The Diagnostic Utility of Natural Killer Cell Subsets in Deep Vein Thrombosis.

Background: Natural killer (NK) cells are important components of adaptive and innate immune responses. NK cell subsets have different functions and may play a role in vascular disorders. This study aimed to evaluate the proportions of NK cells and their subsets to determine whether they can be used as markers of venous thrombosis and to identify whether there was a link between NK cell proportion and citrullinated histone (H3) levels. Patients and Methods: This study included 100 participants divided into Group I (n=50, patients with deep venous thrombosis (DVT)) and Group II (n=50, age- and sex-matched healthy controls). Group I was further categorized into Group Ia (n=25, patients with acute DVT) and Group Ib (n=25, patients with chronic DVT). The proportions of NK cells and their subsets were evaluated by flow cytometry using CD3/CD16/CD56. The levels of citrullinated histones (H3) were estimated using enzyme-linked immunosorbent assay (ELISA). Results: Compared to the control group, DVT patients had a significantly lower proportion of (CD56 dim/CD16+) NK cells, a significantly higher proportion of (CD56-/CD16+) NK cells and a high level of citrullinated histone (H3). Conclusion: NK cell subsets and citrullinated histone (H3) could be used as markers for DVT and as targets for therapeutic drugs to inhibit the formation or progression of thrombosis.

Impact of Toll-Like Receptor 2 and 9 Gene Polymorphisms on COVID-19: Susceptibility, Severity, and Thrombosis.

Background: Toll-like receptors (TLRs) play an important role in activation of innate and adaptive immune responses. Aim: We aimed to detect the association between TLR2 rs5743708 G>A and TLR9 rs5743836 C>T variants and COVID-19 disease susceptibility, severity, and thrombosis by using neutrophil extracellular traps (NETs). Subjects and Methods: We included 100 adult COVID-19 patients as well as 100 age- and gender-matched normal controls. Participants were genotyped for TLR2 rs5743708 and TLR9 rs5743836. Citrullinated Histone (H3) was detected as an indicator of NETs. Results: The mutant (G/A and C/C) genotypes and (A and C) alleles of TLR2 rs5743708 and TLR9 rs5743836, respectively, have been significantly related to a higher risk of COVID-19 infection, representing a significant risk factor for the severity of COVID-19. There was no significant association between the two variants and citrullinated histone (H3). Conclusion: TLR2 rs5743708 and TLR9 rs5743836 variants have been significantly related to a higher risk and severity of COVID-19 infection but had no effect on thrombus formation.

Review: Stem cells and gene therapy.

Both stem cell and gene therapy research are currently the focus of intense research in institutions and companies around the world. Both approaches hold great promise by offering radical new and successful ways of treating debilitating and incurable diseases effectively. Gene therapy is an approach to treat, cure, or ultimately prevent disease by changing the pattern of gene expression. It is mostly experimental, but a number of clinical human trials have already been conducted. Gene therapy can be targeted to somatic or germ cells; the most common vectors are viruses. Scientists manipulate the viral genome and thus introduce therapeutic genes to the target organ. Viruses, in this context, can cause adverse events such as toxicity, immune and inflammatory responses, as well as gene control and targeting issues. Alternative modalities being considered are complexes of DNA with lipids and proteins. Stem cells are primitive cells that have the capacity to self renew as well as to differentiate into 1 or more mature cell types. Pluripotent embryonic stem cells derived from the inner cell mass can develop into more than 200 different cells and differentiate into cells of the 3 germ cell layers. Because of their capacity of unlimited expansion and pluripotency, they are useful in regenerative medicine. Tissue or adult stem cells produce cells specific to the tissue in which they are found. They are relatively unspecialized and predetermined to give rise to specific cell types when they differentiate. The current review provides a summary of our current knowledge of stem cells and gene therapy as well as their clinical implications and related therapeutic options.

Biomedical research in the Middle Eastern countries: update and insight using SCImago Journal Rank indicator.

BACKGROUND: There is a dire need in the Arab world and Middle Eastern countries to reform the higher education, research policy and planning for improving the quality to meet the needs of modern society. The impact factor (IF) was developed in the 1960s by Eugene Garfield of the Institute for Scientific Information (ISI) in the USA. It has been extensively used for more than 40 years. The SCImago Journal Rank (SJR) indicator belongs to this new family of indicators based on eigenvector centrality was introduced since 2007. The SJR indicator is a size-independent metric aimed at measuring the current 'average prest (se text) per paper' of journals for use in research evaluation processes. METHODS: We present the status o the biomedical scientific research in the Middle Eastern countries through the newly developed SJR indicator showing some of the proposed ways that clearly can be applied for enhancing and development of that field in the Middle Eastern countries. RESULTS: During the period from 1996 to 2008, Northern America, Western Europe and Asiatic region are the major contributors of the scientific research Worldwide. In the Middle East, the prominent two main Arab countries are Egypt and Saudi Arabia, nevertheless, they need more planned strategies for optimal contribution to their Middle East, Arab region and the World, despite the tangible achievements of the Arab states in the higher education and scientific research during the last decade. CONCLUSION: The SJR is seemingly satisfactory for ranking the countries for their scientific contribution and impact.

Investigation of Helicobacter pylori infection in Jordanian patients using six enzyme immunoassays for immunoglobulin G (IGG) and IGA testing.

Helicobacter pylori (H. pylori) is the etiologic agent of a variety of gastrointestinal disorders. The rationale of the current study is to evaluate six enzyme immunoassays for detection of anti-H. pylori immunoglobulin G (IgG) and IgA in Jordanian patients. Biopsy specimens and blood samples were obtained from patients underwent the endoscopy unit at Al-Bashir hospital in Jordan. The serum samples were investigated for the presence of anti-H. pylori IgG and IgA antibodies in patients with positive H. pylori biopsy samples. The results showed that IgG utilizing kits are more sensitive than of IgA kits and the IgA kits are more specific than of that IgG kits. Moreover, the biopsy is seemingly the gold standard for diagnosis of H. pylori is followed by H. pylori culture on brucella agar medium. An imperfect relation between the presence of H. pylori infection and the antibody response was existed that could be explained either because of the unsatisfactory sensitivities and specificities of the commercial kits used or because of weak immunological response in our patients to H. pylori antigens. Collectively, the H. pylori diagnosis that depends on the detection of anti-H. pylori antibodies in the hospital setting and in the screening programs should consider another test for confirmation the initial diagnosis.

Helicobacter pylori infection in hepatic encephalopathy: Relationship to plasma endotoxins and blood ammonia.

BACKGROUND/AIM: Hepatic encephalopathy (HE) is frequently observed in patients with advanced liver disease and manifests a wide variety of neuropsychiatric signs and symptoms. Ammonia toxicity and bacterial endotoxins have been suggested as key determinants of HE onset whereas a role for Helicobacter pylori infection has not been established. We investigated the correlation between H. pylori infection and HE severity (evaluated through functional tests) in 60 outpatients with established liver cirrhosis and 20 non-cirrhotic controls. METHODS: Fasting arterial blood ammonia, plasma endotoxins, and H. pylori infection status were investigated in all subjects. RESULTS: H. pylori infection was documented in 35/60 (58%) patients and in 6/20 (30%) controls (P = 0.039). Significant differences were observed between patients with and withoutHE for age, presence of ascites, fasting arterial blood ammonia, plasma endotoxin, and H. pylori infection. Further, a significant increase in fasting arterial blood ammonia and plasma endotoxin was associated with H. pylori infection in cirrhotic patients. Last, medical treatment of H. pylori infection led to a significant decrease in HE severity and fasting arterial blood ammonia levels. CONCLUSION: In conclusion, we submit that H. pylori infection might, in fact, play a role in increasing the circulating levels of ammonia and endotoxins in cirrhotic patients, thus facilitating the onset of HE.

Apoptosis dysregulation in human gastric carcinomas: relationship to anti- and pro-apoptotic protein expression.

Apoptosis and the genes regulating this process have recently become a focus of interest in the study of cancer development and progression. Both Bcl-2 and Bax are transcriptional targets for the tumor supressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage. The coordinate performance of these molecules is crucial for controlling life or death of a cell. Correlations between apoptosis and protein expression of genes controlling this process including Bcl-2, Bax and p53 in gastric cancer were here investigated with gastric tumor samples of forty patients . DNA ploidy pattern was analyzed using flow cytometry and Bcl-2, Bax, and p53 were immunohistochemically localized using specific monoclonal antibodies. In addition, serum Bcl-2 protein was estimated by enzyme linked immunosorbant assay (ELISA). The obtained data showed that the mean serum Bcl-2 protein concentration demonstrated a significant increase (P<0.0001) in positive cases (61.5+/-11.0 unit/ml) compared to the negative ones (47.5+/-3.5 unit/ml). Serum Bcl-2 protein positivity was detected in 13/40 of gastric cancer patients. Immunohistochemical positivity for Bcl-2, Bax, and p53 was shown in 45%, 68%, and 63% of samples, respectively. Positive Bcl-2 and p53 immunostaining was significantly linked with the histological grade (P<0.02 and P<0.009 respectively) and lymph duct invasion (P<0.02 and P<0.001 ). On the other hand, Bax was significantly differed with lymph duct invasion and the ploidy pattern (P<0.03 and P<0.002). In conclusion, the apoptosis-related genes p53, Bcl-2, and Bax are all linked to the occurrence of gastric cancer. Therefore, analysis of their expressions may add useful information concerning tumor behavior.

A close link between Fas, p53 and Apaf-1 in chronic myeloid leukemia.

In chronic myeloid leukemia (CML) proliferation is increased and resistance to apoptosis has been proposed as a mechanism accounting for myeloid cell expansion. There is still controversy on whether apoptosis plays an important role in the regulation of myelopoiesis. This study aims to investigate whether apoptosis-related proteins play a role in the evolution of CML and to identify, the relationship between Fas, p53 and apoptosis protease activating factor (Apaf-1) in CML. We found increased p53 and Apaf-1 messenger ribonucleic acid (mRNA) in patients with CML. However, one patient, who had a p53 point mutation, showed a massive elevation of p53 mRNA during blast crisis yet, conversely, a considerable reduction in Apaf-1 mRNA and Fas mRNA. Our results show an in-vivo linkage between Fas, p53 and Apaf-1 transcription regulation. This suggests that key genes involved in apoptosis are also involved in CML disease progression.

Serum laminin assayed by Slot-Blot-ELISA in patients with combined viral hepatitis C and schistosomiasis.

OBJECTIVES: Hepatic schistosomiasis and chronic hepatitis C virus (HCV) are the most prevalent agents causing hepatic fibrosis in humans. Laminin (LA) has been related to liver fibrosis and subsequent development of portal hypertension in chronic liver disease. There are no available data describing the pattern of laminin in combined HCV and schistosoma-infected patients, thus the rationale of this study was to assess the serum LA as an index of liver fibrosis in patients with schistosomiasis and/or chronic viral hepatitis C and to evaluate a developed Slot-Blot Enzyme-Linked Immunosorbant Assay (Slot-Blot-ELISA) as a method of estimation. DESIGNS AND METHODS: This study included four groups: group I included 34 patients with schistosomiasis, group II included 58 patients infected with HCV, group III included 68 patients with combined chronic viral hepatitis C and schistosomiasis and group IV included 50 healthy individuals who served as a control group. Serum LA was measured in the different groups quantitatively by ELISA and semi-quantitatively by Slot-Blot-ELISA. RESULTS: Significantly higher serum LA concentrations measured by ELISA were found in patients with combined chronic viral hepatitis C and schistosomiasis than in patients with either chronic HCV (P = 0.005) or schistosomiasis (P < 0.001) alone. Serum LA was significantly higher in the patient groups than the control group (P < 0.001). Serum LA concentration was positively correlated with fibrosis grading scores. Semi-quantitative results of serum LA using the developed SB-ELISA were found to have approximately the same power of ELISA results in different groups. The overall sensitivity, specificity, positive predictive value, negative predictive value and efficiency of ELISA for estimation of serum LA were 85.6%, 84.0%, 94.5%, 64.6% and 90%, respectively and for SB-ELISA were 87.5%, 82.0%, 94%, 67.2% and 88%, respectively. CONCLUSIONS: Serum LA was significantly increased in patients coinfected with HCV and Schistosoma mansoni. The newly developed Slot-Blot-ELISA is a simple, rapid and highly sensitive assay for detection of LA in hepatic fibrosis. Moreover, all steps were performed at room temperature without the need to use expensive equipment, and this may enhance the application of this assay in screening programs. Further study is warranted for confirmation of SB-ELISA reproducibility in a large population.

Implications of CEA and p53 overexpression in the poor prognosis of colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent and aggressive types of cancer. Several clinicopathologic features have been studied to identify the prognostic factors that can provide information concerning the favorable or the poor outcome of colorectal cancer. In the present study, the relationship between serum CEA, p53 expression, and DNA index to the different clinicopathological characteristics of colorectal cancer patients was sought. Fifty patients with CRC were included in this study. p53 protein was detected immunohistochemically using specific monoclonal antibodies. Samples were investigated for DNA index using flow cytometry. In addition, the serum CEA was determined using ELISA. The results showed that 27/50 (54%) were positive for p53. Concerning CEA reactivity, it was found that 35/50 (70%) were reactive for CEA. These results indicate that CEA is more sensitive than p53 to detect colorectal cancer. There was a statistically significant difference between the recurrent and nonrecurrent groups in the CRC Duke's stages, survival time, serum CEA (p = 0.001, 0.016, < 0.001, respectively). Kaplan-Meier method and log-rank test showed that the mean survival time for cases positive for both p53 and CEA is significantly different from cases positive for CEA only, positive for p53 only, and negative for both p53 and CEA (p = 0.0002). Survival time was statistically significant with respect to sex, p53, CEA, and Duke's stages (p = 0.006, 0.024, 0.001, 0.017, respectively). Cox regression model showed that the prognosis of colorectal cancer is influenced by sex, p53, CEA reactivity, and CRC Duke's stages (p = 0.014, 0.006, 0.019, 0.014, respectively). In conclusion, the use of more than one tumor marker may successfully aid in the prediction of colorectal cancer prognosis.

p53, Bcl-2 and C-Myc expressions in colorectal carcinoma associated with schistosomiasis in Egypt.

BACKGROUND AND AIMS: Oncogenes and tumor suppressor genes expression are well described in bladder cancer associated with schistosomiasis especially in Egypt. Scarce studies were directed to colorectal cancer (CRC) associated with Schistosoma mansoni (S. mansoni). Apoptosis (programmed cell death) and the genes regulating this process (e.g., Bcl-2) have recently become a focus of interest in the study of cancer development and progression. In the present study, we aimed to investigate the expression pattern of p53, Bcl-2 and C-Myc in CRC tissues obtained from Egyptian colorectal cancer patients divided in two different groups, one associated with Schistosoma mansoni (CRC-Sm) and the other without Schistosoma mansoni (CRC-NSm). METHODS: Seventy-five CRC tumors containing 36 draining lymph node metastatic tumors were immunohistochemically stained using specific monoclonal antibodies for p53, Bcl-2 and C-Myc, in addition the apoptotic activity of these tumors were analyzed. RESULTS AND CONCLUSIONS: Regardless of the S. mansoni infection, the obtained results showed that the apoptotic activity was more evident in p53 diffuse positive tumors (P = 0.021). There was a significant correlation between p53 diffuse positive staining and Bcl-2 positive immunostaining (P = 0.011). Signet ring cell carcinoma and mucinous adenocarcinoma exhibited both intense C-Myc expression than non-mucinous carcinoma (P = 0.001). When adjusting for S. mansoni infection, 58.3% of CRC-Sm cases were Bcl-2 positive compared to only (33.3%) of CRC-NSm (P = 0.046). Apoptotic activity was more evident in the latter group than of CRC-Sm tumors (P = 0.009). p53 and C-Myc expressions were found insignificantly different in CRC-Sm compared with CRC-NSm (P > 0.05). These observations suggest that the genotoxic agents produced endogenously through the course of schistosomiasis mansoni may play a role in CRC-Sm pathogenesis through the dysregulation of apoptosis by alteration the expression pattern of Bcl-2 protein differently from CRC-NSm suggesting a different biological behavior.

Relationship of Helicobacter pylori to Bcl-2 family expression, DNA content, and pathological characteristics of gastric cancer.

BACKGROUND: Despite the fact that the association of Helicobacter pylori with an increased risk of gastric cancer has been well documented, the exact mechanisms of this association have not been fully elucidated. Scarce data on H. pylori infection and its relationship with the different pathological characteristics are available in Egypt. AIM OF THE STUDY: The rationale of the present study was to determine the prevalence of H. pylori in a group of gastric cancer patients and to analyze the relationship between H. pylori infection with the different pathological characteristics including the types of gastric cancer and tumor location within the stomach, in addition, to investigate the Bcl-2 and Bax expressions along with DNA flow cytometric analysis in the gastric cancer patients with and without H. pylori infection. METHODS: Samples were obtained from 66 consecutive patients with gastric cancer (46 males and 20 females). The youngest patient was 20 yr old, the oldest 76 yr with mean age of 52.8 yr. The samples were subjected for histopathological characterization, H. pylori detection, DNA flow cytometric analysis, and Bcl-2 and Bax expressions detection, in addition to apoptosis analysis. RESULTS: The obtained results showed that the H. pylori infection was found in 38/66 (57.6%) [Odds ratio=1.357 with 95% confidence interval (CI) 0.84-2.2]. There was a statistical significance for Bcl-2, Bax, and apoptosis with H. pylori status (p = 0.009, 0.008, 0.032, respectively). On the other hand, There was a statistical significance for H. pylori infection with the disease grade (p = 0.015) and lymph node metastasis (p = 0.05). No statistical significance was found between H. pylori status with the patients' age, gender, tumor site, tumor type, depth of invasion, and stromal reaction. CONCLUSIONS: These data may indicate that the H. pylori infection not only contributes in the disease formation through the apoptosis dysregulation but also takes a part in the disease dissemination and progression. In addition, it may reflect a biologic, pathogenic, and ethnic background affecting the relationship of H. pylori infection to gastric cancer in the Egyptian patients. A high rate of smoking in Egypt and the diet are important factors that may affect such background. Further studies are warranted.

MUC2 and MUC6 apomucins expression in human gastric neoplasm: an immunohistochemical analysis.

Apomucins play important biological roles in cell-cell and cell-extracellular matrix interactions, in cell signaling, and in biological properties of cancer cells. Their specific pattern of expression during the different steps of tumor progression toward adenocarcinoma suggests that they play significant roles in tumorigenesis. The family of secreted mucins, gel-forming components of viscoelastic mucus gels protecting the epithelia, includes mucins MUC2 and MUC6. Their principle function is to contribute in mucus formation by forming a tridimensional network via oligomerization domains to protect underlying epithelia against diverse injuries. The current study was investigated the expression of MUC2 and MUC6 in patients with gastric carcinoma. MUC2 and MUC6 expressions were detected immunohistochemically in gastric cancer biopsies using specific monoclonal antibodies. The results showed that in our gastric carcinoma cases, MUC2 expression was detected in 78.6% of cases. MUC2 expression is increased from well differentiated to moderately differentiated to poorly differentiated gastric adenocarcinoma. On the other hand, MUC6 was detected in 32% of cases. The expression of MUC2 is increasing, which is accompanied by an altered expression of MUC6 in gastric cancer. Therefore, it is concluded that the expression pattern of secreted mucins including MUC2 and MUC6 is altered apparently in gastric carcinoma.

Swords of cell death: caspase activation and regulation.

Apoptosis represents a crucial process in modulating organ development in the embryo, in organ homeostasis in the adult, and in fostering appropriate immunological function. Caspases represent two central classes of molecules that are either involved with the stimulation of the apoptotic cascade (initiator caspases), or the various sequential biological pathways required for its execution (effector caspases). With an eye towards therapeutic opportunities, this review discusses in detail the lineage of initiator and effector caspases, how they are each activated, their substrates, their regulation, and maps out how they interact throughout the process from initiation of the first apoptotic signal to the final consequential breakdown of cellular integrity.

Elevated renin levels in patients with liver cirrhosis and hepatocellular carcinoma.

Liver fibrosis is the common consequence of chronic liver injury of any etiology, disrupting the normal architecture,and causing hepatocellular dysfunction and portal hypertension. Since the renin-angiotensin system (RAS) may be involved in chronic liver diseases, in the present study we assayed renin levels using ELISA in groups of Egyptian patients with liver cirrhosis (N=32) and hepatocellular carcinoma (HCC) (N=67), for comparison with twenty five healthy controls. The results showed significant differences between the control and liver cirrhosis patients (P<0.001) and also the controls and HCC patients (P<0.001), without significant variation between the patient groups. Furthermore, in HCC patients, it was found that the renin levels negatively correlated with serum albumin and prothrombin time (P=0.003 for each) and positively with α-fetoprotein (P=0.04). Thus, it is concluded that renin levels are elevated in patients with liver cirrhosis and HCC and suitable medical intervention should be placed for management of such alteration. Moreover, further studies are warranted to explore its prognostic significance.

Pattern of matrix metalloproteinases-9, P53 and BCL-2 proteins in Egyptian patients with pulmonary Mycobacterium tuberculosis.

Matrix metalloproteinases (MMPs) constitute a large family of enzymes that degrade extracellular matrix proteins (ECM). MMPs are implicated in different pathological conditions such as cancer. Bcl-2 and P53 are key controllers of programmed cell death (PCD) or apoptosis. The aim of the present study was to determine the MMP-9, P53 and Bcl-2 levels in Egyptian patients with Mycobacterium tuberculosis (MTB) (Group I) compared with healthy control individuals (Group II). The concentrations of serum MMP-9 were determined quantitatively using enzyme immunoassay (EIA). P53 and Bcl-2 levels were assayed by flow cytometric analysis using specific monoclones. MMP-9 level was significantly higher in MTB patients compared with healthy control. Similarly, P53 and Bcl-2 levels were increased in MTB patients compared with healthy ones. These data reflect the alteration of MMP-9 level during the course of MTB infection, accompanied with apparent dysregulation of cellular apoptosis as indicated by P53 and Bcl-2 over-expression.

Helicobacter pylori and Hepatitis C Virus Coinfection in Egyptian Patients.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease worldwide. It has been shown that Helicobacter pylori (H. pylori) plays an important role in chronic gastritis, peptic ulcer disease and gastric malignancies, and its eradication has been advocated. The association between H. pylori infection and liver cirrhosis in patients with hepatitis C virus has been documented in different parts of the world; nevertheless, no conclusive data is available in Egypt. MATERIALS AND METHODS: In the present study, the status of H. pylori infection was sought in 90 patients with chronic HCV infection and in 66 HCV-free healthy controls. RESULTS: The study showed that the H. pylori positivity was increased significantly (P = 0.03) in the HCV-infected patients when compared to that in healthy controls, where H. pylori infection was found in 50 (55.6%) out of 90 of the HCV-infected patients versus 26 (39.4%) out of 66 of the healthy controls. In HCV-infected patients, the prevalence of H. pylori infection was increased significantly (P = 0.04) from chronic active hepatitis to cirrhosis. H. pylori infection was present in 6/18 (33.3%), 10/21 (47.6%), 16/27 (59.3%), 18/24 (75.0%) patients with chronic active hepatitis, Child-Pugh score A, Child-Pugh score B and Child-Pugh score C, respectively. More importantly, the prevalence of H. pylori infection in HCV-infected patients was increased very significantly (P = 0.003) with increasing Meld (model for end-stage liver disease) score. The prevalence of H. pylori was documented in 9/28 (32.1%) patients with Meld score >10 and in 41/62 (66.1%) patients with Meld score >10. CONCLUSION: It may be stated that our results collectively reflect a remarkable increase in H. pylori prevalence with advancing hepatic lesions, and the eradication treatment may prove beneficial in those patients with chronic hepatitis C.

Significance of serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in chronic hepatitis C patients.

Liver fibrosis (LF), where the chronic HCV infection is a major cause, is a characteristic of chronic liver diseases. LF results from chronic damage to the liver in conjunction with the accumulation of ECM proteins. Matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) are thought to play an essential role in the hepatic lesions. The available data concerning the circulating levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in chronic hepatitis C are not conclusive. Therefore, the present study was designed to seek the relationship between serum MMP-9, and TIMP-1 to liver status in chronic liver disease in fifty patients divided into three groups (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma). MMP-9 and TIMP-1 were analyzed by the enzyme linked immunosorbent assay (ELISA). The results showed that the lowest serum level of MMP-9 was found in chronic hepatitis patients compared to the control ( P < 0.05). Serum MMP-9 is decreasing during progression of chronic hepatitis to cirrhosis showing the least level in the cirrhotic group. Serum TIMP-1 was significantly higher in the cirrhotic group compared to chronic hepatitis ( P < 0.05) and controls ( P < 0.001). MMP-9 was negatively correlated to both TIMP-1 and the histological severity in chronic hepatitis. There was a positive correlation between TIMP-1 and the degree of fibrosis (r = 0.73, P < 0.001). Lastly, there was a statistically significant increase of MMP-9 ( P < 0.001) and TIMP-1 ( P < 0.05) in HCC patients compared with the other groups. In conclusion, these findings raise the possibility of using serum TIMP-1 as a non-invasive assay in liver fibrosis. Further, the altered balance between circulating MMP-9 and TIMP-1 during HCV infection may play an important role in aggravating liver injury progression in chronic liver diseases.