Diagnosis Of Advanced Fibrosis Research Articles

The value of noninvasive scoring systems for the diagnosis of advanced fibrosis in Egyptian patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that includes a spectrum of liver diseases ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Liver biopsy is the current gold standard for the assessment of fibrosis in patients with NAFLD. However, it is an invasive procedure and not free from complications. We aimed to analyze the diagnostic performance of simple noninvasive scoring systems for the detection of fibrosis in Egyptian patients with NAFLD. Seventy-six patients with biopsy-proven NAFLD were included in the study. Noninvasive scoring systems included AST/ALT ratio (AAR), APRI score, BARD score, FIB-4 score, and NAFLD fibrosis score (NFS). Patients were classified into two groups according to the grade of fibrosis in liver biopsy. Group 1 included 57 patients with no or mild fibrosis (stage 0–2) and group 2 included 19 patients with advanced fibrosis (stage 3–4). The sensitivity, specificity, positive predictive values, negative predictive values, and diagnostic accuracy for relevant cut-offs and area under receiver operating characteristic curves were determined. The area under receiver operating characteristic curves for advanced fibrosis were 0.936 for the FIB-4 score, 0.916 for NFS, 0.907 for the APRI score, 0.840 for AAR, and 0.556 for the BARD score. NFS and the FIB-4 score showed the best diagnostic accuracy (92.6 and 89.7%, respectively), followed by the APRI score (75%), AAR (40.8%), and the BARD score (39.5%). FIB-4 and NFS can be used reliably to diagnose or exclude advanced fibrosis in NAFLD and thus reduce the burden of liver biopsies.

Risk of Liver Decompensation Among HIV/Hepatitis C Virus-Coinfected Individuals With Advanced Fibrosis: Implications for the Timing of Therapy

Most human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-infected patients who are currently receiving boceprevir or telaprevir-based therapy against HCV show cirrhosis. However, the risk of liver decompensation (DC) among HIV/HCV-coinfected patients with stage 3 fibrosis in the short term could be high enough to not allow delays. We aimed at assessing the risk of DC among HIV/HCV-coinfected individuals with advanced fibrosis (F3-F4). Eight hundred ninety-two HIV/HCV-coinfected patients, naive or without sustained virologic response to HCV therapy, were included in this cohort. Fibrosis was staged by biopsy in 317 patients and by liver stiffness measurement (LSM) in 575 individuals. Precirrhosis was defined as an LSM of 9.5-14.6 kilopascals (kPa), and cirrhosis as an LSM of ≥14.6 kPa. For patients with biopsy, the probability of remaining free of DC for F3 vs F4 was 99% (95% confidence interval [CI], 95%-100%) vs 96% (95% CI, 91%-98%) at 1 year, and 98% (95% CI, 94%-100%) vs 87% (95% CI, 81%-92%) at 3 years. The only factor independently associated with DC was fibrosis stage (F4 vs F3, subhazard ratio [SHR], 2.1; 95% CI, 1.07-4.1; P = .032). For patients with LSM, the probability of remaining free of DC for precirrhosis vs cirrhosis was 99% (95% CI, 96%-100%) vs 93% (95% CI, 89%-96%) at 1 year, and 97% (95% CI, 94%-99%) vs 83% (95% CI, 77%-87%) at 3 years. Factors independently associated with DC were platelet count (<100 × 10(3) vs ≥100 × 10(3): SHR, 1.86; 95% CI, 1.01-3.42; P = .046) and LSM (cirrhosis vs precirrhosis: SHR, 5.67; 95% CI, 2.27-14.1; P < .0001). As in patients with cirrhosis, immediate therapy against HCV is warranted for patients with precirrhosis and HIV coinfection, as they are at risk of DC soon after the diagnosis of advanced fibrosis.

Mo1019 Adipose Tissue Insulin Resistance and Lipotoxicity Drive Disease Phenotype and Decline in Pancreatic Beta Cell Function in Nonalcoholic Fatty Liver Disease

BACKGROUND: The evaluation of liver fibrosis in patients with non alcoholic fatty liver disease (NAFLD) is important in predicting to predict the outcome of disease. Liver biopsy is the gold standard whereas the noninvasive scoring systems for liver fibrosis assessment in NAFLD patients have been studied and showed promising results. We aimed to validate the utility of these noninvasive scoring systems to identify patients with advanced fibrosis (.F3) in the Thai NAFLD populationMETHODS: This is a cross sectional study to collect 115 liver biopsy-proven NAFLD patients during Jan 2009-Dec 2011 at the King Chulalongkorn Memorial Hospital (KCMH) and Ramathibodi Hospital, Bangkok, Thailand. Four noninvasive scoring systems including AST/ALT ratio, BARD score, FIB-4 and NAFLD Fibrosis Score (NFS) were used to identify patients with advanced fibrosis. RESULTS: One hundred and fifteen liver biopsy proven NAFLD patients were included with mean age of 50.5+/12.4 years and 49.6% of them were male. Eighty patients (69.6%) had impaired fasting glucose or diabetes. 15 patients (13%) showed advanced fibrosis by liver histology. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of these 4 tools were shown in Table 1. BARD score .2 is the best tool with highest sensitivity to screen patients with advanced fibrosis, followed by NFS with cut-off .-1.455, FIB-4 with cut off .1.45 and AST/ALT ratio .0.8, respectively. By using these 4 noninvasive scoring systems, liver biopsy could potentially be avoided in 60% of patients with NFS, 62% with BARD score, 74% with FIB-4, and 84% with AST/ALT ratio (Table 1). CONCLUSIONS: With the prevalence of advanced liver fibrosis of 13% in Thai NAFLD population, these 4 non invasive scoring systems can be used to identify patients with advanced fibrosis with the acceptable sensitivity and high NPV so that liver biopsy could potentially be avoided in about two-thirds of patients. Table 1. Comparison of four non-invasive scoring systems for the diagnosis of advanced fibrosis in 115 Thai patients with NAFLD

Transient Elastography Might Replace Liver Biopsy in HCV Management

The diagnosis of advanced fibrosis in patients with liver disease is important in guiding both the initiation of screening for complications of cirrhosis and treatment decisions. Liver biopsy is still the current gold standard test for identifying advanced fibrosis; however, less-invasive tests have been described, including a serum test of aspartate aminotransferase to platelet ratio index (APRI) and Fibroscan, …

Three-dimensional magnetic resonance imaging for stringent diagnosis of advanced fibrosis associated with nonalcoholic steatohepatitis.

The definitive diagnosis of nonalcoholic steatohepatitis (NASH) is currently based on histopathological assessment. This study aimed to elucidate the utility of a novel noninvasive method, three-dimensional magnetic resonance imaging (3D-MRI), for diagnosing advanced fibrosis in patients with NASH, using histopathological diagnosis as the reference standard. This retrospective study included 30 consecutive patients who had been diagnosed with NASH by histopathology and had undergone 3D-MRI before biopsy. 3D-MRI provided a three-dimensional reconstruction of the liver from contrast-enhanced hepatobiliary phase MR images. In the present study, histopathological advanced fibrosis was defined as stage 3 and 4 NASH. Advanced fibrosis, diagnosed by 3D-MRI, was considered to be diffuse irregularity of the entire surface of the liver. The diagnostic features of 3D-MRI and the noninvasive evaluation systems (APRI, FIB-4 index, and BARD score) for identifying advanced and nonadvanced fibrosis of NASH were determined and compared. Nine (30%) of the 30 study patients were diagnosed histopathologically with advanced fibrosis, and 11 (37%) of 30 patients were diagnosed with advanced fibrosis using 3D-MRI. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 3D-MRI for diagnosing advanced fibrosis were 100, 90, 82, and 100%, respectively. The sensitivities of APRI, the FIB-4 index, and BARD score ranged from 78 to 89%, the specificities from 71 to 90%, the PPVs from 54 to 78%, and the NPVs from 88 to 94%. Compared with the common noninvasive methods for diagnosing advanced fibrosis associated with NASH, 3D-MRI was more accurate.

Noninvasive diagnosis of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

The spectrum of nonalcoholic fatty liver disease (NAFLD) starts from simple steatosis that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Importantly, patients with NASH and fibrosis are considered a high-risk group for liver and cardiac-related morbidity and mortality. The diagnostic evaluation of patients with NAFLD usually starts with the assessment of an asymptomatic patient with abnormalities in liver injury tests (most commonly elevation of aminotransferases) or referred for evaluation of liver steatosis incidentally found on abdominal imaging performed for other clinical reasons. Most of these patients have components of the metabolic syndrome (obesity, hypertension, hyperlipidemia, diabetes). Liver sonogram and blood tests to rule out other etiologies of liver disease, as well as a detailed history of alcohol intake, are essential to establish the diagnosis. Because of their significantly different clinical outcomes, from a prognostic stand-point, it is very important to establish the distinction between simple steatosis and NASH with or without fibrosis. The three noninvasive diagnostic tests that have been independently validated compared with liver biopsy for diagnosis of NASH and fibrosis are serum levels of CK-18 for diagnosis of NASH and ultrasound elastography and NAFLD fibrosis score for the diagnosis of advanced fibrosis. Serum biomarkers that have been validated (NAFLD fibrosis score, FibroTest) could be used as screening tools in patients with metabolic syndrome. Imaging techniques have been developed and could have a more widespread use in the future, but only ultrasound elastography has been validated extensively. CK-18 is a direct serum biomarker that could be part of the routine diagnostic evaluation for NASH in the near future. Routine tests appear to be more accurate than nonroutine tests for prediction of NAFLD and advanced fibrosis.

A suggested algorithm for using serum biomarkers for the diagnosis of liver fibrosis in chronic hepatitis C infection

Background and study aims Hepatitis C virus infection (HCV) is endemic in Egypt. Liver biopsy is the gold standard for diagnosis and staging of fibrosis in chronic hepatitis C patients. However, it is invasive, associated with sampling error and poses potential complications. A non-invasive alternative is needed. This assessed the accuracy of certain biochemical markers and ultrasonography in predicting the stage of fibrosis in chronic hepatitis C patients. Patients and methods Sixty five patients with chronic HCV were enrolled. Ultrasonographic examination, complete blood count and liver function tests were done. Serum levels of hyaluronic acid (HA) and YKL-40 (a 40-kDa glycoprotein produced by stellate cells) were determined. Liver biopsy was done. Fibrosis was correlated with biochemical markers and ultrasonographic findings. Results Histopathological examination showed that 39 patients (60%) had F1, nine (14%) had F2, 17 (26%) had F3 and none had F0 or F4 scores. A value of alanine aminotransferase (ALT) index < 0.38, HA < 9.7 ng ml −1 or portal vein (PV) cross-sectional area <25.8 mm 2 excluded significant fibroses (⩾F2). A value of aspartate aminotransferase (AST) + ALT < 39.5 or ratio of AST index to the platelet count (APRI) < 0.235 or HA × 100 per platelet (Plt) < 9.534 excluded the presence of advanced fibrosis with 100% negative predictive value (NPV). Using these values, advanced fibrosis could be excluded in 72% of our patients. An APRI value of ⩾1.1 can diagnose advanced fibrosis with 100% positive predictive value (PPV) in 10% of our patients. Hence, only 18% of our patients in whom liver biopsy was recommended were not classified by these parameters. YKL-40 did not help in the diagnosis of advanced fibrosis. Conclusion Applying a simple algorithm based on ALT, AST, platelet count, PV cross-sectional area, in addition to HA level may eliminate the need for liver biopsies in more than 80% of chronic HCV patients.

Evaluation of the nonalcoholic fat liver disease fibrosis score for patients undergoing bariatric surgery

Morbidly obese patients have an increased risk for nonalcoholic fat liver disease. Its severe form, nonalcoholic steatohepatitis may cause liver fibrosis. The diagnosis of advanced fibrosis has great value during the pre operative evaluation for bariatric surgery. Currently, liver biopsy is the gold standard for diagnosis of liver fibrosis. To evaluate the nonalcoholic fat liver disease fibrosis score in morbidly obese patients undergoing Roux-en-Y gastric bypass in our population. One hundred fifty-eight morbidly obese patients that had undergone bariatric surgery were included. Age, body mass index, hyperglycemia, platelet count, albumin and AST/ALT ratio were applied to the score formula. Scores above 0.676 were indicative of advanced liver fibrosis and scores under -1,455 absence of advanced liver fibrosis. These scores were compared to liver biopsy findings. The presence of advanced fibrosis could be diagnosed with good accuracy, with a positive predictive value of 83.7%. The score had a higher accuracy to exclude advanced fibrosis with a negative predictive value of 97%. Twenty-five patients (16%) had scores between the cutoffs points and were identified as indeterminate. The score sensibility and specificity was 83% and 97% respectively. The nonalcoholic fat liver disease fibrosis score has high accuracy to identify and exclude advanced liver fibrosis in morbidly obese patients subjected to bariatric surgery.

Diagnosis of advanced fibrosis in HIV and hepatitis C virus‐coinfected patients via a new noninvasive index: the HGM‐3 index

Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F>or=3) in HIV/hepatitis C virus (HCV)-coinfected patients. We carried out a cross-sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM-3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase-1 and hyaluronic acid. In the EG, the area under the receiver operating characteristic curve (AUC-ROC) of HGM-3 for identification of F>or=3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC-ROC of the HGM-2, FIB-4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM-3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM-3 >0.570 in the EG for F>or=3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F>or=3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG. HGM-3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV-coinfected patients.

Efficacy and Safety of Peginterferon Alfa-2A (40Kd) Plus Ribavirin in Hepatitis C Patients With Advanced Fibrosis and Cirrhosis

The objective of this study is to determine the efficacy and safety of peginterferon alfa-2a (40 KD)/ribavirin in patients with advanced fibrosis. Data from 341 genotype 1/4 patients (99 with bridging fibrosis/cirrhosis) treated for 48 weeks and 1547 genotype 2/3 patients (380 with bridging fibrosis/cirrhosis) treated for 16 or 24 weeks enrolled in three randomized international studies were analyzed. Sustained virological response (SVR) rates decreased progressively from 60% in genotype 1/4 patients without advanced fibrosis to 51% in those with bridging fibrosis and 33% in those with cirrhosis (trend test P = 0.0028); and from 76% to 61% and 57%, respectively, in genotype 2/3 patients treated for 24 weeks (trend test P < 0.0001). Irrespective of genotype, patients without advanced fibrosis were more likely to have an earlier response to treatment that was associated with higher SVR rates and lower relapse rates during untreated follow-up. Among patients with or without a diagnosis of advanced fibrosis, rates of SVR and relapse were similar for patients with similar responses in the first 12 weeks. Compared with patients with less severe disease, SVR rates are significantly lower in patients with advanced fibrosis. However, irrespective of genotype and degree of fibrosis, the time to become hepatitis C virus (HCV) RNA undetectable was the strongest predictor of SVR.

686 Serum hyaluronic acid and the AST/ALT ratio in the diagnosis of advanced fibrosis in patients with non alcoholic liver disease and chronic hepatitis C

686 Serum hyaluronic acid and the AST/ALT ratio in the diagnosis of advanced fibrosis in patients with non alcoholic liver disease and chronic hepatitis C