Evaluation of some liver fibrosis markers in chronic liver diseases

Liver fibrosis is a dynamic bi-directional process involving phases of progression and regression. Its diagnosis is dependent on histopathological examination of biopsy specimens. The aim of this study was to evaluate some non invasive serum markers of liver fibrosis and to correlate them with liver biopsy. Fifty patients with chronic liver diseases matched with 10 age and sex healthy blood donors were included in the study. For both groups; estimation of serum matrix metalloproteinase 9[MMP-9], tissue inhibitor of metalloproteinase 1[TIMP-1] by ELISA technique and haptoglobin by RID, scoring of the age-platelet index [API], AST to platelet ratio index[APRI],and prothrombin time [PT] were done. For the patients, histopathological examination of liver biopsy specimens for assessment of necroinflammatory grade [A] and fibrosis stage [F] applying the METAVIR scoring system. API showed a significant positive correlation with both fibrosis and necroinflammatory activity, by using ROC curve for discrimination of significant fibrosis [F>/= 2] and moderate to severe necroinflammatory activity [A>/= 2], the AUROCs were 0.88 +/- 0.09 and 0.69 +/- 0.16 respectively. In case of Platelet count the AUROC was 0.80 +/- 0.12 for the diagnosis of established cirrhosis [F4]. PT showed a significant positive correlation with fibrosis progression, and it was a sensitive predictor of significant fibrosis and the AUROCs, for [F >/= 2] and [F4] were 0.67 +/- 0.15 and 0.76 +/- 0.15 respectively. While APRI showed a significant positive correlation with both fibrosis stage and necroinflammatory grade and the AUROCs were 0.68 +/- 0.15 and 0.69 +/- 0.15, for [F >/= 2] and [F4] respectively .The mean serum level of MMP-9 was significantly higher in patients than controls [P < 0.05] and showed a significant negative correlation with fibrosis stage [P < 0.05]. By using ROC curve to assess MMP-9 for discrimination of significant fibrosis [F>/= 2] and cirrhosis [F4], the AUROCs were 0.67 +/- 0.17 and 0.69 +/- 0.18 respectively, while for [A>/= 2], it was0.75 +/- 0.16. The mean value of serum TIMP-1 was significantly higher in patients than controls [P < 0.05], with significant positive correlation with necroinflammatory grade[P < 0.05]. The AUROCs for [F>/= 2] and [F4] were 0.58 +/- 0.2 and 0.53 +/- 0.19 respectively, while for [A>/= 2], it was 0.67 +/- 0.17. Haptoglobin showed a significant negative correlation with fibrosis progression[r=-0.4, P < 0.05] and AUROC for [F>/= 2] and [F4] were 0.75 +/- 0.17 and 0.78 +/- 0.15 respectively. MMP-9 was a fair marker of fibrosis as well as inflammatory activity, and TIMP-1 was a sensitive and to a lesser extent specific marker of advanced liver disease, discriminating inflammatory activity rather than fibrosis stage. On the other hand API was the best marker that can discriminate significant fibrosis, while platelet count for diagnosis of cirrhosis. Among the assessed serum markers, haptoglobin, API and PT were the most sensitive predictors of significant fibrosis, while haptoglobin and API were the most sensitive predictors of cirrhosis. Finally, these serum assays, although promising, are still in need of being refined with further prospective studies

Assessment of the relation between serum-ascites albumin concentration gradient with esophageal varices and its complication

We aimed to evaluate the correlation between serumascites albumin concentration gradient [SAAG] with esophageal varices [EV] presence and grading, and to assess the relationship between SAAG measurements and the occurrence of gastrointestinal hemorrhage in cirrhotic patients with ascites. Our study included 45 nonalcoholic cirrhotic cases with ascites. They had routine clinical, ultrasonographic and laboratory investigations including ascitic fluid analysis. They had measurement of SAAG computed. An upper gastrointestinal endoscopy was done in all cases to assess the presence and size of EV. 36 of our patients [80%] had EV. The mean SAAG level was 1.46 +/- 0.27 gm/dL for all cases. No correlation was found between SAAG and any of the studied clinical or biochemical parameters. By using the ROC Curve, a SAAG value at a level of [>1.55gm/dL], was a good predictor of the presence of EV with 100% sensitivity and 71.4% specificity. The presence of EV was positively correlated with serum bilirubin, prothrombin time [PT], and spleen size. Meanwhile, it was negatively correlated with serum albumin, serum total protein, platelet count and total protein in ascetic fluid. On univariate analysis of variants associated with the presence of large esophageal varices, only the presence of splenomegaly could predict high grade varices. On comparing patients with and without bleeding varices, the EV grade, portal vein diameter [PVD], spleen size and creatinine level were significantly higher in the group of bleeding varices [p values were 0.002, 0.006, 0.01 and 0.012 respectively] A SAAG score [>/=1.55 gm/dL] is a useful predictor of the presence of EV in cirrhotic patients with ascites. This finding can assist clinicians in determining the urgency of care and referral for upper gastrointestinal endoscopy in cases with ascites. Meanwhile, SAAG was not valuable in screening and predicting complications, such as bleeding from esophageal varices

Effect of paracentesis on portal venous hemodynamics, cardiopulmonary functions and arterial blood volume in cirrhotic patients

Abdominal paracentesis is an old medical procedure for treatment of tense ascites. Paracentesis induced circulatory dysfunction [PICD] is a complication that can be prevented with the administration of intravenous albumin. The aim of this work is to assess the effects of a single large volume paracentesis [LVP] on portal venous hemodynamics and cardiopulmonary functions in cirrhotic patients with tense ascites. Also, to compare between dextran-70 and albumin as a replacement therapy. Thirty adult patients from either sex with cirrhosis and intractable ascites were randomly allocated into one of three groups subjected to LVP, group I: include 10 patients received human albumin infusion 20%, group II: include 10 patients received dextran -70 infusions and group III: include 10 patients with no replacement therapy. Patients had undergone blood urea blood urea nitrogen [BUN], liver function tests. serum electrolytes [Na+ and K+], ascetic fluid analysis, arterial blood gases [ABG], duplex ultra-sonographic examination of the portal [PV] and splenic veins [SV] with calculation of their velocity and congestive index [CI], standard pulmonary functions tests and echocardiographic estimation of right and Left atrial areas and cardiac output [COP]. Effective arterial blood volume was assessed by measuring plasma renin activity [PRA] and aldosterone concentrations [PAC]. All measurements were done at baseline, 48 hours [hrs.] and on the six day after LVP. All patients reported improvement of their clinical manifestation. Urine output increased in all groups with significant difference between group I and groups II and III at 48 hrs and between group I and III at 6th day. Heart rate slightly increased 48 hrs and then decreased on the 6th day with no significant difference between studied groups while the mean arterial blood pressure slightly decreased in dl groups with only significant difference between pre-tape and 48 hrs and 6th day results in-group III. The mean right and left AA and COP significantly increased in the all groups Right AA was lower in-group III at 48 hrs compared to other two groups. There was significant difference between pre-tape and 48 hrs results of left AA in-group III. At 48 hrs left AA was significantly lower in group III compared to other two groups and in group II compared to group I. On the 6th day, left AA was significantly lower in group III compared to other two groups. The mean FEVI and FVC increased in all groups, while the mean FEVI/FVC showed no significant change. The mean PaO2 increased significantly in all groups. Oxygen saturation increased significantly in all groups at 48 hrs then decreased on the 6th day but still above pre-tape results with significant difference between 48 hrs and 6th day values. PaCO2 decreased significantly in all groups. There was a significant increase in mean PV and SV velocity 48 hrs after LVP with non-significant reduction of their congestion index. BUN significantly increased in group III compared to groups I and II. Serum sodium markedly decreased in group III compared to groups I and II with significant difference between pre-tape, 48 hrs and 6th day results of group III. PRA and PAC non significantly increased in all groups before LVP, in group I, PRA showed no significant changes after LVP, while PAC initially increased after LVP then significantly decreased on the 6th day. In-group II, PRA and PAC significantly increased after LVP with significant difference between pre-tape, 48 hrs and 6th day results of PAC. In-group III there was significant increase in PRA and PAC. As regard PRA, there was significant difference between groups I and II and group III, also between group III and group II at 48 hrs while on the 6th day there was significant difference between groups I and II and group III. As regard, PAC there was significant difference between group I and groups II and III on the 6th day. There was non-significant increased incidence of hyponatremia, hyperkalemia and incidence of PICD in group III. So, we can conclude that LVP with concomitant infusion with appropriate plasma volume expander is quite safe, palliative, and cost effective in patients with advanced cirrhosis and has a fewer complications in comparison to conventional diuretic therapy. LVP has an immediate beneficial effect on arteria blood oxygenation, cardiac functions, provides rapid improvement of lung volumes and improve portal venous dynamics. The low cost, the good tolerance and the safety of the plasma expander, dextran justify its therapeutic usage as useful alternative to human albumin in the management of intractable ascites especially small volume [<5 liter]. Also therapeutic paracentesis without replacement is effective as with albumin or dextran infusion on the outcome of cardiopulmonary functions and portal venous dynamics