Andres E. Ruf

Addition of serum sodium into the MELD score predicts waiting list mortality better than MELD alone

In this study, we investigated the prognostic value of serum sodium and hyponatremia (≤130 mEq/L) in 262 cirrhotic patients consecutively listed, 19 of which died (7%), 175 survived (67%), and 68 underwent liver transplantation (26%) during 3 months of follow‐up. Hyponatremia was present in 63% of patients who died, compared to 13% of those who survived (P < .001), whereas the proportion with elevated creatinine (≥1.4 mg/dL) was low and similar in both groups (10.5 vs. 3%). Prevalence of hyponatremia was higher than that of elevated serum creatinine across all model for end‐stage liver disease (MELD) categories. Using logistic regression, hyponatremia and serum sodium were significant predictors of mortality with concordance statistics (c‐statistics) .753 for hyponatremia, .784 for sodium, .894 for MELD, .905 for MELD plus hyponatremia (P = .006 vs. MELD alone), and .908 for MELD plus serum sodium (P = .026 vs. MELD alone). Risk of death across all MELD scores was higher for patients with hyponatremia than without hyponatremia. Cox regression considering data within 6 months of follow‐up yielded qualitatively similar results, with hyponatremia being a significant predictor of greater mortality risk with an odds ratio of 2.65 (P = .015). Each increase of 1 mEq/L of serum sodium level was associated with a decreased odds ratio of .95 (P = .048). Our results indicate that hyponatremia appears to be an earlier and more sensitive marker than serum creatinine to detect renal impairment and / or circulatory dysfunction in patients with advanced cirrhosis. In conclusion, addition of serum sodium to MELD identified a subgroup of patients with poor outcome in a more efficient way than MELD alone and significantly increased the efficacy of the score to predict waitlist mortality. (Liver Transpl 2005;11:336–343.)

MELD is superior to King's college and Clichy's criteria to assess prognosis in fulminant hepatic failure

Assessment of prognosis in fulminant hepatic failure (FHF) is essential for the need and appropriate timing of orthotopic liver transplantation (OLT). In this study we investigated the prognostic efficacy of Kings College criteria, Clichys criteria, Model for End‐Stage Liver Disease (MELD), and Pediatric End‐Stage Liver Disease (PELD) in 120 consecutive patients with FHF. Survival with medical therapy (18%), death without OLT (15%), and receipt of a liver transplant were similar in adults (n = 64) and children (n = 56). MELD scores were significantly higher in patients who died compared to those who survived without OLT, both in adults (38 ± 7 vs. 26 ± 7, P = 0.0003) and children (39 ± 7 vs. 23 ± 6, P = 0.0004). Using logistic regression analysis in this cohort of patients, concordance statistics were significantly higher for MELD (0.95) and PELD (0.99) when compared to Kings College (0.74) and Clichys criteria (0.68). When data was analyzed in a Cox model including patients receiving transplants and censoring the time from admission, the concordance statistic for MELD (0.77) and PELD (0.79) remained significantly higher than that of Kings College criteria but not higher than that of Clichys criteria. In conclusion, this study is the first to show that MELD and PELD are superior to Kings College and Clichys criteria to assess prognosis in FHF. However, because data was generated from a single center and included a rather low number of patients who survived or died without OLT, further confirmation of our findings is required. Liver Transpl 13:822–828, 2007.

Early and frequent histological recurrence of Crohn's disease in small intestinal allografts.

Background. Recurrence of Crohns disease in small intestinal allografts, although rarely described, can cause serious morbidity and jeopardize graft survival among transplant recipients with Crohns disease. However, systematic studies to determine the frequency, predictors, and clinical implications of recurrent Crohns disease have not been reported Methods. We analyzed our transplant programs experience with small intestinal allografts in patients with Crohns disease based on retrospective review of clinical and pathological records and corresponding pathology slides. Results. Of 67 patients undergoing 70 transplantations between 1998 and 2004, six adults (three males, three females; mean age 48.1 years) had Crohns disease complicated by short gut syndrome and total parenteral nutrition failure. Four survivors surveyed endoscopically for a mean 29 (range, 20–40) months and underwent a mean 37 endoscopic examinations with biopsies (range, 31–44) while on maintenance immunosuppression. Despite absence of any endoscopic or clinical manifestations of Crohns disease throughout this period, two patients had granulomatous enteritis characteristic of Crohns disease in multiple biopsies, one patient in 8/44 examinations (18%) ranging from 34 days to 20 months postoperatively and the other in 6/32 examinations (19%) ranging from 20 days to 22 months postoperatively. No comparable changes occurred in 57 other patients without Crohns disease followed endoscopically under the same protocol Conclusions. Histological recurrence of Crohns disease may occur in small intestinal allografts despite the absence of endoscopic and clinical disease manifestations. Such recurrences are probably not rare, may occur as early as 3 weeks after transplantation, and do not necessarily portend early clinical recurrence or mandate aggressive therapy to prevent allograft loss.

How common is delayed cyclosporine absorption following liver transplantation

The mean time to peak absorption of cyclosporine (CsA) in liver transplant patients is approximately 2 hours, but in some patients the peak occurs later. The goal of this study was, therefore, to investigate the incidence of delayed absorption in 27 de novo liver transplant recipients receiving CsA ≥10 mg/kg/day (C2 monitoring) and in 15 maintenance patients. Patients were categorized as ‘normal’ absorbers (C2 exceeding C4 and C6) or ‘delayed’ absorbers (C4 or C6 exceeding C2), and as ‘good’ (>800 ng/mL at C0, C2, C4, or C6) or ‘poor’ absorbers (C0, C2, C4 and C6 <800 ng/mL) on the day of study. Among de novo patients, 15 (56%) had ‘normal’ CsA absorption and 12 (44%) ‘delayed’ absorption. Good CsA absorption occurred in 16 patients (59%) and poor absorption in 11 (41%). The proportion of poor absorbers was similar in patients with normal (6 / 15, 40%) or delayed (5 / 12, 42%) absorption. Among the 12 delayed absorbers, 11 had peak CsA concentration at C4. Mean C0 level was significantly higher in delayed absorbers (282 ± 96 ng/mL) than in normal absorbers (185 ± 88ng/mL; P = .01). Delayed absorbers reverted to normal absorption (C2 > C4) after a median of 6 days from the day of study, and no cases of delayed absorption were found among maintenance patients. In conclusion, almost 50% of the patients had delayed CsA absorption early posttransplant; around half of these exhibited normal CsA exposure. Measurement of C4 in addition to C2 differentiates effectively between delayed and poor absorbers of CsA such that over‐ or underimmunosuppression can be avoided. (Liver Transpl 2005;11:167–173.)

Visceral Kaposi's Sarcoma Remission After Intestinal Transplant. First Case Report and Systematic Literature Review

Background. Kaposis sarcoma (KS) is an infrequent vascular neoplasm commonly diagnosed as an isolated cutaneous lesion that can involve other organs. So far, there are no data in the literature about the development of KS after intestinal transplant. Methods. In this study, the authors describe a case of “visceral KS” with pulmonary and intestinal involvement and perform a systematic literature review of case reports and single-center series identified in MEDLINE. Results. This case was a 42-year-old man, diagnosed with visceral KS 9 months after receiving an isolated intestinal transplant. He was successfully treated with a combination of sirolimus and liposomal doxorubicin and achieved an 18-month disease-free survival. A total of 54 cases from 27 manuscripts and the present case were analyzed in this study. The mean time from transplant to diagnosis was 17.2 months. Lungs and gastrointestinal tract were the main organs involved. Immunosuppressants were discontinued in two of the three (66.7%) cases, and sirolimus was added in eight cases. Doxorubicin was used in 12 cases. In a univariate analysis, the use of Tacrolimus, type of transplant, and presence of cutaneous KS seem to be the significant predictors of response to therapy and survival; the addition of doxorubicin showed a reduction in graft loss. Conclusions. Treatment of KS in posttransplant patients should be designed aiming to obtain a complete response, irrespective of the organ affected. Only recipients who are able to achieve a sustained response would be able to obtain long-term disease-free survival.

Which is the holy grail in liver transplantation: Hyponatremia, MELD, or a combination?

We read with interest the paper by Ruf et al. published in a recent issue of Liver Transplantation.1 This study aimed to look at the predictive ability of the Model for End-Stage Liver Disease (MELD) with or without the addition of serum sodium level. The authors found that for patients with cirrhosis, MELD in combination with hyponatremia may further increase the predictive ability compared with MELD alone. Although their findings are generally consistent with those in a recent study which showed that serum sodium is an independent poor prognostic predictor in patients with advanced cirrhosis,2 a potential flaw of the study by Ruf et al.1 is that ascites has not been incorporated into the prognostic model to justify its usefulness. It is noteworthy that in the current study by Ruf et al.1 all of the 34 hyponatremic patients also had concomitant clinical ascites. Interestingly, of the 19 patients who died within 3 months of listing, 90% of patients had clinical ascites, compared with 63% who had hyponatremia. These results highly suggest that in addition to hyponatremia, ascites is also possibly a strong negative predictor. Failure to incorporate this important factor into the predictive model for comparison may compromise their results and conclusions. MELD has become the prevailing criteria for organ allocation in liver transplantation. However, the MELD system may not serve all patients equally well and could have certain limitations.3 Another study suggested that inclusion of hepatic encephalopathy into the prognostic model may add additional prognostic value to the MELD score.4 Alternatively, ascites and hyponatremia were two important prognostic predictors, especially in patients with cirrhosis who had lower range MELD scores.5 In addition, MELD has a potential inherent limitation in that the occurrence of encephalopathy or ascites does not correlate well with the MELD score.6 These data indicate that patients with certain unfavorable predictors, such as ascites, hyponatremia, or encephalopathy, do not necessarily have a higher MELD score and the priority for transplantation could be downstaged in the MELD era. We agree that the MELD system is particularly useful as a tool to fairly allocate donor organs in a large patient population as a whole. Nevertheless, since patients awaiting transplantation are intrinsically heterogeneous and could have different clinical scenarios, an additional prognostic predictor that has powerful differentiation ability should be incorporated into the MELD model for further refinement.