Abdel Aziz M. Shaheen

FibroTest and FibroScan for the Prediction of Hepatitis C-Related Fibrosis: A Systematic Review of Diagnostic Test Accuracy

BACKGROUND: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.METHODS: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.RESULTS: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 ∼0.60, the sensitivity and specificity of the FibroTest were 47% (35–59%) and 90% (87–92%). For FibroScan (threshold ∼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.CONCLUSIONS: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.

Diagnostic accuracy of the aspartate aminotransferase‐to‐platelet ratio index for the prediction of hepatitis C–related fibrosis: A systematic review

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.)

Utilization rates, complications and costs of percutaneous liver biopsy: a population‐based study including 4275 biopsies

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.

Weekend Versus Weekday Admission and Mortality From Gastrointestinal Hemorrhage Caused by Peptic Ulcer Disease

BACKGROUND & AIMS 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

A population-based study of pyogenic liver abscesses in the United States: incidence, mortality, and temporal trends.

OBJECTIVES:Few population-based studies have evaluated pyogenic liver abscess (PLA) in North America. We assessed the incidence of PLA and evaluated predictors of mortality.METHODS:We used the Nationwide Inpatient Sample to identify all patients with discharges for PLA (ICD-9 572.0) between 1994 and 2005. Multivariable logistic regression analysis was performed to determine whether mortality was associated with patient and hospital characteristics including comorbidities, interventions, and bacterial cultures. We determined the annual incidence for PLA in the US population and assessed for temporal changes using generalized linear regression models.RESULTS:We identified 17,787 PLA discharges for an overall incidence of PLA of 3.6 (95% confidence interval (CI): 3.5–3.7) per 100,000 population. From 1994 to 2005, the annual average percent increase in incidence was 4.1% (95% CI: 3.4–4.8; P<0.0001). In-hospital mortality was 5.6% (95% CI: 5.3–6.0). Mortality was associated with older age (65–84 vs. 18–34: odds ratio (OR)=2.28 (1.48–3.51)); Medicaid (OR=1.74 (1.36–2.23)) and Medicare (OR=1.48 (1.18–1.85) vs. private insurance; and comorbidities such as cirrhosis (OR=2.48 (1.85–3.31)), chronic renal failure (OR=1.99 (1.28–3.09)), and cancer (OR=2.32 (1.97–2.73)). Patients who underwent percutaneous liver aspiration (OR=0.45 (0.39–0.52)) had lower mortality, whereas surgical drainage (OR=0.87 (0.68–1.10)) and endoscopic retrograde cholangiopancreatography (OR=0.73 (0.52–1.03)) were not associated with mortality. The most commonly recorded bacterial infections were Streptococcus species (29.5%) and Escherichia coli (18.1%). Patients with bacteremia or septicemia (OR=3.88 (3.36–4.48)) had an increased risk of death.CONCLUSIONS:The incidence of PLA is increasing and is associated with significant mortality that is attributable to several modifiable risk factors.

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

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.)

Impact of Liver Disease, Alcohol Abuse, and Unintentional Ingestions on the Outcomes of Acetaminophen Overdose

BACKGROUND & AIMS Acetaminophen overdose is the most common cause of acute liver failure in the U.S. and other Western countries. Unintentional overdoses, alcohol abuse, and underlying liver disease might increase the risk of hepatotoxicity. In this population-based study, we examined outcomes of acetaminophen overdose, with particular attention to these risk factors. METHODS Patients hospitalized for acetaminophen overdose between 1995 and 2004 were identified retrospectively by using administrative data. Comorbid conditions, suicidal intent, and hepatotoxicity were identified by using International Classification of Diseases-Ninth Revision-Clinical Modification and International Statistical Classification of Diseases and Health-Related Problems, 10th revision diagnostic codes. RESULTS During the 10-year interval, 1543 patients were hospitalized for acetaminophen overdose; 34% were alcohol abusers, 3% had liver disease, and 13% overdosed unintentionally. Seventy patients (4.5%) developed hepatotoxicity. Unintentional overdoses (odds ratio [OR], 5.18; 95% confidence interval [CI], 3.00-8.95), alcohol abuse (OR, 2.21; 95% CI, 1.30-3.76), underlying liver disease (OR, 3.50; 95% CI, 1.57-7.77), and N-acetylcysteine treatment (OR, 6.75; 95% CI, 2.78-16.39) were independently associated with hepatotoxicity. Fifteen patients (1.0%) died in-hospital; risk factors included older age, unintentional overdoses, alcohol abuse, comorbidities including liver disease, and hepatotoxicity (14% vs 0.3%; P < .0005). During a median follow-up of 5.2 years (range, 1 day-11.0 years), 79 patients (5.1%) died. Approximately half of these deaths were due to preventable conditions including suicide, substance abuse, and trauma. CONCLUSIONS In this population-based study, acetaminophen overdose had a relatively benign short-term course but was associated with substantial long-term mortality caused by preventable conditions. Acetaminophen-related hepatotoxicity is more common in patients with unintentional overdoses, alcohol abuse, and underlying liver disease.

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.

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 (∼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. Liver Transpl 16:56–63, 2010.

Predicting in-hospital mortality in patients with cirrhosis: Results differ across risk adjustment methods†

Risk‐adjusted health outcomes are often used to measure the quality of hospital care, yet the optimal approach in patients with liver disease is unclear. We sought to determine whether assessments of illness severity, defined as risk for in‐hospital mortality, vary across methods in patients with cirrhosis. We identified 258,731 patients with cirrhosis hospitalized in the Nationwide Inpatient Sample between 2002 and 2005. The performance of four common risk adjustment methods (the Charlson/Deyo and Elixhauser comorbidity algorithms, Disease Staging, and All Patient Refined Diagnosis Related Groups [APR‐DRGs]) for predicting in‐hospital mortality was determined using the c‐statistic. Subgroup analyses were conducted according to a primary versus secondary diagnosis of cirrhosis and in homogeneous patient subgroups (hepatic encephalopathy, hepatocellular carcinoma, congestive heart failure, pneumonia, hip fracture, and cholelithiasis). Patients were also ranked according to the probability of death as predicted by each method, and rankings were compared across methods. Predicted mortality according to the risk adjustment methods agreed for only 55%–67% of patients. Similarly, performance of the methods for predicting in‐hospital mortality varied significantly. Overall, the c‐statistics (95% confidence interval) for the Charlson/Deyo and Elixhauser algorithms, Disease Staging, and APR‐DRGs were 0.683 (0.680–0.687), 0.749 (0.746–0.752), 0.832 (0.829–0.834), and 0.875 (0.873–0.878), respectively. Results were robust across diagnostic subgroups, but performance was lower in patients with a primary versus secondary diagnosis of cirrhosis. Conclusion: Mortality analyses in patients with cirrhosis require sensitivity to the method of risk adjustment. Because different methods often produce divergent severity rankings, analyses of provider‐specific outcomes may be biased depending on the method used. (HEPATOLOGY 2008.)