Background and aim: Malondialdehyde (MDA) results from lipid peroxidation of polyunsaturated fatty acids and it is a marker for oxidative stress. Its level is higher in cirrhotic patients with viral etiology than in matched healthy con- trols. So, it may strongly correlate with Portal Hypertension (PH) in cirrhotic patients. This work aims at evaluation of the relevance between plasma MDA level and portal hyperten- sion in cirrhotic patients.

      Methods: 30 patients with cirrhotic portal hypertension and esophageal varices, and 30 healthy control participants were included in a case control study. These patients were admitted to Tropical Medicine Department, Ain Shams Uni- versity Hospital.

      Results: MDA level was found with a high significance in the studied patients with cirrhotic portal hypertension than in the healthy control group with p-value < 0.001. Also, a significant positive correlation between MDA level and PV diameter in the Child-Pugh score of the studied patients was found. Conclusion: there was a strong correlation between the increased plasma MDA level and hemodynamic disor- der and portal hypertension in cirrhotic patients. As a result, MDA acts as a new non-invasive diagnostic marker of portal hypertension in patients with liver cirrhosis.

      malondialdehyde (MDA) concentration: Using Enzyme- Linked Immunosorbent Assay (ELISA) test. Serum MDA was measured by Enzyme Linked Immunosorbent Assay (ELISA), us- ing Human MDA ELISA KIT by Glory Science Co., Ltd 2400 Veter- ans Blvd. Suite 16 - 101, Del Rio, TX 78840, USA.

      Abdominal ultrasonography with doppler: Abdominal ul- trasound with measurement of Portal Vein (PV) caliber and PV duplex. In addition to detection of Abdominal portosystemic collaterals in the form of recanalized paraumbilical vein, spleno- renal collaterals, dilated left and short gastric veins.

      Equipment used: Hitachi, EUB-5500, 2-5 MHz convex probe, (China, Mainland); the patients were examined in supine po- sition with emphasis on liver by an experienced sonographist, who was blind to all biochemical characteristics of the partici- pants.

• Upper gastrointestinal

Statistical analysis Descriptive statistics:

• Mean, Standard deviation (± SD) and range for numerical data.

• Frequency and percentage of non-numerical

Analytical statistics:

• Student T Test was used to assess the statistical signifi- cance of the difference between two study group

• Correlation analysis (using Pearson’s method): To assess the strength of association between two quantitative The correlation coefficient denoted symboli- cally “r” defines the strength (magnitude) and direction (positive or negative) of the linear relationship between two variables.

• The ROC Curve (Receiver Operating Characteristic) pro- vides a useful way to evaluate the Sensitivity and specific- ity for quantitative Diagnostic measures that categorize cases into one of two

      The studied patients are divided into 21 males (70%) and 9 females (30%) with mean age (57.13 ± 6.90) as described in table 1. Also, all the 30 patients (100%) had HCV and only one patient (3.3%) had combined HCV and HBV (Table 1).

      The laboratory investigations of the studied patients re- vealed Hb (gm/dl) with mean (9.69 ± 1.64), WBCS (X103/dl) with mean (5.80 ± 3.19) and Plts (X103/dl) with mean (77.07 ± 31.91), the results of Liver profile showed Albumin (gm/dl) with mean (3.08 ± 0.28), T.Bilirubin (mg/dl) with mean (1.55 ± 0.55)

      and INR with mean (1.40 ± 0.20) (Table 2).

      The clinical findings of the studied patients showed that 10 (33.3%) patients had hepatomegaly, 30 (100.0%) patients had splenomegaly and 9 (30%) patients had ascites (Table 3). As re- gard the esophageal varices, 8 (26.6%) of the studied patients had small OV, 6 (20.0%) had medium OV, 7 (23.3%) had large OV and 2 (6.66%) had eradicated OV (Table 4). Twenty-three (76.6%) of the studied patients had mild PHG and 5 (16.6%) had severe PHG (Table 5).

      The mean of MDA level among the studied patients was (228.50 ± 136.20) nM which was higher and statistically signifi- cant than the mean of MDA level among the group of healthy controls which was (30.37 ± 18.73) nM with p-value < 0.001 as seen in Figure 1 and Table 6.

      Correlation between MDA and laboratory parameters in studied patients showed that there was no statistically signifi- cant correlation (Table 7). No statistically significant correlation found between the level of MDA and degree of O.V (Table 8).

      A significant positive correlation was illustrated between MDA level and PV diameter of the studied patients as described in Table 9 and Figure 2. A statistically significant difference was observed between MDA plasma level and abdominal collaterals being 290.25 ± 124.97 nM in the studied patients with abdom- inal collaterals and 49.02 ± 40.63 nM in the studied patients without abdominal collaterals as seen in Table 10 and Figure 3.

      The Receiver Operating Characteristic Curve (ROC) in Figure 4 shows that the best cut-off point for MDA in prediction of cir- rhotic patients together with PH is found at > 45 nM with sensi- tivity of 100% and specificity of 90%.

Figure 1: The mean level of MDA among the studied patients was (228.50 ± 136.20) and the mean level of MDA among the control group was (30.37 ± 18.73).

Figure 2: Showed increase in the level of MDA with increase in PV diameter.

Figure 3: Showed statistically significant positive correlation found between the level of MDA (nM) and abdominal collaterals.

Figure 4: Showed statistically significant positive correlation found between the level of MDA (nM) and abdominal collaterals.

Table 1

Table 1: Demographic data of the studied patients as regard age, gender and etiology of liver disease.

Table 2

Table 2: Laboratory investigations among the studied patients.

Table 3

Table 3: The relevant clinical findings on local examination of the studied patients.

Table 4

Table 4: Oesophageal varices among patients group.

Table 5

Table 5: Portal hypertensive gastropathy in patients group.

Table 6

Table 6: Comparison between control group and patients group regarding MDA level.

Table 7

Table 7: Correlation of MDA level with the laboratory investigations of the studied patients.

Table 8

Table 8: Correlation of MDA level with degree of oesophageal varices (O.V).

Table 9

Table 9: Correlation of MDA level with portal vein (PV) diameter of the studied patients.

Table 10

Table 10: Correlation of MDA level with ultrasound findings regarding abdominal collaterals of studied patients.

      Malondialdehyde (MDA), a typical aldehydic product, results from polyunsaturated fatty acids peroxidation [3]. The lipid per- oxidation degree can be estimated by the MDA amount in tis- sues, which considers an oxidative stress marker. MDA has been found to be up-expression significantly in patients with liver cirrhosis [6]. Plasma MDA concentrations are higher in patients with liver cirrhosis due to viral etiology than in matched healthy controls [7].

      Regarding the clinical data of the studied patients in this study, all our patients had splenomegaly and 9 patients (30%) had ascites. These results agreed with results of Sherlock and Dooley, 2002 [9] who reported that splenomegaly and ascites were the commonest portal hypertensive signs in patients with liver cirrhosis. Also Berzigotti et al., 2013[10] confirmed that and agreed with the conclusion of Sharma et al. [11] that sple- nomegaly was present as an independent predictor for esopha- geal varices presence, while ascites was explained by cirrhosis, portal hypertension and splanchnic vasodilation resulting main- ly from increased production of nitric oxide which represented the main pathophysiological mechanism of ascites [12].

      In our study, the mean haemoglobin level was low at 9.69 gm/dl ± 1.64 in patients with cirrhotic portal hypertension. Fur- ther, the mean platelet level was also low in patients with liver cirrhosis at 77.07 ×103/dl ± 31.91. These results were similar to results of Ohta et al. [13] who found that the mean haemoglo- bin level was 11.2 gm/dl ± 1.7 in cirrhotic patients with portal hypertension. Additionally, investigators in other studies report- ed that the mean platelet levels were lower at 104-109 × 103/dl and 93-109 × 103/dl, respectively, in cirrhotic patients with por- tal hypertension [14,15]. These findings could be attributed to the severity of portal hypertension causing hypersplenism [16].

      In the present study, MDA level was found with a high signifi- cance in the studied patients than in the healthy control group with p-value < 0.001. Similarly, in another study, where 60 liver cirrhotic patients and 30 healthy controls were enrolled, it was found that the MDA plasma level was significantly higher in cir- rhotic patients than the controls (P < 0.001); and it increased significantly according to the severity of liver fibrosis and portal hypertension (P < 0.01) [17].

      Similarly, investigators in other studies reported that the virus-related cirrhotic patients had a higher oxidant level of MDA, and suggested that more oxidants stress and weaker anti- oxidants protection existed in the cirrhotic patients than in the control cohort [1,18].

      In our study, we found a statistically significant positive cor- relation between MDA level and PV diameter in the studied pa- tients. Similarly, another study found that MDA level of patients with liver cirrhosis was significantly associated with the width of the portal vein [17], which could be contributed to the fact that the vessel diameter width of the venous system was positively linked to the portal vein pressure in portal hypertension caused by cirrhosis [19].

      Finally, this Receiver Operating Characteristic Curve (ROC) shows that the best cut-off point for MDA in prediction of cirrhot- ic patients with portal hypertension was found at > 45 nM with sensitivity of 100% and specificity of 90%, while Sheng-Lan et al.

      [17] showed that the cut-off value of plasma MDA to differenti- ate between cirrhotic patients and the control was 426.5 nM, with sensitivity and specificity at 78.2% and 86.2%, respectively.

      The portal hypertension is defined by the pathological in- crease in the pressure of the portal venous system, and cir- rhosis is the commonest cause of the portal hypertension. The outcome results showed that the MDA level was significantly higher in the cirrhotic patients with portal hypertension than in the healthy ones and directly correlated with the PVD, esopha- geal varices, PHG, Child Pugh score. So, MDA acts as an impor- tant non-invasive diagnostic marker of portal hypertension in Egyptian patients with liver cirrhosis.

      Ethics approval and consent to participate: Written consent was taken from each patient who agreed to participate in the research process. The agreement for participation of the sub- jects was taken after the aim of the study has been simply ex- plained to them prior to data collection. They were assured that anonymity and confidentiality would be guaranteed and about their right to withdraw from the study at any time without giv- ing any reason. Values, culture, and beliefs were respected. This was done according to the regulations of the research ethical committee, Faculty of Medicine, Ain Shams University. The number of the ethical approval is 137/2017 (2/4/2017).

      Consent for publication: Informed consent to publish pa- tients’ data was signed by all participants prior to the beginning of the research.

      Availability of data and material: The data used to support the findings of the study will be shared on reasonable request to the corresponding author.

      Competing Interests: The authors declare that there is no

      conflict of interest.

      Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sec- tors.

      Authors’ Contributions: Ahmed A. EL-khattib, Enas H. Allam and Kareem A. Abd El-hafeez designed the research; Nourhan

1. Thabet performed the research; Ahmed A. EL-khattib, Enas H. Allam and Kareem A. Abd El-hafeez contributed analytic tools; Ahmed A. EL-khattib, Enas H. Allam, Kareem A. Abd El-hafeez analyzed the data; Safaa R. Askar wrote the paper.