The model for end-stage liver disease (MELD) was developed to predict short-term mortality in patients with cirrhosis. It has since become the standard tool to prioritize patients for liver transplantation. We assessed the value of pretransplant MELD in the prediction of posttransplant survival. We identified adult patients who underwent liver transplantation at our institution during 1991-2002. Among 2,009 recipients, 1,472 met the inclusion criteria. Based on pretransplant MELD scores, recipients were stratified as low risk (Յ15), medium risk (16-25), and high risk (Ͼ25). The primary endpoints were patient and graft survival. Mean posttransplant follow-up was 5.5 years. One-, 5-and 10-year patient survival was 83%, 72%, and 58%, respectively, and graft survival was 76%, 65%, and 53%, respectively. In univariable analysis, patient and donor age, patient sex, MELD score, disease etiology, and retransplantation were associated with posttransplantation patient and graft survival. In multivariable analysis adjusted for year of transplantation, patient age Ͼ65 years, donor age Ͼ50 years, male sex, and retransplantation and pretransplant MELD scores Ͼ25 were associated with poor patient and graft survival. The impact of MELD score Ͼ25 was maximal during the first year posttransplant. In conclusion, older patient and donor age, male sex of recipient, retransplantation, and high pretransplant MELD score are associated with poor posttransplant outcome. Pretransplant MELD scores correlate inversely with posttransplant survival. However, better prognostic models are needed that would provide an overall assessment of transplant benefit relative to the severity of hepatic dysfunction. Liver Transpl 12: 440-447, 2006.
Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma‐derived C3A cells express anti‐inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End‐Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3‐5 days of continuous ELAD treatment plus SOC. After a minimum follow‐up of 91 days, overall survival (OS) was assessed by using a Kaplan‐Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent‐to‐treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380–393 2018 AASLD.
Hypersplenism is a common manifestation of portal hypertension in the cirrhotic. More than half of cirrhotics will have low platelet counts, but neutropenia is much less common. Despite being common in the cirrhotic population, the presence of hypersplenism is of little clinical consequence. The presence of hypersplenism suggests more advanced liver disease and an increase in risk of complications, but there is no data showing that correcting the hypersplenism improves patient survival. In most series, the most common indications for treating the hypersplenism is to increase platelet and white blood cell counts to allow for use of drugs that suppress the bone marrow such as interferon alpha and chemotherapeutic agents. There are several approaches used to treat hypersplenism. Portosystemic shunts are of questionable benefit. Splenectomy, either open or laparoscopically, is the most effective but is associated with a significant risk of portal vein thrombosis. Partial splenic artery embolization and radiofrequency ablation are effective methods for treating hypersplenism, but counts tend to fall back to baseline long-term. Pharmacological agents are also effective in increasing platelet counts. Development of direct acting antivirals against hepatitis C will eliminate the most common indication for treatment. We lack controlled trials designed to determine if treating the hypersplenism has benefits other than raising the platelet and white blood cell counts. In the absence of such studies, hypersplenism in most patients should be considered a laboratory abnormality and not treated, in other words forget it.
With the widespread use of oral aloe vera and other herbal products, clinicians faced with a case of acute hepatitis that is not readily diagnosed should question patients about herbal use.
We found significant differences in liver allograft supply and demand--but these differences had only a modest effect on patient outcomes. Redistricting and allocation-sharing schemes should seek to equalize regional supply and demand rather than attempting to equalize patient outcomes.
Models to project survival after liver transplantation are important to optimize outcomes. We introduced the survival outcomes following liver transplantation (SOFT) score in 2008 (1) and designed to predict survival in liver recipients at three months post-transplant with a C statistic of 0.70. Our objective was to validate the SOFT score, with more contemporaneous data from the OPTN database. We also applied the SOFT score to cohorts of the sickest transplant candidates and the poorest-quality allografts. Analysis included 21 949 patients transplanted from August 1, 2006, to October 1, 2010. Kaplan-Meier survival functions were used for time-to-event analysis. Model discrimination was assessed using the area under the receiver operating characteristic (ROC) curve. We validated the SOFT score in this cohort of 21 949 liver recipients. The C statistic was 0.70 (CI 0.68-0.71), identical to the original analysis. When applied to cohorts of high-risk recipients and poor-quality donor allografts, the SOFT score projected survival with a C statistic between 0.65 and 0.74. In this study, a validated SOFT score was informative among cohorts of the sickest transplant candidates and the poorest-quality allografts.
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