Transplantation: impact of pretransplant renal insufficiency.

Pre-liver transplant renal dysfunction is associated with decreased survival following transplantation and is also a prognostic indicator of posttransplant chronic kidney disease. Selection of patients for combined liver/kidney transplantation versus orthotopic liver transplantation alone (OLTa) is often difficult given the lack of a reliable method to predict which patients will have ongoing severe renal dysfunction in the absence of concomitant kidney transplantation. We hypothesized that most patients with pretransplant renal dysfunction (serum creatinine > or = 1.5 mg/dL for at least 2 weeks prior to and at time of transplant) will not experience a rapid decline in estimated glomerular filtration rates (eGF) post-OLTa to the point of necessitating consideration for kidney transplantation, even in the setting of calcineurin inhibitor-based immunosuppression. We performed a single-center retrospective study of 60 OLTa patients with pretransplant renal dysfunction transplanted between 2000 and 2005. Kaplan-Meier analysis was performed of the time interval to develop eGFR < 20 mL/minute post-OLTa. At OLTa, the mean patient age was 59 years, and median serum creatinine was 1.8 mg/dL; 42% patients were hepatitis C-positive, 32% were diabetic, 38% had kidney dysfunction > 12 weeks, and 5% were receiving hemodialysis. After 36 months median follow-up post-OLTa, only 8 patients (13%) with significant renal dysfunction pre-OLTa achieved eGFR < 20 mL/minute. Patients with pretransplant kidney dysfunction > 12 weeks were at increased risk for eGFR < 20 mL/minute (hazard ratio = 5.3, P = 0.04), a risk that escalated after adjustment for age and serum creatinine at transplant (hazard ratio = 8.9, P = 0.01). Significant predictors of eGFR < 20 mL/minute post-OLTa in this patient cohort were the presence of diabetes and the serum creatinine level at transplant. In conclusion, few patients with preexisting renal dysfunction, especially if <12 weeks duration, experience a significant drop in eGFR post-OLTa.

A critical review of candidacy for orthotopic liver transplantation in alcoholic liver disease.

The majority of candidates with end-stage alcoholic liver disease (ESALD) in the United States who are eligible for referral for liver transplantation (LT) are not being referred. There is a lack of firm consensus for the duration of abstinence from alcohol as well as what constitutes good psychosocial criteria for listing for LT. Evidence shows that the general public and the practicing physicians outside the transplant community perceive that patients with a history of alcohol abuse will make poor transplant candidates. However, physicians in the transplant community perceive selected patients with ESALD as good candidates. When considering patients for listing for LT, 3 months of alcohol abstinence may be more ideal than 6 months. Patients with a lack of social support, active smoking, psychotic or personality disorders, or a pattern of nonadherence should be listed only with reservation. Those who have a diagnosis of alcohol abuse as opposed to alcohol dependence may make better transplant candidates. Patients who have regular appointments with a psychiatrist or psychologist in addictions treatment training also seem to do more favorably.

Association between proton pump inhibitor use and spontaneous bacterial peritonitis.

Proton pump inhibitors (PPIs) increase enteric bacterial colonization, overgrowth, and translocation, all effects which might predispose to spontaneous bacterial peritonitis. We investigated whether PPI usage is associated with spontaneous bacterial peritonitis. Our retrospective case-control study included 116 consecutive cirrhotic patients with ascites who underwent diagnostic paracentesis upon hospital admission (2002-2005). Spontaneous bacterial peritonitis was defined as paracentesis yielding >or=250 polymorphonuclear leukocytes/ml. We performed logistic regression to determine the risk of spontaneous bacterial peritonitis by PPI usage. Of the 116 subjects, 32 had spontaneous bacterial peritonitis. Patient characteristics were similar between groups with and without infection, with the exception of the Model for End-Stage Liver Disease score (median: 23 and 18, respectively; P = 0.002). Crude and adjusted odds ratios for the development of spontaneous bacterial peritonitis by exposure to PPIs were 1.22 (95% confidence interval: 0.52-2.87) and 1.05 (0.43-2.57), respectively. In conclusion, we did not find a positive association between PPI use and spontaneous bacterial peritonitis.

Association between model for end-stage liver disease and spontaneous bacterial peritonitis.

OBJECTIVE: To determine whether a greater Model for End-Stage Liver Disease (MELD) score is associated with a greater risk of spontaneous bacterial peritonitis (SBP). METHODS: Our retrospective case-control study enrolled 271 consecutive patients with cirrhosis and ascites who underwent diagnostic paracentesis upon hospital admission (2002-2005). After excluding immunosuppressed patients, those recently exposed to antibiotics, those with a potential confounding etiology for ascites, and those with a prior history of SBP, 111 were included in the study. SBP was defined as a paracentesis yielding>or=250 neutrophils/mL ascites fluid. Multivariable logistic regression was performed to determine the odds ratio for the development of SBP associated with MELD score and grouped MELD score (or=25). Potential confounders assessed included age, diabetes mellitus, gender, race, alcohol use, serum sodium, and etiology of liver disease. RESULTS: Twenty-nine of 111 hospitalized patients with cirrhosis were found to have SBP. Patient characteristics were similar between groups with and without SBP. The mean MELD score for patients with SBP was 24 and for those without 18 (P=0.0003). The odds ratio for developing SBP by each MELD point was 1.11 (1.05-1.19, P=0.001). Patients with MELD>or=25 had an odds ratio of 9.67 (2.35-39.82, P=0.002) for SBP, compared to subjects with MELD

Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation.

Small uncontrolled series have suggested that sirolimus favorably impacts renal function after orthotopic liver transplantation (OLT). We sought to retrospectively compare renal dysfunction between cohorts exposed to sirolimus-based and calcineurin inhibitor-based immunosuppression. We retrospectively studied 79 patients converted to sirolimus-based immunosuppression and 100 control subjects continued on calcineurin inhibitor-based immunosuppression after OLT at our institution from 2000 to 2005. We collected clinical, demographic, and medication history. Renal dysfunction was defined as two or more wk of creatinine > or =2.0 mg/dL. Cohorts were compared using Kaplan-Meier survival analysis and Cox proportional hazards modeling. Patients began sirolimus a median 83 d post-OLT and were followed on the medication for median 359 d. Patients in both the sirolimus and calcineurin inhibitor cohorts had median creatinine 1.2 mg/dL at study entry. Sirolimus-based immunosuppression was associated with a 1.8 (0.8-4.3, p = 0.17) hazards ratio for renal dysfunction. Adjusting for presence of hepatocellular carcinoma, combined kidney/liver transplantation, and age, the hazards ratio was 2.0 (0.8-4.8, p = 0.13). These point estimates were not substantially altered after subgroup analysis of sirolimus as the lone immunosuppressant, duration of exposure, and time between OLT and sirolimus conversion. In conclusion, our retrospective, controlled study showed that conversion to sirolimus after OLT did not protect against renal dysfunction. The effect of sirolimus on renal function will need to be prospectively evaluated in a prospective, randomized trial.

Effects of hepatitis C-induced liver fibrosis on survival in kidney transplant candidates.

We sought to investigate survival among kidney transplant candidates with varying degrees of liver fibrosis. We studied 108 patients with hepatitis C+ who underwent pre-kidney transplant liver biopsy (1992-2004). Eighteen patients had advanced fibrosis (bridging fibrosis or cirrhosis), and 90 had lesser degrees of fibrosis. Advanced fibrosis patients were younger and had lower prevalence of diabetes. Survival was similar between those with and without advanced fibrosis among all 108 patients (P = 0.92) and among the 58 patients who underwent kidney transplantation (P = 0.83). Fibrosis stage was associated with a 1.1 (0.72, 1.7; P = 0.65) adjusted hazards ratio for mortality among all 108 patients and a 0.64 (0.24, 1.73; P = 0.38) adjusted hazards ratio among the 58 patients who underwent kidney transplantation. These data support the premise that non-liver disease comorbidities are more important outcome determinants in this population. Kidney transplantation alone may be considered in patients with hepatitis C with compensated cirrhosis or bridging fibrosis.

Recurrence of diseases following orthotopic liver transplantation.

Long-term graft survival and mortality after liver transplantation continue to improve. However, disease recurrence remains a major stumbling block, especially among patients with hepatitis C. Chronic hepatitis C recurs to varying degrees in nearly all patients who undergo transplantation. Transplantation for hepatitis C is associated with higher rates of graft failure and death compared with transplantation for other indications, and retransplantation for hepatitis C related liver failure remains controversial. Recurrence of hepatitis B has been markedly reduced with improved prophylactic regimens. Further, rates of hepatocellular carcinoma recurrence have also decreased, as improved patient selection criteria have prioritized transplantation for those with a low risk of recurrence. Primary biliary cirrhosis recurs in some patients, but it is often relatively mild. Autoimmune liver disease has also been shown to have a relatively benign post-transplantation course, but some studies have indicated that it slowly progresses in most recipients. It has been recently reported that alcoholic liver disease liver transplant recipients who return to drinking have worsened mortality. In such patients worse outcomes are not due to graft failure, but instead to other comorbidities. Recurrences of other diseases, including nonalcoholic steatohepatitis and primary sclerosing cholangitis, are now being recognized as having potentially detrimental effects on graft survival and mortality. Expert clinical management may help prevent and treat complications associated with disease recurrence.

Successful aspiration and ethanol sclerosis of a large, symptomatic, simple liver cyst: case presentation and review of the literature.

Simple liver cysts are congenital with a prevalence of 2.5%-4.25%. Imaging, whether by US, CT or MRI, is accurate in distinguishing simple cysts from other etiologies, including parasitic, neoplastic, duct-related, and traumatic cysts. Symptomatic simple liver cysts are rare, and the true frequency of symptoms is not known. Symptomatic simple liver cysts are predominantly large (> 4 cm), right-sided, and more common in women and older patients. The vast majority of simple hepatic cysts require no treatment or follow-up, though large cysts (> 4 cm) may be followed initially with serial imaging to ensure stability. Attribution of symptoms to a large simple cyst should be undertaken with caution, after alternative diagnoses have been excluded. Aspiration may be performed to test whether symptoms are due to the cyst; however, cyst recurrence should be expected. Limited experience with both laparoscopic deroofing and aspiration, followed by instillation of a sclerosing agent has demonstrated promising results for the treatment of symptomatic cysts. Here, we describe a patient with a large, symptomatic, simple liver cyst who experienced complete resolution of symptoms following cyst drainage and alcohol ablation, and we present a comprehensive review of the literature.

Quality of life in refractory ascites: transjugular intrahepatic portal-systemic shunting versus medical therapy.

Uncontrolled studies suggest that transjugular intrahepatic portal-systemic shunting (TIPS) may improve quality of life in patients with refractory ascites. We hypothesized that any improvement of quality of life in patients with TIPS would be matched in controls due to the competing effects of improved ascites and worsened hepatic encephalopathy. Thus, an analysis of quality of life was performed using original data from the North American Study for the Treatment of Refractory Ascites, a multicenter trial of 109 patients randomized to TIPS or repeated large volume paracentesis (LVP) for refractory ascites. Short form 36 (SF-36) surveys were completed at baseline and at 6- and 12-month follow-up. Variables analyzed were: randomization group, number of LVP performed, cumulative volume from LVP, shortness of breath, abdominal distention, abdominal pain, diuretic usage, confusion, hospitalizations, and emergency room visits. Outcomes were changes in physical component scale (PCS) and mental component scale (MCS) of SF-36 results. We constructed multivariable, mixed effects models, including randomization group and baseline MCS and PCS. Changes in PCS and MCS from baseline were similar between the two randomization groups. In multivariate analysis, PCS improvement was associated with lack of confusion, improved ascites, and lack of hospitalizations, but not directly with randomization group. Improvement in MCS was associated with randomization to TIPS and lack of confusion. In conclusion, patients with refractory ascites randomized to TIPS or repeated LVP had similar changes in quality of life. Competing effects of hepatic encephalopathy, requirement for repeated LVP, and need for hospitalizations explain similar changes in quality of life between the two groups.

Renal function after orthotopic liver transplantation is predicted by duration of pretransplantation creatinine elevation.

In patients with recent onset renal insufficiency, the decision to perform combined kidney/liver transplantation (CKLT) vs. orthotopic liver transplantation alone (OLTa) can be difficult. We hypothesized that duration of renal dysfunction may correlate with creatinine elevation after liver transplantation. We retrospectively identified 69 liver transplantation patients with pretransplantation creatinine > or =1.5 mg/dL (53 OLTa, 13 CKLT). Variables analyzed were presence of hepatorenal syndrome, creatinine, Model for End-Stage Liver Disease score, albumin, age, race, gender, cause of liver disease, diabetes mellitus, hypertension, and history of ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, renal replacement therapy (RRT), and transjugular intrahepatic portosystemic shunting. Duration of pretransplantation renal dysfunction was predictive of 6- and 12-month creatinine post-OLTa. Area under the receiver operating characteristic (ROC) curve for prediction of 12-month renal insufficiency by renal dysfunction duration was 0.71; optimal duration cutoff was 3.6 weeks. We applied a multivariable model, derived from OLTa patients, to CKLT subjects with definite or possible hepatorenal syndrome. Predicted 12-month creatinine without renal transplantation was >2.0 mg/dL for each patient. CKLT patients as opposed to OLTa patients had longer duration of renal dysfunction (median, 18.1 vs. 2.7 weeks, P < 0.001), higher creatinine (median 4.0 versus 1.7 mg/dL, P < 0.001), and higher rate of pretransplantation RRT (62% vs. 7%, P < 0.001). Adjusting for baseline characteristics, CKLT patients had lower creatinine than OLTa patients at 6 months (P =0.15) and 12 months (P =0.01) after transplantation. In conclusion, duration, but not cause, of renal dysfunction predicts renal outcome in OLTa recipients. Prospective studies may use duration of renal dysfunction to help identify CKLT candidates.

Severity of liver disease does not predict osteopenia or low bone mineral density in primary sclerosing cholangitis.

BACKGROUND: The association between metabolic bone disease and cholestatic liver disease has been poorly characterized. To date a single institution has published data suggesting that in primary sclerosing cholangitis (PSC), advanced liver disease predicts advanced bone disease. AIM: To determine the association between the severity of liver disease and bone mineral density (BMD) in PSC patients. METHODS: We identified 30 PSC patients who had undergone dual energy X-ray absorptiometry (DXA) scan. We compared lumbar spine DXA scores between patients with more and less advanced liver disease. RESULTS: Nine patients were osteopenic (30%), and one patient was osteoporotic. Five patients were female (17%), and none was postmenopausal. BMD was not different between patients listed and not listed for liver transplantation (P = 0.49) or between patients with and without hepatic decompensation (P = 0.63). Model for end-stage liver disease (MELD) score (P = 0.99) and the modified Mayo risk score (P = 0.25) did not predict BMD. CONCLUSIONS: Our study is the first to suggest that low bone density cannot be predicted by the severity of liver disease in PSC. Perhaps other known risk factors for osteoporosis will be important predictors of abnormal bone density in this patient population.