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.
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.
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.
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.
The development of noninvasive markers of liver fibrosis is a clinical and research priority. The aspartate aminotransferase‐to‐platelet ratio index (APRI) is a promising tool with limited expense ...and widespread availability. Our objective was to systematically review the performance of the APRI in hepatitis C virus (HCV)–infected patients. Random effects meta‐analyses and areas under summary receiver operating characteristic curves (AUC) were examined to characterize APRI accuracy for significant fibrosis (stages 2–4) and cirrhosis. In 22 studies (n = 4,266), the summary AUCs of the APRI for significant fibrosis and cirrhosis were 0.76 95% confidence interval (CI), 0.74–0.79 and 0.82 (95%CI, 0.79–0.86), respectively. For significant fibrosis, an APRI threshold of 0.5 was 81% sensitive and 50% specific. At a 40% prevalence of significant fibrosis, this threshold had a negative predictive value (NPV) of 80%, but could reduce the necessity of liver biopsy by only 35%. For cirrhosis, a threshold of 1.0 was 76% sensitive and 71% specific. At a 15% cirrhosis prevalence, the NPV of this threshold was 91%. Higher APRI thresholds had suboptimal positive predictive values except in settings with a high prevalence of cirrhosis. APRI accuracy was not affected by the prevalence of advanced fibrosis, or study and biopsy quality. However, the accuracy for cirrhosis was greater in studies including human immunodeficiency virus (HIV)/HCV–co‐infected patients. Conclusion: The major strength of the APRI is the exclusion of significant HCV‐related fibrosis. Future studies of novel markers should demonstrate improved accuracy and cost‐effectiveness compared with this economical and widely available index. (HEPATOLOGY 2007.)
The accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognostication and treatment decisions. Due to the limitations of biopsy, noninvasive alternatives including ...FibroTest and FibroScan have been developed. Our objective was to systematically review studies describing the accuracy of these tests for predicting HCV-related fibrosis.
Studies comparing FibroTest or FibroScan versus biopsy in HCV patients were identified via an electronic search. Random effects meta-analyses and areas under summary receiver operating characteristics curves (AUC) were examined to characterize test accuracy for significant fibrosis (F2-4) and cirrhosis. Heterogeneity was explored using meta-regression.
Twelve studies were identified, 9 for FibroTest (N = 1,679) and 4 for FibroScan (N = 546). In heterogeneous analyses for significant fibrosis, the AUCs for FibroTest and FibroScan were 0.81 (95% CI 0.78-84) and 0.83 (0.03-1.00), respectively. At a threshold of approximately 0.60, the sensitivity and specificity of the FibroTest were 47% (35-59%) and 90% (87-92%). For FibroScan (threshold approximately 8 kPa), corresponding values were 64% (50-76%) and 87% (80-91%), respectively. Methodological quality, the length of liver biopsy specimens, and inclusion of special populations did not explain the observed heterogeneity. However, the diagnostic accuracy of both measures was associated with the prevalence of significant fibrosis and cirrhosis in the study populations. For cirrhosis, the summary AUCs for FibroTest and FibroScan were 0.90 (95% CI not calculable) and 0.95 (0.87-0.99), respectively.
FibroTest and FibroScan have excellent utility for the identification of HCV-related cirrhosis, but lesser accuracy for earlier stages. Refinements are necessary before these tests can replace liver biopsy.
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.
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.
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%).
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.
Background: Liver biopsy is an important tool in the management of patients with liver disease. Because biopsy practices may be changing, we studied patterns of use in a large Canadian Health Region. ...We aimed to describe trends in biopsy utilization and the incidence and costs of complications from a population‐based perspective.
Methods: Administrative databases were used to identify percutaneous liver biopsies performed between 1994 and 2002. Significant complications were identified by reviewing medical records of patients hospitalized within 7 days of a biopsy and those with a diagnostic code indicative of a procedural complication. Analyses of biopsy rates employed Poisson regression.
Results: Between 1994 and 2002, 3627 patients had 4275 liver biopsies (median 1 per patient; range 1–12). Radiologists performed the majority (90%), particularly during the latter years (1994 vs. 2002: 73 vs. 98%; P<0.0001). The overall annual biopsy rate was 54.8 per 100 000 population with a 41% (95% CI 23–61%) increase between 1994 and 2002. Annual increases were greatest in males and patients 30–59 years. Thirty‐two patients (0.75%) had significant biopsy‐related complications (1994–1997 vs. 1998–2002: 1.28 vs. 0.44%; P=0.003). Pain requiring admission (0.51%) and bleeding (0.35%) were most common. Six patients (0.14%) died; all had malignancies. The median direct cost of a hospitalization for complications was $4579 (range $1164–29 641).
Conclusions: Liver biopsy rates are increasing likely owing to the changing epidemiology and management of common liver diseases. The similarity of the complication rate in our population‐based study with estimates from specialized centres supports the safety of this important procedure.
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.
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.
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).
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.
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 ≈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. (HEPATOLOGY 2009.)
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.
Management of upper gastrointestinal bleeding (UGIB) often requires urgent endoscopic intervention; limitations in its availability on weekends might be associated with increased mortality, compared ...with patients admitted on weekdays.
We used the 1993-2005 U.S. Nationwide Inpatient Sample to identify patients hospitalized for UGIB caused by peptic ulceration. Differences in in-hospital mortality between patients admitted on weekends and weekdays were evaluated by using logistic regression models, adjusting for patient and clinical factors including the timing of upper endoscopy.
Between 1993 and 2005, there were 237,412 admissions to 3,166 hospitals for peptic ulcer-related UGIB. Compared with patients admitted on a weekday, those admitted on the weekend had an increased risk of death (3.4% vs 3.0%; adjusted odds ratio OR, 1.08; 95% confidence interval CI, 1.02-1.15), higher rates of surgical intervention (3.4% vs 3.1%; OR, 1.09; 95% CI, 1.03-1.15), prolonged hospital stays, and increased hospital charges (P < .0001 for all comparisons). Patients admitted on the weekend had a longer mean time to endoscopy (2.21 +/- 0.01 vs 2.06 +/- 0.01 days; P < .0001) and were less likely to undergo endoscopy on the day of admission (30% vs 34%; P < .0001). After adjusting for the timing of endoscopy, weekend admission remained an independent predictor of increased mortality (OR, 1.12; 95% CI, 1.05-1.20).
Patients admitted to hospital on the weekend for peptic ulcer-related hemorrhage have higher mortality and more frequently undergo surgery. Although wait times for endoscopy are prolonged in patients hospitalized on the weekend, this delay does not appear to mediate the weekend effect for mortality.
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 m2 ), 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.
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