Shahid Habib

The survival outcomes following liver transplantation (SOFT) score: validation with contemporaneous data and stratification of high‐risk cohorts

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.

Survival of cystic fibrosis patients undergoing liver and liver-lung transplantations.

BACKGROUND We evaluated the outcome of combined liver-lung transplantation (L-LTx) in cystic fibrosis (CF) patients with liver transplantation (LTx) for CF liver disease. METHODS The United Network for Organ Sharing (UNOS) data were analyzed from October 1987 to August 2009. RESULTS Of 294 patients (210 children), 265 (90.1%) received an LTx and 29, an L-LTx. Patient survival was: adult LTx, 80%, 74%, and 67% at 1, 3, and 5 years, and L-LTx, 72%, 61.4%, and 61.4% (P = .7); pediatric LTx, 85%, 82%, and 74% at 1, 3, and 5 years, and L-LTx, 83%, 83%, and 83% (P = .4). Pediatric patients had a slight survival advantage over adults for LTx (P = .08). Graft survival, not affected by immunosuppression regimens, was similar to patient survival. CONCLUSIONS The outcome of L-LTx appears similar to LTx in CF providing support for the prospect of a combined transplant.

Geographic inequities in liver allograft supply and demand: Does it affect patient outcomes?

Background Significant geographic inequities mar the distribution of liver allografts for transplantation. Methods We analyzed the effect of geographic inequities on patient outcomes. During our study period (January 1 through December 31, 2010), 11,244 adult candidates were listed for liver transplantation: 5,285 adult liver allografts became available, and 5,471 adult recipients underwent transplantation. We obtained population data from the 2010 United States Census. To determine the effect of regional supply and demand disparities on patient outcomes, we performed linear regression and multivariate Cox regression analyses. Results Our proposed disparity metric, the ratio of listed candidates to liver allografts available varied from 1.3 (region 11) to 3.4 (region 1). When that ratio was used as the explanatory variable, the R2 values for outcome measures were as follows: 1-year waitlist mortality, 0.23 and 1-year posttransplant survival, 0.27. According to our multivariate analysis, the ratio of listed candidates to liver allografts available had a significant effect on waitlist survival (hazards ratio, 1.21; 95% confidence interval, 1.04–1.40) but was not a significant risk factor for posttransplant survival. Conclusion 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.

Early liver retransplantation in adults

Up to 23% of liver allografts fail post‐transplant. Retransplantation is only the recourse but remains controversial due to inferior outcomes. The objective of our study was to identify high‐risk periods for retransplantation and then compare survival outcomes and risk factors. We performed an analysis of United Network for Organ Sharing (UNOS) data for all adult liver recipients from 2002 through 2011. We analyzed the records of 49 288 recipients; of those, 2714 (5.5%) recipients were retransplanted. Our analysis included multivariate regression with the outcome of retransplantation. The highest retransplantation rates were within the first week (19% of all retransplantation, day 0–7), month (20%, day 8–30), and year (33%, day 31–365). Only retransplantation within the first year (day 0–365) had below standard outcomes. The most significant risk factors were as follows: within the first week, cold ischemia time >16 h [odds ratio (OR) 3.6]; within the first month, use of split allografts (OR 2.9); and within the first year, use of a liver donated after cardiac death (OR 4.9). Each of the three high‐risk periods within the first year had distinct causes of graft failure, risk factors for retransplantation, and survival rates after retransplantation.

Big spleens and hypersplenism: fix it or forget it?

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.

Vasopressin V2-receptor antagonists in patients with cirrhosis, ascites and hyponatremia.

Hyponatremia is a common problem in patients with advanced cirrhosis. It develops slowly (paralleling the rate of progression of the liver disease) and usually produces no neurological symptoms, although it may exacerbate hepatic encephalopathy. For patients awaiting liver transplantation a low serum sodium level is a strong predictor of pretransplant mortality, independent of the Model for End-stage Liver Disease score (MELD). The pathogenesis of hyponatremia is related to the hemodynamic changes and secondary neurohormonal adaptations that occur in patients with cirrhosis and ascites. The nonosmotic release of arginine vasopressin is the principle cause of the hyponatremia and vasopressin-receptor antagonists are a new class of drugs recently approved for treatment of cirrhotic hyponatremia. In this article we review the safety and efficacy of V2-receptor antagonists in patients with cirrhosis, ascites and hyponatremia.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial

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, Maddreys 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.

A critical analysis of early death after adult liver transplants.

The 15% mortality rate of liver transplant recipients at one yr may be viewed as a feat in comparison with the waiting list mortality, yet it nonetheless leaves room for much improvement. Our aim was to critically examine the mortality rates to identify high‐risk periods and to incorporate cause of death into the analysis of post‐transplant survival.

Differential Simultaneous Liver and Kidney Transplant Benefit Based on Severity of Liver Damage at the Time of Transplantation

Background We evaluated the concept of whether liver failure patients with a superimposed kidney injury receiving a simultaneous liver and kidney transplant (SLKT) have similar outcomes compared to patients with liver failure without a kidney injury receiving a liver transplantation (LT) alone. Methods Using data from the United Network of Organ Sharing (UNOS) database, patients were divided into five groups based on pre-transplant model for end-stage liver disease (MELD) scores and categorized as not having (serum creatinine (sCr) ≤ 1.5 mg/dL) or having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT, 14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis. Results Survival in those (liver failure with renal dysfunction) receiving SLKT was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD group with renal dysfunction with or without SLKT. In high MELD recipients (MELD > 30) with renal dysfunction, presence of renal dysfunction affects the outcome and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of renal dysfunction at the time of transplantation does affect post-transplant survival, but survival is improved with SLKT. Conclusions SLKT improved 1-year survival only in low MELD (16 - 20) recipients but not in other groups. Performance of SLKT should be limited to patients where a benefit in survival and post-transplant outcomes can be demonstrated.

Slower Fibrosis Progression Among Liver Transplant Recipients With Sustained Virological Response After Hepatitis C Treatment

Background The natural course of hepatic fibrosis in HCV allograft recipients with sustained virological response (SVR) after anti-HCV therapy remains debatable. The aim of this study was to examine the progression of fibrosis in a cohort of patients who achieved SVR compared with those without treatment. Methods The 167 patients who met the inclusion and exclusion criteria were chosen from a transplant database. All patients were required to have histological evidence of recurrent HCV infection post-liver transplantation and a follow-up biopsy. The 140 of these patients had received anti-viral therapy. Twenty-seven patients were identified as controls and were matched with the treatment group in all respects. The patients were categorized into four groups based on treatment response: 1) no treatment (control) (n = 27); 2) non-responders (n = 81); 3) relapsers (n = 32); and 4) SVR (n = 27). The endpoint was the stage of fibrosis on the follow-up liver biopsy. Results The treated and untreated groups were similar in clinical characteristics at the time of transplantation and prior to the initiation of treatment. The 72% of the cohort showed a fibrosis progression of ≥ 1 stage; this change did not significantly differ between the patient groups. Nonetheless, the fibrosis progression rate was the highest in the untreated group and lowest in the patients who achieved SVR. A coefficient of determination was used. Improvements in fibrosis scores were found with greater treatment duration. These improvements were most evident with the achievement of SVR. Conclusions In conclusion, SVR after anti-viral therapy for recurrent hepatitis C infection post-transplantation was associated with slower fibrosis progression and significantly improved graft survival.