Sociodemographic differences in early access to liver transplantation services.

The question of whether health care inequities occur before patients with end-stage liver disease (ESLD) are waitlisted for transplantation has not previously been assessed. To determine the impact of gender, race and insurance on access to transplantation, we linked Pennsylvania sources of data regarding adult patients discharged from nongovernmental hospitals from 1994 to 2001. We followed the patients through 2003 and linked information to records from five centers responsible for 95% of liver transplants in Pennsylvania during this period. Using multinomial logistic regressions, we estimated probabilities that patients would undergo transplant evaluation, transplant waitlisting and transplantation itself. Of the 144,507 patients in the study, 4361 (3.0%) underwent transplant evaluation. Of those evaluated, 3071 (70.4%) were waitlisted. Of those waitlisted, 1537 (50.0%) received a transplant. Overall, 57,020 (39.5%) died during the study period. Patients were less likely to undergo evaluation, waitlisting and transplantation if they were women, black and lacked commercial insurance (p < 0.001 each). Differences were more pronounced for early stages (evaluation and listing) than for the transplantation stage (in which national oversight and review occur). For early management and treatment decisions of patients with ESLD to be better understood, more comprehensive data concerning referral and listing practices are needed.

Tacrolimus conversion improves hyperlipidemic states in stable liver transplant recipients.

With improvements in surgical technique and the advent of new and more effective immunosuppressive agents, survival rates in liver transplant recipients have dramatically improved. However, hyperlipidemia frequently develops in patients administered cyclosporine-based immunosuppression long-term, although it appears to occur less often with newer, tacrolimus-based regimens. We sought to determine whether an isolated change in the baseline immunosuppressive regimen (cyclosporine to tacrolimus) would improve hyperlipidemic states in these patients. Twenty-one long-term stable liver transplant recipients with hyperlipidemia, manifested by elevated cholesterol and/or triglyceride levels, were offered conversion to tacrolimus from cyclosporine A therapy. Lipid profiles were monitored at baseline (while on cyclosporine therapy) and at 1 and 3 months after conversion to tacrolimus therapy. There were no other medication manipulations. After conversion to tacrolimus therapy, mean cholesterol levels decreased from 251 to 202 mg/dL at 1 month (P <.001) and 194 mg/dL at 3 months (P <.001). Similarly, triglyceride levels decreased from 300 to 207 mg/dL by 1 month (P =.011) and 203 mg/dL by 3 months (P <.001). There was also a statistically significant decrease for very low-density lipoprotein levels at 3 months (P =.005) and low-density lipoprotein levels at 1 and 3 months (P =.013 and P =.014, respectively). High-density lipoprotein levels did not significantly change after conversion to tacrolimus therapy. Conversion was not accompanied by adverse side effects, and patients tolerated the change well. In conclusion, simple conversion from cyclosporine to tacrolimus-based immunosuppression therapy is safe and improves posttransplantation hyperlipidemia in a subgroup of liver transplant recipients.

Controlled non-heart-beating donor liver transplantation: a successful single center experience, with topic update.

BACKGROUND: The critical shortage of transplantable organs necessitates utilization of unconventional donors. We describe a successful experience of controlled non-heart-beating donor (NHBD) liver transplantation. METHODS: Controlled NHBDs had catastrophic head injury, prognosis for no meaningful recovery, decision to withdraw life support, and subsequent consent for donation. After stopping mechanical ventilation in the operating room, death determination by a nontransplant caregiver, and rapid aortic cannulation, liver and kidneys were recovered. RESULTS: Controlled NHBDs contributed 5% of hepatic allografts (8/164) from August 1996 through June 1999 (9% in 1998). Sixteen NHBDs afforded 8 livers and 24 kidneys. Liver donors (n=8) were 11-66 years old; half were >50 years old. Premortem alanine aminotransferase was 25-157 U/L. Arrest occurred 3-27 min after stopping ventilation. Perfusion started 3-5 min after incision, and <22 min after hypotension (mean arterial pressure: <50 mmHg). Patient and graft survivals are 100% at 18+/-12 months follow-up. There was no intraoperative complication, reperfusion syndrome, poor graft function, primary nonfunction, arterial thrombosis, biliary complication, or serious infection. Postoperative day 2 prothrombin time was 13+/-1 sec. Peak alanine aminotransferase was 980+/-601 U/L. Intensive care unit and posttransplant lengths of stay were 2+/-2 and 10+/-7 days, respectively. Soon after transplantation there was frequent temporary hyperbilirubinemia (five of eight recipients; bilirubin peak: 7-29 mg/dl, 2-3 weeks after transplantation) and rejection (4/8 recipients, <3 weeks after transplantation). CONCLUSIONS: NHBDs significantly and safely expanded our donor pool. NHBD surgeons must be capable of rapid procurement. Cautious liberalization of criteria for accepting livers from NHBDs with confounding risk factors is justified. Refined ethics guidelines would broaden approval of NHBDs.

Idiopathic adulthood ductopenia: case report and review of the literature.

The clinical and pathological findings of idiopathic ductopenia were studied in a 30-year-old woman who initially manifested jaundice and pruritus. Serum biochemical tests of liver function indicated severe and progressive cholestasis. Viral hepatitis markers and circulating autoantibodies were absent. The patient had a normal cholangiogram and lacked evidence of inflammatory bowel disease. Histological examination of a liver specimen showed severe cholestasis and absence of interlobular bile ducts. Severe jaundice and intractable pruritus developed in the patient and served as the indications for liver transplantation 4 months after initial examination. Transplantation resulted in prompt and complete resolution of the jaundice and pruritus. Two types of idiopathic adulthood ductopenia associated with different prognoses are recognized. Patients with type 1 idiopathic adulthood ductopenia are asymptomatic or manifest symptoms of cholestatic liver disease. They tend to have less destruction of the intrahepatic bile ducts on liver biopsy specimens. Their clinical course ranges from spontaneous improvement to progression to biliary cirrhosis. In contrast, patients with type 2 idiopathic adulthood ductopenia generally manifest initial symptoms of decompensated biliary cirrhosis, have extensive destruction of the intrahepatic bile ducts on liver biopsy, and frequently require orthotopic liver transplantation.

Clinical predictors of pulmonary hypertension in patients undergoing liver transplant evaluation.

Clinical prediction of portopulmonary hypertension (PPHTN) is critical in the preoperative evaluation of candidates for orthotopic liver transplantation (OLT) because of its association with significant morbidity and mortality. To determine the clinical, laboratory, and echocardiographic predictors of PPHTN, we retrospectively evaluated 55 candidates before OLT. From those, 8 candidates had pulmonary hypertension ([HTN] group A) and 47 candidates did not (group B). Pulmonary HTN was defined as a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater and either elevated pulmonary vascular resistance or normal pulmonary artery wedge pressure. The significant predictors of PPHTN were (1) systemic arterial HTN (63% in group A v 9% in group B; P <.001), (2) loud pulmonary component of the second heart sound (38% v 2%; P =. 001), (3) right ventricular (RV) heave (38% v 4%; P =.002), (4) RV dilatation by echocardiogram (63% v 0%; P <.001), (5) RV hypertrophy by echocardiogram (38% v 0%; P =.001), and (6) echocardiogram-estimated systolic PAP (SPAP) greater than 40 mm Hg (63% v 2%; P <.001). The sensitivity of these variables for the detection of pulmonary HTN ranges from 37% to 63%, and their specificity from 91% to 100%. We conclude that several clinical and echocardiographic features are significantly associated with pulmonary HTN in patients with cirrhosis. In particular, echocardiogram-estimated SPAP greater than 40 mm Hg is strongly associated with pulmonary HTN and is specific. These predictors, however, are not sensitive enough to identify all the patients with PPHTN. Therefore, the evaluation of a combination of these variables may be useful for the preoperative identification of pulmonary HTN in liver transplant candidates.

Long-term care of the liver transplant recipient.

Many liver transplant recipients are now reaching survival beyond 5 years from the liver transplant procedure, and many others are alive more than a decade from acquiring their new liver. Orthotopic liver transplant recipients enjoy the benefits of normal liver function, but a variety of metabolic and other medical problems often develop that require diagnosis and adequate management. These problems include hyperlipidemia, obesity, diabetes mellitus, renal disfunction, arterial hypertension, bone disease and neuropsychiatric syndromes. The gastroenterologist, internist, or local family physician is frequently called on to identify and treat these postoperative complications in conjunction with physicians at the transplant center.

The significance of hepatitis G virus in serum of patients with sporadic fulminant and subfulminant hepatitis of unknown etiology.

Excluding acute hepatic failure caused by drugs, the etiology of fulminant hepatitis (FH) remains unknown in many patients. There are conflicting data about a possible pathogenic role for the hepatitis G virus (HGV) in patients with cryptogenic fulminant hepatitis (non-A-E FH). We investigated the presence of circulating HGV in 36 patients with well-documented non-A-E fulminant and 5 patients with subfulminant hepatitis from 3 geographic locations in the United States. Serum HGV RNA was determined by reverse transcriptase-polymerase chain reaction using primers from the NS5 region of the HGV genome. HGV RNA was also measured before and after liver transplantation in 5 patients and at different time points in 7 patients. Serum samples were recoded and reanalyzed for HGV RNA using different primer sets to assess the validity of the HGV RNA assay. HGV was present in serum of 14 of the 36 patients (38.8%) with non-A-E fulminant hepatitis. Twenty percent of patients from the Northeast, 11% of the patients from the Southeast, and 50% from the Mid-Atlantic regions of the United States had circulating HGV RNA. The use of therapeutic blood products was significantly associated with the presence of serum HGV RNA (P <.02). Retesting for HGV RNA with different primers was positive in all but 1 case. HGV RNA is not causally related to non-A-E fulminant hepatitis. The finding of HGV RNA in serum from these patients is likely related to the administration of blood product transfusion after the onset of fulminant hepatitis.

Common medical diseases after liver transplantation.

Liver transplantation is now routinely used as a definitive treatment for patients with advanced cirrhosis. As survival after transplantation in most centers is at or above 70% to 80% at 1 year, an increasing number of liver transplant recipients requires further medical care. Several medical complications may develop during the immediate or long-term postoperative periods, including renal dysfunction, arterial hypertension, neurological complications, and psychiatric complications. In addition, other metabolic complications often develop in a more insidious manner, such as obesity, hyperlipidemia, diabetes mellitus, and posttransplant bone disease. Because the liver allograft function is frequently normal in many recipients experiencing the above-mentioned complications, the gastroenterologist, internist, or family practitioner frequently has a role in the diagnosis and management of these complications. In this review, we discuss the basic pathophysiological concepts and suggest guidelines for the diagnosis and management of frequent medical problems encountered after liver transplantation.

Successful use of an enhanced immunosuppressive protocol with plasmapheresis for ABO-incompatible mismatched grafts in liver transplant recipients.

Graft and patient survival rates after transplantation of ABO-incompatible liver allografts have been poor. We used plasmapheresis and a potent immunosuppressive regimen to control hemagglutinin levels and prevent early rejection. Ten patients who had a United Network for Organ Sharing status of 4 received ABO-incompatible allografts. Quadruple immunosuppression consisted of OKT3, Cytoxan, cyclosporine, and steroid taper; prostaglandin E-1 was administrated intravenously the first week. All patients underwent perioperative plasmapheresis to maintain hemagglutinin levels < 1:16. Patient survival was 80%; graft survival was 60% at 140-505 days. The rejection rate was 90%. Three recipients (A1-->O) lost their grafts to severe rejection at 5, 12, and 30 days after transplantation. All 3 had pretransplantation hemagglutinin levels > or = 1:100. Elevated hemagglutinin levels preceded the diagnosis of severe acute cellular rejection; plasmapheresis failed to lower anti-A titers in these 3 patients. We conclude that in an urgent setting, lowering of preformed hemagglutinins via plasmapheresis in combination with quadruple induction immunosuppression allows liver transplantation across ABO barriers. In patients with high baseline levels of preformed hemagglutinins, the risk of subsequent graft loss may be increased and transplantation with an ABO-incompatible graft may serve as a lifesaving intermediate step.

Evidence that the systematic analysis of bile cytology permits monitoring of hepatic allograft rejection.

Cytologic analysis was performed on 128 bile specimens collected by schedule from 12 liver transplant recipients over a 4-month period. Clinical diagnoses at the time of specimen collection were determined retrospectively, as follows: clinically stable, 75; acute rejection, 15; CMV hepatitis, 1; systemic infection, 8; ischemic injury, 24 (all within the first 4 days postop); nonclassifiable, 5. Bile analysis was done by a blinded investigator. Specimens contained ductal epithelial cells (EC) and inflammatory cells (IC), which were counted using Cytospin slide preparations. Greater than 10 cells/slide were seen in 93.3% of rejections, 91.7% of ischemic injuries, 100% of systemic infections, and 14.6% of stable patients. In samples collected after POD 4, IC were seen in 86.7% of rejections, yielding a specificity of 94.4% (P less than 0.001). If lymphoblastic cells were also seen, the specificity increased to 96.6%. Five specimens were obtained the day before the clinical diagnosis of rejection; all demonstrated IC. Seven specimens were obtained 3 days after beginning therapy for rejection. In 5 the bile contained no IC, and clinical improvement occurred; in the 2 in whom IC were found, further therapy was subsequently required. IC were seen in 5 of 8 specimens taken when systemic infection was present; the clinical setting allowed differentiation from rejection. Only 1 case of CMV hepatitis was included, thus no conclusions can be drawn for this entity. Cytoplasmic vacuolization of EC was observed in 30% of cases, in these, cyclosporine levels were significantly higher (989.9 +/- 356.9 vs. 672.8 +/- 421.2, P = 0.02). In summary, bile cytology analysis aides in the monitoring of the onset and duration of rejection. It may be an indicator of persistent rejection, and it may help prevent overimmunosuppression in those cases with normal cytological findings.

Simultaneous laparotomy and endoscopy for control of bleeding gastric ulcerations after liver transplantation without enterotomy.

Treatment of gastric peptic ulcerations, which requires both medical and surgical coordination in its management, is a complex subject. Despite advances in the medical therapy of ulcers, medications have little impact on the course of bleeding peptic ulceration. Newer endoscopic techniques of injection with adrenaline or alcohol, heater probes, and vicaps electrodes have controlled bleeding in many patients. Still, a subset of patients remains who will require surgical interventions with gastrotomy and oversewing of the ulcer crater. We describe a new technique for management of the acute gastric ulcer bleeding that avoids gastrotomy and potential contamination in the post-transplant patient.

Danazol-induced hepatocellular adenomas. A case report and review of the literature.

We report a case of hepatocellular adenomas in a 39-year-old woman who had been taking danazol for uterine fibroids. To our knowledge, this is the first case in which multiple hepatocellular adenomas were discovered after only 6 months of danazol intake.

Dilated periportal lymphatics mimicking an anastomotic bile leak after liver transplantation.

Transhepatic cholangiography is commonly performed during postoperative evaluation of liver transplant patients. The authors describe a potential pitfall in the interpretation of these studies and illustrate that dilated interrupted lymphatics of the donor liver can mimic a periductal leak of contrast material.