Faculty Bibliography

With the implementation of the Model for End-Stage Liver Disease (MELD) scoring system, the number of combined liver-kidney transplants (CLKT) has increased dramatically. The United Network for Organ Sharing (UNOS) dataset was analysed for adult recipients with renal failure for the period between February 2002 and April 2006. This group was subdivided into patients on hemodialysis (HD) and to those not on HD prior to transplantation. All recipients in renal failure (serum creatinine > or =2.5 mg/dl) at the time of transplantation were included. A total of 1397 subjects were in renal failure but not on HD (18% received a CLKT, 82% underwent LT alone). Another 1740 subjects were on HD prior to transplantation (41% received a CLKT while 59% received a LT). In dialysis-dependent recipients, Cox regression analysis demonstrated CLKT had an independent protective effect. In subjects on HD, CLKT had improved survival at 1 year (79.4 vs. 73.7%, P = 0.004). In patients in renal failure without HD, CLKT was not protective. CLKT subjects had a nonsignificant difference in survival as compared with patients who had undergone liver transplantation alone, at 1 year (81.0% vs. 78.8%, P > 0.10). In subjects undergoing CLKT, there was improved survival at 1 year as compared with LT-alone patients on hemodialysis; however, in patients with renal failure, but not on hemodialysis, there was no difference in survival when comparing CLKT to LT-alone.

BACKGROUND/AIMS/OBJECTIVE:Non-alcoholic steatohepatitis (NASH) is a growing public health problem. Evaluation of risk factors for fibrosis in NASH will help to target resources to reduce development of cirrhosis. This study had two aims; the first to compile longitudinal histological data to characterize the natural history of fibrosis progression in NASH, and second, to identify predictive factors for progression to advanced fibrosis (stage 3 or greater) in NASH. METHODS:Subjects had to have a histological diagnosis compatible with NASH on their initial biopsy, received no intervention of proven histological benefit, and undergone two liver biopsies with at least an interval of one year between them. RESULTS:Ten studies were selected comprising 221 patients. 37.6% had progressive fibrosis over a mean follow-up interval of 5.3 years (SD, 4.2 years, median, 3.7 years, range 1.0-21.3 years). Proportional hazards regression analysis demonstrated that age (HR=0.98, p=0.009) and inflammation on initial biopsy (any inflammation, HR=2.5, p=0.001; grade 1, HR=2.5, p=0.001; grade 2, HR=2.4, p=0.003) are independent predictors of progression to advanced fibrosis. Other traditional parameters (e.g. obesity, diabetes, hypertension) were not statistically significant predictors. CONCLUSIONS:Presence of inflammation on the initial biopsy and age are independent predictors of progression to advanced fibrosis in patients with NASH.

Advanced age has been shown to be a risk factor for survival in primary liver transplantation. We sought to determine the independent influence of recipient age on retransplantation survival. The UNOS dataset was analyzed for adult, nonstatus 1, liver retransplantations since February 27, 2002. The univariate effect of age on 90-day and 1-year survival was analyzed. Multivariate survival models were used to determine 90-day, 1-year, and overall survival. Recipient age, donor age, model for end-stage liver disease (MELD) score, and hepatitis C status were used to construct multivariable survival models. Some 2141 liver retransplantations were analyzed. Overall, increasing recipient age was independently predictive of increasing mortality after liver retransplantation. In recipients between 18 and 60, there remained a direct relationship between age and mortality. However, in recipients aged over 60, increasing age was not independently associated with 90-day mortality (P = 0.88) and 1-year mortality (P = 0.74), despite adjusting for donor age, MELD score, and viral hepatitis status, suggesting that their original liver condition, their co-morbidities or perioperative condition plays an important role in retransplantation survival. Increasing recipient age up to 60, adversely affects liver retransplantation survival. After 60, there are no additional risks. Advanced age alone should not be an exclusionary factor when considering liver retransplantation; only the overall ability of the patient to tolerate a major surgery should be the determining factor.

Using outcomes data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, we performed a cost-effectiveness analysis exploring the costs and benefits of living donor liver transplantation (LDLT). A multistage Markov decision analysis model was developed with treatment, including medical management only (strategy 1), waiting list with possible deceased donor liver transplantation (DDLT; strategy 2), and waiting list with possible LDLT or DDLT (strategy 3) over 10 years. Decompensated cirrhosis with medical management offered survival of 2.0 quality-adjusted life years (QALYs) while costing an average of $65,068, waiting list with possible DDLT offered 4.4-QALY survival and a mean cost of $151,613, and waiting list with possible DDLT or LDLT offered 4.9-QALY survival and a mean cost of $208,149. Strategy 2 had an incremental cost-effectiveness ratio (ICER) of $35,976 over strategy 1, whereas strategy 3 produced an ICER of $106,788 over strategy 2. On average, strategy 3 cost $47,693 more per QALY than strategy 1. Both DDLT and LDLT were cost-effective compared to medical management of cirrhosis over our 10-year study period. The addition of LDLT to a standard waiting list DDLT program is effective at improving recipient survival and preventing waiting list deaths but at a greater cost.

This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

The coagulopathy of liver disease is complex and often unpredictable. Despite clear evidence of an increased tendency for bleeding in patients who have cirrhosis, many circumstances also promote local and systemic hypercoagulable states. The consequences of hypercoagulability include the obvious morbidity and mortality of portal vein thrombosis, deep vein thrombosis, and pulmonary embolism, but possibly also include other end-organ syndromes, such as portopulmonary hypertension, hepatorenal syndrome, and spontaneous bacterial peritonitis. A more subtle contribution also could be responsible for progression of early fibrosis to decompensated cirrhosis. Future research is needed to elucidate specific mechanistic pathways that might lead to local hypercoagulation and the clinical interventions that might prevent morbidity and mortality related to hypercoagulation in patients who have cirrhosis.

BACKGROUND:Hepatic hydrothorax in the setting of decompensated cirrhosis is a challenging and common clinical problem. Traditional therapies such as diuretics and transjugular intrahepatic portosystemic shunts can be effective therapies in selected patients but in patients ineligible for, or intolerant of, these traditional therapies, few effective therapeutic options remain for the management of hepatic hydrothorax. METHODS:We present a series of 5 consecutive patients with refractory hepatic hydrothorax who underwent combined thorascopically guided mechanical and chemical pleurodesis aided by an intraperitoneal drain that prevented reaccumulation of the ascites while pleural inflammation and adhesion were progressing. We speculate that the prolonged contact between the parietal and visceral pleura allowed by prevention of reaccumulation of intraabdominal ascites and subsequent flux through the pleural space enhanced the efficacy of this procedure in comparison with those presented in the literature. RESULTS:Despite the fact that all of our patients presented with decompensated cirrhosis, the surgical procedure and subsequent hospitalization were tolerated well by our entire cohort. Colonization of the pleural and peritoneal drainage fluid was a common complication of this procedure but was not associated with prolonged morbidity or mortality. CONCLUSIONS:We present a therapy for the difficult clinical problem of refractory hepatic hydrothorax that may allow selected patients an opportunity for prolonged symptomatic control.

OBJECTIVES/OBJECTIVE:Lymph nodes normally have prominent centrally located blood vessels, which may become obliterated with tumor infiltration. The presence of intranodal vasculature has been noted to coincide with benign cytology. We sought to determine the test characteristics of the presence of intranodal mediastinal vasculature during endoscopic ultrasound (EUS). METHODS:67 mediastinal lymph nodes evaluated by EUS in 66 patients over a 1-year period were evaluated for the presence of intranodal vasculature, which was considered benign when it traversed through the node without disruption. RESULTS:Of the 67 lymph nodes evaluated, 29 (43%) were found to be malignant on cytopathologic review. Benign vascular markings were present in 15/67 (22.4%) lymph nodes evaluated. All 15 (100%) of these nodes were found to have benign fine-needle aspiration (FNA) results. The presence of benign vasculature had a negative predictive value of 100%. CONCLUSIONS:The presence of intranodal vasculature was universally associated with a benign diagnosis. The addition of this EUS finding improves the ability to characterize lymph nodes and predict the likelihood of malignant involvement.

BACKGROUND:Current management of malignant gastric outlet obstruction (GOO) includes surgical diversion or enteral stent placement for unresectable cancer. We analyzed the long-term results, predictive factors of outcomes, and complications associated with enteral stents with focus on their management. METHODS:Between 1997 and 2007, 46 patients with malignant GOO underwent placement of self-expandable metal stents (SEMS) for palliation. Patients were captured prospectively after 2001 and followed until complication or death. Patency, management of complications, and long-term survival were analyzed. RESULTS:Forty-six patients had a mean survival of 152 +/- 235 days and a mean SEMS patency rate of 111 +/- 220 days. SEMS patency rates of 98%, 74%, and 57% at 1, 3, and 6 months were seen. Thirteen patients presented with obstruction and included two SEMS migration, two early occlusion, one fracture, four malignant ingrowth, and four with delayed clinical failure. Interventions included seven endoscopic revisions with three SEMS replacements. Six had percutaneous endoscopic gastrostomy with jejunal arm placed. Two patients eventually underwent surgical bypass. Two patients required surgery for complications including delayed duodenal perforation and aortoenteric fistula. CONCLUSIONS:SEMS effectively palliate gastric outlet obstructions that result from upper gastrointestinal malignancies. Their benefits offset potential complications or malfunctions, when a pluridisciplinary approach is adopted.