=41) or ligation (n=39), 24 hours after control of bleeding. RESULTS: Mean follow up was 581 days in the ligation group and 678 days in the TIPS group. The two year survival rate was 57% in the TIPS group and 56% in the ligation group (NS); the incidence of variceal rebleeding after two years was 18% in the TIPS group and 66% in the ligation group (p<0.001). Uncontrolled rebleeding occurred in 11 patients in the ligation group (eight were rescued by emergency TIPS) but in none of the TIPS group. The incidence of encephalopathy at two years was 47% in the TIPS group and 44% in the ligation group (NS). CONCLUSIONS: TIPS did not increase the two year survival rate compared with variceal band ligation after variceal bleeding in cirrhotic patients with moderate or severe liver failure. It significantly reduced the incidence of variceal rebleeding without increasing the rate of encephalopathy.

A case of giant cell hepatitis recurring after liver transplantation and treated with ribavirin.

A patient who underwent orthotopic liver transplantation for giant cell hepatitis with cirrhosis and in whom giant cell hepatitis recurred twice after orthotopic liver transplantation is reported. He was treated with ribavirin with an excellent result. The literature on this subject is reviewed. This observation clearly confirms the efficacy of ribavirin for the treatment of giant cell hepatitis, thus providing evidence for its viral origin.

Treatment of chronic bleeding from gastric antral vascular ectasia (GAVE) with estrogen-progesterone in cirrhotic patients: an open pilot study.

OBJECTIVE: Gastric antral vascular ectasia (GAVE) is a rare cause of chronic bleeding in cirrhotic patients. Treatment of GAVE with surgical or nonsurgical portal decompression, beta-blockers, or endoscopic therapy provides disappointing results. In the present study, we evaluated the efficacy of estrogen-progesterone therapy, which has been reported to control chronic bleeding in gastrointestinal vascular malformations, such as Osler-Weber Rendu disease or angiodysplasia, in GAVE-related chronic bleeding. METHODS: Six cirrhotic patients who bled chronically from GAVE were included. Three had alcoholic cirrhosis, two cryptogenic cirrhosis, and one primary biliary cirrhosis. Grade 1 esophageal varices were noted in four patients. Bleeding could not be controlled by beta-blockers, and endoscopic therapy was not considered given the extension of the antral vascular lesions. RESULTS: Before the start of therapy, transfusion requirements averaged 3.5 units/month over a 1.5-11 month period of observation. Patients were then treated with a combination of ethynil estradiol 30 microg and noretisterone 1.5 mg daily. During follow-up (range 3-12 months), bleeding did not recur in four patients; in one patient, treatment with estrogen progesterone decreased the need for transfusions from 4 units/month to 1.4 unit/month; this patient stopped the treatment inadvertently after 6 months and severe anemia recurred with a need for 4 units of blood in the following month; reintroduction of the treatment resulted in an increase of hemoglobin levels without the need for blood transfusions during the following 4 months. In the last patient, a 5-month treatment did not improve chronic bleeding. CONCLUSIONS: The present study suggests that estrogen-progesterone therapy is useful in the treatment of chronic bleeding related to GAVE; however, these findings require confirmation by a controlled trial.

Lack of relationship between preoperative measures of the severity of cirrhosis and short-term survival after liver transplantation.

The purpose of this study was to evaluate the prognostic value of clinical measures of the severity of disease in cirrhotic patients who were candidates for liver transplantation at our institution. The records of the 132 cirrhotic patients who were candidates for a first transplantation between January 1, 1987, and December 31, 1994, were reviewed. One hundred nine patients (82.6%) received grafts, and 23 (17.4%) died while on the waiting list. The variables examined included level of medical urgency at the time of enlistment, date of transplantation, serum creatinine level, variables that constitute the Child-Pugh score and Shaw's risk score (serum bilirubin and albumin, prothrombin time, ascites, encephalopathy, nutritional status, age, and operative blood loss), and 6-month survival status after transplantation. The proportion of patients who died awaiting a graft increased as a function of the Child-Pugh score at enlistment (score 5-6, 0%, n = 6; score 7-9, 7%, n = 54; score 10-11, 18%, n = 33; score 12-15, 33%, n = 39; P = .01). Six-month survival rates after transplantation were similar irrespective of the Child-Pugh score or Shaw's risk score. Stepwise multiple logistic regression models identified the degree of ascites, serum bilirubin, and operative blood loss as significant variables for the prediction of overall mortality 6 months posttransplantation (model chi 2 = 12.8; P = .025; r = 0.32), but the model explained only 10% of the outcomes observed. We concluded that the Child-Pugh score is a valid prognostic index for survival up to the time of transplantation for cirrhotic patients on the waiting list; however, clinical measures of the severity of cirrhosis are poor predictors of 6-month survival after transplantation.

Clearance by the liver in cirrhosis. III. Propranolol uptake by the isolated perfused human liver.

In cirrhosis, intrahepatic shunts and capillarization of sinusoids can result in impaired extraction of substrates by the liver irrespective of the metabolic capacity of the liver (intact hepatocyte theory). To evaluate the role of anomalies of uptake in impaired drug disposition, we studied the steady-state hepatic clearance and single-pass hepatic uptake of propranolol in isolated perfused livers obtained from patients with cirrhosis at the time of transplantation and from organ donors with normal liver architecture. The kinetics of propranolol transport in the liver were characterized by means of the multiple-indicator dilution technique, and the outflow pattern of propranolol in the hepatic veins was resolved into throughput material, which had swept past the hepatocytes along with albumin, and returning material, which had entered the cells but returned in the outflow after escaping cellular sequestration and metabolism. The steady-state clearance of propranolol was decreased in cirrhotics compared with organ donors, and the outflow profile differed between the two groups. In cirrhotic livers, half of the propranolol in the outflow consisted of throughput material and the other half of returning material; in organ donors, all of the propranolol in the outflow was returning material. In the presence of albumin and alpha 1-acid glycoprotein in the perfusate, about 80-85% of propranolol was protein bound; removal of albumin and alpha 1-acid glycoprotein from the perfusate it cirrhotic livers resulted in an increase in the free fraction of propranolol, an increase in steady-state extraction, and a decrease in the throughput component of propranolol in the outflow. We conclude that impaired uptake of protein-bound propranolol, as a result of capillarization and intrahepatic shunts, contributes to its impaired elimination in cirrhosis.

The hepatic microcirculation in the isolated perfused human liver.

In cirrhosis, capillarization of sinusoids could result in impaired exchanges between the hepatocytes and the blood perfusing the liver and contribute to liver failure irrespective of the metabolic capacity of the liver. To characterize anomalies of the hepatic microcirculation, we used the multiple-indicator dilution approach in isolated perfused livers obtained from patients with cirrhosis at the time of transplantation, and from organ donors with normal or near-normal livers or hepatic steatosis. In organ donors, the sinusoidal volume and the permeability of sinusoids to albumin, sucrose, and water were found to be comparable to that of normal dog and rat livers. The sinusoidal volume and the extravascular volume (EVV) accessible to diffusible tracers were larger after hepatic artery than after portal vein injection, probably because of an unshared arterial sinusoidal bed. In cirrhotic livers, two kinds of alterations were found: the appearance of a barrier between the sinusoids and the hepatocytes (capillarization) and intrahepatic shunts. The extravascular space accessible to albumin decreased with increasing severity of cirrhosis, and the diffusion of sucrose in the space of Disse showed a barrier-limited pattern, instead of the normal flow-limited behavior. In cirrhotic livers, a correlation was found between the hepatic extraction of indocyanine green (ICG) and the extravascular space accessible to albumin (r = .84, P < .05), suggesting that the impaired access of this protein-bound dye to the hepatocyte surface contributed to its impaired elimination. Intrahepatic shunts were found between portal and hepatic vein (21% +/- 16% of portal flow), but not between hepatic artery and hepatic veins. We conclude that (1) the behavior of diffusible tracers in human livers with normal liver architecture is comparable to that reported in normal animals; (2) the permeability of sinusoids in cirrhotic livers is abnormal, (3) permeability changes are related to changes in liver function in cirrhosis.

[Reduction of blood loss in orthotopic liver transplantation with the use of aprotinin]. / Réduction des pertes sanguines en transplantation orthotopique du foie par l'utilisation d'aprotinine.

UNLABELLED: The impact of aprotinin on blood losses during orthotopic liver transplantation (OLT) has been studied retrospectively. PATIENTS AND METHODS: From September 1984 to July 1995, 152 patients underwent 168 OLT in our center. Seventy three patients (group I) received epsilon-aminocaproic acid as an antifibrinolytic agent and 95 patients (group II) received aprotinin. RESULTS: There was a significant reduction in the mean duration of the surgery (I = 743 +/- 25 min; II = 302 +/- 10 min; p < 0.001) and in the post reperfusion time (I = 282 +/- 13 min; II = 126 +/- 6 min; p < 0.001) in the group II. The need for blood products during the operation was also reduced (blood units; I = 21.7 +/- 2.3 units; II = 4.6 +/- 0.4 units; p < 0.001). There was less infectious and hemorrhagic complications requiring reoperation in group II. We have not seen an increased incidence of thrombotic complications in the patients receiving aprotinin. Other variables such as the use of hemoclips, veno-venous bypass and the type of preservation solution were also considered. CONCLUSION: Aprotinin use during OLT is efficient and superior to epsilon-aminocaproic acid in reducing blood losses. Combined with the non-utilisation of a veno-venous by-pass and the use of hemoclips, it helps reduce the operating time and the postoperative complications.

Hepatic artery: effect of a meal in healthy persons and transplant recipients.

Thirty healthy volunteers and 12 liver allograft recipients (two with cirrhotic changes seen at microscopy) were given a standard meal. Doppler sonography of the right and left hepatic arteries, the superior mesenteric artery, and the portal vein was performed. The change in hepatic arterial resistance was evaluated with the resistive index (RI). After the standard meal, portal venous flow increased in both the healthy volunteers and allograft recipients (more so in the latter group). Superior mesenteric arterial RI decreased in all subjects. A postprandial increase in hepatic arterial RI, likely reflecting constriction of the hepatic artery, was seen in both groups. It was absent in the two patients with recurrent transplant cirrhosis. These results show the importance of examining hepatic arterial flow in the fasting subject, since high resistance after a meal may be falsely interpreted as a sign of disease. Absence of a postprandial change in resistance of the hepatic artery could signal abnormal liver function.

[Not Available]. / La polyvalence en médecine familiale.

A Quebec doctor offers his thoughts on the basic principles of family medicine and the need for dialogue on the programs and models our residents are offered.

Surgical treatment of severe postshunt hepatic encephalopathy.

Hepatic encephalopathy is a major complication of portal-systemic shunts with an incidence ranging up to 52%. A small fraction of these patients are refractory to medical therapy. Shunt ligation and colonic procedures are the main surgical approaches. The goal of the latter is to diminish the colonic absorption of nitrogenous substances which are involved in the pathophysiology of hepatic encephalopathy. Six patients, whose average age was 55.7 +/- 2.6 years, were operated for severe postshunt encephalopathy requiring 4.3 +/- 0.9 admissions for a total duration of 76 +/- 26 days over 1-11 years. One patient had undergone a splenoral shunt and 5 had a portacaval shunt. One ligation of the shunt and 5 colon exclusions were performed. The average postoperative hospital stay was 21.5 +/- 3.9 days. The mean follow-up was 47 +/- 20 months. The patient with the shunt ligation remains free of encephalopathy 94 months after the procedure and has not bled from his esophageal varices. Among the 5 colon exclusion patients, there were 1 death and 3 complications. Three patients were completely relieved of their hepatic encephalopathy. One of those 3 died of a subarachnoid hemorrhage 28 months after the surgery. The fourth still needs medication to control a persistent, although improved, encephalopathy that required 2 further hospitalizations. Colon exclusion is a useful intervention in very selected cases. It has a lower operative mortality than total colectomy and the advantage over shunt ligation of not reestablishing hypertension in the portal system.

[Development of organ transplantation in Quebec from 1985 to January 1990]. / Evolution de la transplantation d'organes au Québec de 1985 à janvier 1990.

In Québec, the first organ transplantations have been realized in 1958. Several kidney transplant programs started at that time. Cardiac, liver, pancreas and lungs programs followed and reached a full development in the eighties when Cyclosporin became available. Today, there are 4 university transplant programs in Québec (McGill, Montréal, Laval and Sherbrooke) with a total of 7 kidney, 4 liver, 4 heart, 2 pancreas and 2 lungs centers. More than 2,900 transplantations have been realized. Since 1970, organ procurement and distribution is organized by a central agency called Québec-Transplant (previously Métro-transplantation). Organ donation is done on a voluntary basis as every where in North America. More than 90% of the organs comes from cadaveric donors and more than 90% of the relatives accept organ donation. 50% of the donors have deceased from head trauma and 50% from cerebral hemorrhage. In 1989, multi-organ harvesting has been realized in 64% of the donors. Despite efforts and progresses, the number of patients awaiting an organ transplant is steadily growing and outlast the number of available organs. It is hoped that maximal utilisation of the donors and growing exchanges at a national and international level will help to solve this crucial problem.

Isolated perfused cirrhotic human liver obtained from liver transplant patients: a feasibility study.

Cirrhotic livers obtained from eight patients who underwent orthotopic liver transplantation were perfused through the portal vein and hepatic artery in a closed recycling system for periods ranging from 2 to 7 hr. An average perfusion flow of 451 ml/min was used, with about 80% coming from the portal vein and 20% from the hepatic artery. The livers appeared to remain viable as assessed by gross appearance, stable portal vein and hepatic artery pressures, oxygen consumption and bile production. The extraction ratio of indocyanine green by the perfused livers averaged 0.098 (range = 0.023 to 0.168); that of propranolol averaged 0.445 (range = 0.126 to 0.813). Using the multiple-indicator dilution-curve method, shunts greater than 15 microns in diameter were demonstrated between the portal and hepatic veins in six of eight cases, whereas shunts from the hepatic artery to the hepatic veins were absent. Perfusion of human livers obtained during hepatic transplantation is a fairly simple procedure that will allow researchers to gain new insights into cirrhosis in humans.

Prognostic value of indocyanine green and lidocaine kinetics for survival and chronic hepatic encephalopathy in cirrhotic patients following elective end-to-side portacaval shunt.

The objective of this study was to assess the prognostic value of spontaneous portosystemic shunting and liver function for survival and spontaneous hepatic encephalopathy after end-to-side portacaval shunt in cirrhotic patients. One hundred ninety-eight patients with variceal hemorrhage as shown by endoscopy were evaluated. Forty-five were excluded because of uncontrollable hemorrhage; 84 were rejected because they were poor operative risk, had portal vein thrombosis or had been previously treated with beta-blockers, sclerotherapy or surgery. The remaining 69 patients were enrolled in this prospective study. There were 43 patients with alcoholic cirrhosis, 23 with cryptogenic cirrhosis and three with primary biliary cirrhosis. The severity of liver disease was assessed according to the Pugh classification: 37 patients (54%) had Pugh's score 5 to 7, 26 (38%) had 8 to 10 and six (8%) had 11 to 12. Indocyanine green intrinsic clearance was used as a probe of preoperative liver function and lidocaine systemic availability as an index of spontaneous preoperative shunting. All the patients underwent an elective end-to-side portacaval shunt. The length of minimal follow-up was 40 months. One-year survival was 76% and 5-year survival was 46%. During follow-up, 25 patients died from their liver disease and 11 patients died from various causes unrelated to their liver disease. Spontaneous chronic encephalopathy occurred in 16 patients (23%). Age, Pugh's score, active alcoholism, indocyanine green intrinsic clearance and lidocaine systemic availability were tested as prognostic factors in a multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and hepatic hemodynamics after variceal hemorrhage: effects of propranolol and placebo.

Hepatic and systemic hemodynamics were measured in 19 cirrhotic patients with variceal bleeding enrolled in a controlled trial of propranolol for the prevention of rebleeding. The patients were studied on three separate occasions. The first study was performed before randomization within 24 h of the bleeding episode, once hemodynamic stabilization had been achieved. The second study was performed after 10 days of treatment, and the third after 6 mo without rebleeding. Propranolol dosage was titrated according to blood levels. Wedged and free hepatic venous pressures and the hepatic venous pressure gradient were recorded. Hepatic blood flow and cardiac output were also measured. Before treatment, the groups of patients treated with propranolol (n = 11) or placebo (n = 8) were comparable according to clinical, biochemical, and hemodynamic parameters. After 10 days, hepatic venous pressure gradient decreased similarly in the two groups (-20% in the propranolol group, -25% in the placebo group). Cardiac output fell only in the propranolol group (-40%). Hepatic blood flow remained unchanged in either group. After 6 mo, hepatic venous pressure gradient remained lower than the values from the first (within 24 h of bleeding) study in both the propranolol group (n = 5) and the placebo group (n = 6). Our results suggest that portal pressure increases shortly after hemorrhage with a return to baseline values 10 days later, and that propranolol does not further magnify these changes. Spontaneous changes in hepatic hemodynamics after variceal hemorrhage must be taken into account when evaluating the effect of pharmacologic agents on portal pressure.

Emergency portacaval shunt for variceal hemorrhage. A prospective study.

Emergency portacaval shunt for variceal bleeding is associated with a high operative mortality, particularly if used as a last resort. Because of this, a strong case has been made against emergency shunt. This report describes an experience with emergency portacaval shunt for the treatment of variceal bleeding when used systematically after hemodynamic stabilization and control of the bleeding episode with balloon tamponade, if necessary, in patients with mild or moderate liver disease. The population studied comprised 62 consecutive patients who rebled from varices while participating in a controlled trial of propranolol for the prevention of rebleeding. Of the 62 patients, nine died of massive hemorrhage and 53 survived the hemorrhage. Of the 53 survivors, 11 had severe liver disease and were not considered for shunt surgery. Of the remaining 42 patients with mild or moderate liver disease, 36 had emergency central portacaval shunt. The interval between endoscopic diagnosis of variceal bleeding and surgery averaged 19 +/- 3 hours (mean +/- SE). The operative mortality rate, defined as in-hospital mortality, was 19%. One- and 2-year survival rates were 78% and 71%, respectively. The incidence of postoperative hepatic encephalopathy was 36%; all patients responded favorably to protein restriction and lactulose. Thus, under specific conditions, emergency portacaval shunt results in an acceptable long-term survival rate. In patients with mild or moderate liver disease, emergency portacaval shunt should be considered when other forms of treatment for the prevention of variceal rebleeding have failed.

Propranolol for the prevention of recurrent variceal hemorrhage: a controlled trial.

We conducted a prospective, randomized single-blind trial of propranolol for the prevention of recurrent variceal bleeding. Seventy-nine patients shown to have variceal hemorrhage at endoscopy were included in the study within 72 hr following diagnosis. Fifty-seven patients had alcoholic cirrhosis, 10 cryptogenic cirrhosis, 6 posthepatitic cirrhosis, 4 biliary cirrhosis, 1 portal vein thrombosis without cirrhosis and 1 idiopathic portal hypertension. The severity of liver disease at inclusion was assessed according to the Pugh modification of the Child-Turcotte classification: 9 (11%) had Class A; 41 (52%) Class B, and 29 (37%) Class C disease. Patients were randomly assigned by sealed envelope to the propranolol group (42 patients) or the placebo group (37 patients). Propranolol dosage was titrated in order to produce plasma concentrations of propranolol of 50 to 150 ng per ml. beta-blockade was also confirmed by isoproterenol testing. The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 31 and 21% in the propranolol group, and 25 and 17% in the placebo group; both differences were not significant. Cumulative 1 and 2 years survival were also comparable: 64 and 54% in the propranolol group vs. 70 and 63% in the placebo group. There was no evidence for a therapeutic effect of propranolol after adjusting for potential confounding variables by multiple logistic regression. We conclude that propranolol is not effective for the prevention of variceal rebleeding, when administered early following the initial bleed, in cirrhotics unselected with respect to the severity of the liver disease.