A quantitative metabolomics profiling approach for the noninvasive assessment of liver histology in patients with chronic hepatitis C.

BACKGROUND: High-throughput technologies have the potential to identify non-invasive biomarkers of liver pathology and improve our understanding of basic mechanisms of liver injury and repair. A metabolite profiling approach was employed to determine associations between alterations in serum metabolites and liver histology in patients with chronic hepatitis C virus (HCV) infection. METHODS: Sera from 45 non-diabetic patients with chronic HCV were quantitatively analyzed using (1)H-NMR spectroscopy. A metabolite profile of advanced fibrosis (METAVIR F3-4) was established using orthogonal partial least squares discriminant analysis modeling and validated using seven-fold cross-validation and permutation testing. Bioprofiles of moderate to severe steatosis (≥33 %) and necroinflammation (METAVIR A2-3) were also derived. The classification accuracy of these profiles was determined using areas under the receiver operator curves (AUROCSs) measuring against liver biopsy as the gold standard. RESULTS: In total 63 spectral features were profiled, of which a highly significant subset of 21 metabolites were associated with advanced fibrosis (variable importance score >1 in multivariate modeling; R(2) = 0.673 and Q(2) = 0.285). For the identification of F3-4 fibrosis, the metabolite bioprofile had an AUROC of 0.86 (95 % CI 0.74-0.97). The AUROCs for the bioprofiles for moderate to severe steatosis were 0.87 (95 % CI 0.76-0.97) and for grade A2-3 inflammation were 0.73 (0.57-0.89). CONCLUSION: This proof-of-principle study demonstrates the utility of a metabolomics profiling approach to non-invasively identify biomarkers of liver fibrosis, steatosis and inflammation in patients with chronic HCV. Future cohorts are necessary to validate these findings.

A Model to Identify Sarcopenia in Patients With Cirrhosis.

BACKGROUND & AIMS: The severe depletion of muscle mass at the third lumbar vertebral level (sarcopenia) is a marker of malnutrition and is independently associated with mortality in patients with cirrhosis. Instead of monitoring sarcopenia by cross-sectional imaging, we investigated whether ultrasound-based measurements of peripheral muscle mass, measures of muscle function, along with nutritional factors, are associated with severe loss of muscle mass. METHODS: We performed a prospective study of 159 outpatients with cirrhosis (56% male; mean age, 58 ± 10 years; mean model for end-stage liver disease score, 10 ± 3; 60% Child-Pugh class A) evaluated at the Cirrhosis Care Clinic at the University of Alberta Hospital from March 2011 through September 2012. Lumbar skeletal muscle indices were determined by computed tomography or magnetic resonance imaging. We collected clinical data and data on patients' body composition, nutrition, and thigh muscle thickness (using ultrasound analysis). We also measured mid-arm muscle circumference, mid-arm circumference, hand grip, body mass index, and serum level of albumin; patients were evaluated using the subjective global assessment scale. Findings from these analyses were compared with those from cross-sectional imaging, for each sex, using logistic regression analysis. RESULTS: Based on cross-sectional imaging analysis, 43% of patients had sarcopenia (57% of men and 25% of women). Results from the subjective global assessment, serum level of albumin, and most nutritional factors were significantly associated with sarcopenia. We used multivariate analysis to develop a model to identify patients with sarcopenia, and developed a nomogram based on body mass index and thigh muscle thickness for patients of each sex. Our model identified men with sarcopenia with an area under the receiver operating characteristic curve value of 0.78 and women with sarcopenia with an area under the receiver operating characteristic curve value of 0.89. CONCLUSIONS: In a prospective study of patients with cirrhosis, we found that the combination of body mass index and thigh muscle thickness (measured by ultrasound) can identify male and female patients with sarcopenia almost as well as cross-sectional imaging (area under the receiver operating characteristic curve values of 0.78 and 0.89, respectively). These factors might be used in screening and routine nutritional monitoring of patients with cirrhosis.

Liver stiffness by transient elastography predicts liver-related complications and mortality in patients with chronic liver disease.

BACKGROUND: Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) is a validated method for noninvasively staging liver fibrosis. Most hepatic complications occur in patients with advanced fibrosis. Our objective was to determine the ability of LSM by TE to predict hepatic complications and mortality in a large cohort of patients with chronic liver disease. METHODS: In consecutive adults who underwent LSM by TE between July 2008 and June 2011, we used Cox regression to determine the independent association between liver stiffness and death or hepatic complications (decompensation, hepatocellular carcinoma, and liver transplantation). The performance of LSM to predict complications was determined using the c-statistic. RESULTS: Among 2,052 patients (median age 51 years, 65% with hepatitis B or C), 87 patients (4.2%) died or developed a hepatic complication during a median follow-up period of 15.6 months (interquartile range, 11.0-23.5 months). Patients with complications had higher median liver stiffness than those without complications (13.5 vs. 6.0 kPa; P<0.00005). The 2-year incidence rates of death or hepatic complications were 2.6%, 9%, 19%, and 34% in patients with liver stiffness <10, 10-19.9, 20-39.9, and ≥40 kPa, respectively (P<0.00005). After adjustment for potential confounders, liver stiffness by TE was an independent predictor of complications (hazard ratio [HR] 1.05 per kPa; 95% confidence interval [CI] 1.03-1.06). The c-statistic of liver-stiffness for predicting complications was 0.80 (95% CI 0.75-0.85). A liver stiffness below 20 kPa effectively excluded complications (specificity 93%, negative predictive value 97%); however, the positive predictive value of higher results was sub-optimal (20%). CONCLUSIONS: Liver stiffness by TE accurately predicts the risk of death or hepatic complications in patients with chronic liver disease. TE may facilitate the estimation of prognosis and guide management of these patients.

Validation of the five-variable Model for End-stage Liver Disease (5vMELD) for prediction of mortality on the liver transplant waiting list.

BACKGROUND: Modifications to the Model for End-Stage Liver Disease (MELD) have been proposed to improve prioritization of liver transplant (LT) candidates. Using a U.S. database, we derived a revised MELD including sodium and albumin [5-variable MELD (5vMELD)] that improved prediction of waiting list mortality. Our objectives were to confirm the association between hypoalbuminaemia and mortality and to externally validate 5vMELD in Canadian LT candidates. METHODS: Among adults registered on the LT waiting list at the University of Alberta (01/2000-10/2009), Cox regression determined the association between albumin and 1-year waiting list mortality. The discrimination of MELD, MELDNa and 5vMELD for predicting 1-year mortality were compared using c-statistics. RESULTS: Among 677 patients, 17% died and 51% underwent LT within 1 year of listing. Median serum albumin was 3.1 g/dl (IQR 2.6-3.6) and 70% of patients were hypoalbuminaemic (albumin <3.5 g/dl). One-year mortality in patients with normal serum albumin and hypoalbuminaemia were 14% and 29% respectively (P = 0.004). For patients with serum albumin between 2.0 and 4.0 g/dl, an approximately linear, inverse relationship was observed between albumin and 1-year mortality [adjusted hazard ratio (HR) 1.45; 95% CI 1.03-2.03; P = 0.03]. For this outcome, the c-statistic of 5vMELD (0.778) was superior to those of MELD (0.754) and MELDNa (0.765) (both P ≤ 0.05). CONCLUSIONS: Hypoalbuminaemia is an independent predictor of mortality on the LT waiting list. Compared with MELD and MELDNa, 5vMELD improves prediction of mortality suggesting that modification of these scores to include serum albumin should be considered as a means of prioritizing LT candidates.

Survival after hepatic resection: impact of surgeon training on long-term outcome.

BACKGROUND: Mortality for liver resection has remarkably improved owing to multiple factors. We sought to determine the impact of the various types of fellowship training on patient survival after liver resection. METHODS: Patients who underwent hepatic resection between 1995 and 2004 in either the Calgary or Capital health regions (Edmonton) of Alberta, Canada, were identified using ICD-9 and -10 codes. Primary outcomes included in-hospital mortality and patient survival according to surgeon volume and training type (surgical oncology v. hepatobiliary v. others). RESULTS: A total of 1033 patients underwent hepatic resection. Surgeon volume was not predictive of either in-hospital mortality (adjusted odds ratio 0.63, 95% confidence interval [CI] 0.32-1.20) or patient survival (unadjusted hazard ratio 1.11, 95% CI 0.82-1.51). Nonsignificance was also demonstrated for a surgeon's type of fellowship training. CONCLUSION: The various modes of fellowship training do not appear to influence inhospital mortality or patient survival after hepatic resection.

CONTEXTE: Le taux de mortalité dans les cas de résection du foie a diminué considérablement à cause de multiples facteurs. Nous avons cherché à déterminer l'effet des divers types de formation au niveau du fellowship sur la survie des patients après une résection du foie. MÉTHODES: Les patients qui ont subi une résection hépatique entre 1995 et 2004 dans les régions sanitaires de Calgary ou de la Capitale (Edmonton) de l'Alberta, au Canada, ont été identifiés au moyen des codes CIM-9 et 10. La mortalité à l'hôpital et la survie des patients selon le volume de patients traités par le chirurgien et le type de la formation (oncologie chirurgicale c. hépatobiliaire c. autres) ont constitué les principales mesures de résultats. RÉSULTANTS: Au total, 1033 patients ont subi une résection hépatique. Le volume de patients traités par le chirurgien n'était pas un prédicteur de mortalité à l'hôpital (rapport de cotes rajusté, 0,63, intervalle de confiance [IC] à 95 % 0,32­1,20) ni de survie du patient (rapport de risque non rajusté, 1,11, IC à 95 % 0,82­1,51). On a aussi démontré la non importance de la formation au niveau du fellowship selon le type de chirurgien. CONCLUSIONS: Les divers modes de formation au niveau du fellowship ne semblent pas avoir d'effet sur la mortalité à l'hôpital ou la survie des patients après une résection hépatique.

B-cell depletion with rituximab in patients with primary biliary cirrhosis refractory to ursodeoxycholic acid.

OBJECTIVES: Rituximab, an anti-CD20 monoclonal antibody that selectively depletes B cells, has shown promise in autoantibody-associated, immune-mediated disorders. As ursodeoxycholic acid (UDCA) is not successful in all patients with primary biliary cirrhosis (PBC), additional treatment options are necessary. The objective of this study was to assess the safety and efficacy of rituximab in patients with PBC refractory to UDCA. METHODS: Fourteen PBC patients refractory to UDCA received two rituximab infusions (1,000 mg) 2 weeks apart. The primary efficacy outcome was normalization and/or 25% improvement in serum alkaline phosphatase (ALP) concentration at 6 months. RESULTS: The median age was 53 years, and 92% were female and antimitochondrial antibody (AMA) positive. The median UDCA dosage was 15.3 mg/kg/day (interquartile range 14.5-17.8). Although rituximab was well tolerated, one patient withdrew due to an asthma exacerbation during the first infusion. Effective B-cell depletion was observed in the remaining 13 patients, including three that developed human anti-chimeric antibodies. ALP normalization and/or ≥ 25% improvement was observed in three patients (23%) at 6, 12, and 18 months. Significant reductions in median ALP (from 259 U/l at baseline to 213 U/l at 6 months; median decrease 16%), and serum IgM and AMA levels were observed at 6 months. Although fatigue was stable, pruritus improved in 60% of patients at 12 months (vs. 8% with worsening pruritus). CONCLUSIONS: Selective B-cell depletion with rituximab was safe and associated with a significant decrease in autoantibody production, but had limited biochemical efficacy in PBC patients with an incomplete response to UDCA.

Revision of MELD to include serum albumin improves prediction of mortality on the liver transplant waiting list.

BACKGROUND: Allocation of donor livers for transplantation in most regions is based on the Model for End-Stage Liver Disease (MELD) or MELD-sodium (MELDNa). Our objective was to assess revisions to MELD and MELDNa that include serum albumin for predicting waiting list mortality. METHODS: Adults registered for liver transplantation in the United States (2002-2007) were identified from the United Network for Organ Sharing (UNOS) database. Cox regression was used to determine the association between serum albumin and 3-month mortality, and to derive revised MELD and MELDNa scores incorporating albumin ('MELD-albumin' and '5-variable MELD [5vMELD]'). RESULTS: Among 40,393 patients, 9% died and 24% underwent transplantation within 3 months of listing. For serum albumin concentrations between 1.0 and 4.0 g/dL, a linear, inverse relationship was observed between albumin and 3-month mortality (adjusted hazard ratio per 1 g/dL reduction in albumin: 1.44; 95% CI 1.35-1.54). The c-statistics for 3-month mortality of MELD-albumin and MELD were 0.913 and 0.896, respectively (P<0.001); 5vMELD was superior to MELDNa (c-statistics 0.922 vs. 0.912, P<0.001). The potential benefit of 5vMELD was greatest in patients with low MELD (<15). Among low MELD patients who died, 27% would have gained ≥10 points with 5vMELD over MELD versus only 4-7% among low MELD survivors and high MELD (≥15) candidates (P<0.0005). CONCLUSION: Modification of MELD and MELDNa to include serum albumin is associated with improved prediction of waiting list mortality. If validated and shown to be associated with reduced mortality, adoption of 5vMELD as the basis for liver allograft allocation may improve outcomes on the liver transplant waiting list.

Hospital performance reports based on severity adjusted mortality rates in patients with cirrhosis depend on the method of risk adjustment .

BACKGROUND: Hospital outcome report cards are used to judge provider performance, including for liver transplantation. We aimed to determine the impact of the choice of risk adjustment method on hospital rankings based on mortality rates in cirrhotic patients. MATERIAL AND METHODS: We identified 68,426 cirrhotic patients hospitalized in the Nationwide Inpatient Sample database. Four risk adjustment methods (the Charlson/Deyo and Elixhauser algorithms, Disease Staging, and All Patient Refined Diagnosis Related Groups) were used in logistic regression models for mortality. Observed to expected (O/E) death rates were calculated for each method and hospital. Statistical outliers with higher or lower than expected mortality were identified and rankings compared across methods. RESULTS: Unadjusted mortality rates for the 553 hospitals ranged from 1.4 to 30% (overall, 10.6%). For 163 hospitals (29.5%), observed mortality differed significantly from expected when judged by one or more, but not all four, risk adjustment methods (25.9% higher than expected mortality and 3.6% lower than expected mortality). Only 28% of poor performers and 10% of superior performers were consistently ranked as such by all methods. Agreement between methods as to whether hospitals were flagged as outliers was moderate (kappa 0.51-0.59), except the Charlson/Deyo and Elixhauser algorithms which demonstrated excellent agreement (kappa 0.75). CONCLUSIONS: Hospital performance reports for patients with cirrhosis require sensitivity to the method of risk adjustment. Depending upon the method, up to 30% of hospitals may be flagged as outliers by one, but not all methods. These discrepancies could have important implications for centers erroneously labeled as high mortality outliers.

Risk of comorbidities on postoperative outcomes in patients with inflammatory bowel disease.

BACKGROUND: The effect of comorbidities on postoperative outcomes in patients with inflammatory bowel disease (IBD) has not been explored adequately. We evaluated the prevalence of comorbidities and their effect on postoperative outcomes after an IBD-related operation. METHODS: The Nationwide Inpatient Sample database was used to identify 35 588 patients with IBD who underwent an IBD-related operation from January 1, 1995, through December 31, 2005. The presence of comorbid illness was assessed using the Elixhauser index. Multiple logistic regression analysis was performed to evaluate the effect of comorbidities on mortality rate after adjusting for age, sex, race, health insurance status, and admission type. Linear regression models were used to evaluate health care resource use. RESULTS: Postoperative mortality was 1.9%. As the number of comorbidities increased (ie, 0, 1, 2, or ≥3), postoperative mortality increased (0.4%, 1.5%, 3.3%, and 7.9%, respectively). Congestive heart failure (odds ratio, 3.50 [95% confidence interval, 2.63-4.62]), liver disease (3.15 [2.00-4.97]), thromboembolic disease (4.19 [3.37-5.21]), and renal disease (8.74 [5.44-14.05]) were associated with a significant increase in mortality rate. Comorbidities associated with an increased risk of mortality also were associated with a significant increase in length of stay and hospital charges. CONCLUSIONS: Comorbidities were common in patients with IBD and they significantly increased the risk of postoperative mortality and health care use in patients with IBD.

Amoebic liver abscess in USA: a population-based study of incidence, temporal trends and mortality.

BACKGROUND: Amoebic liver abscess (ALA) may be associated with significant morbidity and mortality, but nationwide American data is unavailable. Our objective was to describe ALA epidemiology and outcomes in USA from a population-based perspective. METHODS: Patients hospitalized with ALA between 1993 and 2007 were identified using the Nationwide Inpatient Sample. Patient characteristics, interventions and outcomes including mortality were determined. The annual incidence of ALA and temporal trends were determined using the negative binomial regression models. RESULTS: Between 1993 and 2007, 848 hospitalizations for ALA, corresponding to ∼4100 hospitalizations nationwide, were identified. The annual incidence was 1.38 per million population with a 2.4% [95% confidence interval (CI) 0-4.8%; P=0.06] average annual decline during this study. Most patients were hospitalized in western (54%) and southern states (27%), and 48% were Hispanic. Males (incidence rate ratio vs. females: 4.53; 95% CI 4.19-4.90) had the highest incidence rates. Percutaneous and surgical drainage was required in 48 and 7% of patients respectively. Although length of stay [median, 6 days; interquartile range (IQR) 4-10] and hospital charges (US$25,345; IQR US$15,030-42, 275) were substantial, in-hospital mortality was rare (0.8%). Females [odds ratio (OR) 6.12; CI 1.39-26.8], patients ≥ 60 years (OR 13.3; 95% CI 2.5-71.5), and those with ≥ 3 comorbidities (OR 5.80; 95% CI 1.30-25.8), particularly malnutrition, had an increased risk of death. CONCLUSIONS: ALA is rare and the incidence has decreased in USA. Young, Hispanic males in southwestern states are most frequently affected. Mortality caused by ALA is lower than what was reported previously.

Elective resection of colon cancer by high-volume surgeons is associated with decreased morbidity and mortality.

BACKGROUND: The purpose of this study was to determine whether morbidity and mortality in patients undergoing elective resection of colon cancer are associated with surgeon or hospital volume. METHODS: Using the Nationwide Inpatient Sample database, we identified all adult patients who underwent elective resection for colon cancer as their primary procedure between 2003 and 2007. Cases were divided into three groups according to the mean number of resections performed annually by each surgeon: low volume (≤4/year), intermediate volume (5-9/year), or high volume (≥10/year). Annual hospital case-load was also categorized as low volume (≤30/year), intermediate volume (31-60/year), and high volume (≥61/year). Multiple logistic regression models were used to identify differences in morbidity and mortality. RESULTS: A total of 54,000 patients underwent resection of colon cancer by 7,313 surgeons in 1,398 hospitals. After adjusting for important covariates including hospital volume, colon cancer resection by high-volume surgeons was an independent predictor of decreased morbidity (odds ratio [OR], 0.91; 95% CI, 0.85-0.97) and mortality (OR, 0.75; 95% CI, 0.65-0.86). Mortality was lowest among patients operated on by high-volume surgeons in high-volume hospitals (2.2% vs. 3.9%; OR, 0.56; 95% CI, 0.46-0.68). CONCLUSIONS: In patients undergoing elective resection of colon cancer, procedures done by high-volume surgeons are associated with decreased morbidity and mortality.

Gender, renal function, and outcomes on the liver transplant waiting list: assessment of revised MELD including estimated glomerular filtration rate.

BACKGROUND & AIMS: The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation (LT) may present a disadvantage for women by including serum creatinine, which is typically lower in females. Our objectives were to investigate gender disparities in outcomes among LT candidates and to assess a revised MELD, including estimated glomerular filtration rate (eGFR), for predicting waiting list mortality. METHODS: Adults registered for LT between 2002 and 2007 were identified using the UNOS database. We compared components of MELD, MDRD-derived eGFR, and the 3-month probability of LT and death between genders. Discrimination of MELD, MELDNa, and revised models including eGFR for mortality were compared using c-statistics. RESULTS: A total of 40,393 patients (36% female) met the inclusion criteria; 9% died and 24% underwent LT within 3 months of listing. Compared with men, women had lower median serum creatinine (0.9 vs. 1.0 mg/dl), eGFR (72 vs. 83 ml/min/1.73 m(2)), and mean MELD (16.5 vs. 17.2; all p <0.0005), but within most MELD strata, had higher bilirubin and INR. After adjusting for relevant covariates including creatinine and body weight, women were less likely than men to receive a LT (hazard ratio [HR] 0.85; 95% CI 0.79-0.87) and had greater 3-month mortality (HR 1.13; 95% CI 1.05-1.21). Revision of MELD and MELDNa to include eGFR did not improve discrimination for 3-month mortality (c-statistics: MELD 0.896, MELD-eGFR 0.894, MELDNa 0.911, MELDNa-eGFR 0.905). CONCLUSIONS: Women are disadvantaged under MELD potentially due to its inclusion of creatinine. However, since including eGFR in MELD does not improve mortality prediction, alternative refinements are necessary.

Morbidity and mortality following colorectal surgery in patients with end-stage renal failure: a population-based study.

PURPOSE: The risk of abdominal surgery in patients with end-stage renal failure is poorly defined. Our objective was to describe outcomes of colorectal surgery in dialysis patients from a population-based perspective. METHODS: We analyzed the 1993 to 2007 Nationwide Inpatient Sample to identify patients hospitalized for colorectal surgery. The effect of renal failure on mortality, complications, length of stay, and charges was evaluated using logistic regression models. RESULTS: Between 1993 and 2007, there were 755,343 admissions for colorectal surgery in the Nationwide Inpatient Sample database; 5806 patients (0.77%) were receiving dialysis treatment (87.4% hemodialysis, 4.9% peritoneal dialysis, 7.7% method not specified). Patients undergoing dialysis had an increased risk of mortality (22.1% vs 2.8%; adjusted OR 4.83; 95% CI 4.58-5.31) and complications (52.1% vs 34.0%; adjusted OR 2.04; 95% CI 1.90-2.17). Dialysis patients undergoing nonelective procedures had a 2-fold higher mortality rate than patients having had elective surgery (25.5% vs 10.3%; adjusted OR 2.01; 95% CI 1.65-2.43). In nonelective surgery, independent predictors of mortality included procedures with an end-stoma (adjusted OR 1.86; 95% CI 1.58-2.18), age over 60 (adjusted OR 1.73; 95% CI 1.43-2.08), total colectomy (adjusted OR 1.68; 95% CI 1.27-2.22), vascular insufficiency as surgical indication (adjusted OR 1.58; 95% CI 1.32-1.90), nonprivate insurance coverage (adjusted OR 1.38; 95% CI 1.07-1.77) and malnutrition (adjusted OR 1.26; 95% CI 1.01-1.59). CONCLUSIONS: Patients receiving dialysis treatment have an increased risk of morbidity and mortality following colorectal surgery. Elective procedures are associated with a 10% rate of mortality in this population. Dialysis patients are especially susceptible to infectious and pulmonary complications after colorectal resection. Additional studies are necessary to refine risk stratification in this high-risk patient population.

Validation of coding algorithms for the identification of patients with primary biliary cirrhosis using administrative data.

BACKGROUND: Large-scale epidemiological studies of primary biliary cirrhosis (PBC) have been hindered by difficulties in case ascertainment. OBJECTIVE: To develop coding algorithms for identifying PBC patients using administrative data--a widely available data source. METHODS: Population-based administrative databases were used to identify patients with a diagnosis code for PBC from 1994 to 2002. Coding algorithms for confirmed PBC (two or more of antimitochondrial antibody positivity, cholestatic liver biochemistry and/or compatible liver histology) were derived using chart abstraction data as the reference. Patients with a recorded PBC diagnosis but insufficient confirmatory data were classified as 'suspected PBC'. RESULTS: Of 189 potential PBC cases, 119 (60%) had confirmed PBC and 28 (14%) had suspected PBC. The optimal algorithm including two or more uses of a PBC code had a sensitivity of 94% (95% CI 71% to 100%) and positive predictive values of 73% (95% CI 61% to 75%) for confirmed PBC, and 89% (95% CI 82% to 94%) for confirmed or suspected PBC. Sensitivity analyses revealed greater accuracy among women, and with the use of multiple data sources and one or more years of data. Inclusion of diagnosis codes for conditions frequently misclassified as PBC did not improve algorithm performance. CONCLUSIONS: Administrative databases can reliably identify patients with PBC and may facilitate epidemiological investigations of this condition.

The outcomes of pregnancy in patients with cirrhosis: a population-based study.

BACKGROUND: The outcomes of pregnancy in patients with cirrhosis are poorly described. Our objective was to assess obstetric outcomes in cirrhotic women and their infants from a population-based perspective. METHODS: We analysed the 1993-2005 US Nationwide Inpatient Sample database to identify obstetric hospitalizations among patients with cirrhosis (n=339) and controls matched on age, hospital and year (n=6625). The effect of cirrhosis on maternal and fetal outcomes was evaluated using regression models with adjustment for patient and hospital factors. RESULTS: Between 1993 and 2005, 114 antepartum and 225 delivery admissions in cirrhotic patients were identified. The estimated mean number of deliveries nationwide increased from 68 to 106 annually between 1993 and 1999 and 2000 and 2005 (P=0.0004). Patients with cirrhosis were more likely to deliver by caesarean [42 vs. 28%; adjusted odds ratio (OR) 1.41; 95% confidence interval (CI) 1.06-1.88]. Maternal (1.8 vs. 0%; P<0.0001) and fetal mortality (5.2 vs. 2.1%; P<0.0001), antepartum admission (OR 2.97; 95% CI 2.24-3.96), and maternal (OR 2.03; 95% CI 1.60-2.57) and fetal complications (OR 3.66; 95% CI 2.74-4.88) were greater among cirrhotic patients than controls. Gestational hypertension, placental abruption and uterovaginal haemorrhage were more common in patients with cirrhosis; their infants had higher rates of prematurity and growth restriction. Hepatic decompensation occurred in 15%, including ascites in 11% and variceal haemorrhage in 5%. In women with decompensation, maternal and fetal mortality were 6 and 12% respectively. CONCLUSIONS: Although rare, pregnancies among women with cirrhosis are increasing. Cirrhotic patients and their infants have an increased risk of obstetric complications, emphasizing the importance of close maternal-fetal monitoring during pregnancy.

Pregnancy outcomes among liver transplant recipients in the United States: a nationwide case-control analysis.

Liver transplant recipients and their infants may have an increased risk of obstetric complications. Our objective was to describe pregnancy outcomes in women with a prior transplant from a population-based perspective. We analyzed the 1993-2005 US Nationwide Inpatient Sample database to identify obstetric hospitalizations among transplant recipients (n = 206) and controls matched by age, hospital, and year (n = 4060). The effect of prior transplantation on maternal and fetal outcomes was evaluated with regression models with adjustments for patient and hospital factors, including admission to a transplant center. Between 1993 and 2005, 146 delivery admissions among liver transplant recipients were identified. Cesarean deliveries were more common among transplant recipients (38% versus 24%; P = 0.0001); however, this difference was not significant after multivariate adjustment [OR (odds ratio) = 0.87; 95% confidence interval (CI) = 0.60-1.27]. Maternal mortality was similar among cases and controls (0% versus 0.02%; P = 1.00), but transplant patients had higher rates of fetal mortality (6.3% versus 2.0%; P = 0.0006), antepartum admission (OR = 2.27; 95% CI = 1.59-3.25), and maternal (OR = 2.63; 95% CI = 1.82-3.80) and fetal complications (OR = 2.49; 95% CI = 1.68-3.70). Gestational hypertension (30% versus 9%; P < 0.0001) and postpartum hemorrhage (8% versus 3%; P = 0.009) were more common among transplant recipients; their infants had higher rates of prematurity (27% versus 11%; P < 0.0001), distress (10% versus 5%; P = 0.005), and growth restriction (5% versus 2%; P = 0.05) but not congenital anomalies. Hospitalization in a transplant center ( approximately 50%) was associated with similar obstetric outcomes. In conclusion, although most pregnancy outcomes are favorable, liver transplant recipients and their infants have an increased risk of obstetric complications. Additional studies evaluating mechanisms aimed at reducing these complications are necessary.

Epidemiology and natural history of primary biliary cirrhosis in a Canadian health region: a population-based study.

UNLABELLED: The recent epidemiology and outcomes of primary biliary cirrhosis (PBC) in North America are incompletely described, partly due to difficulties in case ascertainment. In light of their availability, broad coverage, and limited expense, administrative databases may facilitate such investigations. We used population-based administrative data (inpatient, ambulatory care, and physician billing databases) and a validated International Classification of Diseases coding algorithm to describe the epidemiology and natural history of PBC in the Calgary Health Region (population approximately 1.1 million). Between 1996 and 2002, the overall age/sex-adjusted annual incidence of PBC was 30.3 cases per million (48.4 per million in women, 10.4 per million in men). Although the incidence remained stable, the prevalence increased from 100 per million in 1996 to 227 per million in 2002 (P < 0.0005). Among 137 incident cases with a total follow-up of 801 person-years from diagnosis (median 5.8 years), 27 patients (20%) died and six (4.4%) underwent liver transplantation. The estimated 10-year probabilities of survival, liver transplantation, and transplant-free survival were 73% (95% confidence interval [CI] 60%-83%), 6% (95% CI 2.5%-12.6%), and 68% (95% CI 55%-78%), respectively. Survival in PBC patients was significantly lower than that of the age/sex-matched Canadian population (standardized mortality ratio 2.87; 95% CI 1.89-4.17); male sex (hazard ratio [HR] 3.80; 95% CI 1.85-7.82) and an older age at diagnosis (HR per additional year, 1.06; 95% CI 1.03-1.10) were independent predictors of mortality. CONCLUSION: This population-based study demonstrates that the burden of PBC in Canada is high and growing. Survival of PBC patients is significantly lower than that of the general population, emphasizing the importance of developing new therapies for this condition.

Morbidity and mortality following coronary artery bypass graft surgery in patients with cirrhosis: a population-based study.

BACKGROUND: The risk of cardiac surgery in patients with cirrhosis is poorly defined. Our objective was to describe outcomes of coronary artery bypass graft (CABG) surgery in cirrhotic patients from a population-based perspective. METHODS: We analysed the 1998-2004 Nationwide In-patient Sample to identify patients hospitalized for CABG surgery. The effect of cirrhosis on mortality, complications, length of stay (LOS) and charges was evaluated using logistic regression models. RESULTS: Between 1998 and 2004, there were 403 094 CABG admissions; 711 patients (0.2%) had cirrhosis. The average annual number of surgeries increased 4.2% [95% confidence interval (CI) 0.7-7.8] in cirrhotic patients, but decreased 5.5% (3.4-7.5) in non-cirrhotic patients. Patients with cirrhosis had an increased risk of mortality [17 vs. 3%; adjusted odds ratio (OR) 6.67; 95% CI 5.31-8.31], complications [43 vs. 28%; OR 1.99 (95% CI 1.72-2.30)] and greater LOS and charges (P<0.0001). Predictors of mortality included age over 60 (OR 2.21; 95% CI 1.31-3.73), female gender (OR 1.92; 95% CI 1.08-3.41), ascites (OR 3.80; 95% CI 1.95-7.39) and congestive heart failure (OR 1.75; 95% CI 1.08-2.84). Hospital volume and off-pump CABG did not affect mortality. CONCLUSIONS: Patients with cirrhosis have an increased risk of morbidity and mortality following CABG surgery. Additional studies are necessary to refine risk stratification in this high-risk patient population.

Characteristics of patients with cirrhosis who are discharged from the hospital against medical advice.

BACKGROUND & AIMS: Patients discharged from hospital against medical advice are at risk of adverse health outcomes. The frequency and predictors of self-discharge in cirrhotic patients have not been examined. METHODS: By using the 1993-2005 US Nationwide Inpatient Sample, we identified 581,380 cirrhotic patients who had been admitted to hospitals. The proportion discharged against medical advice and predictors of self-discharge were analyzed by using regression models with adjustments for clinical factors, including illness severity. RESULTS: Of the patients with cirrhosis identified, 2.8% left their hospital against medical advice. Self-discharge was most common in patients with alcoholic cirrhosis (4.2%) and hepatitis B or C ( approximately 3%) and least common among those with chronic cholestasis (0.4%). Independent predictors of self-discharge included male sex, younger age, non-private insurance, and admission to urban, nonteaching hospitals. Patients undergoing surgery and those with more comorbidities were less likely to leave against medical advice, whereas those with human immunodeficiency virus, drug and alcohol abuse, or psychosis were more likely to leave against medical advice. Self-discharge was less common among patients with hepatic decompensation (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.76-0.82), primary liver cancer (OR, 0.49; 95% CI, 0.41-0.59), or prior transplantation (OR, 0.37; 95% CI, 0.25-0.55). Length of stay and hospital charges were lower in patients discharged against medical advice (P < .0001). CONCLUSIONS: Approximately 1 in 36 hospitalized cirrhotic patients leave hospital against medical advice. Self-discharge is most common among patients with alcoholic cirrhosis, lower socioeconomic status, psychiatric disorders, substance abuse, and less severe liver disease. These findings might assist in the prevention of self-discharge and, ultimately, improve health outcomes in patients with cirrhosis.