Background
Liver transplantation for peri-hilar cholangiocarcinoma (pCCA) following neoadjuvant chemoradiation achieves excellent long-term survival in carefully selected patients with early-stage ...unresectable pCCA and patients with primary sclerosing cholangitis (PSC)–associated pCCA. Strict adherence to selection criteria, aggressive neoadjuvant therapy, operative staging prior to transplantation, and several technical accommodations during the transplant operation are necessary for success. In this review, we provide a contemporaneous overview of liver transplantation for pCCA, including selection criteria, neoadjuvant therapy, operative staging, and technical aspects of liver transplantation unique to patients with pCCA and an irradiated operative field. We also discuss several evolving trends intended to improve patient outcomes.
Results and Conclusion
Intention-to-treat and patient outcomes after liver transplantation for PSC-associated pCCA are superior to de novo pCCA. Outcomes between living donor liver transplantation (LDLT) and deceased donor liver transplantation are similar for patients with PSC-associated pCCA. However, LDLT for de novo pCCA shows a trend toward more disease recurrence and worse patient survival. A period of waiting time before transplant may be beneficial in selecting for patients with superior outcomes after transplant. Compared with liver transplantation for other indications, there is an increased risk of late arterial and portal vein complications, presumably due to the radiation. However, with close follow-up and prompt intervention for vascular complications, graft loss can be avoided. Neoadjuvant therapy and liver transplantation can achieve results comparable with resection for patients with early-stage unresectable pCCA and is the treatment of choice for patients with pCCA arising in the setting of PSC.
Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, ...approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients.
Survival after living donor liver transplantation (LDLT) in the United States is excellent. However, the significance of pretransplant kidney disease on outcomes in this population is poorly ...understood.
This was a retrospective cohort study of 2806 LDLT recipients nationally between January 2010 and June 2020. Recipients with estimated glomerular filtration rate <40 mL/min/1.73 m2 (eGFR-low) or requiring dialysis were compared. Multivariable survival analyses evaluated (1) eGFR-low as a predictor of post-LDLT survival and (2) the survival of LDLT versus deceased donor liver transplant (DDLT) alone with eGFR-low.
From 2010 to 2020, 140 (5.0%) patients had eGFR-low and 18 (0.6%) required dialysis pre-LDLT. The number of LDLTs requiring dialysis between 2017 and 2020 outnumbered the prior 7 y. Overall LDLT experience was greater at centers performing LDLT in recipients with renal dysfunction (P < 0.001). LDLT recipients with eGFR-low had longstanding renal dysfunction: mean eGFR 3-6 mo before LDLT 42.7 (±15.1) mL/min/1.73 m2. Nearly half (5/12) of eGFR-low recipients with active kidney transplant (KT) listing at LDLT experienced renal recovery. Five patients underwent early KT after LDLT via the new "safety net" policy. Unadjusted survival after LDLT was worse with eGFR-low (hazard ratio 2.12 versus eGFR ≥40 mL/min/1.73 m2; 95% confidence interval, 1.47-3.05; P < 0.001), but no longer so when accounting for mean eGFR 3-6 mo pre-LDLT (hazard ratio, 1.27; 95% confidence interval, 0.82-1.95; P = 0.3). The adjusted survival of patients with eGFR-low receiving LDLT versus deceased donor liver transplant alone was not different (P = 0.08).
Overall, outcomes after LDLT with advanced renal dysfunction are acceptable. These findings are relevant given the recent "safety net" KT policy.
Sex-based disparities in liver transplantation (LT) are incompletely understood. We assessed the role of height, Model for End-Stage Liver Disease (MELD), MELD-Na, and exception points in the ...disparate access to LT.
Adults waitlisted for LT at Organ Procurement and Transplantation Network between 2002 and 2013 were included. Covariates associated with likelihood of LT were analyzed by Cox proportional model. In a separate cohort of waitlisted adults with glomerular filtration rate measurement by iothalamate clearance (n = 611), we determined the number of creatinine-derived MELD points in men versus women, across all ranges of glomerular filtration rate. The impact of correcting the MELD score deficit in women on LT was modeled.
Among 90 720 Organ Procurement and Transplantation Network registrants, women had higher mortality than men (4 years after listing: 22% vs 18%, P < 0.0001), and lower likelihood of LT (49% vs 58%, P < 0.0001); women were 20% less likely to be transplanted (hazard ratio, 0.80; 95% confidence interval, 0.78-0.81). Differences in height and MELD exception scores accounted for most of the LT deficit in women (hazard ratio, 0.91; 95% confidence interval, 0.89-0.94). Women received between 1 and 2.4 fewer creatinine-derived MELD points than men with similar renal dysfunction. MELD-Na worsened the gender disparity. Addition of 1 or 2 MELD points to women significantly impacted LT access.
Differences in height and MELD exception points explained most of the sex-based disparity in LT. Additionally, MELD score underestimated disease severity in women by up to 2.4 points and MELD Na exacerbated this disparity. The degree of underestimation based on MELD had significant impact on allocation.
Liver transplantation for cholangiocarcinoma Rosen, Charles B.; Heimbach, Julie K.; Gores, Gregory J.
Transplant international,
July 2010, Letnik:
23, Številka:
7
Journal Article
Recenzirano
Summary
Liver transplantation following high dose neoadjuvant radiotherapy with chemosensitization achieves excellent results for patients with early stage, unresectable hilar cholangiocarcinoma or ...cholangiocarcinoma arising in the setting of primary sclerosing cholangitis.
Background and Aims
Alcoholic hepatitis (AH) is diagnosed by clinical criteria, although several objective scores facilitate risk stratification. Extracellular vesicles (EVs) have emerged as ...biomarkers for many diseases and are also implicated in the pathogenesis of AH. Therefore, we investigated whether plasma EV concentration and sphingolipid cargo could serve as diagnostic biomarkers for AH and inform prognosis to permit dynamic risk profiling of AH subjects.
Approach and Results
EVs were isolated and quantified from plasma samples from healthy controls, heavy drinkers, and subjects with end‐stage liver disease (ESLD) attributed to cholestatic liver diseases and nonalcoholic steatohepatitis, decompensated alcohol‐associated cirrhosis (AC), and AH. Sphingolipids were quantified by tandem mass spectroscopy. The median plasma EV concentration was significantly higher in AH subjects (5.38 × 1011/mL) compared to healthy controls (4.38 × 1010/mL; P < 0.0001), heavy drinkers (1.28 × 1011/mL; P < 0.0001), ESLD (5.35 × 1010/mL; P < 0.0001), and decompensated AC (9.2 × 1010/mL; P < 0.0001) disease controls. Among AH subjects, EV concentration correlated with Model for End‐Stage Liver Disease score. When EV counts were dichotomized at the median, survival probability for AH subjects at 90 days was 63.0% in the high‐EV group and 90.0% in the low‐EV group (log‐rank P value = 0.015). Interestingly, EV sphingolipid cargo was significantly enriched in AH when compared to healthy controls, heavy drinkers, ESLD, and decompensated AC (P = 0.0001). Multiple sphingolipids demonstrated good diagnostic and prognostic performance as biomarkers for AH.
Conclusions
Circulating EV concentration and sphingolipid cargo signature can be used in the diagnosis and differentiation of AH from heavy drinkers, decompensated AC, and other etiologies of ESLD and predict 90‐day survival permitting dynamic risk profiling.
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