Muscle cramps: a 'complication' of cirrhosis.

Muscle cramps are a common complaint in clinical practice. They are associated with various metabolic, endocrine, neurological and electrolyte abnormalities. A variety of hypotheses have been generated to explain the cause of muscle cramping, yet none has been able to support a consistent pathophysiological mechanism. Muscle cramps are painful, involuntary contractions of skeletal muscle. They occur frequently in individuals with cirrhosis, regardless of the etiology, and are thought to be a symptom of cirrhotic-stage liver disease. The pathophysiology of these cramps remains elusive; hence, a specific therapy has not been identified. Many therapeutic approaches have been offered, yet their efficacy, safety and mechanism of action remain poorly defined. This review defines muscle cramps and illuminates its prevalence in the cirrhotic individual. Current theories relating to the pathogenesis of muscle cramps are reviewed, and an overview of the various pharmacological agents that have had therapeutic success for this distressing and frustrating symptom is provided.

Primary biliary cirrhosis and hemolytic anemia confusing serum bilirubin levels.

Hemolysis is observed in more than 50% of patients with cirrhosis. However, there has been little documentation of the association of primary biliary cirrhosis with autoimmune hemolytic anemia. Two cases, found within a single practice, of primary biliary cirrhosis coexisting with autoimmune hemolysis and a third case coexisting with hereditary spherocytosis are presented. Anemia in such patients is commonly attributed to chronic disease, and hyperbilirubinemia is attributed to primary biliary cirrhosis. These patients were considered for liver transplantation until the diagnosis of a comorbid hemolytic process was established. This association may be more prevalent than previously recognized. A diagnosis of comorbid hemolysis must always be considered in context with anemia and serum bilirubin levels that rise out of proportion to the severity of the primary biliary cirrhosis.

Biliary reconstruction without T tubes or stents in liver transplantation: report of 502 consecutive cases.

Although T tubes and stents are widely used as part of the routine biliary reconstruction in liver transplantation, they have inherent complications and there is no proof that they are beneficial to healing. We do not use T tubes or anastomotic stents, and we reviewed our experience with 502 consecutive, whole-size liver grafts to determine the incidence and nature of biliary complications. Duct-to-duct (D-D) and Roux-en-Y loop-to-duct (RY-D) anastomoses were performed in 321 and 176 cases, respectively. In 62% of cases, the donor gallbladder was transplanted and an external catheter cholecystostomy was fashioned to provide for postoperative cholangiography. In the remaining cases the gallbladder was removed. Biliary complications of all types occurred after 13.5% of the transplants. Anastomotic complications (stricture, obstruction, or leak) occurred in 8.2% of the cases, and they were least frequent (4.0%) with RY-D reconstructions. Gallbladder-related complications accounted for one quarter of all biliary complications, and they outweighed the advantage of convenient access to the biliary tree for cholangiography. Four patients (0.9%) died of biliary complications. We conclude that routine reconstruction of the biliary tract without T tubes or stents is a safe technique in liver transplantation. Retaining the donor gallbladder as a method of providing cholanglography is not necessary.

Is the Mayo model for predicting survival useful after the introduction of ursodeoxycholic acid treatment for primary biliary cirrhosis?

Treatment of patients with primary biliary cirrhosis (PBC) using ursodeoxycholic acid (UDCA) leads to a reduction in serum bilirubin. The first objective of this study was to assess the performance of certain prognostic indicators for PBC after the introduction of treatment with UDCA. Serum bilirubin is an important prognostic indicator for PBC and an important component of the Mayo model for grading patients into risk categories. In an analysis of patients enrolled in the Canadian multicenter trial, the Mayo score was calculated before and after treatment with UDCA. After treatment, the Mayo score continued to divide patients with PBC into groups with varying risk. In addition, the serum bilirubin alone was shown to do the same even after the introduction of treatment with UDCA. A second objective was to establish whether UDCA had an effect on long-term (2- to 6-year) survival in patients with PBC.

Central pontine myelinolysis and cyclosporine neurotoxicity following liver transplantation.

In a recent series of 44 liver transplants we identified both extrapontine myelinolysis (EPM) - characteristic of cyclosporine neurotoxicity - and central pontine myelinolysis (CPM) in 5 recipients posttransplant. An additional 2 recipients had EPM only posttransplant. MRIs performed in 4 asymptomatic recipients were normal. Large perioperative shifts in serum sodium, hypomagnesemia, and high cyclosporine levels may play a role in the development of these lesions, although the evidence from this study is inconclusive. In addition to supportive care, dilantin was started in patients who had seizures; aggressive magnesium replacement was initiated for hypomagnesemia, and cyclosporine levels were reduced in all patients. All patients demonstrated a slow steady recovery and all but 2 are at home at the time of writing. CPM may be more prevalent than previously appreciated following liver transplantation, although its prognosis may not be as dismal.

Use of OKT3 monoclonal antibody as induction therapy for control of rejection in liver transplantation.

This report details a single center's experience with OKT3 induction immunosuppression for liver transplantation. One hundred ninety-nine consecutive, unselected adult liver recipients received OKT3 therapy for 9-10 days combined with low-dose steroids and azathioprine. Cyclosporine was begun to overlap with the last few days of OKT3 therapy. The average dose of OKT3 was 45 mg. Fifty-two patients (26.1%) experienced 57 episodes of acute rejection. The median time of onset of rejection was 18 days after grafting. Seventy-eight percent of the rejection episodes were steroid-sensitive. Recurrent rejection was uncommon and the need for OKT3 retreatment was infrequent. One year actuarial graft and patient survival was 79.7% and 82.3% respectively. Based on this evidence, it appears that OKT3 prophylaxis provides good control of acute rejection with a very low incidence of recurrent rejection.

Employment after liver transplantation.

The objective of this study was to study the factors affecting employment after liver transplantation. The employment status and health status of 203 adult liver transplant recipients was assessed retrospectively in a survey comprising an employment questionnaire, the Sickness Impact Profile (SID), and the Medical Outcomes Survey (MOS). The patient population consisted of all surviving adult patients who had undergone liver transplantation between 1982 and 1992 at our institution and who had survived a minimum of 9 months. Fifty-seven percent of the recipients were employed and 43% of the recipients were unemployed. Eighteen percent of the recipients considered themselves not well enough to work. Other reasons cited for not working in the unemployed patients were early retirement (8%), return to school (3%), family reasons (3%), no work available (3%), and chose not to work (3%). Patient age, duration of disability before transplantation, and type of job before transplantation significantly affected posttransplantation employment status. Health status measurements predicting employment were ambulation, home management, physical functioning, and pain. Older recipients and those who were continuously out of the workforce for several years before transplantation were the least likely to return to gainful employment after liver transplantation. These findings have implications for assessing the success of liver transplantation and the implementation of strategies to fully rehabilitate patients after liver grafting.

Anti-B cell antibodies for the treatment of monoclonal Epstein-Barr virus-induced lymphoproliferative syndrome after multivisceral transplantation.

Epstein-Barr virus-induced lymphoproliferative syndrome (EBV-LPS) is associated with OKT3 therapy in transplant patients. Response to chemotherapy or radiation is generally poor, while polyclonal EBV-LPS has had favorable responses to therapy with CD21 and CD24 monoclonal antibodies. Oligoclonal disease has not been previously reported to respond to therapy with CD21 and CD24. We report a 27-y old woman who developed a monoclonal EBV-LPS (confirmed by southern analysis of tumour for EBV DNA) after 180 mg of OKT3 for a multivisceral transplant. The patient achieved clinical remission for more than 2 months, but later died from cytomegalovirus pneumonia. Levels of CD21 and CD24 were > 2000 ng/ml during therapy and no human anti-mouse antibodies were formed. Peripheral blood B cells were cleared during therapy. We conclude that CD21 and CD24 monoclonal antibodies may be of value in the therapy of oigoclonal EBV-LPS, and merit further study.

Normal fasting volume and postprandial emptying of the denervated donor gallbladder in liver transplant recipients.

BACKGROUND/AIMS: Truncal vagotomy causes gallbladder dilatation and possibly cholelithiasis. During liver transplantation, when the gallbladder is transplanted with the donor liver, the gallbladder and liver are extrinsically denervated. The aim of this study was to determine whether extrinsic denervation affects gallbladder volume and postprandial emptying. METHODS: To evaluate fasting gallbladder volume, 26 transplant recipients underwent ultrasonography. Twenty-eight normal volunteers were controls. To evaluate postprandial contractility, seven transplant recipients underwent radionuclide gallbladder-emptying studies. Gastric emptying and cholecystokinin release were simultaneously determined after a fatty meal to exclude a difference in gallbladder stimulus. Sixteen normal volunteers were controls. RESULTS: There were no differences in fasting gallbladder volume or postprandial contractility, gastric emptying, and cholecystokinin release between transplant patients and controls. Median fasting and postprandial gallbladder volumes for the transplant recipients (95% confidence) were 16 mL (12-34 mL) and 3 mL (0-8 mL), respectively, and for controls were 18 mL (13-21 mL; P = 0.73) and 3 mL (1-6 mL; P = 0.97), respectively. CONCLUSIONS: These data do not show gallbladder dilatation or impaired postprandial gallbladder contraction in the extrinsically denervated gallbladder. This finding suggests that gallbladder dilatation may be caused by the unopposed activity of the sympathetic system after truncal vagotomy.

The Canadian Multicenter Double-blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis.

Ursodeoxycholic acid, a dihydroxyl bile acid normally present in human beings in minimal amounts, becomes incorporated into the bile salt pool when taken orally. In cholestasis, bile acids are retained in the liver and are hepatotoxic. Ursodeoxycholic acid is the least-known hepatotoxic bile acid, has choleretic properties and is reported to benefit patients with chronic cholestasis. In a nationwide Canadian controlled trial, 222 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (14 mg/kg/body wt/day) or placebo for 24 mo. Only patients with a diagnosis confirmed by liver biopsy and serum positive for antimitochondrial antibodies were enrolled; 88% were symptomatic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow-up. Treated patients (111) and controls (111) were comparable with regard to age, gender, biochemical parameters and liver histological condition. Although treatment was not associated with any improvement in symptoms, ursodeoxycholic acid therapy caused the bilirubin to fall significantly within the first 3 mo of therapy (p < 0.001). Significant falls in serum alkaline phosphatase, aminotransferases, cholesterol and IgM levels were also noted in the treated group. Improvement in some histological features was observed but there was no difference between the groups in the number of patients who reached the endpoints of death or liver transplantation. Ursodeoxycholic acid, given to patients with primary biliary cirrhosis, leads to an improvement in serum markers of cholestasis. A larger sample size is needed to determine whether ursodeoxycholic acid therapy has a beneficial effect on the survival of patients with primary biliary cirrhosis.