الفهرس 
DEFINITION AND CLASSIFICATION OF ASCITESOnly 14 pages are availabe for public view
 |  | from | 256 |  |  |
| | | from | 256 | | |
Abstract
Ascites is the most common of the three major complications of cirrhosis; the other complications are hepatic encephalopathy and variceal hemorrhage. Approximately 50% of patients with “compensated” cirrhosis, i.e., without having developed one of these complications, develop ascites during 10 years of observation. Ascites is the most common complication of cirrhosis that leads to hospital admission. Development of fluid retention in the setting of cirrhosis is an important landmark in the natural history of chronic liver disease: approximately 15% of patients with ascites developed in 1 year and 44% developed in 5 years.
Malignant ascites is the condition in which fluid containing cancer cells collects within the abdomen. It is usually caused by ovarian, endometrial, breast, esophageal, gastric, colorectal, lung, pancreatic, hepatobilliary and primary peritoneal carcinomas. Sometimes ascites is the sole manifestation of internal malignancies.
The underlying cause of ascites is frequently obvious from the history and physical examination. However, it is important to exclude other causes of ascites, the essential investigations on admission include a diagnostic paracentesis with measurement of ascitic fluid albumin or protein, ascitic fluid neutrophil count, ascitic culture and ascitic fluid cytology should be requested when there is a clinical suspicion of underlying malignancy.
In attempt to identify a reliable test to discriminate between malignant and non malignant ascites, various biochemical markers in the serum and ascitic fluid were evaluated. These markers include total protein, lactate dehydrogenase, serum albumin and SAAG.
High mobility group box 1 (HMGB1), also known as amphoterin or HMG1, belongs to a group of chromatin associated non-histone proteins. Proteins of the HMGB family, comprising HMGB1, HMGB2, and HMGB3, are characterized by two DNA-binding domains called HMG boxes. Currently the best analyzed member of this group is HMGB1. HMGB1 an intracellular protein, which can be secreted for example by activated monocytes, macrophages, and astrocytes and can be released by necrotic or damaged cells.
Recently, it was reported that HMGB1 was found to be highly expressed in human pleural and peritoneal effusions due to cancer and inflammation. Compared to transudates, the average level of HMGB1 was significantly higher in exudates.
The differential diagnosis of ascites is a common clinical problem. Thus we aim in this study to measure the level of HGMB1 in ascites due to liver cirrhosis and malignant ascites to evaluate its role in differentiating the two conditions.
In our study 30 patientts were included and classified into 2 groups; group I included 15 patients with ascites due to liver cirrhosis (proved to have no ascitic fluid infection or malignancy), group 2: including 15 patients with malignant ascites: (of non hepatic origin & without secondary bacterial infection).
All patients evaluated clinically and subjected to the following investigation:
Complete history taking, thorough clinical examination, laboratory investigations (e.g: CBC, liver function tests, kidney function tests, viral markers & tumor markers), diagnostic paracentesis performed for all patients at admission under aseptic conditions , and the obtained ascitic fluid (AF) was used for: routine biochemical tests (including determination of ascitic fluid albumin for calculation of SAAG), cytological examination, microbiological examination, estimation of HMGB1 level in ascitic fluid samples by PCR technique. Also imaging diagnosis such ultrasonography or CT, MRI (whenever needed) and any other investigations needed for exclusion of some patients.
There is no statistical significant difference between the 2 studied groups regarding age, gender and special habits of medical importance as smoking & alcohol.
By history taking and medical examination, the symptoms and signs suggestive of liver cell failure are predominant in patients with hepatic ascites in comparison to patients with malignant ascites.
Also laboratory investigations are supporting the diagnosis of decompansated liver disease in hepatic patients than in malignant patients.
Diagnostic paracentesis was performed for all included patients. All ascitic fluid samples in hepatic group are transudate while in malignant patients, all are exudates.
The mean of ascitic fluid albumin in hepatic group (0.81 ± 0.24 g/dl) which is less than that in malignant group (1.81 ± 0.39 g/dl) (P < 0.01).
Recently several studies were carried out addressing ‘newer’ biomarkers for differentiation between hepatic and malignant ascites.
There is statistical highly significant difference between two groups as regard ascitic fluid HMGB1. As malignant group showed significantly higher mean of HMGB1 (15.23 ± 40.65 ng/ml) than hepatic group (0.37 ± 0.62 ng/ml) (P < 0.01).
Our study shows that the sensitivity of HMGB1 in the studied group is 93.3%, specificity of the test is 80%, positive predictive value is 82.4%, negative predictive value is 92.3%, the diagnostic accuracy is 86.7% and the cut off value is 0.48ng/dl.
Our results show that there is no significant correlation between ascitic fluid HMGB1 and age, gender and laboratory investigations in both studied groups. Also our study reveals that there is no significant correlation between ascitic fluid HMGB1 and the ascitic fluid findings including physical, chemical and cytological examinations. More studies are needed to verify these results.
HMGB1 can be used as a discriminating marker between malignant ascites and ascites due to liver cirrhosis.