Liver transplantation for primary sclerosing cholangitis.

UNLABELLED: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that progresses to end-stage liver disease. This report is a retrospective analysis of a Canadian centre experience with liver transplantation (LT) for PSC. Of 1107 LTs performed between 1984 and 2002, 132 were performed on 111 patients with PSC. Patient survival at 1, 3, 5, and 10 years was 84.5%, 84.5%, 83.4%, and 68.9%, respectively. Graft survival at 1, 3, 5, and 10 years was 80.8%, 79.8%, 72.7%, and 55.3%. These were not significantly different from overall patient survival (P =.91) or graft survival (P =.28) in non-PSC patients transplanted over the same time period. Early mortality was predominantly related to primary nonfunction and multi-organ failure; late mortality was predominantly related to malignancy. No patient with known cholangiocarcinoma (CCA) underwent LT, but three patients had an incidental CCA noted on explant pathology. All three died of widespread metastatic disease (10.8, 38.0, and 39.8 months after LT). Nineteen patients lost their primary grafts requiring retransplantation, and two of these patients required a third transplant. Recurrent PSC was detected in six patients and suspected in another six. Four patients have been retransplanted for recurrent PSC. Chronic rejection was detected in nine patients. Eight have required retransplantation. The incidence of biliary complications was 16.2%. CONCLUSIONS: LT is effective therapy for PSC. Patient and graft survival is comparable to that seen in patients transplanted for indications other than PSC, but long-term graft survival may be lower. Recurrent PSC and chronic rejection are the major determinants of graft loss.

Survival after liver transplantation for hepatocellular carcinoma.

BACKGROUND: Selection criteria for patients with hepatocellular carcinoma (HCC) suitable for liver transplantation (LT) include tumor size and number and vascular invasion. There has been a recent trend to expand the transplant criteria for HCC. We reviewed our experience to determine survival following LT based on tumor characteristics. METHODS: A retrospective analysis was performed on 72 patients with HCC who underwent LT between 1985 and July 2002. The Milan criteria were applied for LT candidacy for HCCs that were deemed unresectable from anatomical considerations and/or the severity of underlying cirrhosis. Patients were divided into four groups: group 1: patients with known HCC who satisfied the selection criteria (n = 22); group 2: patients with known HCC that exceeded the criteria (n = 17); group 3: patients with incidental HCC found at pathological examination of the explant (n = 33); group 4: contemporary LT recipients without HCC (n = 935). RESULTS: In the known HCC group, the interval between listing as status 2 and transplantation was 72.2 +/- 133.6 days (median 23 days). Three-year patient survival was 80.2% in group 1, 35.8% in group 2, 63.2% in group 3, and 81.5% in group 4. In group 2 patients, the tumors were significantly larger, had more nodules, and were more often bilobar. In group 3, five (15%) exceeded the criteria mainly because of tumor size and four patients died within 3 years post-LT (three from tumor recurrence). CONCLUSION: Liver transplantation for HCC yields acceptable survival in early-stage tumors, particularly if transplanted soon after listing. Long-term survival was inferior in patients with multiple tumors and tumors that were greater than 5 cm in diameter.

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.

Long term follow-up of patients with chronic hepatitis C treated with interferon alpha.

Interferon alpha (IFN alpha) treatment for chronic hepatitis C induces a sustained biochemical and virological response at six months after completing 24 weeks of therapy in approximately 10% of patients. The long term durability of this 'sustained' response is still controversial. The aim of this multicentre study was to assess the long term virological response in patients considered to have achieved a sustained biochemical response six months after completing IFN treatment. The majority (36 of 41) of the sustained responders identified had been treated for six months with IFN therapy. Twenty-nine of the 41 patients (70%) had undetectable hepatitis C virus (HCV) RNA after a mean follow-up of 38 months after cessation of treatment (range six to 92 months). All but one of those 29 individuals had normal serum alanine aminotransferase (ALT) levels. Of the 16 patients (out of 41) who had been tested for HCV RNA six months after treatment, HCV RNA remained undetectable in 14 (88%) at final follow-up. Serum ALT values in the 11 of 12 patients whose HCV RNA was positive at final follow-up were lower than pretreatment values, and in six cases were within the normal range. The long term sustained virological response in those considered a 'sustained responder' six months after receiving only six months of IFN is high. Measurement of ALT is an unreliable marker of sustained response to therapy.

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.

Small bowel transplantation. A life-saving option for selected patients with intestinal failure.

Thirty-seven patients were listed for small bowel transplantation; 16 were transplanted and 15 died while waiting for a donor. Cyclosporine (N = 6) or tacrolimus (N = 10) were used for immune suppression. Graft rejection rates were lower in the combined liver/small bowel grafts than the isolated intestinal transplants (1/7 vs 5/7; P < 0.01) All of the cyclosporine group have died; the median survival was 25.7 months with two patients living more than five years. The tacrolimus group had fewer infections and a shorter hospital stay. All but two are alive with a median survival of 13 months. Seven of eight long-term survivors are off intravenous feedings. We conclude that small bowel transplantation is a life-saving option for patients with intestinal failure who cannot be maintained on total parenteral nutrition.

An analysis of late deaths after liver transplantation.

Late deaths (after more than 1 year) after liver transplantation were analyzed in a series of 464 consecutive patients who received liver grafts between 1982 and 1993. Recipients who survived the first posttransplant year (n = 365) had actuarial 5- and 10-year survival rates of 92% and 84%, respectively. Thirty-five patients died between 1.1 and 7.6 years after transplantation (mean, 3.2 +/- 1.9 years). The most common causes of death were related to immunosuppression (40%), namely, chronic rejection, opportunistic infection, and lymphoma. The second most common causes of death were related to the primary disease for which liver transplantation was performed (34.3%), mainly recurrence of hepatobiliary malignancy and hepatitis B. Eight patients (22.9%) died of unrelated and unpredicted causes, most commonly of cardiovascular disease. Although the survival of liver recipients who live beyond the first posttransplant year is excellent, control of rejection and the consequences of chronic immunosuppression are continual threats. Modification of immunosuppression may help in decreasing the mortality of long-term survivors. In addition, better selection of recipients and effective adjuvant therapies (antiviral and antineoplastic) are needed in patients in whom the primary liver disease is notorious for recurrence.

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.