Evaluation Of Chronic Liver Disease Research Articles

Performance of Non-invasive Biomarkers of Liver Fibrosis Amongst Hispanics and African Americans.

Liver biopsy is the gold standard for fibrosis staging. However, it is limited by significant complications. Non-invasive markers of fibrosis have been developed as an alternative to liver biopsy. The performance of these different markers varies with the etiology of liver fibrosis and possibly amongst different ethnicities. We aim to assess the performance of non-invasive markers of liver fibrosis amongst Hispanics and African Americans. This is a retrospective cohort analysis of patients who had liver biopsy as part of their evaluation of chronic liver disease. One hundred and twenty-six records were analyzed. Univariate and multivariate analyses were performed. Probit regression receiver operating characteristic curve analysis was used to assess the sensitivity of the different non-invasive biomarkers and underlying variables with respect to liver biopsy. The following non-invasive markers for fibrosis were used: Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), age-platelet, AST/alanine aminotransferase (AST/ALT) ratio, fibrosis cirrhosis index (FCI), and fibrosis index (FI). About two-thirds of the study population were African Americans with majority of the study population having chronic liver disease from viral infection. Minimal to no fibrosis by the METAVIR (an acronym for Meta-analysis of Histological Data in Viral Hepatitis) score was found in 58% of patients compared to 42% with moderate to severe fibrosis. Hispanics were more likely than Blacks to have hepatic steatosis. Age significantly increased the sensitivity and specificity of APRI and age-platelet scores. The AST/ALT score had a lower sensitivity for liver fibrosis in women compared to men in our study population. The sensitivity of FIB-4 and age-platelet was higher in Hispanics compared to African Americans while the opposite was the case for APRI, AST/ALT, FCI, and FI. Non-invasive biomarkers are useful in detecting liver fibrosis. FIB-4 and age-platelet have a high sensitivity in Hispanics while African Americans have a high sensitivity for APRI, AST/ALT, FCI, and FI. It is worth noting that these non-invasive biomarkers had variable performances when ethnicity, age, and sex were considered in our population.

Endoscopic Ultrasound-Guided Portal Pressure Gradient Measurement, Is It Ready for Prime Time?

Portal hypertension is a serious complication of advanced liver disease. Portal pressure gradient measurement accurately determines severity of portal hypertension, prognosis, and guides medical therapy. Conventionally, interventional radiology-guided hepatic venous portal gradient measures portal pressure gradient indirectly using specialized balloon catheter. Recent advances in endoscopy have paved the novel method of endoscopic ultrasound-guided direct portal pressure gradient measurement to evaluate portal hypertension with equivalent safety in both animal models and humans studies. With the expansion of Endo-Hepatology practice, a concept of “one stop shop” is becoming more popular which is a comprehensive endoscopic approach in the evaluation of chronic liver disease. During the same endoscopic procedure, patients could be evaluated for esophageal or gastric varices, portal hypertensive gastropathy, EUS-guided elastography, EUS-guided portal pressure measurement and EUS-guided liver biopsy when suspecting advanced liver disease or diagnosis remains uncertain. This article focuses on the overview of portal hypertension and EUS-guided interventions such as EUS-guided portal pressure measurement, EUS-guided elastography and EUS-guided liver biopsy in the evaluation of individuals with advanced liver disease.

Cellular senescence and hepatitis B-related hepatocellular carcinoma: An intriguing link.

Chronic hepatitis B is mainly responsible for the morbidity and mortality from hepatitis B virus (HBV)-related complications, including hepatocellular carcinoma (HCC) and decompensated cirrhosis. Hepatocellular carcinoma remains the main challenge in the management of not only undiagnosed and/or untreated but also diagnosed and treated patients with chronic HBV infection, as its incidence decreases but is not eliminated even after many years of effective anti-HBV therapy. The exact mechanisms used by HBV to cause malignant transformation remain uncertain, although much of the available data are in favour of a pathogenetic role of HBx protein. Senescence is a cellular state, in which cells lose their ability to proliferate. This biological mechanism may function in a dual mode, namely being both cancer-protective as a result of reduced cellular proliferation, but also cancer-enhancing as a result of modulation of the tissular microenvironment by immune cells during persistent accumulation of senescent cells. Protein X of HBV protein exhibits many similarities in terms of the implemented mechanisms of action and pathways related to the biological process of cellular senescence. Concurrently, insufficient clearance of both senescent and precancerous hepatocytes combined with inadequate immune surveillance as a result of immunosenescence caused by chronic HBV infection may lead to hepatocarcinogenesis. Thus, the effect of HBV seems to be critical as a connecting link between cellular senescence and development of HCC. An ongoing research is underway towards identifying and validating markers of hepatocyte senescence, which could improve the landscape for evaluation of chronic liver disease, thereby providing valuable information in terms of HBV-related carcinogenesis.

MR elastography of liver: current status and future perspectives.

Non-invasive evaluation of liver fibrosis has evolved over the last couple of decades. Currently, elastography techniques are the most widely used non-invasive methods for clinical evaluation of chronic liver disease (CLD). MR elastography (MRE) of the liver has been used in the clinical practice for nearly a decade and continues to be widely accepted for detection and staging of liver fibrosis. With MRE, one can directly visualize propagating shear waves through the liver and an inversion algorithm in the scanner automatically converts the shear wave properties into an elastogram (stiffness map) on which liver stiffness can be calculated. The commonly used MRE method, two-dimensional gradient recalled echo (2D-GRE) sequence has produced excellent results in the evaluation of liver fibrosis in CLD from various etiologies and newer clinical indications continue to emerge. Advances in MRE technique, including 3D MRE, automated liver elasticity calculation, improvements in shear wave delivery and patient experience, are promising to provide a faster and more reliable MRE of liver. Innovations, including evaluation of mechanical parameters, such as loss modulus, displacement, and volumetric strain, are promising for comprehensive evaluation of CLD as well as understanding pathophysiology, and in differentiating various etiologies of CLD. In this review, the current status of the MRE of liver in CLD are outlined and followed by a brief description of advanced techniques and innovations in MRE of liver.

Elastography in the evaluation of liver allograft.

Elastography is an established technique in the evaluation of chronic liver diseases. While there is a large clinical experience and data available regarding the performance of elastography in native liver, elastography experience with liver grafts is limited and still growing. Both ultrasound-based elastography techniques and MR Elastography (MRE) are useful in the assessment of liver fibrosis in liver transplants. Technical modifications for performing elastography will be required for optimum evaluation of the graft. In general, caution needs to be exercised regarding the use of elastography immediately following transplantation as post-operative changes, perioperative conditions/complications, inflammation, and rejection can cause increased stiffness in the graft. In the follow-up, detection of increased stiffness with elastography is useful for predicting development of fibrosis in the graft. Adjunctive MRI or ultrasound with Doppler also provides comprehensive evaluation of anatomy, vascular anastomosis and patency, biliary tree, and stiffness for fibrosis. In this review, we provide a brief overview of elastography techniques available followed by the literature review of elastography in the evaluation of grafts and illustration with clinical examples.

Impact of the size of liver biopsies on the evaluation of chronic liver disease –a study by artificial sampling

Impact of the size of liver biopsies on the evaluation of chronic liver disease –a study by artificial sampling

Magnetic Resonance Elastography of Liver: Current Update.

The first clinical application of magnetic resonance elastography (MRE) was in the evaluation of chronic liver disease (CLD) for detection and staging of liver fibrosis. In the past 10 years, MRE has been incorporated seamlessly into a standard magnetic resonance imaging (MRI) liver protocol worldwide. Liver MRE is a robust technique for evaluation of liver stiffness and is currently the most accurate noninvasive imaging technology for evaluation of liver fibrosis. Newer MRE sequences including spin-echo MRE and 3 dimensional MRE have helped in reducing the technical limitations of clinical liver MRE that is performed with 2D gradient recalled echo (GRE) MRE. Advances in MRE technology have led to understanding of newer mechanical parameters such as dispersion, attenuation, and viscoelasticity that may be useful in evaluating pathological processes in CLD and may prove useful in their management.This review article will describe the changes in CLD that cause an increase in stiffness followed by principle and technique of liver MRE. In the later part of the review, we will briefly discuss the advances in liver MRE.

A new computer aided diagnosis system for evaluation of chronic liver disease with ultrasound shear wave elastography imaging.

Classify chronic liver disease (CLD) from ultrasound shear-wave elastography (SWE) imaging by means of a computer aided diagnosis (CAD) system. The proposed algorithm employs an inverse mapping technique (red-green-blue to stiffness) to quantify 85 SWE images (54 healthy and 31 with CLD). Texture analysis is then applied involving the automatic calculation of 330 first and second order textural features from every transformed stiffness value map to determine functional features that characterize liver elasticity and describe liver condition for all available stages. Consequently, a stepwise regression analysis feature selection procedure is utilized toward a reduced feature subset that is fed into the support vector machines (SVMs) classification algorithm in the design of the CAD system. With regard to the mapping procedure accuracy, the stiffness map values had an average difference of 0.01 ± 0.001 kPa compared to the quantification results derived from the color-box provided by the built-in software of the ultrasound system. Highest classification accuracy from the SVM model was 87.0% with sensitivity and specificity values of 83.3% and 89.1%, respectively. Receiver operating characteristic curves analysis gave an area under the curve value of 0.85 with [0.77-0.89] confidence interval. The proposed CAD system employing color to stiffness mapping and classification algorithms offered superior results, comparing the already published clinical studies. It could prove to be of value to physicians improving the diagnostic accuracy of CLD and can be employed as a second opinion tool for avoiding unnecessary invasive procedures.

Liver-specific magnetic resonance contrast medium in the evaluation of chronic liver disease.

ABSTRACTThe hepatobiliary-specific contrast medium (gadoxetic acid – Primovist®) is primarily used to improve detection and characterization of focal hepatic lesions, such as in chronic liver disease patients with suspected hepatocellular carcinoma. Since the contrast medium is selectively taken up by functioning hepatocytes in the late hepatobiliary phase, it helps to detect typical hepatocellular carcinoma, which show low signal intensity on this phase. This imaging feature also assists in differentiating regenerative/dysplastic nodules from early hepatocellular carcinomas (with over 90% accuracy), as well as hypervascular hepatocellular carcinomas from arterial pseudo-enhancement foci. Future perspectives include its use in quantification of hepatic function and fibrosis.

The role of ultrasound elastographic techniques in chronic liver disease: Current status and future perspectives

This review illustrates the state of the art clinical applications and the future perspectives of ultrasound elastographic methods for the evaluation of chronic liver diseases, including the most widely used and validated technique, transient elastography, followed by shear wave elastography and strain imaging elastography. Liver ultrasound elastography allows the non-invasive evaluation of liver stiffness, providing information regarding the stage of fibrosis, comparable to liver biopsy which is still considered the gold standard; in this way, it can help physicians in managing patients, including the decision as to when to start antiviral treatment.The characterization of focal liver lesions and the prognostic role of the elastographic technique in the prediction of complications of cirrhosis are still under investigation.

Effect of Meal Ingestion on Liver Stiffness in Patients with Cirrhosis and Portal Hypertension

Background and AimsLiver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population.MethodsIn 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured.ResultsPost-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes.ConclusionsLiver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Evaluation of Chronic Liver Disease: Does Ultrasound Scoring Criteria Help?

Noninvasive approaches for assessment of liver histology include routine laboratory tests and radiological evaluation. The purpose of our study was to determine the utility of a simplified scoring system based on routinely evaluated ultrasound features for the evaluation of chronic liver disease and correlate it with the histological findings. For this cross-sectional analytical study the data was collected prospectively by nonprobability purposive sampling technique. The ultrasound variables/parameters and their assigned scoring system that was a modified version adopted from published literature were evaluated. Sensitivity, specificity, positive and negative predictive values of the liver morphological score and combined score of liver morphology and sizes was determined using stage and grade as reference standard. Our results show a high sensitivity and PPV of liver morphological sonographic evaluation for the staging and grading of CLD respectively thus supporting it as a screening diagnostic strategy. Of the three liver morphology variables, specificity of liver surface evaluation was highest for the stage of fibrosis and grade of inflammation. The simplified ultrasound scoring system evaluated in our study is clinically relevant and reproducible for differentiating patients with CLD with mild or no fibrosis from moderate to severe fibrosis.

Prospective validation of two models for ultrasonographic diagnosis of cirrhosis

To perform a prospective validation and comparative analysis of two ultrasonographic diagnostic scores of cirrhosis in patients with silent liver disease. cross-sectional study, prospective and blind. ROC curves evaluated the diagnostic utility of: a) Bologna score (BS): assessment of liver surface nodularity and portal flow velocity, and b) Cadiz score (CS): assessment of liver echo structure, portal vein caliber and spleen area. Liver biopsy was considered the gold standard for the diagnosis of cirrhosis. One hundred and thirteen patients, 76 men and 37 women, mean age 44 years old (range 18-73 years) referred for evaluation of chronic liver disease without clinical or biochemical evidence of advanced disease (absence of jaundice, ascites, encephalopathy, malnutrition or coagulopathy). Cirrhosis was diagnosed in 25 patients (22.1%). BS: sensitivity 84%, specificity 79.5%, area under the ROC curve 86.7%. CS: sensitivity 84%, specificity 89.8%, area under the ROC curve 92.4%. Portal vein was not displayed in 7 patients(6%) and portal flow velocity was not recorded in 13 (11.5%). These results agree with those obtained in the original articles developing both scores. There were no statistically significant differences between the two scores. Specificity reached 97% with joint use of both models, but sensitivity decreased to 72%. Presence or absence of cirrhosis in patients with silent liver disease can be established by Doppler ultrasound with high diagnostic accuracy. The joint use of both scores has high diagnostic specificity. Both diagnostic models are highly re-producible.

Comparison of acoustic radiation force impulse imaging (ARFI) to liver biopsy histologic scores in the evaluation of chronic liver disease: A pilot study

Background and aims. Acoustic Radiation Force Impulse Imaging (ARFI) is a novel non invasive technique studying the localized mechanical properties of tissue by utilising short, high intensity acoustic pulses (shear wave pulses) to assess the mechanical response (tissue displacement), providing a measure of tissue elasticity. The aim of this study is to investigate the feasibility of ARFI imaging as a non-invasive method for the assessment of liver fibrosis compared to liver biopsy scores.Materials and methods. A prospective blind comparison study of ARFI elastography (Virtual Touch Imaging™, ACUSON S2000 Ultrasound Unit, Siemens, Mountain View CA) in a consecutive series of patients who underwent liver biopsy for assessment of fibrosis in chronic liver disease. ARFI shear-wave propagation velocity was measured in meters per second. Mean ARFI velocities were compared with both Batts-Ludwig (F0 to F4) and Modified Ishak scores (F0 to F4) for fibrosis in liver biopsy findings. Twenty-one patients with chronic liver disease (Hepatitis C (HCV) = 16, Hepatitis B (HBV) = 1, both HCV and HBV = 1 Alcoholic liver disease (ALD) = 1, others = 2) underwent ARFI and liver biopsy on the same day.Results. The Spearman correlation coefficients between the median values of the ARFI measurements and the histological fibrosis stage of the Modified Ishak score and Batts-Lud-≥ wig score were both highly significant (p < 0.01) with rho = 0.69 and rho = 0.72 respectively. The median ARFI (total 180 replications; minimum 5, maximum 10 measurements per patients) velocities for our study population range from 0.92 to 4.17 m/sec. Areas under the receiver operating characteristic curve for the accuracy of ARFI imaging was 1.00 and 0.35, for the diagnosis of moderate fibrosis (histologic fibrosis stage, F ≥ 2) and 0.85 and 0.85 respectively for Ishak and Batts-Ludwig score, for the diagnosis of cirrhosis.Conclusion. ARFI imaging has a strong correlation with the fibrosis stage of both Batts-Ludwig and shak score in chronic liver disease. It’s accuracy in prediction of severe fibrosis and cirrhosis is maximal in comparison with earlier stages.

What is the role of diagnostic laparoscopy in a gastroenterology unit?

Diagnostic laparoscopy is known to be a relatively safe invasive procedure. However, its use has decreased owing to the development of imaging techniques, and fewer gastroenterologists now practice diagnostic laparoscopy. Our aim was to examine the role of diagnostic laparoscopy in a gastroenterology unit in the era of advanced imaging techniques. We retrospectively reviewed 855 diagnostic laparoscopy cases. Its safety and efficacy were evaluated for various indications. No mortality was observed, and complications were noted in ten patients (1.2%). Among the indications were evaluation of chronic liver disease (n = 673), liver tumor (n = 15), ascites of unknown origin and peritoneal disease (n = 142), and staging of intra-abdominal malignancy (n = 25). In patients with chronic liver disease, 461 were diagnosed as having chronic viral hepatitis, based on clinical data including imaging studies, but the diagnosis was changed to cirrhosis after a laparoscopic exam in 69 patients (15.0%). In patients with ascites of unknown origin and peritoneal disease, the diagnostic yield was 87.2% (123/141). In 24 (19.5%) of the 123 patients, the diagnosis changed or the less probable diagnosis was confirmed after laparoscopic examination. The confirmed diagnoses were mainly primary peritoneal disease, including peritoneal tuberculosis, in 17 patients, peritoneal metastatic carcinoma in five, and mesothelioma in two. Diagnostic laparoscopy in a gastroenterology unit is safe and useful, especially for confirmation of liver cirrhosis and primary peritoneal disease evaluation.

Fat or Fiction

Purpose: Hepatic steatosis (or fatty liver) is common in the United States and frequent in patients with chronic hepatitis C (CHC), where it may lead to disease progression and hinder response to HCV therapy. Therefore, it is important to recognize fatty liver. Liver biopsy confirms the degree of fat, inflammation and fibrosis, but is invasive. Hepatic ultrasound is well-tolerated, non-invasive and provides good information. It is commonplace to trust the results of an ultrasound suggesting fatty liver, but there are conflicting reports on its accuracy. Therefore, we retrospectively examined liver biopsies and compared the histologic results to the ultrasound interpretations. We selected patients with chronic liver disease, primarily CHC, in order to evaluate the accuracy of ultrasound in identifying fatty liver in a typical clinical setting. Methods: Liver biopsies were reviewed on 131 patients who had a random liver biopsy performed for evaluation of chronic liver disease (89% had CHC). The biopsies were graded for fat (grades 0–3), inflammation (grades 0–4) and fibrosis (stages 0–4). Ultrasound interpretations were grouped into 3 categories- ‘normal’, ‘fatty liver’ and ‘non-specific’, and then compared to histologic results. Results: A ‘normal’ ultrasound interpretation was correct in excluding significant fat (grades 2–3) 95.8% of the time, but 25% had some fat (grades 1–3) on biopsy, representing false negatives. Furthermore, 37.5% had significant fibrosis (stages 2–4) and 8.3% had significant inflammation (grades 2–4). A ‘fatty liver’ interpretation was only correct in identifying some fat on biopsy in 36.4% and significant fat in 11.4%, yielding many false positives. In addition, 47.7% had significant fibrosis and 18.2% had significant inflammation. A ‘non-specific’ interpretation was associated with 25.6% significant fat, 53.8% significant fibrosis and 23.1% significant inflammation. The sensitivity of ultrasound for detecting fat ranged from 32.0–88.2 and the specificity ranged from 40.4–65.4, depending on the degree of fat on biopsy and the sonographic interpretation considered to be significant. Conclusions: Ultrasound is inaccurate for diagnosing hepatic steatosis in patients with chronic liver disease; echogenic alterations are more likely to be the result of fibrosis or inflammation in this setting. Therefore, in patients with chronic liver disease, the ultrasound diagnosis of fatty liver is more ‘fiction’ than ‘fat’.

Diagnostic laparoscopy.

Since the early part of the 20th century, diagnostic laparoscopy has become an important tool in the armamentarium of surgeons and gastroenterologists alike. Its indications have expanded from initial attempts at tamponading internal hemorrhage to avoidance of unnecessary laparotomies with accurate staging of malignancies, treatment of a multitude of intra-abdominal pathologies, and even as a resource for evaluating blunt abdominal trauma and chronic abdominal pain. Its accuracy has been demonstrated in the evaluation of chronic liver diseases, in comparison with other diagnostic modalities. Many further technical advances have been introduced in recent years. Gastroenterology training programs should include formal diagnostic laparoscopy training as part of their curriculum.

Value of regional cerebral blood flow in the evaluation of chronic liver disease and subclinical hepatic encephalopathy.

Regional changes in cerebral blood flow in patients with chronic hepatitis, cirrhosis and subclinical hepatic encephalopathy were investigated in the present study using single photon emission computed tomography (SPECT). Twenty patients with cirrhosis, 11 patients with chronic hepatitis, and nine healthy controls were included in the study. Cerebral SPECT were obtained for all patients. The percentages of cerebral blood flow of 14 regions to the cerebellar blood flow were determined. Only the patients with cirrhosis underwent psychometric evaluation: visual evoked potentials (VEP) measurements and electroencephalogram (EEG) recordings along with blood levels of albumin, bilirubin, and ammonia were measured and prothrombin time was determined in cirrhotic patients. These patients were classified according to the Child-Pugh classification. Among cirrhotic patients, six had abnormal results in VEP studies, 11 in psychometric tests and with six in EEG evaluation. Any abnormality in psychometric tests and/or VEP studies is taken as the main criterion; subclinical hepatic encephalopathy was detected in 12 of 20 patients. According to SPECT results in patients with subclinical encephalopathy, a statistically significant decrease in cerebral blood flow in right thalamus and nearly significant decrease in left thalamus were observed. Regional blood flow was significantly higher in the frontal lobes of patients with cirrhosis when compared with healthy controls. Similarly, cerebral blood flow in frontal and cingulate regions was significantly higher in patients with chronic hepatitis than in healthy controls. There was no relationship between cerebral blood flow and blood levels of ammonia or Child-Pugh score, in cirrhotic patients. Significant changes in cerebral blood flow may be present in chronic liver diseases and the authors suggest that the measurement of changes in cerebral blood flow might be useful in detecting subclinical hepatic encephalopathy.

A 12 years audit of upper gastrointestinal endoscopic procedures.

Evaluation of upper gastrointestinal (GI) endoscopy in terms of indications, diagnostic efficacy, and diseases diagnosed. Retrospective, observational case series. DHQ Teaching Hospital, Rawalpindi, from March 1990 to December 2001. Patients who underwent upper GI endoscopy in 12 years were included. Upper GI endoscopies were performed according to standard protocol. Endoscopic diagnoses were based on widely accepted criteria. Of the 8481 patients, 4935 (58.2%) were female and 3546 (41.8%) male. Mean patient age was 40.5 years. Dyspepsia (42.6%), upper GI bleed (32.8%), and evaluation of chronic liver disease (10.2%) were common indications of the procedure. An endoscopic diagnosis was possible in 82.6% patients. Varices, gastritis, duodenitis, and combined lesions were common endoscopic diagnosis. Gastritis and duodenitis were most frequent causes of upper GI bleed. We noted more gastric ulcers compared to duodenal ulcers. Females had significantly more normal endoscopies, p-value=0.02. Upper GI endoscopy is an effective procedure. Dyspepsia evaluation is commonest indication for upper GI endoscopy in our patients. Etiology of upper GI bleed, and incidence of duodenal ulcer compared to gastric ulcer in our patients are different than described in literature. Females have significantly more normal endoscopies.

Serum Paraoxonase Activity: A New Additional Test for the Improved Evaluation of Chronic Liver Damage

Paraoxonase 1 (PON1) is an ester hydrolase present in serum and in the liver. The aims of the present study were to investigate the following: (a) the relationship between serum PON1 activity alterations and the degree of liver damage in patients with chronic liver disease; (b) the influence of genetic variability on serum PON1 activity; and (c) the efficacy of serum PON1 activity measurement, alone and in combination with standard liver function tests, in the assessment of liver damage. We studied 68 patients with liver cirrhosis, 107 patients with chronic hepatitis, and 368 apparently healthy volunteers. Baseline and salt-stimulated PON1 activities were measured by the hydrolysis of paraoxon. PON1 genotyping at positions 55 and 192 was analyzed by PCR and restriction isotyping. Baseline and stimulated PON1 activities were decreased (P <0.001) in chronic hepatitis and in liver cirrhosis. PON1 activity was significantly correlated with serum total proteins, albumin, and bilirubin in patients but not in controls. There were no significant differences with respect to allele and genotype frequencies between patients and controls. The combination of baseline serum PON1 with five standard biochemical tests had a higher classification accuracy (94% of patients; 96% of controls) than the five standard tests alone (75% of patients; 96% of controls). ROC plots demonstrated a high diagnostic accuracy for baseline serum PON1 [area under the curve, 0.89 (95% confidence interval, 0.86-0.93) in chronic hepatitis and 0.96 (95% confidence interval, 0.94-0.99) in cirrhosis]. Baseline PON1 provided the highest ROC area for cirrhosis vs controls. The significant decrease of PON1 activity in chronic liver diseases is related to the degree of hepatic dysfunction and not to allelic or genotypic differences. Addition of serum PON1 activity measurement to the current battery of tests may improve the evaluation of chronic liver diseases.