Evolution of anterior segment reconstruction after live donor adult liver transplantation: a single-center experience.

Controversy exists regarding the best method for venous outflow reconstruction after live donor liver transplantation using right lobe grafts. Some authors advocate routine inclusion of the middle hepatic vein with the graft, whereas others favor a more selective approach. In this report, we examine the evolution of our decision making and technique of selective anterior venous segment reconstruction during live donor adult liver transplantation performed in 226 recipients. We have developed a simplified back-bench procedure using sequential-composite anastomosis using various vascular conduits with syndactylization to the right hepatic vein creating a single large-outflow anastomosis in the recipient. Conduits used include iliac artery or vein allograft, recanalized umbilical vein, cryopreserved iliac artery allograft, and 6-mm synthetic expanded polytetrafluoroethylene vascular graft. This technique can be performed quickly, safely, and under cold storage conditions and results in excellent outcome while minimizing donor risk.

Improved survival after live donor adult liver transplantation (LDALT) using right lobe grafts: program experience and lessons learned.

We present our program experience with 85 live donor adult liver transplantation (LDALT) procedures using right lobe grafts with five simultaneous live donor kidney transplants using different donors performed over a 6-year period. After an "early" 2-year experience of 25 LDALT procedures, program improvements in donor and recipient selection, preoperative imaging, donor and recipient surgical technique and immunosuppressive management significantly reduced operative mortality (16% vs. 3.3%, p = 0.038) and improved patient and graft 1-year survival in recipients during our "later" experience with the next 60 cases (January 2001 and March 2005; patient survival: early 70.8% vs. later 92.7%, p = 0.028; graft survival: Early 64% vs. later 91.1%, p = 0.019, respectively). Overall patient and graft survival were 82% and 80%. There was a trend for less postoperative complications (major and minor) with program experience (early 88% vs. later 66.7%; p = 0.054) but overall morbidity remained at 73.8%. Biliary complications (cholangitis, disruption, leak or stricture) were not influenced by program experience (early 32% vs. later 38%). Liver volume adjusted to 100% of standard liver volume (SLV) within 1 month post-transplant. Despite a high rate of morbidity after LDALT, excellent patient and graft survival can be achieved with program experience.

Histological recurrence and progression of hepatitis C after orthotopic liver transplantation: influence of immunosuppressive regimens.

Post-orthotopic liver transplantation (OLT) recurrence of hepatitis C is virtually universal, but histological progression of disease is not. This study examines long-term clinical and liver histological features at and after OLT to elucidate factors predictive of hepatitis C recurrence and progression after OLT. A blinded retrospective review of clinical, serological, and histopathologic features of 65 patients who underwent OLT for hepatitis C and Non A Non B hepatitis was conducted. Histological findings of recurrent hepatitis C and progression (fibrosis, >or= grade 2 by last follow-up) were correlated with clinical parameters. Histological recurrence of hepatitis C was seen in 43 of 65 patients, with progression in 19 patients. Histological findings in the native liver and post-OLT biopsy specimen at the time of recurrence showed no correlation with hepatitis C recurrence and progression. Patients treated with azathioprine (AZA)-containing immunosuppressive regimens experienced less recurrence (6 of 17 v 37 of 48 patients; P < .005) and progression (1 of 17 v 18 of 48 patients; P = .014) than those without AZA as part of their immunosuppressive regimen. No difference was seen between patients treated with cyclosporine versus those administered FK506 (P > .05). Histological recurrence of hepatitis C after OLT is seen in 66% of patients with progressive disease and 29% of all patients. The grade of inflammation in the native liver at the time of OLT and time of recurrence is not predictive of progression. AZA-containing regimens reduce histological recurrence and progression of hepatitis C in post-OLT patients.

Adult-to-adult live donor liver transplantation: a short-term clinicopathologic study.

With the success of pediatric live donor liver transplantation (LDLT) and the continued shortage of cadaveric donors, adult-to-adult LDLT has been performed at some centers, including ours. We performed a detailed histologic review of all liver specimens obtained from 9 adult recipients at and after LDLT and correlated these findings with the patients' course and outcome. Five patients had histologic evidence of biliary tract pathology; 3 of 5 required surgical or radiologic intervention. The other 2 had clinically insignificant biliary disease. Diffuse hepatocytic hemorrhagic necrosis secondary to massive portal blood flow after portal venous revascularization resulted in graft failure and retransplantation in a single patient with severe preoperative portal hypertension. Two perioperative deaths were caused by sepsis and multiorgan failure (day 25) and generalized thrombosis related to factor V Leiden (day 6). The preoperative diagnosis, presence of portal vein thrombosis in the native liver, postoperative cholangiopathy, and subcapsular hemorrhagic necrosis in donor liver wedge biopsies did not affect the short-term outcome. In conclusion, biliary tract pathology is common after adult-to-adult LDLT but does not negatively affect graft or patient survival. Infrequent but catastrophic vascular complications related to portal hemodynamics or thrombosis can result in graft loss and/or patient death.

Life-threatening hypophosphatemia after right hepatic lobectomy for live donor adult liver transplantation.

Life-threatening hypophosphatemia (phosphorus < 1.0 mg/dL) has been reported only once after liver resection for tumor and was associated with a significant increase in postoperative complications. Hypophosphatemia is associated with reversible cardiac dysfunction, hypoventilation, and impaired immunity. The purpose of this study was to determine the incidence of hypophosphatemia after elective right hepatic lobectomy for live donor adult liver transplantation (LDALT), investigate the associated complication rate and surgical outcome of live liver donors, and determine the efficacy of prospective treatment with phosphate repletion as part of total parenteral nutrition (TPN). Evaluation of 30 donors who provided 30 right-lobe grafts between December 1998 and January 2000 was performed. Of the initial 18 live liver donors (group 1), 10 donors were treated with TPN that contained slightly more (35 +/- 8 mmol/d) than the recommended daily allowance (RDA) of phosphorus (30 mmol/d) starting on postoperative day 1. The last 12 donors (group 2) were prospectively studied and administered similar TPN with 2 times the RDA for phosphorus (60 mmol/d). All donors in group 1 developed hypophosphatemia that was either life threatening (phosphorus < 1.0 mg/dL) in 70% or severely depleted (phosphorus, 1.5 to 1.1 mg/dL) in 30%. With more aggressive phosphate repletion (group 2), only 8% developed life-threatening (phosphorus < 1.0 mg/dL) hypophosphatemia and 30% developed severe (phosphorus, 1.1 to 1.5 mg/dL) hypophosphatemia. Results suggest that hypophosphatemia is a universal event after LDALT and may have contributed to the observed complications in this study. Repletion of phosphorus at twice the RDA abrogates the incidence of hypophosphatemia and may reduce donor morbidity. Institutions performing LDALT should carefully monitor live liver donors for hypophosphatemia and correct abnormal phosphate levels. Additional studies are needed to determine whether more aggressive parenteral repletion can prevent postoperative hypophosphatemia and thus improve outcomes.

Histologic recurrence-free outcome after orthotopic liver transplantation for chronic hepatitis B.

Recurrent hepatitis B (HB) following orthotopic liver transplantation (OLT) for chronic disease is common. However, an unpredictable minority of patients follow a recurrence-free course. Clinical, virologic, and pathologic data from patients surviving longer than 60 days (n=24) with pathologically confirmed nonrecurrence of HB following OLT for chronic HB were reviewed to identify factors associated with nonrecurrence of HB. Nine of 24 patients had no histologic and immunohistologic evidence of recurrent HB. In addition to pre-OLT hepatitis B e antigen (HBeAg) negativity, coexisting delta and anti-HB therapy/prophylaxis, other acquired viral infections and their therapy, and severe acute rejection due to noncompliance were considered the possible protective factors against HB recurrence in these 9 patients. Histologic and, particularly immunopathologic, evaluation of liver biopsies must be utilized in definitively diagnosing recurrence of HB.

Livers from patients with apolipoprotein A-I amyloidosis are not suitable as "domino" donors.

Orthotopic liver transplantation, by eliminating the major site of amyloidogenic protein synthesis, is currently the only definitive treatment of most hereditary amyloidoses. Because of the minimal parenchymal involvement, the explanted livers from familial amyloidotic polyneuropathy (FAP) patients have been transplanted into non-FAP patients in a "domino" fashion. The aim of this study was to evaluate the extent of amyloid deposits in explanted livers from two patients with apolipoprotein A-I amyloidosis, with the Arg26 mutation, to determine their suitability as domino donors. A detailed histologic review of the explanted livers from two patients was performed and assessed for the extent of amyloid deposition by routine and Congo red stains. Both patients had identical histopathologic features. The liver parenchymal involvement was strikingly severe. Large patches of amyloid separated hepatic cords, with accentuation around the central veins. All portal triads were consistently and markedly involved with amorphous eosinophilic deposits within the connective tissue compressing the bile ducts and vascular structures. Hilar vessels had patchy deposits. No involvement of hilar nerve branches was seen. The hepatic parenchyma is extensively involved in hereditary Apolipoprotein A-I amyloidosis, with the Arg26 mutation. These livers, removed at orthotopic liver transplantation, are not suitable for domino donation.

Live donor adult liver transplantation using right lobe grafts: donor evaluation and surgical outcome.

HYPOTHESIS: Live donor adult liver transplantation (LDALT) is a safe and efficacious treatment for patients with end-stage liver disease. DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit. PATIENTS: From December 10, 1998, through April 10, 2000, a single team performed 15 LDALT procedures with 2 simultaneous living donor kidney transplants. During this period, 66 potential donors were screened and evaluated. INTERVENTIONS: Potential donors were evaluated with 3-dimensional helical computed tomographic scan, including volume renderings for hepatic lobar volume, vascular anatomy, virtual resection planes, and morphologic features. Suitable donors undergo complete medical and psychiatric evaluation and preoperative arteriography. MAIN OUTCOME MEASURES: Donor demographics, evaluation data, operative data, hospital length of stay, and morbidity. RESULTS: A total of 38 men (58%) and 28 women (42%) were evaluated with 15 donors participating in LDALT. Two additional donors provided kidney grafts for simultaneous transplantation at the time of LDALT. Thirty-two donors (48%) were rejected for either donor or recipient reasons, and 10 patients (15%) elected not to participate after initial screening. Three-dimensional volume renderings by helical computed tomographic scan predicted right lobe liver volume within 92% of actual graft volume. Donor morbidity, including all complications, was 67% with no mortality. Residual liver regenerated to approximately 70% of initial volume within 1 week and 80% within 1 month after surgery. CONCLUSIONS: Donor evaluation is an important component of LDALT. Significant donor morbidity is encountered even with careful selection. To minimize donor morbidity, groups considering initiating living donor programs should have expertise in hepatic resection and vena cava preservation using the "piggyback" technique during liver transplantation.

Preliminary results of a liver allocation plan using a continuous medical severity score that de-emphasizes waiting time.

Liver allocation remains problematic because current policy prioritizes status 2B or 3 patients by waiting time rather than medical urgency. On February 21, 2000, we implemented a variance to the United Network for Organ Sharing liver allocation policy that redefined status 2A by much more rigid, definable criteria and prioritized status 2B patients by using a continuous medical urgency score based on the Child-Turcotte-Pugh score and other medical conditions. In this system, waiting time is used only to differentiate status 2B candidates with equal medical urgency scores. Comparing the 6-month period (period 1; n = 67) before implementation of this system to the 6-month period after implementation (period 2; n = 75), there was a significant reduction in the number of transplantations performed for patients listed as status 2A (46.3% to 14.7%; P =.002) and an increase in the number of patients listed as status 2B who received transplants (44.8% to 70.7%; P =.10). Most dramatically, there was a 37.1% reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62 deaths in period 2 (P =.005), with the most significant reduction for patients removed from this list at status 2B (52 v 18 patients; P =.04). There were 3 postoperative deaths in each period, with only 1 graft lost in period 2. Status 2B patients with the greatest degree of medical urgency received transplants without multiple peer reviews requesting elevation to 2A status. We conclude that a continuous medical urgency score system allocates donor livers much more fairly to those in medical need and reduces waiting list mortality without sacrificing efficacy.

Steatosis in donor and transplant liver biopsies.

The purpose of this study was to identify the significance and clinical correlation of steatosis in donor and posttransplantation liver biopsies. One hundred twenty-six liver biopsies with fatty change from 86 liver transplant patients were reviewed. Micro- and macro-steatosis were graded semiquantitatively and correlated with clinical and other pathologic parameters. Fifty-one donor biopsy specimens, from 50 patients, had combinations of micro- (predominantly) and macro-steatosis. One of 2 patients with high-grade micro- and macro-steatosis required a retransplantation on the third day. Three early deaths were not related to graft dysfunction. In 36 patients, steatosis developed after transplantation. In 13 of 36, steatosis was seen in the early postoperative period with a background of severe ischemic injury, 6 of whom died within 45 days posttransplantation. Other causes of steatosis developing after liver transplantation included hepatitis C (n = 12), alcoholic steatohepatitis (n = 3), diabetes mellitus or obesity (n = 7) and poor nutrition (n = 2). The presence of steatosis in 1 patient's donor and all posttransplantation biopsy specimens remained unexplained. In conclusion, (1) microsteatosis in donor liver biopsy specimens has no effect on graft function; (2) ischemic injury with development of steatosis in the early posttransplantation period may be associated with poor clinical outcome; and (3) steatosis in the posttransplantation period is uncommon and usually related to recurrent or acquired hepatitis C.

Liver transplantation for autoimmune hepatitis: a long-term pathologic study.

Autoimmune hepatitis (AIH) after liver transplantation (LT) may recur and is difficult to diagnose. Our aims were to define the histopathology of and factors related to AIH recurrence. Fourteen of 475 patients received LT for AIH; 2 died perioperatively. Liver specimens (native and post-LT biopsies) from 12 other patients were reviewed and correlated with pre- and post-LT clinical course and outcome. Recurrent AIH was seen in 5 of 12 patients, 35 to 280 days post-LT as lobular hepatitis with acidophil bodies and lymphoplasmacytic infiltrate. Portal/interface hepatitis was seen with disease progression and 2 of 5 patients developed cirrhosis. Of 7 nonrecurrent patients, 1 had acquired hepatitis C with lobular/portal hepatitis and none developed cirrhosis. Histology suggestive of overlap syndrome was seen in 3 of 12 native livers with no effect on post-LT course or pathology. High-grade necroinflammation was present in native livers at LT in 5 of 5 cases with recurrent AIH and in 1 of 7 without recurrence (P <.01). Pre-LT disease duration, donor/recipient gender distribution, HLA studies, and rejection episodes did not correlate with AIH recurrence. We conclude that (1) recurrent AIH is not uncommon and was seen in 42% of patients with lymphoplasmacytic lobular, portal, and interface hepatitis; (2) acidophil bodies with lymphoplasmacytic cells are seen in early recurrent AIH; (3) recurrent AIH appears at variable time periods post-LT, and the progression is slow; and (4) high-grade inflammation in native liver at LT is a strong predictor of recurrent AIH.

Orthotopic liver transplantation for familial amyloidotic polyneuropathy: a pathological study.

Familial amyloidotic polyneuropathy (FAP), a hereditary form of systemic amyloidosis with clinically significant neuropathy and cardiomyopathy, is caused by a genetic defect of the transthyretin gene, which is mostly synthesized in the liver. Orthotopic liver transplantation (OLT) is thought to eliminate the amyloidogenic protein and currently is the only definitive treatment for this disorder. The aim of this study was to define the distribution and extent of amyloid deposition in tissues from these patients and evaluate the suitability of the resected FAP livers for transplantation into non-FAP patients. Surgical specimens from 14 patients removed at the time of OLT and autopsy tissues from 3 of the 14 were examined histologically using hematoxylin and eosin and Congo red-stained sections. The extent of amyloid deposits was evaluated, semiquantitatively graded from negative to marked, and correlated with clinical course and patient outcome. Amyloid deposits were consistently seen in hilar and vagus nerves. Liver lobular involvement was minimal in 1 and absent in the other 13 cases, with portal arterial amyloid deposits seen in 7 cases. At autopsy, extensive amyloid deposition in the heart was seen in all 3 cases with involvement of the conduction system. The extent of amyloid deposition at OLT did not correlate with the duration of symptoms before OLT or patient outcome after OLT. In conclusion, liver parenchymal involvement in FAP is minimal, and these explants are suitable for grafting in non-FAP patients. The recipients of such grafts must be carefully observed for the development of any amyloid-related disease, particularly cardiomyopathy. Of the tissues removed at OLT, the histopathologic confirmation of FAP is most consistently made by the examination of hilar and vagus nerves.

Recurrent hepatitis B, hepatitis C, and combined hepatitis B and C in liver allografts: a comparative pathological study.

Although recurrence of viral hepatitis in liver transplants is common, data comparing recurrent hepatitis B (HB), hepatitis C (HC), and co-existing dual hepatitis B and C (HB&C) are sparse. Posttransplantation liver biopsies, along with molecular, serological, immunohistochemical, and clinical data from 27 patients with pretransplantation diagnosis of chronic viral hepatitis, were reviewed. The patients were placed into 4 groups: Group I, with pretransplantation HB (n = 8); group II, with pretransplantation HC (n = 10); group III with pretransplantation HC and anti-HB surface or core antibody (n = 4); and group IV, with pretransplantation HB&C (n = 5). The histopathologic findings and patient outcome were compared in the 4 groups. A high rate of recurrence of viral hepatitis was seen for all 4 groups: Group I = 100%, group II = 90%, Group III = 100%, and group IV = 80%, with the mean (median) recurrence time of 308 (224), 82 (52), 61 (64), and 125 (70) days, respectively. The number of deaths (their median survival times) were: group I = 4 (374 days), group II = 4 (794 days), group III = 1 (1,143 days), and group IV = 5 (448 days). The earliest histological findings of lobular injury was the presence of acidophil bodies and Kupffer cell hyperplasia, the latter being more prominent in recurrent HC cases. Recurrent HB presented in 2 forms: early (before 150 days) with poor survival and with either severe necroinflammatory histology or with features of fibrosing cholestatic hepatitis, and delayed (after 150 days), with mild necro-inflammatory activity and prolonged survival. HC with or without anti-HB antibodies had early recurrence, but the course was slowly progressive. Patients with HB&C had recurrence of both viruses; however, the course was dictated by HB virus.

Cytological location and further characterization of the Third chromosome resistance gene in Drosophila melanogaster.

Mutations in the Third chromosome resistance (Tcr; 3-39.6) gene confer dominant resistance to alpha-methyl dopa and suggest the gene is involved in catecholamine metabolism. Evidence for involvement in catecholamine metabolism comes from the three phenotypes associated with the mutant Tcr chromosomes--dominant resistance, dominant rescue of partially complementing l(2)amd alleles, and recessive lethal phenotypes. Only dominant resistance to alpha s-methyl dopa, however, was mapped to the Tcr locus. Both recessive lethality and dominant rescue of l(2)amd alleles have now been mapped to the Tcr gene and, through the isolation of a new deletion in the region, we demonstrate these phenotypes are due to a loss of Tcr function. This deletion places the Tcr gene in the 69B4-5 to 69C8-11 region. Additionally, we have tested and verified three predictions of the biochemical model proposed by Bishop, Sherald, and Wright (1989) for the function of the Tcr protein.

Interaction of tallow and hay particle size on ruminal parameters.

Four nonlactating ruminally cannulated Holstein cows were used in a 4 x 4 Latin square experiment with 4 21-d periods to determine if the effects of dietary fat would be affected by hay particle length. Treatments consisted of two levels of tallow (0 and 5%) and two hay particle lengths (short-cut and long-cut) in a 2 x 2 factorial. Diets contained alfalfa hay, corn silage, and concentrate [1:1:2, dry matter (DM) basis] fed as a total mixed ration (TMR) once per day. Samples of the 0 and 5% tallow TMR were ground and incubated in situ in polyester bags for 24 and 48 h. Ruminal samples were taken on day 21 at 0800 h and at 2-h intervals until 1600 h. The total tract digestibilities of acid detergent fiber (ADF) and neutral detergent fiber (NDF) were not affected by tallow or by hay by tallow interactions. There was a trend for tallow to improve total tract digestibility of crude protein (CP) (70.2 vs. 74.7%). After 48 h of ruminal incubation, tallow significantly decreased the digestibilities of DM, ADF, and NDF. No hay length by tallow interactions for DM, NDF, ADF or CP digestibilities occurred after 24 or 48 h. Tallow increased concentrations of propionate and decreased concentrations of acetate and valerate and the acetate-to-propionate ratio. Total volatile fatty acids increased when tallow was added to diets with short-cut hay, which suggests that when unprotected fat is added to diets with a high level of hay, a short-cut hay length may be advantageous. This result may be due to shorter rumen retention time of feed particles, which reduces the time for fatty acids to exert antimicrobial effects. Or, it may because the increased surface area of the hay particle provides more area for microbial attachment and increased fermentation.

Sarcoidosis with selective involvement of a second liver allograft: report of a case and review of the literature.

A case of sarcoidosis recurrent in a patient's second liver allograft is described. There was no granulomatous disease seen in the patient's first liver allograft. After the second orthotopic liver transplantation (OLT), the patient was successfully treated for acute rejection, aspergillus infection, and cytomegalovirus viremia. Approximately 2 months after the second OLT, the patient was treated with long-term interferon-alpha for recurrent hepatitis C. Five years after the operation, he experienced liver failure secondary to recurrent hepatitis and underwent a third OLT. This is only the second reported case of sarcoidosis recurrent in the liver parenchyma of a transplanted organ and the first in which interferon-alpha might have played a role.

Cavernous hemangioma of the liver: anatomic resection vs. enucleation.

HYPOTHESIS: Patient outcome and the development of major intra-abdominal postoperative complications following removal of cavernous hemangiomas of the liver are affected by methods of resection. DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit in a tertiary care referral medical center. PATIENTS: Between December 1, 1987, and December 1, 1997, 28 patients underwent the surgical removal of cavernous hemangioma either by hepatic resection or enucleation. Indications for the operation were pain, enlarging tumors, uncertain diagnosis, or rupture. MAIN OUTCOME MEASURES: The technique of tumor removal, hospital course, and the development of intra-abdominal complications. Independent factors influencing the development of complications were ascertained by multivariate analysis. RESULTS: Twenty-four female and 4 male patients (age, 47.5+/-12.4 [mean +/- SD] years) underwent either enucleation (n = 23) or liver resection (n = 5). Lesions ranged from 2 to 16 cm in their postresection diameter. No surgical (30-day) mortality was observed. Four major intra-abdominal complications were found: 1 episode of intraoperative bleeding requiring abdominal packing and 3 intra-abdominal fluid collections requiring percutaneous drainage. Enucleation was the only independent factor found by univariate and multivariate analyses to be associated with a reduction in the number of intra-abdominal complications (P = .04). CONCLUSIONS: Cavernous hemangiomas of the liver can be removed safely by either hepatic resection or enucleation. Enucleation is associated with fewer intra-abdominal complications and should be the technique of choice when tumor location and technical factors favor enucleation.

Distal splenorenal shunt: role, indications, and utility in the era of liver transplantation.

HYPOTHESIS: The distal splenorenal shunt (DSRS) continues to play an important role in the management of recurrent variceal bleeding with minimal negative impact on subsequent orthotopic liver transplantation (OLT). DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit in a tertiary referral medical center. PATIENTS: From August 1, 1985, through October 31, 1997, a single team of surgeons performed 81 DSRS procedures for recurrent variceal hemorrhage. Eleven patients undergoing OLT subsequent to DSRS were compared with a group of 274 patients undergoing OLT without any previous shunt during the same period. MAIN OUTCOME MEASURES: Operative time, use of blood products, length of hospital stay, perioperative complications, and survival rates. RESULTS: Operative (30-day) mortality for DSRS was 6% (n = 5). From follow-up information available for 74 patients, the 1- and 5-year survival rates were 86.4% (n = 64) and 74.3% (n = 55), respectively. Recurrent variceal bleeding and hepatic encephalopathy occurred in 5 (6.8%) and 11 patients (14.9%), respectively, after DSRS. In 9 patients, DSRS was used as salvage for failed transjugular intrahepatic portosystemic shunt. CONCLUSIONS: Distal splenorenal shunt is a safe, durable, and effective treatment for controlling recurrent variceal hemorrhage in patients with acceptable operative risk and good liver function. It does not compromise future liver transplantation and can considerably delay the time until transplantation is required. Given the early occlusion rate and need for constant surveillance, transjugular intrahepatic portosystemic shunting should be reserved for patients with Child C classification cirrhosis with chronic hemorrhage or intractable ascites or as an emergency procedure for patients with uncontrollable bleeding using endoscopic therapy.

Fibrosis/cirrhosis after orthotopic liver transplantation.

The causes and pathologic changes leading to fibrosis and cirrhosis after orthotopic liver transplantation (OLT) are not fully defined. The computerized pathology files were searched for cases of fibrosis/cirrhosis after OLT. Of 493 grafts from 435 patients, 35 grafts from 32 patients of posttransplantation liver fibrosis/cirrhosis were identified and retrieved (7%). Detailed histopathologic examinations of all post-OLT liver biopsy specimens were performed in conjunction with clinical, virologic, serologic, and molecular diagnostics information. Two cases with subcapsular septa and fibrous tissue close to hilum were excluded as false positives. Fibrosis/cirrhosis was confirmed in the remaining 33 grafts. In 20, the underlying cause was recurrent viral hepatitis, including eight with hepatitis C, 10 with hepatitis B, and two with combined hepatitis C and B. Another two with pretransplantation chronic hepatitis B developed cirrhosis without detectable virologic markers after OLT; these were biliary type secondary to obstruction in one, and chronic changes due to severe graft ischemia in one. Three patients acquired hepatitis C after OLT, with molecular confirmation available in two. In five patients, the underlying causes were Budd-Chiari syndrome and autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent primary biliary cirrhosis, alcohol-induced liver disease, and recurrent bile duct carcinoma. Three cases had centrilobular fibrosis but without bridging septa or cirrhosis as a result of chronic rejection. It was concluded that (1) Cirrhosis after OLT is uncommon (7%). (2) Chronic rejection does not lead to cirrhosis, but it may result in centrilobular fibrosis. (3) In most (70%) cases, cirrhosis after OLT is attributed to recurrent or acquired viral hepatitis.

A simple screening test for variant transthyretins associated with familial transthyretin amyloidosis using isoelectric focusing.

Variant forms of the plasma protein transthyretin (TTR) are associated with the most frequently occurring type of familial systemic amyloidosis. Organ system involvement in transthyretin type amyloidosis (ATTR) is often similar to that which occurs in light chain amyloid disease (AL). The proper diagnosis of ATTR is important since treatment (liver transplantation) differs from that in AL (chemotherapy). We present a two-step test to screen sera for variant TTRs using non-denaturing gel electrophoresis performed in 7.5% acrylamide (PAGE) followed by isoelectric focusing (IEF) between pH 4.0 and 7.0 in 2.5 M urea. Serum samples from 110 patients with amyloidosis and their relatives were tested using this IEF technique and compared to genetic mutation results. Sera from patients with ATTR who underwent liver transplantation were also examined prior to and following surgery. IEF analysis showed the presence of both wild-type and variant TTR in 74 of the 110 serum samples tested. Genomic DNA from peripheral blood was used to identify TTR gene mutations in 77 of the 110 patients. Fifteen variants including Val122Ile, preponderant in the African-American population, could be demonstrated by IEF. The sensitivity of IEF was 96% (74/77) and the specificity was 100% (33/33). The predictive values for a positive or negative result were 100% (74/74) and 92% (33/36), respectively. There were no false-positive results and 4% (3/77) false-negative results. In sera from patients with ATTR who underwent liver transplantation, variant TTR was detected by IEF before, but not after, surgery. A simple, accurate, sensitive method is presented as a useful screening test for variant transthyretins associated with ATTR.