The evolution of liver transplantation during 3 decades: analysis of 5347 consecutive liver transplants at a single center.

OBJECTIVE: To analyze a 28-year single-center experience with orthotopic liver transplantation (OLT) for patients with irreversible liver failure. BACKGROUND: The implementation of the model for end-stage liver disease (MELD) in 2002 represented a fundamental shift in liver donor allocation to recipients with the highest acuity, raising concerns about posttransplant outcome and morbidity. METHODS: Outcomes and factors affecting survival were analyzed in 5347 consecutive OLTs performed in 3752 adults and 822 children between 1984 and 2012, including comparisons of recipient and donor characteristics, graft and patient outcomes, and postoperative morbidity before (n = 3218) and after (n = 2129) implementation of the MELD allocation system. Independent predictors of survival were identified. RESULTS: Overall, 1-, 5-, 10-, and 20-year patient and graft survival estimates were 82%, 70%, 63%, 52%, and 73%, 61%, 54%, 43%, respectively. Recipient survival was best in children with biliary atresia and worst in adults with malignancy. Post-MELD era recipients were older (54 vs 49, P < 0.001), more likely to be hospitalized (50% vs 47%, P = 0.026) and receiving pretransplant renal replacement therapy (34% vs 12%, P < 0.001), and had significantly greater laboratory MELD scores (28 vs 19, P < 0.001), longer wait-list times (270 days vs 186 days, P < 0.001), and pretransplant hospital stays (10 days vs 8 days, P < 0.001). Despite increased acuity, post-MELD era recipients achieved superior 1-, 5-, and 10-year patient survival (82%, 70%, and 65% vs 77%, 66%, and 58%, P < 0.001) and graft survival (78%, 66%, and 61% vs 69%, 58%, and 51%, P < 0.001) compared with pre-MELD recipients. Of 17 recipient and donor variables, era of transplantation, etiology of liver disease, recipient and donor age, prior transplantation, MELD score, hospitalization at time of OLT, and cold and warm ischemia time were independent predictors of survival. CONCLUSIONS: We present the world's largest reported single-institution experience with OLT. Despite increasing acuity in post-MELD era recipients, patient and graft survival continues to improve, justifying the "sickest first" allocation approach.

Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen-positive patients after liver transplantation.

Hepatitis B virus (HBV) reinfection and recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) are associated with increased graft failure and reduced patient survival. We evaluated the effects of both HCC recurrence and HBV reinfection on the long-term survival of these patients after OLT. One hundred seventy-five patients underwent OLT for HBV-related liver diseases and were the subjects of this retrospective study. We assessed risk factors for HBV reinfection, HCC recurrence, and survival post-OLT using univariate and multivariate analyses. During a mean follow-up of 43.0 +/- 42.0 months, 88 of 175 (50.3%) patients transplanted for HBV-related liver disease had HCC prior to OLT. Thirteen (14.8%) of these patients had HCC recurrence after OLT. The mean time for recurrence of HCC was 26.1 +/- 31.9 months. Twelve of 175 (6.9%) patients developed HBV reinfection after liver transplantation. The mean time for HBV reinfection was 28.7 +/- 26.4 months. Ten of these 12 (83.3%) patients had HCC prior to OLT, and 5 (50%) developed recurrence of HCC. On multivariate analyses, pre-OLT HCC and recurrence of HCC post-OLT were significantly associated with HBV reinfection after transplantation (P = 0.031 and P < 0.001, respectively). HCC recurrence after OLT was associated with lymphovascular invasion (P < 0.001) and post-OLT chemotherapy (P < or = 0.001). The 3- and 5-year survival rates were significantly decreased in patients with HBV reinfection (P = 0.007) and in patients with HCC recurrence after OLT (P = 0.03). In conclusion, pre-OLT HCC and HCC recurrence after transplantation were associated with HBV reinfection and with decreased patient survival. Hepatitis B immunoglobulin and antiviral therapy was only partially effective in preventing HBV reinfection in patients with HCC recurrence.

Pretransplant variables associated with quality of life in liver transplant recipients.

OBJECTIVE: With an increasing number of liver transplant recipients living, understanding quality-of-life issues is essential. Our goal is to identify pretransplant variables associated with post-transplant quality of life in liver transplant recipients. METHODS: Three hundred and eight liver transplant recipients were administered the Short Form 36 and a basic demographical questionnaire. Variables associated with post-transplant quality of life were studied in a multivariate regression analysis. Interaction terms were used to examine effect modification. RESULTS: Male gender, longer pretransplant work hours and interaction term between work hours and male gender were independently associated with Physical Functioning. Work hours positively correlated with Role-Physical, while viral hepatitis and ascites were negatively associated with Role-Physical. Ascites and viral hepatitis were independently negatively associated with Bodily Pain. Encephalopathy, hepatocellular carcinoma and viral hepatitis were independently associated with General Health. Ascites was also negatively associated with Social Functioning, Role-Emotional, Bodily Pain, General Health and Vitality. Viral hepatitis was negatively correlated with Vitality and Mental Functioning. CONCLUSIONS: Pretransplant variables such as ascites, encephalopathy, hepatocellular carcinoma, viral hepatitis, work hours, time unable to work and gender were significantly associated with post-transplant quality of life in liver transplant recipients. Interventions addressing these issues may be initiated to improve the post-transplant quality of life.

The MELD score in advanced liver disease: association with clinical portal hypertension and mortality.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score is a measure of chronic liver disease severity. Patients awaiting transplantation are assessed using this score. However, it has recently been suggested that changes in MELD score may be as important as the absolute MELD score in predicting short-term survival. However, clinical factors that affect the MELD score are unknown. We sought to identify predictors of mortality for potential transplant patients and examine factors that might predict changes in MELD score. MATERIALS AND METHODS: Between January 1, 2002, and July 30, 2004, we retrospectively examined risk factors of 429 adult patients awaiting liver transplantation at the University of California at Los Angeles (UCLA). Analysis of the data was performed using demographics, manifestations of portal hypertension, time between last MELD recorded and event, and laboratory values. Significant factors in univariate analysis were further studied using Cox proportional hazards regression multivariate analysis. RESULTS: At mean follow-up of 2.15 years (+/-1.49 years), 71 patients (16.5%) had MELD scores that increased 5-10 points, 22 had changes of 10-15 points, and 14 had changes of 15-20 points. Manifestations of portal hypertension, laboratory values, and etiology of liver disease did not predict changes in MELD score. However, development of hepatic encephalopathy (HR, 3.95; P=.002; 95% CI, 1.70 to 9.42) and MELD score (HR, 1.04; P=.001; 95% CI, 1.004 to 1.08) were associated with variceal bleeding. Also, MELD score (HR, 1.07; P<.001; 95% CI, 1.05 to 1.09), refractory ascites (HR, 2.15; P=.002; 95% CI, 1.31 to 3.53), and alcoholic cirrhosis (HR, 0.40; P=.04; 95% CI, 0.18 to 0.94) were independent predictors of mortality. CONCLUSIONS: Encephalopathy and MELD score were associated with variceal bleeding. Patients with an elevated MELD score, refractory ascites, and alcoholic cirrhosis had increased mortality while on the liver transplant list. No factors predicting changes in the MELD score were identified.

Employment and quality of life in liver transplant recipients.

The purposes of liver transplantation (LT) include the extension of survival, improvement in quality of life, and the return of the recipient as a contributing member of society. Employment is one measure of the ability to return to society. The aim of this study is to determine the factors affecting employment/subemployment after LT. A total of 308 adult liver transplant recipients who were seen at the University of California, Los Angeles were administered the Medical Outcomes Short Form 36 (SF-36) and a questionnaire regarding work history and insurance coverage. Multivariate analysis were used to identify independent variables associated with posttransplantation employment. Interaction terms were used to examine effect modification. Of 308 transplant recipients, 218 (70.8%) worked prior to transplantation, and 78 (27%) worked posttransplantation. Pretransplant variables that were independently associated with posttransplantation employment included the following: lack of disability income (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.32-7.18; P = 0.36); health maintenance organization (HMO)/preferred provider organization (PPO) insurance (OR = 3.08; 95% CI, 1.32-7.18; P < 0.01); the number of hours worked (OR = 1.17; 95% CI, 1.08-1.28; P < 0.01); and the lack of diabetes mellitus (OR = 0.23; 95% CI, 0.70-0.73; P < 0.01). An interaction term between disability income and hours worked prior to transplantation (OR = 0.16; 95 % CI, 0.03-0.83; P = 0.03) was independently associated with posttransplantation employment. In a separate regression model of SF-36 responses, posttransplantation physical functioning (OR = 1.17; 95% CI, 1.10-1.26; P < 0.01) and role-physical (OR = 1.1; 95% CI, 1.02-1.16; P < 0.01) were independently associated with employment after transplantation. In conclusion, HMO or PPO insurance, lack of disability income coverage prior to transplant, the absence of diabetes mellitus, the number of hours worked prior to transplantation, and high physical functioning were associated with posttransplantation employment.

Anemia in liver transplant recipients undergoing antiviral treatment for recurrent hepatitis C.

Adherence to antiviral therapy is essential to achieve sustained virological responses in patients treated for hepatitis C. An important limitation to use of appropriate doses of ribavirin is development of anemia. The aim of this study is to identify risk factors associated with anemia in liver transplant recipients undergoing treatment for recurrent hepatitis C virus (HCV). Retrospective analysis was performed on 115 adult liver transplantation (LT) recipients who received antiviral treatment. Anemia was defined as hemoglobin of <10 gm/dL or the use of erythropoietin replacement therapy. Variables found to be significant in univariate analysis were further studied in multivariate analysis. The mean (+/- standard deviation [SD]) age of our cohort was 52.1 (+/- 8.8) yr. Anemia developed in 44 patients (38.3%). Mean (+/- SD) onset of anemia was 8.9 (+/- 6.8) weeks after initiation of antiviral therapy. A total of 30 patients (26%) required erythropoietin replacement, at a mean (+/- SD) of 7.9 (+/- 6.0) weeks after start of antiviral treatment. A total of 27 patients (24%) required ribavirin dose reduction, at a mean (+/- SD) time to dose reduction of 8.1 (+/- 6.3) weeks. In univariate analysis, body mass index (BMI) (P < 0.01), mycophenolate mofetil use (P = 0.05), trimethoprim-sulfamethoxazole (P = 0.02), and age (P = 0.02) were statistically significant. In conclusion, in multivariate analysis, BMI (P < 0.01) and age (P = 0.02) were found to be independent predictors of anemia. Anemia is common in liver transplant recipients treated for recurrent HCV. Special vigilance is required for older patients and patients with a low BMI.

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.

Mortality predictors in liver transplant recipients with recurrent hepatitis C cirrhosis.

BACKGROUND/AIM: Recipients of orthotopic liver transplant for hepatitis C (HCV) invariably develop recurrent disease. The risk factors for death and retransplantation following the development of cirrhosis from HCV are unclear. The aim of this study was to identify predictors of survival in liver transplant recipients who develop cirrhosis from recurrent HCV. METHODS: We reviewed records of patients who underwent liver transplantation for cirrhosis due to HCV between January 1990 and December 2001. Prognostic factors of patient survival following the development of recurrent cirrhosis were identified through multivariate analysis. RESULTS: During the study period, 511 patients underwent transplantation for HCV cirrhosis. Of these, 65 patients (13%) developed biopsy proven recurrent cirrhosis from HCV; 43 (8%) were relisted for transplantation, and 24 (5%) underwent retransplantation. The overall Kaplan-Meier patient survival rates after the histologic diagnosis of cirrhosis at 1 and 5 years were 66% and 30%, respectively. A multivariate Cox proportional hazards model showed patients with higher last (i.e. at follow-up or prior to retransplantation) International normalized ratio (INR) values (hazard ratios (HR)=2.02, 95% confidence interval 1.26, 3.24, P<0.01) to have an increased risk of death. CONCLUSION: Our results suggested survival was decreased after the diagnosis of cirrhosis from recurrent HCV. Higher INR was associated with an increased risk of death following the development of cirrhosis.

MELD fails to measure quality of life in liver transplant candidates.

Previous studies have demonstrated an association between Child Turcotte-Pugh (CTP) class and impaired quality of life. However, the relationship between the model for end-stage liver disease (MELD) score and quality of life (QOL) has not been well studied. In this study, quality of life questionnaires (Medical Outcomes Short Form 36 [SF-36] and the Chronic Liver Disease Questionnaire [CLDQ]) were administered to 150 adult patients awaiting liver transplantation. We also collected demographic data and laboratory results and recorded manifestations of hepatic decompensation. The study found that all domains of the SF-36 and CLDQ were significantly lower in our patient cohort than in normal controls (P < .001). There was a moderate negative correlation between CPT class and physical components of the SF-36 (r = -.30), while there was a weak negative correlation (r = -.10) between CPT class and the mental component. There was a negative moderate correlation between CPT class and overall CLDQ (r = -.39, P < .001) and a weak correlation (r = -.20) between MELD score and overall CLDQ score. Both encephalopathy (correlation coefficient = -.713, P = .004) and ascites (correlation coefficient = -.68, P = .006) were predictive of the QOL using CLDQ (adjusted R(2) = .1494 and f = 0.000). In conclusion, in liver transplant candidates, the severity of liver disease assessed by the MELD score was not predictive of QOL. The presence of ascites and/or encephalopathy was significantly associated with poor quality of life. CTP correlates better to QOL, probably because it contains ascites and encephalopathy.

Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience.

OBJECTIVE: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed. METHODS: Retrospective analysis of 3200 consecutive OLTs that were performed at our institution, between February 1984 and December 31, 2001. RESULTS: Of 2662 recipients, 578 (21.7%) and 659 (24.7%) were pediatric and urgent patients, respectively. Overall 1-, 5-, 10-, and 15-year patient and graft survival estimates were 81%, 72%, 68%, 64% and 73%, 64%, 59%, 55%, respectively. Patient survival significantly improved in the second (1992-2001) versus the era I (1984-1991) of transplantation (P < 0.001). Similarly, graft survival was better in the era II of transplantation (P < 0.02). However, biliary and infectious complications increased in era II. When OLT indications were considered, best recipient survival was obtained in children with biliary atresia (82%, 79%, and 78% at 1, 5, and 10 years, respectively), while malignant disease in adult patients resulted in the worst outcomes of 68% and 43% at 1 and 5 years, post-OLT. Further, patients <18 years and nonurgent recipients exhibited superior survival when compared with recipients >18 years (P < 0.001) or urgent patients (P < 0.001). Of 13 donor and recipient variables, era of OLT, recipient age, urgent status, donor age, donor length of hospital stay, etiology of liver disease, retransplantation, warm and cold ischemia, but not graft type (whole, split, living-donor), significantly impacted patient survival. CONCLUSIONS: Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be achieved.

Hepatitis C positive grafts may be used in orthotopic liver transplantation: a matched analysis.

Hepatitis C (HCV)-positive liver grafts have been increasingly used in patients with decompensated liver disease from HCV because of critical shortage of available organs. Fifty-nine recipients of HCV-positive grafts were matched to patients who received HCV-negative grafts. All recipients were transplanted for HCV liver disease. Matching variables were (1) status, (2) pre-transplant creatinine, (3) recipient age, (4) donor age, (5) warm ischemia time, and (6) year of transplantation. Both unmatched and matched analyses were performed on patient survival, graft survival, and time to HCV recurrence. There was no significant statistical difference in patient, graft, or HCV recurrence-free survival between recipients of HCV-positive and HCV-negative grafts with matched and unmatched analyses (p > 0.05). The 3-year estimates of HCV disease-free survival were 12% (+/- 9%) and 19% (+/- 7%) using HCV-positive and -negative grafts, respectively. The use of HCV-positive grafts in recipients with HCV does not appear to affect patient survival, graft survival, or HCV recurrence when compared with the use of HCV-negative grafts. Our results suggest that HCV-positive grafts can be used in a HCV liver transplant recipient.

Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C.

The efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is not well defined. This study examines the variables that may determine the outcome of OLT for HCC in HCV patients. From 1990 to 1999, 463 OLTs were performed for HCV cirrhosis. Of these patients, 67 with concurrent HCC were included in the study. Univariate and multivariate analyses considered the following variables: gender, pTNM stage, tumor size, number of nodules, vascular invasion, incidental tumors, adjuvant chemotherapy, preoperative chemoembolization, alpha-fetoprotein (AFP) tumor marker, lobar distribution, and histological grade. Overall OLT survival of HCV patients diagnosed with concomitant HCC was significantly lower when compared to patients who underwent OLT for HCV alone at 1, 3, and 5 years (75%, 71%, and 55% versus 84%, 76%, and 75%, respectively; P < 0.01). Overall survival of patients with stage I HCC was significantly better than patients with stage II, III, or IV (P < .05). Eleven of 67 patients developed tumor recurrence. Sites of recurrence included transplanted liver (5), lung (5), and bone (1). Twenty-four of 67 patients (36%) died during the follow-up time. Causes of deaths included recurrent HCC in 8 of 24 patients (12%) and recurrent HCV in 3 of 24 patients (4.5%), whereas 13 (19.5%) patients died from causes that were unrelated to HCV or HCC. Both univariate and multivariate analysis demonstrated that pTNM status (I versus II, III, and IV; P < .05) was a reliable prognostic indicator for patient survival. Presence of vascular invasion (P = .0001) and advanced pTNM staging (P = .038) increased risk of recurrence. Multivariate analysis showed that pretransplant chemoembolization and adjuvant chemotherapy reduced risk of death after OLT in HCC recipients. In conclusion, this study demonstrates the effectiveness of OLT for patients with HCC in a large cohort of chronic HCV patients. Advanced tumor stage, and particularly vascular invasion, are poor prognostic indicators for tumor recurrence. Early pTNM stage, adjuvant chemotherapy, and preoperative chemoembolization were associated with positive outcomes for patients who underwent OLT for concomitant HCV and HCC.

Outcomes of acute rejection after interferon therapy in liver transplant recipients.

Interferon alfa has been increasingly used against recurrent hepatitis C (HCV) disease in post-liver transplant (LT) recipients. A serious potential adverse effect is acute rejection. We reviewed our experience using interferon-based therapy (interferon or pegylated interferon with or without ribavirin) for treating recurrent HCV in LT recipients. Forty-four LT recipients were treated with interferon for recurrent HCV. Five of the 44 patients developed acute rejection during interferon-based therapy. These 5 patients started treatment of 42.4 +/- 33.89 months (mean +/- SD) after LT. Mean (+/- SD) histological activity index and fibrosis scores before initiating antiviral therapy were 8.8 (+/- 1.92) and 2.6 (+/- 0.55), respectively. Patients were treated for 3.3 +/- 2.28 months (mean +/- SD) prior to rejection. At the time of rejection, HCV load was not detectable in 4 of the 5 recipients. All 5 patients had tolerated interferon therapy, and none had stopped therapy because of adverse effects. The rejection was successfully treated in 3 patients. In 2 of those 3 patients, cirrhosis eventually developed. In the 2 patients who did not respond to rejection treatment, immediate graft failure occurred, leading to re-LT in 1 patient and death from sepsis in the other. In conclusion, the results indicate that further studies are needed to assess the safety of interferon in LT recipients. Interferon-based therapy may lead to acute rejection and subsequent graft loss and should therefore be used with caution. Treated recipients may also develop progressive cirrhosis despite achieving a sustained virological response.

MELD score predicts 1-year patient survival post-orthotopic liver transplantation.

The Model for End-Stage Liver Disease (MELD) is an important predictor in patients awaiting orthotopic liver transplantation (OLT). However, the model's association with posttransplant patient survival is unclear. We studied 1-year patient survival in 404 adult patients who underwent OLT at the University of California Los Angeles. The hazard rates of patient survival according to the MELD strata and United Network for Organ Sharing (UNOS) statuses were assessed by Proportional Hazard Cox regression analysis. The difference in survival for MELD strata and UNOS status were compared using the Cox model. There was a significant difference in 1-year patient (P =.0006) survival using different MELD strata, whereas there was a trend according to UNOS status (P =.051). Increased rate of death was observed in recipients of OLT with higher MELD scores (> 36, hazard ratio 3.9; 95% CI 1.55, 10.27) and more urgent UNOS status (2A; hazard ratio, 1.99; 95% CI 1.07, 3.7). The MELD stratum is better associated with 1-year patient survival in liver transplant recipients than UNOS statuses. Patient survival was worse with higher MELD scores.

Outcomes of hepatitis C- and hepatitis B core antibody-positive grafts in orthotopic liver transplantation.

The use of hepatitis B core antibody (HBcAb)- and hepatitis C virus antibody (HCV+) liver grafts for transplantation in selected populations has not affected patient and graft survival. We reexamined the clinical outcomes of using these HBcAb+ and HCV+ grafts at our institution, in addition to studying recipients of combined HBcAb+/HCV+ grafts. We identified 377 patients who underwent transplantation for either hepatitis B and/or hepatitis C, or received both HBcAb+ and HCV+ grafts. Patient and graft survival at 5 years posttransplantation was 73% and 71%, respectively, in the HBcAb+ grafts compared with 81% and 75% in the HBcAb- grafts (P =.65; P =.94). For HCV+ grafts, patient and graft survival at 5 years posttransplantation was 89% and 73%, respectively, compared with 69% and 59% in the HCV- grafts; (P =.22; P =.77). The 5-year patient and graft survival rate in those who received combined HBcAb+/HCV+ grafts was 74% and 69%, respectively, and there was no statistical difference compared with the HBcAb+ and HCV+ grafts (P =.76; P =.90). The 5-year patient and graft survival rate in patients who received dual HBV prophylaxis with hepatitis B immunoglobulin (HBIg) and lamivudine was 88% and 84%, respectively, which was significantly higher than for patients who received single prophylaxis or no prophylaxis (P <.01; P =.02). Our study supports previous observations that patient and graft survival is not affected with the use of HBcAb+ and HCV+ grafts, and that dual prophylaxis with HBIg and lamivudine offers substantial survival benefits. Furthermore, the use of combined HBcAb+/HCV+ grafts did not impact patient or graft survival. This provides a potential new pool of donor livers that can be used for transplantation in select patients.

Discordance between ALT values and fibrosis in liver transplant recipients treated with ribavirin for recurrent hepatitis C.

Hepatitis C virus (HCV) recurrence is a serious problem after orthotopic liver transplantation (OLT). The role of ribavirin as a single agent to treat recurrent HCV is controversial. Our aim was to evaluate the correlation between alanine aminotransferase (ALT) levels and histological findings in OLT recipients treated with ribavirin monotherapy for recurrent HCV. The mean [+/- standard error (SE)] age of 11 patients was 50.1 (SE +/- 8.6) years. The estimated mean dose and duration of ribavirin treatment (+/- SE) was 661.5 (+/- 52.5) mg and 20.4 (+/- 1.7) months, respectively. Five patients required either dose reduction or erythropoietin. We found a significant decrease of mean (+/- SE) ALT value from 246 +/- 44.8 U/L to 109.4 +/- 49.1 U/L (p = 0.002) in patients treated with ribavirin. However, there was also significant worsening of interface activity (p = 0.03) and fibrosis (p = 0.02). No significant association was found between ALT values and (i) stage of hepatic fibrosis, (ii) interface activity, (iii) lobular activity and (iv) HCV RNA values. Our results suggest that HCV disease can progress despite a significant decrease in ALT values. ALT values are inadequate markers of the ribavirin monotherapy and can lead to erroneous conclusions of efficacy.

Donor and recipient outcomes in right lobe adult living donor liver transplantation.

Severe donor organ shortage has provided the impetus for adult living donor liver transplantation (ALDLT). Despite rapid implementation and expansion of the procedure, outcome analysis of ALDLT is still incomplete. This study analyzed both donor and recipient outcomes after ALDLT at a single center. ALDLT performed at UCLA between August 1999 and November 2001 were reviewed retrospectively. Twenty recipients (14 men and 6 women) with a mean age of 48.8 +/- 9.7 (29 to 66) years underwent right lobe ALDLT. By computed tomograpy (CT), graft/recipient weight ratio (GRWR) was 1.3 +/- 0.3 (1 to 2.2). Overall 1-year patient and graft survival rates were 95% and 85%, respectively. One recipient died of heart failure with normal liver function 5 months after transplantation. Three grafts (14%) were lost and all three patients underwent successful cadaveric retransplantation. Complications were classified according to the Clavien grading system with all but 3 recipients encountering at least one complication. Nine (45%) had grade 1 (minor), 10 (50%) had grade 2 (potentially life threatening without residual disease/disability), 3 (14%) had grade 4A (retransplantation) and one grade 4B (death). Right lobectomy for living donation was performed in 20 patients (12 men, 8 women). Residual left lobe volumes were 36 +/- 5.3 (23.9 to 47.9)% of total donor liver volume. No donor required intensive care unit admission and median hospital stay was 7.5 (6 to 14) days. One donor was aborted after intraoperative biopsy showed > 50% macrovesicular steatosis. No donor mortality or long-term complications were encountered. Five grade 1 minor complications, by Clavien Classification, occurred in 4 of 20 (20%) donors. ALDLT using right lobe grafts is an effective procedure to expand a severely depleted donor, but is associated with a high complication rate despite good survival outcomes. Continuous standardized reporting of ALDLT outcomes is required to allow successful and safe implementation of the procedure.

Pretransplant model to predict posttransplant survival in liver transplant patients.

OBJECTIVE: To develop a prognostic model that determines patient survival outcomes after orthotopic liver transplantation (OLT) using readily available pretransplant variables. SUMMARY BACKGROUND DATA: The current liver organ allocation system strongly favors organ distribution to critically ill recipients who exhibit poor survival outcomes following OLT. A severely limited organ resource, increasing waiting list deaths, and rising numbers of critically ill recipients mandate an organ allocation system that balances disease severity with survival outcomes. Such goals can be realized only through the development of prognostic models that predict survival following OLT. METHODS: Variables that may affect patient survival following OLT were analyzed in hepatitis C (HCV) recipients at the authors' center, since HCV is the most common indication for OLT. The resulting patient survival model was examined and refined in HCV and non-HCV patients in the United Network for Organ Sharing (UNOS) database. Kaplan-Meier methods, univariate comparisons, and multivariate Cox proportional hazard regression were employed for analyses. RESULTS: Variables identified by multivariate analysis as independent predictors for patient survival following primary transplantation of adult HCV recipients in the last 10 years at the authors' center were entered into a prognostic survival model to predict patient survival. Accordingly, mortality was predicted by 0.0293 (recipient age) + 1.085 (log10 recipient creatinine) + 0.289 (donor female gender) + 0.675 urgent UNOS - 1.612 (log10 recipient creatinine times urgent UNOS). The above variables, in addition to donor age, total bilirubin, prothrombin time (PT), retransplantation, and warm and cold ischemia times, were applied to the UNOS database. Of the 46,942 patients transplanted over the last 10 years, 25,772 patients had complete data sets. An eight-factor model that accurately predicted survival was derived. Accordingly, the mortality index posttransplantation = 0.0084 donor age + 0.019 recipient age + 0.816 log creatinine + 0.0044 warm ischemia (in minutes) + 0.659 (if second transplant) + 0.10 log bilirubin + 0.0087 PT + 0.01 cold ischemia (in hours). Thus, this model is applicable to first or second liver transplants. Patient survival rates based on model-predicted risk scores for death and observed posttransplant survival rates were similar. Additionally, the model accurately predicted survival outcomes for HCV and non-HCV patients. CONCLUSIONS: Posttransplant patient survival can be accurately predicted based on eight straightforward factors. The balanced application of a model for liver transplant survival estimate, in addition to disease severity, as estimated by the model for end-stage liver disease, would markedly improve survival outcomes and maximize patients' benefits following OLT.

Hepatocellular carcinoma screening in patients waiting for liver transplantation: a decision analytic model.

De novo hepatocellular carcinoma (HCC) may have a large impact on patients waiting for liver transplantation. The presence of HCC can lead to a status upgrade or removal from the waitlist. Our aim is to compare costs and outcomes of different liver cancer surveillance strategies. A Markov-based decision analytic model is created to simulate costs and health outcomes for a hypothetical cohort awaiting liver transplantation undergoing HCC screening. Three strategies of HCC screening are compared with the referent strategy of using alphafetaprotein (AFP) level alone: (1) ultrasound (U/S), (2) AFP plus U/S, and (3) computed tomography (CT). Screening is performed for all strategies at 6-month intervals. Selected tumors are treated locally. Costs and clinical outcomes are discounted. Using baseline assumptions, incremental cost-effectiveness ratios (ICERs) for U/S, U/S plus AFP, and CT are $60,300/life-year saved (LY), $74,000/LY, and $101,100/LY, respectively. The most cost-effective strategy was dependent on the relative costs of each screening modality. U/S screening becomes the dominant strategy when the cost of an AFP test is decreased. Our results show that screening with CT is associated the greatest gain in life expectancy and greatest costs. U/S screening strategy is the preferred screening strategy based on the lowest ICER. Ultimately, costs of the screening modalities determine the most cost-effective strategy.