Rise Stribling

Orthotopic liver transplantation for primary sclerosing cholangitis. A 12-year single center experience.

OBJECTIVE The purpose of this study was to analyze a single centers 12-year experience with 127 orthotopic liver transplantations (OLT) for primary sclerosing cholangitis (PSC). SUMMARY BACKGROUND DATA Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown origin that occurs most commonly in young men and is associated frequently (70-80%) with inflammatory bowel disease (IBD). Patients with PSC also are at risk for the development of cholangiocarcinoma (CCA) and those with IBD for colon carcinoma. Although the course of PSC is variable, it frequently is progressive, leading to cirrhosis and requirement for OLT. METHODS The medical records of 127 consecutive patients undergoing OLT for PSC from July 1, 1984, to May 30, 1996, were reviewed. Actuarial patient and graft survival was determined at 1,2, and 5 years. The incidence and outcome of patients with CCA, recurrent sclerosing cholangitis, and post-transplant colon carcinoma was determined. Results were analyzed by way of stepwise Cox regression to determine the statistical strength of independent associations between pretransplant covariates and patient survival. The median follow-up period was 3.01 years. Incidental cholangiocarcinoma (ICCA) was defined as a tumor < 1 cm in size that was discovered at the time of pathologic sectioning of the explanted liver. RESULTS Ninety-two patients (72%) had associated IBD. Seventy-nine (62%) had undergone previous biliary tract surgery. One hundred seven patients (84%) received a single graft, whereas 20 patients (16%) required 22 retransplants. Patients received either cyclosporine- (n = 76) or tacrolimus- (n = 51) based immunosuppression. The 1-, 2-, and 5-year actuarial patient survivals were 90%, 86%, and 85%, respectively, whereas graft survival was 82%, 77%, and 72%, respectively. The presence of previous biliary surgery had no effect on patient survival. Ten patients (8%) had ICCA and their survival was not significantly different from patients without ICCA (100%, 83%, and 83% at 1, 2, and 5 years, respectively). Four patients were known to have CCA at the time of OLT, all recurred within 6 months, and had a significantly worse outcome (p < 0.0001). Recurrent sclerosing cholangitis developed in 11 patients (8.6%). The patient and graft survival in this group was not different from those in whom recurrence did not develop (patient; 100%, 90%, and 90%; graft: 80%, 70%, and 52%). Thirty patients (23%) underwent colectomy after liver transplantation for dysplasia-carcinoma or symptomatic colitis. Of the nine covariates entered into the Cox multivariate regression analysis, only common bile duct frozen section biopsy specimen showing CCA was predictive of a survival disadvantage. CONCLUSIONS Liver transplantation provides excellent patient and graft survival rates for patients affected with PSC independent of pretransplant biliary tract surgery. Incidental cholangiocarcinoma does not affect patient survival significantly. However, known CCA or common duct frozen section biopsy specimen or both showing CCA are associated with poor recipient survival, and OLT should be proscribed in these cases. Recurrent PSC occurs in approximately 9% of cases but does not affect patient survival. Post-transplant colectomy does not affect patient survival adversely.

Troglitazone-induced fulminant hepatic failure

Troglitazone (Rezulin, Parke-Davis, Morris Plains, New Jersey), the first marketed member of a new class of oral agents for type II diabetes mellitus, the thiazolidinediones, has a number of attractive attributes. It reduces insulin resistance and increases insulin-stimulated glucose disposal, resulting in improved glycemic control and decreased insulin requirements in treated patients (1, 2). In addition, it is dosed once a day, is readily absorbed from the gastrointestinal tract, does not induce hypoglycemia, and does not appear to interact with other medications. Because of these attributes, troglitazone has enjoyed widespread use since its introduction in March 1997. In premarketing clinical trials of troglitazone, mild hepatotoxicity identified as reversible elevations of alanine aminotransferase (ALT) greater than three times normal were seen in less than 2% of treated patients (3). However, since the drug was released, several cases of more severe, even fatal, episodes of hepatitis have been reported (4–7). Here we report three cases of apparent troglitazone-induced fulminant liver failure prospectively identified through the Acute Liver Failure Study Group (ALFSG), a consortium of 14 academic medical centers with the purpose of collecting data regarding the etiology, treatment, and outcome of patients with acute liver failure. The cases highlight the potential hepatotoxicity of troglitazone and reinforce the need for close monitoring of all patients taking the drug.The three reported cases demonstrate that troglitazone is an idiosyncratic hepatotoxin that can lead to irreversible liver injury. Thus, troglitazone should be prescribed with caution and should not be used as a first-line agent in the treatment of type II DM when potentially less toxic alternatives are available. It remains to be seen whether the hepatotoxicity associated with troglitazone is a drug-class effect or specific to troglitazone. Other thiazolidinediones currently in clinical trials may be able to provide the therapeutic benefits of troglitazone without significant hepatotoxicity. If troglitazone is used, frequent monitoring of serum aminotransferases and symptoms is mandatory. However, as illustrated by these and other cases reported to date, the onset of troglitazone-induced liver injury is insidious and temporally variable. Thus, the value of close monitoring and when, if ever, it is safe to stop such monitoring are currently unclear.

Successful liver transplantation following medical management of portopulmonary hypertension: a single-center series.

Severe portopulmonary hypertension (POPH) is an absolute contraindication to orthotopic liver transplantation (OLT). Vasodilators have been used, but the safety of subsequent transplantation and the reversibility of pulmonary hypertension after transplantation are uncertain. This study examined the feasibility and post‐transplant effects of liver transplantation following medical control of POPH. Eight consecutive patients (three females and five males, ages 39–51) with POPH as their only contraindication to transplantation were treated with continuous intravenous epoprostenol. Liver transplantation was considered if the mean pulmonary artery pressure (PAM) was lowered to <35 mmHg. Epoprostenol 2–8 ng/kg/min successfully improved hemodynamics in seven of eight patients, usually within 6.5 months of initiating therapy. PAM declined from an average of 43–33 mmHg (p = 0.03); mean pulmonary vascular resistance declined from 410 to 192 dyn s cm−5 (p = 0.01) and cardiac output increased from 6.6 to 10 L/min (p = 0.02). Six of the seven responders were actively listed for liver transplantation. Two died on the waiting list; the remaining four were transplanted and remain alive and well 9–18 months post‐OLT—two without vasodilators, and two on oral medication. We conclude that pulmonary vasodilators permit safe liver transplantation in some cases, and that POPH may be reversible after transplantation.

In situ splitting of the cadaveric liver for two adult recipients

BACKGROUND Split-liver transplantation offers a unique opportunity to expand the existing donor pool. However, it has previously been stated that due to inadequate liver volume the advantages of split-liver transplantation would be lost when attempting to split the liver for two adult recipients. In this study, we sought to determine the safety, efficacy, and applicability of split-liver transplantation in select adult liver transplant recipients. METHODS Liver allografts for eight adult recipients were procured by in situ splitting of four adult cadaveric livers. The donor ages were 17, 19, 22, and 25 years and weights were 72, 77, 78, and 87 kg, respectively. In situ splitting resulted in three right trisegmental grafts, one right lobe graft, one left lobe graft, and three left lateral segmental grafts. The median recipient age was 49 years (range 38-61 years), whereas the median recipient weight was 84 kg (range 78-98 kg) for the right-sided grafts and 52 kg (range 51-53 kg) for recipients of the left-sided grafts. The median graft-to-recipient body weight ratio for right trisegmental, right lobe, left lobe, and left lateral segmental grafts was 1.31%, 1.26%, 1.35%, and 0.70%, respectively. RESULTS Overall patient and graft survival in this series is 100%. All prothrombin times were normalized within 4 days of transplantation. No evidence of ascites or prolonged hyperbilirubinemia was encountered in any right- or left-sided graft recipient. The incidence of hepatic artery, portal vein, and hepatic vein thrombosis is 0%, 0%, and 0%, respectively. Hepatic arterial anastomotic bleeding and a cut surface bile leak each occurred in one patient. Median United Network for Organ Sharing (UNOS) waiting time was 242 days (range 4-454 days) for the patients to which the donor liver was allocated. In contrast, the median waiting time for the four patients receiving the extra split-liver graft was reduced significantly to 37 days (range 21-101 days) (P<0.02). CONCLUSIONS This study demonstrates that split-liver transplantation can expand the cadaveric donor liver pool available for select adult liver transplant recipients. When both the donor organ and the transplant recipient are chosen carefully, split-liver transplantation can be safely performed without a delay in allograft function, increase in technical complications, or compromise in graft or patient survival.

Long-term follow-up of portopulmonary hypertension patients after liver transplantation

Portopulmonary hypertension (POPH) occurs in 5.3% to 8.5% of patients with advanced liver disease. The rate of survival in the absence of orthotopic liver transplantation (OLT) is reportedly 38% at 3 years and 28% at 5 years. Moderate to severe POPH [mean pulmonary artery pressure (MPAP) ≥ 35 mm Hg] is associated with a perioperative mortality rate of 50%. Single‐center series have demonstrated the feasibility and short‐term efficacy of OLT after POPH is controlled with vasodilators, but long‐term outcomes have not been reported. Our aim was to determine graft and patient survival rates and the effects of OLT on pulmonary hypertension (PHT) in patients undergoing transplantation for POPH at our center. Four hundred eighty‐eight adult patients underwent transplantation between June 2004 and January 2011, and 7 underwent transplantation for POPH after their MPAP was reduced to ≤35 mm Hg with vasodilators. These 7 patients included 3 men and 4 women with ages ranging from 39 to 54 years at the time of OLT. All patients received IV EPO or inhaled EPO during the perioperative period, and all were weaned off EPO over the course of 3 days to 8 months. Both the graft and patient survival rates were 85.7% after a median follow‐up of 7.8 years. One patient had recurrent hepatitis C virus cirrhosis and recurrent POPH and died from multiorgan failure unrelated to PHT. Four of the remaining 6 patients required oral vasodilator therapy for persistent PHT. Only 2 of the 7 patients (4.4 and 8.5 years after OLT) did not have PHT. In conclusion, patients with POPH responsive to vasodilator therapy may have excellent long‐term graft and patient survival after OLT. Despite the alleviation of portal hypertension by OLT, most patients have persistent or recurrent PHT that can be controlled with oral vasodilators. Liver Transpl 20:724‐727, 2014.

Liver transplantation for decompensated cirrhosis after jejunoileal bypass: a strategy for management.

BACKGROUND Although jejunoileal bypass results in end-stage liver disease in up to 100% of patients, little is known about outcome after liver transplantation. METHODS The clinical courses of six patients who underwent liver transplantation at UCLA for decompensated cirrhosis owing to a jejunoileal bypass were reviewed. Liver function, allograft pathology, renal function, and nutritional status were assessed. RESULTS Of the four patients with an intact jejunoileal bypass, two of the three who were biopsied had recurrent steatotic liver disease. The two patients whose jejunoileal bypass was reversed at the time of liver transplantation had lower alkaline phosphatase, lower creatinine, higher albumin, and higher cholesterol, and were more obese than their counterparts with intact bypasses. CONCLUSIONS Patients undergoing liver transplantation for jejunoileal bypass-associated liver disease should, if possible, have their bypass reversed at the time of transplantation; otherwise, they must be followed closely and be biopsied routinely. Recurrent liver disease should prompt reversal of the jejunoileal bypass.

ADULT LIVER TRANSPLANTATION FOR METABOLIC LIVER DISEASE

Liver replacement provides an effective method of replacing a failing liver, and corrects the underlying defect in many metabolic conditions. Results of liver transplantation for metabolic diseases have been encouraging, with the exception of hereditary hemochromatosis, in which infectious and for which cardiac complications appear to increase posttransplant mortality. An improved understanding of the underlying genetic and molecular defect will lead to advances in medical therapy and perhaps will decrease the need for liver replacement. The prospects of gene therapy are being pursued for many metabolic disorders, however until this research leads to direct clinical application, liver transplantation remains the only effective option for many patients with metabolic liver disease.