Pediatric Liver Transplant Recipients Who Undergo Transfer to the Adult Healthcare Service Have Good Long-Term Outcomes.

Liver transplantation has transformed survival for children with liver disease necessitating the transfer of a growing number of patients to the adult healthcare service. The impact of transfer on outcomes remains unclear. The aim of this single-center study of 137 consecutive pediatric liver transplant recipients was to examine the effect of transfer on patient and graft survival. The median time from transplant to transfer was 10.4 years and the median age of the patients at transfer was 18.6 years. After transfer, there were 5 re-transplants and 12 deaths in 14 patients. The estimated posttransfer 10-year patient and graft survival was 89.9% and 86.2%, respectively. Overall, 4 patients demonstrated graft loss as a consequence of chronic rejection. Graft loss was associated with older age at first transplant (p = 0.008). When compared to young adult patients transplanted in the adult center, the transferred patients did not have inferior graft survival from the point of transfer (HR 0.28; 95% CI 0.10-0.77, p = 0.014). This suggests that transfer did not impact significantly on graft longevity. In conclusion, pediatric liver transplant recipients who undergo transfer to the adult service have good long-term outcomes.

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury.

Donation after cardiac death (DCD) liver transplantation is associated with an increased frequency of hepato-biliary complications. The implications for renal function have not been explored previously. The aims of this single-center study of 88 consecutive DCD liver transplant recipients were (1) to compare renal outcomes with propensity-risk-matched donation after brain death (DBD) patients and (2) in the DCD patients specifically to examine the risk factors for acute kidney injury (AKI; peak creatinine ≥2 times baseline) and chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m(2) ). During the immediate postoperative period DCD liver transplantation was associated with an increased incidence of AKI (DCD, 53.4%; DBD 31.8%, p = 0.004). In DCD patients AKI was a risk factor for CKD (p = 0.035) and mortality (p = 0.017). The cumulative incidence of CKD by 3 years post-transplant was 53.7% and 42.1% for DCD and DBD patients, respectively (p = 0.774). Importantly, increasing peak perioperative aspartate aminotransferase, a surrogate marker of hepatic ischemia reperfusion injury, was the only consistent predictor of renal dysfunction after DCD transplantation (AKI, p < 0.001; CKD, p = 0.032). In conclusion, DCD liver transplantation is associated with an increased frequency of AKI. The findings suggest that hepatic ischemia reperfusion injury may play a critical role in the pathogenesis of post-transplant renal dysfunction.

Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis.

Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status.

Donor HLA-C genotype has a profound impact on the clinical outcome following liver transplantation.

Late allograft dysfunction is a significant problem following liver transplantation and its pathogenesis is uncertain. HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors (KIRs) that regulate the cytotoxic activity of natural killer (NK) cells. HLA-C alleles can be allocated into two groups, termed HLA-C1 and HLA-C2, based on their KIR specificity. HLA-C2 interactions are more inhibiting to NK cell activation. We studied the clinical importance of HLA-C genotype in a large liver transplant cohort and found that possession of at least one HLA-C2 allele by the donor allograft was associated with less histological evidence of chronic rejection and graft cirrhosis, a 16.2% reduction in graft loss (p = 0.003) (hazard ratio: 2.7, 95% CI 1.4-5.3) and a 13.6% improvement in patient survival (p = 0.01) (hazard ratio: 1.9, 95% CI 1.1-3.3) at 10 years. Transplantation of an HLA-C2 homozygous allograft led to a particularly striking 26.5% reduction in graft loss (p < 0.001) (hazard ratio: 7.2, 95% CI 2.2-23.0) at 10 years when compared to HLA-C1 homozygous allografts. Donor HLA-C genotype is therefore a major determinant of clinical outcome after liver transplantation and reveals the importance of NK cells in chronic rejection and graft cirrhosis. Modulation of HLA-C and KIR interactions represents an important novel approach to promote long-term graft and patient survival.

Cholangiocarcinoma complicating primary sclerosing cholangitis: a 24-year experience.

AIM: To report the prevalence and outcome of cholangiocarcinoma arising in primary sclerosing cholangitis for a British tertiary referral centre. METHODS: All patients diagnosed with primary sclerosing cholangitis and concurrent cholangiocarcinoma were identified from a prospectively maintained departmental database, and the mode of presentation, management and outcome were determined. RESULTS: Of 370 patients with primary sclerosing cholangitis, 48 patients (13%) were diagnosed with a cholangiocarcinoma within a median time of 0.51 months (range: 0-73.12) from presentation to the unit. Mode of presentation included: inoperable tumours (n = 14); incidental findings in transplant hepatectomy specimens (n = 13); primary sclerosing cholangitis follow-up (n = 9); transplant work-up (n = 5); transplant waiting list (n = 5); suspected tumour confirmed at transplant (n = 1), and incidental finding at cholecystectomy (n = 1). The diagnosis was confirmed by: radiology-guided biopsy (n = 27); MRI (n = 3); CT (n = 2); laparoscopy or laparotomy (n = 2), and frozen section at transplant (n = 1). Management consisted of: transplantation (n = 14, including 1 abandoned); hepatic resection (n = 8), and palliation through stenting (n = 26). The overall median survival of the cohort was 4.9 months (range: 0.09-104.5). Median survival ranged from 2.6 months (range: 0.09-35.3) for palliation to 7.6 months (range: 0.6-99.6) for transplantation and 52.8 months (range: 3.7-104.5) for resection. There was no difference in survival between the transplant and resection groups (p = 0.14). CONCLUSIONS: Cholangiocarcinoma is a common finding in primary sclerosing cholangitis and regular screening of this cohort of patients at referring centres is advocated to detect early tumours, as surgical treatment at an early stage offers significantly better outcomes for this cohort of patients.

The impact of ileal pouch-anal anastomosis on graft survival following liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Liver transplantation is the only life-extending intervention for primary sclerosing cholangitis (PSC). Given the co-existence with colitis, patients may also require colectomy; a factor potentially conferring improved post-transplant outcomes. AIM: To determine the impact of restorative surgery via ileal pouch-anal anastomosis (IPAA) vs retaining an end ileostomy on liver-related outcomes post-transplantation. METHODS: Graft survival was evaluated across a prospectively accrued transplant database, stratified according to colectomy status and type. RESULTS: Between 1990 and 2016, 240 individuals with PSC/colitis underwent transplantation (cumulative 1870 patient-years until first graft loss or last follow-up date), of whom 75 also required colectomy. A heightened incidence of graft loss was observed for the IPAA group vs those retaining an end ileostomy (2.8 vs 0.4 per 100 patient-years, log-rank P = 0.005), whereas rates between IPAA vs no colectomy groups were not significantly different (2.8 vs 1.7, P = 0.1). In addition, the ileostomy group experienced significantly lower graft loss rates vs. patients retaining an intact colon (P = 0.044). The risks conferred by IPAA persisted when taking into account timing of colectomy as related to liver transplantation via time-dependent Cox regression analysis. Hepatic artery thrombosis and biliary strictures were the principal aetiologies of graft loss overall. Incidence rates for both were not significantly different between IPAA and no colectomy groups (P = 0.092 and P = 0.358); however, end ileostomy appeared protective (P = 0.007 and 0.031, respectively). CONCLUSION: In PSC, liver transplantation, colectomy + IPAA is associated with similar incidence rates of hepatic artery thrombosis, recurrent biliary strictures and re-transplantation compared with no colectomy. Colectomy + end ileostomy confers more favourable graft outcomes.

Primary hepatocellular cancer in the explanted liver: outcome of transplantation and risk factors for HCC recurrence.

AIM: To evaluate the risk of recurrence of hepatocellular cancer (HCC) after liver transplantation (LT). METHODS: The clinical records of 104 patients with HCC in the explanted liver were examined. RESULTS: HCC recurrence occurred in 12 patients. Recurrence was observed in all patients with a single nodule greater than 5 cm. Among the 5 patients with more than 3 tumours with a maximum diameter of 4.5 cm, no recurrence occurred. The survival rates were 81% and 64% at 1 and 5 years, respectively; the recurrence-free survival at 1 and 5 years was, respectively, 93% and 82%. Pre-LT alpha-fetoprotein (AFP) increased at a greater magnitude in patients who experienced recurrence, compared to those who did not. Tumour diameter, differentiation, satellitosis, AFP and the magnitude of AFP increase were predictive of recurrence. The 1- and 5-year recurrence-free survival for the 68 patients who had a single nodule up to 5 cm, or up to 3 nodules all less than 4.5 cm and with a maximum cumulative diameter of 8 cm, or more than 3 nodules all less than 2.5 cm, were 95% and 92%, respectively. For the 13 patients not meeting these criteria, the 1- and 5-year recurrence-free survival was, respectively, 75% and 54% (log Rank test p=0.019). CONCLUSIONS: Patients with more than 3 small HCC nodules before LT could still have a good outcome without recurrence. A rapid increase in AFP could be useful in identifying patients with a greater risk of post-LT HCC recurrence.

Increased incidence of chronic rejection in adult patients transplanted for autoimmune hepatitis: assessment of risk factors.

BACKGROUND/AIM: It remains uncertain whether autoimmune hepatitis (AIH), as an original indication for orthotopic liver transplantation (OLTX), predisposes to the development of chronic rejection (CR) after surgery and published reports on heterogeneous groups of patients provided conflicting data. In this work we analyzed the incidence and risk factors for CR in a large cohort of adult patients transplanted for AIH in our unit. RESULTS: A total of 1190 adult patients received OLTX in our center between 1982 and 1998. A total of 77 patients (6.5%) were transplanted for AIH and 12 (15.6%) patients from this group developed clinical and histological features of CR within a median time of 3.5 months after OLTX. Patients with AIH who developed CR were younger than other AIH patients at OLTX (32 vs. 44.2 ys; P=0.015) and more often had histological features of moderate or severe acute rejection (83 vs. 34%; P=0.002) on early post-OLTX biopsies. The incidence of CR in AIH patients was significantly higher than in subjects transplanted for other indications such as primary biliary cirrhosis (8.2%; P<0.05), primary sclerosing cholangitis (5.2%; P<0.05) or alcoholic cirrhosis (2.0%; P<0.001). Also, we observed a tendency to decreased incidence of CR with time in all transplanted subjects. CONCLUSIONS: Apart from younger age at OLTX and higher incidence of severe acute rejection, patients with AIH who developed CR did not differ from other subjects transplanted for this indication. Unlike other studies, not stratified by diagnosis, recipient CMV negative status, young donor age, and HLA DR matching were not identified as risk factors for CR in AIH.

Timing, significance, and prognosis of late acute liver allograft rejection.

Liver allograft rejection is usually divided into acute (cellular) rejection and chronic (ductopenic) rejection. Most cases of acute rejection occur within four weeks of transplantation. There is a paucity of published literature on late acute rejection (LAR) in liver allografts and little is known about factors affecting its occurrence and outcome. To study the predisposing factors, clinical presentation, and prognosis of LAR, data prospectively collected on consecutive adult patients who underwent liver transplantation between 1982 and 1994, were analyzed. LAR was defined as histologically confirmed acute cellular rejection occurring 30 or more days after liver transplantation. Of the 717 patients, 59 (7.5%) had 71 episodes of LAR. Fifty-seven episodes were seen during the first year after transplantation, the remaining occurring between 1 and 6 years. Age, sex, pretransplant diagnosis, donor match of HLA, and blood groups was not associated with risk of LAR. Twenty-seven (38%) episodes were preceded by subtherapeutic blood levels of cyclosporine/FK506 (< 100 ng/ml and < 5 ng/ml, respectively) while an additional 6 (8%) had marginally low blood levels (< 150 ng/ml and < 10 ng/ml, respectively). Treatment with high-dose prednisolone resulted in complete resolution of rejection in 36 (51%) episodes, partial response in 21, and no response in 14 patients. Sixteen patients (27%) developed chronic rejection and graft loss. Development of chronic rejection was not affected by age or sex of the patient, timing of LAR, or histological severity of AR. Delayed response to therapy during an earlier episode of AR, and histological findings of centrilobular necrosis or bile duct loss at the time of diagnosis of LAR were associated with high risk of progression to chronic rejection and graft loss.

A positive crossmatch in liver transplantation--no effect or inappropriate analysis? A prospective study.

BACKGROUND: Controversy over the relationship of preformed lymphocytotoxic antibodies and liver graft outcome remains. Because graft loss associated with preformed lymphocytotoxic antibodies probably occurs early after transplant, analysis of long-term survival is of questionable value. We therefore prospectively analyzed the effect on short- and long-term graft survival of the presence of lymphocytotoxic alloantibody in 207 primary adult liver allograft recipients. METHODS: Pretransplant serum was tested for donor-specific lymphocytotoxic antibodies and panel-reactive antibodies (PRA) using donor splenic lymphocytes and lymphocytes obtained for routine tissue typing. RESULTS: A positive crossmatch was detected in 24 recipients (11.5%): T-cell positive in 11 recipients and B-cell positive in 13 recipients. PRA were detected in 68 of 179 recipients tested (37.4%). High T-cell PRA (>55%) was detected in 17 recipients, and high B-cell PRA was detected in 20 recipients. Low PRA (<15%) against T cells was detected in 19 recipients and against B cells in 24 recipients. Graft failures occurred in 5 of 24 (21%) crossmatch-positive recipients and in 7 of 172 (4%) crossmatch-negative recipients. Graft survival was significantly lower in crossmatch-positive recipients at 1 month after transplant (chi-square=10.3, P=0.00133) but not at 3 months or 1 year. Causes of early graft loss were associated with immunological mechanisms, whereas later losses were due to nonimmunological mechanisms. CONCLUSIONS: Early graft loss may be increased in those recipients who are crossmatch positive. However, the logistical problems and consequences associated with allocation probably outweigh the benefits of prospective crossmatching.

Use of grafts procured from organ transplant recipients.

BACKGROUND: Massive intracerebral bleeding may cause brain stem death in transplant (Tx) recipients early or late postTx. We addressed the question as to whether Tx recipients may safely be used as organ donors. In particular, it is feared that exposure to immunosuppressive drugs may render those organs unsuitable for Tx. METHODS: We reviewed two case reports of liver grafts procured from Tx patients. In addition, we conducted a survey within United Kingdom Transplant Support Service Authority (UKTSSA) to delineate the UK experience in that area. RESULTS: Donor 1 was an 50-year-old heart Tx recipient who became brain stem dead due to cerebral bleeding 8 months postTx. His liver was used in an 55-year-old patient with PBC who is alive and well more than 22 months postTx. Donor 2 was a 22-year-old kidney Tx patient who developed cerebral bleeding 4 years postTx. His liver was used in a 65-year-old patient with PBC who is doing well more than 27 months postTx. During the study period of 1989-1995, 13 organs (9 kidneys, 3 hearts, 1 liver) were procured from 6 brain stem dead Tx patients (3 long, 2 heart, and 1 kidney Tx patients). Seven recipients are enjoying satisfactory graft function 1 to 7 years postTx; one kidney Tx recipient was relisted 4 years postTx due to chronic rejection; five functionning grafts were lost to patient death; primary nonfunction was seen in one heart Tx recipient. CONCLUSIONS: Tx patients can be successfully used as organ donors. In particular, chronic exposure to immunosuppression is not per se a contraindication to donation. Tx physicians confronted with the rare and tragic event of brain stem death in a Tx patient should not a priori exclude these patients from donation.

Poor outcome in patients with diabetes mellitus undergoing liver transplantation.

BACKGROUND: Relatively few studies have examined the influence of pretransplant diabetes on survival after an orthotopic liver transplant (OLT), and those published to date show only minor increases in infection rates among diabetics and no increase in mortality. METHODS: We examined the effect of diabetes mellitus on survival after OLT. 1005 adults underwent OLT between 1982 and May 1997. Seventy-eight patients with pretransplant diabetes mellitus (7.8% of all OLT, 38 insulin treated, 25 tablet treated, 15 diet controlled) were identified and compared with controls matched for age, sex, and date of first transplant and also with all nondiabetic adult liver recipients undergoing OLT during the same period. RESULTS: In patients undergoing OLT survival was worse in diabetics than in the comparison group (P=0.002) and vs. all adult nondiabetics undergoing (n=927) (P=0.004); in diabetics with alcoholic liver disease (ALD) vs. all nondiabetics with alcoholic liver disease (P= <0.0001); and in insulin-treated compared with non-insulin-treated diabetics (P=0.05). Multivariate analysis showed type of diabetes (P=0.001) and ALD (P=0.024) to be the most significant independent variables adversely affecting survival. Survival in diabetics undergoing OLT could be further stratified according to whether diabetics were insulin treated. CONCLUSIONS: Poorer outcome in the diabetics undergoing OLT, particularly in those with ALD, suggests the need for a more detailed pre-OLT assessment of these patients, particularly those with insulin and tablet controlled diabetes.

Chronic renal failure following liver transplantation: a retrospective analysis.

BACKGROUND: Liver transplant recipients are at risk of chronic renal disease, principally as a result of nephrotoxicity of the commonly used immunosuppressive agents cyclosporine and tacrolimus. We have investigated the incidence of chronic renal failure and its risk factors in our transplant population, which was treated predominantly with cyclosporine. METHODS: A single-center retrospective study was done of 883 consecutive adult patients receiving a first liver transplant between 1982 and 1996. Potential risk factors for the development of chronic renal failure were recorded, including serial measurements of cyclosporine therapy and renal function. RESULTS: Severe chronic renal failure (serum creatinine level >250 microM/L for at least 6 months) developed in 25 patients, representing 4% of patients surviving 1 year or more. Twelve of these patients developed end-stage renal failure and mortality was 44%. The predominant cause of renal failure was cyclosporine nephrotoxicity. Serum creatinine as early as 3 months after surgery was strongly associated with the eventual development of severe chronic renal failure (P=0.001), and this group could be further subdivided into two groups with differing risk factors. The first group had early (<1 year) renal dysfunction, with older age (P=0.03), cytomegalovirus infection (P=0.03), need for perioperative renal replacement therapy (P=0.06), and regrafting (P=0.06) as risk factors for eventual renal failure; the second group had late-onset (>1 year) renal dysfunction, with cyclosporine levels at 1 month after surgery (P=0.007) and daily and cumulative cyclosporine dosage at 5 years (P=0.01 for both) as risk factors. CONCLUSIONS: With improved survival of liver transplant recipients, chronic renal failure has become an important cause of morbidity and is associated with a high mortality. Many patients at risk of severe chronic renal failure may be identified at an early stage. Treatment regimens that avoid or prevent cyclosporine-induced nephrotoxicity are urgently required for this population.

Acute liver allograft rejection--is treatment always necessary?

A group of 195 consecutive adult patients who received a primary orthotopic liver allograft were reviewed retrospectively to analyze the incidence of rejection, the response to antirejection therapy, and the impact of acute rejection on the development of ductopenic rejection. The diagnosis of acute rejection (AR) was based on a combination of clinical and histological criteria, and 69.7% of the patients had at least one episode of acute rejection. Only 6.7% of the patients failed to respond to steroids and were treated with OKT3. Four (2.3%) patients developed acute vanishing bile duct syndrome (within 60 days) and 6 (3.5%) patients developed chronic rejection. Eight patients who spontaneously recovered from AR without additional immunosuppression are described in detail. In addition to histological damage, all developed significant hepatic dysfunction. Except for one patient who died from disseminated fungal infection, the 7 remaining patients are alive with excellent graft function 7 to 21 months posttransplant. While severe AR and recurrent AR should be treated without delay, some patients with mild-to-moderate rejection and hepatic dysfunction may resolve without additional immunosuppression.

Transplantation for end stage liver disease related to alpha 1 antitrypsin.

Alpha 1 antitrypsin deficiency (AT) is an autosomal recessive disease associated with chronic liver disease in adults and children and emphysema in adults. The disease is one of the most common inherited disorders of the Caucasian population of North Europe and North America and is the most common genetic reason for pediatric orthotopic liver transplantation (OLTx), although it is a rare indication in adults. The natural history of the disease is unpredictable and the pathogenesis of the liver injury unclear. Thirty-five patients with histologically apparent alpha 1 AT accumulation in the liver (22 adults, 13 children) have been transplanted in this center. Clinical features were correlated with the pretransplant phenotype, serum alpha 1 antitrypsin levels and potential precipitating factors. All children were PiZZ homozygotes, most of whom had presented with neonatal hepatitis. The majority of adult patients were heterozygotes presenting with portal hypertension and liver cirrhosis. Current one-year posttransplant survival figures are 73% for adults and 87.5% for children. Replacement of the cirrhotic liver results in acquisition of the donor phenotype, a rise in serum levels of alpha 1 antitrypsin, and apparent prevention of associated disease.

Can effluent hyaluronic acid or creatine kinase predict sinusoidal injury severity after cold ischemia?

It is well recognized that current selection criteria used to assess liver grafts before implantation are inaccurate and correlate poorly with graft outcome. A bench or laboratory-based test that could indicate the extent of liver injury immediately before implantation would be a valuable adjunct to clinical assessment. Hyaluronic acid (HA) and creatine kinase (BB component; CK-BB) levels in the caval effluent after liver perfusion have been suggested as indicators of preservation injury. Our objective was to investigate the relevance of preserved liver effluent HA and CK-BB as a predictor of early graft function. Perfused liver effluent HA and CK-BB levels were measured. Graft function was measured in terms of peak serum aspartate transaminase and its level on day 5 postoperatively as well as peak bilirubin level and prothrombin time. The cold ischemia time (CIT) was recorded. Statistical comparisons were made among HA level, CK-BB level, CIT, and graft function parameters. The study was conducted at The Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. Fifty patients undergoing OLT were studied. HA level was measured in 50 patients and CK-BB level in 30 patients. The main outcome measures were graft function and graft outcome. The graft function data are grouped according to effluent HA levels above or below 400 micrograms/L. Thirteen patients (26%) had a level below 400 micrograms/L and the remaining 37 (74%) were above this threshold. There were no significant differences between the groups for these indicators of graft function. There was no difference between the 2 groups for CIT. The overall median HA level was 1212 micrograms/L (range 39-4000 micrograms/L). The median total CK activity in the perfusate was 302 IU/L (range 118-1155 IU/L). The proportion of CK-BB activity from this total was 146 IU/L (8-641 IU/L), or 48% of the total CK activity. In a multiple regression analysis with CK-BB activity as the dependent variable, there was no demonstrable numerical relationship to graft function. In a separate multiple regression analysis similar results were obtained for HA. We conclude that the level of HA or CK-BB levels should not be used in determining the suitability for implantation of a harvested hepatic allograft.

Steroid withdrawal from long-term immunosuppression in liver allograft recipients.

Corticosteroids were withdrawn from the immunosuppressive regimen of 168/197 (85%) of liver transplant patients who survived for more than three months. In 14, steroids were restarted for reasons other than rejection. The remaining 154 patients were evaluated for the occurrence of rejection and graft loss. Risk factors for the development of rejection after steroid withdrawal were assessed. There were 13 episodes of rejection in 12 (7.8%) grafts; 7 (4.5%) experienced acute cellular rejection, and 6 (3.9%) developed chronic ductopenic rejection. All cases of acute rejection resolved with high-dose steroids. Graft and patient loss due to chronic rejection was 3 (1.9%) and 2 (1.3%), respectively. Chronic rejection resolved in 1 patient, 1 was successfully retransplanted, and in the other 2 the principal cause of death was recurrent tumor. None of the risk factors examined (primary indication for transplant, severity of previous acute rejection, use of OKT3, retransplantation, ABO blood group donor/recipient match, CMV infection, and CsA mono versus CsA and AZA double therapy) were associated with the development of chronic rejection poststeroid withdrawal. The prevalence of side effects, after steroid withdrawal, was low; 66% of patients never required antihypertensive medication; 14% experienced a significant septic episode, and only 4 died with sepsis as the major factor. There were no fungal sepsis and no new cases of diabetes. Withdrawal of corticosteroids after 3 months can be successfully achieved in the majority of liver allograft recipients and is associated with a low rate of rejection, graft loss, and complications attributable to immunosuppressive medication.

Portal vein thrombosis in adults undergoing liver transplantation: risk factors, screening, management, and outcome.

BACKGROUND: Portal vein thrombosis (PVT) has been seen as an obstacle to liver transplantation (LTx). Recent data suggest that favorable results may be achieved in this group of patients but only limited information from small size series is available. The present study was conducted in an effort to review the surgical options in patients with PVT and to assess the impact of PVT on LTx outcome. Risk factors for PVT and the value of screening tools are also analyzed. METHODS: Adult LTx performed from 1987 through 1996 were reviewed. PVT was retrospectively graded according to the operative findings: grade 1: <50% PVT +/- minimal obstruction of the superior mesenteric vein (SMV); grade 2: grade 1 but >50% PVT; grade 3: complete PV and proximal SMV thrombosis; grade 4: complete PV and entire SMV thrombosis. RESULTS: Of 779 LTx, 63 had operatively confirmed PVT (8.1%): 24 had grade 1, 23 grade 2, 6 grade 3, and 10 grade 4 PVT. Being male, treatment for portal hypertension, Child-Pugh class C, and alcoholic liver disease were associated with PVT. Sensitivity of ultrasound (US) in detecting PVT increased with PVT grade and was 100% in grades 3-4. In patients with US-diagnosed PVT, an angiogram was performed and ruled out a false positive US diagnosis in 13%. In contrast with US, angiograms differentiated grade 1 from grade 2, and grade 3 from grade 4 PVT. Grade 1 and 2 PVT were managed by low dissection and/or a thrombectomy; in grade 3 the distal SMV was directly used as an inflow vessel, usually through an interposition donor iliac vein; in grade 4 a splanchnic tributary was used or a thrombectomy was attempted. Transfusion requirements in PVT patients (10 U) were higher than in non-PVT patients (5 U) (P<0.01). In-hospital mortality for PVT patients was 30% versus 12.4% in controls (P<0.01). Patients with PVT had more postoperative complications, renal failure, primary nonfunction, and PV rethrombosis. The overall actuarial 5-year patient survival rate in PVT patients (65.6%) was lower than in controls (76.3%; P=0.04). Patients with grade 1 PVT, however, had a 5-year survival rate (86%) identical to that of controls, whereas patients with grades 2, 3, and 4 PVT had reduced survival rates. The 5-year patient survival rate improved from the 1st to the 2nd era in non-PVT patients (from 72% to 83%; P<0.01), in grade 1 PVT (from 53% to 100%; P<0.01), and in grades 2 to 4 PVT (from 38% to 62%; P=0.11). CONCLUSIONS: The value of US diagnosis in patients with PVT depends on the PVT grade, and false negative diagnoses occur only in incomplete forms of PVT (grades 1-2). The degree of PVT dictates the surgical strategy to be used, thrombectomy/low dissection in grade 1-2, mesoportal jump graft in grade 3, and a splanchnic tributary in grade 4. Taken altogether, PVT patients undergo more difficult surgery, have more postoperative complications, have higher in-hospital mortality rates, and have reduced 5-year survival rates. Analysis by PVT grade, however, reveals that grade 1 PVT patients do as well as controls; only grades 2 to 4 PVT patients have poorer outcomes. With increased experience, results of LTx in PVT patients have improved and, even in severe forms of PVT, a 5-year survival rate >60% can now be achieved.