Non-invasive Markers Of Liver Fibrosis Research Articles

Matrix metalloproteases and their tissue inhibitors in non-alcoholic liver fibrosis of human immunodeficiency virus-infected patients.

AIMTo investigate the relationships among diverse metalloproteases (MMPs) and their tissue inhibitors (TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus (HIV)-infected patients.METHODSSingle nucleotide polymorphisms (SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus (HCV) coinfection. A total of 158 patients were included, 57 of whom were HCV-coinfected. All patients drank < 50 g ethanol/day. Diverse SNPs (MMP-1 -1607 1G/2G, MMP-8 -799C/T, MMP-9 -1562 C/T, MMP-13 -77A/G, TNF-α -308 G/A, CCR5-∆32), and serum levels of MMPs (2, 3, 8, 9 and 10) and TIMPs (1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis (F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kPa.RESULTSA total of 34 patients (21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2 (P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values (P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements (P = 0.01). Multivariate analyses showed that high levels of MMP-2 (OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2 (OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender (OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2.CONCLUSIONCertain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIV-infected patients with/without HCV coinfection.

Study of Some Serum Biochemical Markers of Liver Fibrosis in Patients with Chronic HCV

Chronic hepatitis C is a major cause of cirrhosis, hepatocellular carcinoma and HCV related end stage liver disease, in many countries it is the first cause of liver transplantation. The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years. Establishing accurate staging of liver disease is very important for enabling both therapeutic decisions and prognostic evaluations. A liver biopsy is considered the gold standard for assessing the stage of hepatic fibrosis, but it has many limitations. During the last decade, several noninvasive markers for assessing the stage of hepatic fibrosis have been developed. Some have been well validated and are comparable to liver biopsy. This paper focused on some noninvasive biochemical markers used to stage liver fibrosis. The aim of this study was to evaluate some serum biochemical markers for diagnosing liver fibrosis in patients with CHC. This study was conducted on 50 patients who were divided into two groups: group 1 included 25 patients with F1 liver fibrosis; group 2 enrolled 25 patients with F2 liver fibrosis (according to metavir scoring system) and fit for the combination therapy (Pegyalated interferon + riba virin). Results: Serum HA. SHASTA index and FIBRO-Q LEVEL were significantly higher in patient with grade-2 fibrosis than grade F1 patients. From the previous study, we can conclude that these parameters could be useful noninvasive markers of liver fibrosis and cost-effective alternative to other serum markers for staging liver fibrosis and for determining the timing of HCV treatment.

Non-invasive tests and markers for liver fibrosis

Chronic liver disease is characterized by liver fibrosis, which may lead to cirrhosis. Conventional serum-based liver function tests do not give information on either the presence or the rate of progress of liver fibrosis. The reference diagnostic test to detect fibrosis is liver biopsy, a procedure subject to various limitations, including risk of patient injury and sampling error. Serum markers have been evaluated for the determination of fibrosis either singly or combined as a panel of markers, however diagnostic accuracy is greatest in studies using a panel together with an algorithm, which generates a predictive score. Serum marker models, especially those targeted at hepatitis C, have multiplied in spectacular fashion over the last five years, with most models regularly achieving a median area under the receiver operating characteristic curve (ROCC) of 0.80 versus liver biopsy. Five years after publication of the first major serum marker model, the first study to document clinical outcomes reported that applying the model to hepatitis C patients improved prediction of decompensated cirrhosis and survival compared to liver biopsy. An obstacle to widespread adoption of serum marker models has been the lack of uniform performance indicators, such as diagnostic odds ratios and likelihood ratios. This review highlights the most well-established noninvasive biomarkers to-date, with a particular emphasis on serum

The informative value of non-invasive liver fibrosis markers in patients with nonalcoholic fatty liver disease

To estimate the diagnostic and informative value of clinical and laboratory parameters in the development and progression of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) to enhance efficiency of their treatment. An open-label case-control study included 77 patients with NAFLD. Clinical and laboratory examinations were done. To search for additional noninvasive fibrosis markers, the investigators studied the serum concentrations of insulin, leptin, adiponectin, matrix metalloproteinase-9 (MMP-9) and its inhibitors, such as tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) and TIMP-2. All the patients underwent elastometry to assess the degree of liver fibrosis with the Metavir scale with the use of a Fibroscan machine. The serum levels of low-density lipoproteins, glucose, MMP-9, and leptin proved to be most informative in assessing the progression of the initial stages (1-2) of fibrosis, as were the increased liver size detected by physical examination, systolic blood pressure, carbohydrate metabolic disorders, alanine/aspartate aminotransferase levels, waist-to-hip ratio, TIMP-1, and TIMP-2 in evaluating the progression of Stage II fibrosis 2 to Stage 3. The clinical and laboratory parameters can serve as reliable noninvasive markers that reflect the progression of fibrotic changes in liver tissue.

Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Could Not Always Predict Early Cirrhosis in Non-Viral Liver Diseases.

Background: Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA(+)-M2BP) is a novel non-invasive marker of liver fibrosis. The goal of the study was to investigate whether the novel serum biomarker WFA(+)-M2BP or other non-invasive markers are useful for the prediction of liver fibrosis in patients with nonalcoholic steatohepatitis (NASH), autoimmune hepatitis (AIH), and primary biliary cholangitis (PBC). Methods: We examined a significant correlation between serum WFA(+)-M2BP levels and histological staging of fibrosis in several chronic liver diseases, such as NASH, AIH, and PBC. Results: WFA(+)-M2BP could not predict hepatic fibrosis in these patients. We also showed that the level of platelet counts is a useful predictor of hepatic fibrosis progression in patients with NASH, AIH, and PBC. There was a significant correlation between staging of fibrosis and grading of activity in the liver in all groups except for AIH patients. Conclusion: Platelet counts can predict hepatic fibrosis in patients with NASH, AIH, or PBC. Clinicians should pay attention to the grading of liver activity in the use of WFA(+)-M2BP.

Forns index as a useful noninvasive predictor of esophageal varices in liver cirrhosis

Background&lt;br /&gt;Rupture and bleeding from esophageal varices are major complications of portal hypertension and associated with a high mortality rate. Non-invasive serum markers of liver fibrosis could be used as predictors of esophageal varices in cirrhotic patients. The objective of this study was to assess the performance of Forns index as a noninvasive predictor in diagnosing esophageal varices.&lt;br /&gt;&lt;br /&gt;Methods&lt;br /&gt;A cross-sectional study was done in 51 cirrhotic patients who were admitted to Adam Malik hospital, Medan. Demographic and clinical data were recorded and laboratory tests were performed, so that Forns index could be calculated. The difference between Forns index and size of esophageal varices as determined by endoscopy was tested by independent-t and Mann-Whitney analysis. The diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, likelihood ratios and areas under the receiver operating characteristic curves (AUROC). &lt;br /&gt;&lt;br /&gt;Results&lt;br /&gt;Of the 51 patients with esophageal varices included in this study, the size of esophageal varices comprised F2 (37.3%), F3 (33.3), and F1 (29.4%). Most patients were of Child-Plug C type (52.6%). There was a significant difference between Forns index and grade of esophageal varices. The AUROC for Forns index was 0.717 (95% CI: 0.561 - 0.872) and the cut-off &amp;gt;7.92 was highly predictive to diagnose large esophageal varices with a sensitivity of 63.9%, specificity of 73.3%, PPV of 85.2%, NPV of 45.8% and accuracy of 71.7%.&lt;br /&gt;&lt;br /&gt;Conclusion&lt;br /&gt;Forns index was significantly increased in large esophageal varices. Forns index is a good noninvasive predictor of esophageal varices in cirrhotic patients.

The importance of serum biglycan levels as a fibrosis marker in patients with chronic hepatitis B.

Liver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the potential risks of liver biopsy, many studies related to non-invasive biomarkers of hepatic fibrosis have been performed. We aimed to assess the diagnostic value of serum biglycan as a non-invasive fibrosis marker in chronic hepatitis B patients. This study included 120 patients with biopsy-proven hepatitis B patients and 60 healthy controls. Fibrosis stage and necroinflammatory activity were assessed in liver biopsy specimens. Biglycan level was measured using an ELISA assay. Serum biglycan levels of chronic hepatitis B patients were found to be significantly higher than those of healthy controls (337.3±363.0pg/mL vs 189.1±61.9pg/mL, respectively, P<.001). There was a statistically significant positive correlation between serum biglycan level and fibrosis stage (P=.004; r=.213). Besides, a statistically significant positive correlation was found between serum biglycan level and necroinflammatory activity (P<.001; r=.271). The AUROC of BGN levels was 0.702 for fibrosis stage, differentiating patients from healthy controls with statistical significance (P<.001). The AUROC of BGN levels was 0.632 for necroinflammatory activity score, differentiating patients from healthy controls with statistical significance (P=.004). Serum biglycan might be used as a non-invasive marker of liver fibrosis. Further studies are needed to evaluate the usefulness of this marker.

Assessment of transient elastography in Japanese patients with non-alcoholic fatty liver disease.

Transient elastography (TE) is a non-invasive method for predicting liver fibrosis. However, there are limited data regarding the performance of TE in Japanese patients with non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate the association between liver stiffness measurement (LSM) by TE and liver fibrosis stage, and define a cut-off value for predicting liver fibrosis. A total of 171 Japanese patients with biopsy-proven NAFLD underwent LSM using TE with FibroScan. The area under the receiver operating characteristic curve of LSM and other non-invasive markers of liver fibrosis were compared to determine the most accurate method of predicting liver fibrosis. Liver stiffness measurement significantly correlated with fibrosis stage (P <0.001). The areas under the receiver operating characteristic curve of LSM for fibrosis stage ≥1 and ≥3 was 0.85 and 0.91, respectively and were higher than those of the aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, fibrosis-4 index, and NAFLD fibrosis score. The best cut-off values of LSM fibrosis stage ≥1 and ≥3 were 7.2kPa (sensitivity 78.5%, specificity 78.3%) and 10.0kPa (sensitivity 89.5%, specificity 87.6%), respectively. The combination of LSM (≥10kPa) and type IV collagen 7 s (≥6.0ng/mL) had a specificity of 97.6% for advanced fibrosis. The LSM in patients with high alanine aminotransferase levels or high body mass index was associated with false positive results regarding advanced fibrosis. In NAFLD patients, TE has excellent utility for the assessment of liver fibrosis, particularly for advanced stage cases. The cut-off value of LSM by TE for predicting liver fibrosis stage ≥3 is 10.0kPa in Japanese NAFLD patients.

Multiplex Serum Protein Analysis Identifies Novel Biomarkers of Advanced Fibrosis in Patients with Chronic Liver Disease with the Potential to Improve Diagnostic Accuracy of Established Biomarkers.

Background and AimsNon-invasive markers of liver fibrosis are urgently required, especially for use in non-specialist settings. The aim of this study was to identify novel serum biomarkers of advanced fibrosis.MethodsWe performed an unbiased screen of 120 serum analytes including cytokines, chemokines and proteases in 70 patients (35 without fibrosis, 35 with cirrhosis on biopsy), and selected a panel of 44 candidate biomarkers, which were subsequently measured in a mixed-etiology cohort of 432 patients with known serum HA, PIIINP and TIMP1 (which comprise the validated Enhanced Liver Fibrosis (ELF) test). Multivariate logistic regression modelling was used to generate models for the prediction of advanced or significant fibrosis (METAVIR ≥F3 and ≥F2, respectively); in addition to identifying biomarkers of disease activity and steatohepatitis.ResultsSeventeen analytes were significantly differentially expressed between patients with no advanced fibrosis and patients with advanced fibrosis, the most significant being hyaluronic acid (HA) and matrix metalloproteinase (MMP) 7 (p = 2.9E-41 and p = 1.0E-26, respectively). The optimal model for the prediction of advanced fibrosis comprised HA, MMP7, MMP1, alphafetoprotein (AFP) and the AST to platelet ratio index (APRI). We demonstrate enhanced diagnostic accuracy (AUROC = 0.938) compared to a model comprising HA, PIIINP and TIMP1 alone (ELF) (AUROC = 0.898, p<0.0001, De Long’s test).ConclusionsWe have identified novel serum biomarkers of advanced liver fibrosis, which have the potential to enhance the diagnostic accuracy of established biomarkers. Our data suggest MMP7 is a valuable indicator of advanced fibrosis and may play a role in liver fibrogenesis.

Histological Evaluation of Non-alcoholic Fatty Liver Disease and Its Correlation with Different Noninvasive Scoring Systems with Special Reference to Fibrosis: A Single Center Experience

Although liver biopsy remains the gold standard for the diagnosis of non-alcoholic fatty liver disease [NAFLD], many non-invasive markers of liver fibrosis have recently been proposed and assessed as surrogates of liver biopsy. To evaluate the degree of liver fibrosis by different non-invasive fibrosis scoring systems and to compare each non-invasive fibrosis scoring system with histological fibrosis stage. The study population consists of consecutive patients with biopsy proven NAFLD. Complete medical history was taken and physical examination was done in all patients along with appropriate biochemical evaluations. NAFLD fibrosis score, BARD score, BAAT score and APRI score were calculated and each score was compared with histological fibrosis staging. The study population consisted of 60 patients having mean age 39.73 years (SD 9.62, range 17-63 years) including 51 (85%) males and 9 (15%) females. On histology fibrosis was present in 68.3% (41/60) patients. Out of 60 patients 41 had fibrosis and among them 17, 22, 2 patients had grade 1, 2, 3 fibrosis respectively and no one had grade 4 fibrosis. 61.67% (37/60) had definite NASH. Comparing the fibrosis of histology with the noninvasive scoring systems, the sensitivity and specificity of NAFLD fibrosis score were 5.56% and 100% respectively. BARD score had 45.83% sensitivity and 80.55% specificity. The sensitivities of BAAT score and APRI score were 0% and 29.16% respectively and the specificities were 100% and 97.22% respectively. The noninvasive scoring systems like NFS, BARD, BAAT, and APRI are not sensitive enough to detect fibrosis but highly specific to include fibrosis if scores are more than cut-off values in our cohort, however they cannot replace liver biopsy. Newer more efficient non-invasive scoring systems have to be devised for the Indian NAFLD population.

A Comprehensive Analysis of the Impact of HIV on HCV Immune Responses and Its Association with Liver Disease Progression in a Unique Plasma Donor Cohort.

ObjectiveHuman Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV) co-infection is recognized as a major cause of morbidity and mortality among HIV-1 infected patients. Our understanding of the impact of HIV infection on HCV specific immune responses and liver disease outcome is limited by the heterogeneous study populations with genetically diverse infecting viruses, varying duration of infection and anti-viral treatment.MethodsViral-specific immune responses in a cohort of 151 HCV mono- and HIV co-infected former plasma donors infected with a narrow source of virus were studied. HCV and HIV specific T cell responses were correlated with clinical data.ResultsHIV-1 accelerated liver disease progression and decreased HCV specific T cell immunity. The magnitude of HCV specific T cell responses inversely correlated with lower HCV RNA load and reduced liver injury as assessed by non-invasive markers of liver fibrosis. HIV co-infection reduced the frequency of HCV specific CD4+ T cells with no detectable effect on CD8+ T cells or neutralizing antibody levels.ConclusionOur study highlights the impact of HIV co-infection on HCV specific CD4+ T cell responses in a unique cohort of patients for both HCV and HIV and suggests a crucial role for these cells in controlling chronic HCV replication and liver disease progression.

Noninvasive indirect serum markers of liver fibrosis in patients with chronic viral hepatitis

Noninvasive indirect serum markers of liver fibrosis in patients with chronic viral hepatitis

Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care.

Diagnosing native liver fibrosis and esophageal varices using liver and spleen stiffness measurements in biliary atresia: a pilot study.

Biliary atresia commonly leads to liver fibrosis and cirrhotic complications, including esophageal varices. To evaluate liver and spleen stiffness measurements using acoustic radiation force impulse (ARFI) imaging for diagnosing grade of liver fibrosis and predicting the presence of esophageal varices in patients treated for biliary atresia. ARFI imaging of the spleen and native liver was performed in 28 patients with biliary atresia. We studied the relation between ARFI imaging values and liver histology findings (n=22), upper gastrointestinal endoscopy findings (n=16) and several noninvasive test results. Diagnostic accuracy was assessed using receiver operating characteristic curve analyses. Liver stiffness measurements exhibited a significant difference among the different grades of liver fibrosis (P=0.009), and showed higher values in patients with high-risk esophageal varices than in the other patients (P=0.04). The areas under the receiver operating characteristic curves of liver stiffness measurements for liver fibrosis grades ≥ F2, ≥F3 and = F4 were 0.83, 0.93 and 0.94, respectively. Patients with high-risk esophageal varices were preferentially diagnosed by the combined liver and spleen stiffness measurements (area under the curve, 0.92). Liver and spleen stiffness measurements using ARFI imaging are potential noninvasive markers for liver fibrosis and esophageal varices in patients treated for biliary atresia.

Transient elastography in autoimmune hepatitis: Timing determines the impact of inflammation and fibrosis

There is an unmet need for the non-invasive monitoring of fibrosis progression in patients with autoimmune hepatitis (AIH). The aim of this study was to assess the diagnostic performance of transient elastography in patients with AIH and to investigate the impact of disease activity on its diagnostic accuracy. Optimal cut-offs were defined in a prospective pilot study (n=34) and the diagnostic performance of transient elastography validated in an independent second cohort (n=60). To explore the impact of disease activity on liver stiffness, patients were stratified according to biochemical response and the time interval between start of immunosuppression and transient elastography. Liver stiffness strongly correlated with histological fibrosis stage (pilot study: ρ=0.611, p<0.001; validation cohort: ρ=0.777, p<0.0001). ROC curves defined an area under the receiver operating curve of 0.95 for diagnosing cirrhosis at the optimal cut-off of 16kPa. The performance of transient elastography was impaired when patients were analysed in whom transient elastography was performed within 3months from start of treatment. In this setting, liver stiffness correlated with histological grading (ρ=0.558, p=0.001), but not with staging. In contrast, using the cut-off of 16kPa, the accuracy for diagnosing cirrhosis was excellent in patients treated for 6months or longer (area under the receiver operating curve 1.0). Liver inflammation has a major impact on liver stiffness in the first months of AIH treatment. However, transient elastography has an excellent diagnostic accuracy for separating severe from non-severe fibrosis after 6months of immunosuppressive treatment. Transient elastography is a special ultrasound scan, which assesses liver stiffness as a surrogate marker for liver fibrosis/scarring. Transient elastography has been shown to be a reliable non-invasive method to assess liver fibrosis in various chronic liver diseases, it takes less than 5min and has a high patient acceptance. The current study validated for the first time this technique in a large cohort of patients with autoimmune hepatitis (AIH) and demonstrates that it is a reliable tool to detect liver fibrosis in treated AIH. For the monitoring of potential disease progression under treatment, the validation of liver stiffness as non-invasive marker of liver fibrosis will greatly improve patient care in autoimmune hepatitis.

Sipa1l1 is an early biomarker of liver fibrosis in CCl4-treated rats.

ABSTRACTAt present, several procedures are used for staging liver fibrosis. However, these methods may involve clinical complications and/or present diagnostic uncertainty mainly in the early stages of the disease. Thus, this study was designed to unveil new non-invasive biomarkers of liver fibrosis in an in vivo model of fibrosis/cirrhosis induction by CCl4 inhalation by using a label-free quantitative LC-MS/MS approach. We analyzed 94 serum samples from adult Wistar rats with different degrees of liver fibrosis and 36 control rats. Firstly, serum samples from 18 CCl4-treated rats were clustered into three different groups according to the severity of hepatic and the serum proteome was characterized by label-free LC-MS/MS. Furthermore, three different pooled serum samples obtained from 16 control Wistar rats were also analyzed. Based on the proteomic data obtained, we performed a multivariate analysis which displayed three main cell signaling pathways altered in fibrosis. In cirrhosis, more biological imbalances were detected as well as multi-organ alterations. In addition, hemopexin and signal-induced proliferation-associated 1 like 1 (SIPA1L1) were selected as potential serum markers of liver fibrogenesis among all the analyzed proteins. The results were validated by ELISA in an independent group of 76 fibrotic/cirrhotic rats and 20 controls which confirmed SIPA1L1 as a potential non-invasive biomarker of liver fibrosis. In particular, SIPA1L1 showed a clear diminution in serum samples from fibrotic/cirrhotic rats and a great accuracy at identifying early fibrotic stages. In conclusion, the proteomic analysis of serum samples from CCl4-treated rats has enabled the identification of SIPA1L1 as a non-invasive marker of early liver fibrosis.

Serum hyaluronic acid as non invasive biomarker to predict liver fibrosis in viral hepatitis patients.

Fibrosis is a hallmark histologic event of viral hepatitis and is characterized by the excessive accumulation and reorganization of the extracellular matrix (ECM). The gold standard for assessment of fibrosis is liver biopsy. As this procedure has various limitations, including risk of patient injury and sampling error. Serum Hyaluronic acid as non invasive marker for liver fibrosis is desirable. The present study aims to determine the serum hyaluronic acid (HA) levels as biochemical marker of hepatic fibrosis and cirrhosis and correlate it with the degree of hepatic fibrosis. Serum HA level in chronic hepatitis patients (n=60) are divided into two groups, group1: included 30 patients positive for anti-HCV (antibodies), group 2 included 30 patients positive for HBsAg, and controls (n=10) were assessed by ELISA and liver histopathological parameters were evaluated by the modified Knodell score and microscopic examination of liver biopsies from patients. Individuals in healthy control group have normal levels of HA (mean 14.3, SD: 5.5) while the levels of HA were elevated in patients of HCV alone (mean 103.6±28.0) and in patient of HCV (mean 104.5± 37.5).Also levels of HA were poorly elevated in HBV alone (mean 62.2± 15.5) and in HBV (mean 45.8± 12.4). showed that serum HA levels are well correlated with HAI in patients of HBV & HCV groups where, there was significant increase in HA levels by increase of HAI by liver biopsy P < 0.001.HA levels and stages of fibrosis were well correlated in patients of HBV and HCV group. Where, this is a significant increase in HA levels when Considering F0 to F6 scores by liver biopsy (P < 0.001). Serum HA is a useful non-invasive marker of liver fibrosis. There is a strong positive correlation between serum HA levels and degree of liver fibrosis. The concentration of serum HA rises according to progression of liver fibrosis.

Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein may predict liver fibrosis and progression to hepatocellular carcinoma in patients with chronic hepatitis B virus infection.

Serum glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) is a reliable, non-invasive marker of liver fibrosis. This study assessed the ability of WFA+ -M2BP to diagnose liver fibrosis in patients with chronic hepatitis B virus (HBV) infection and evaluated WFA+ -M2BP as a predictor of hepatocellular carcinoma (HCC) development. Serum WFA+ -M2BP values were retrospectively evaluated in 112 treatment-naïve patients with HBV-related chronic hepatitis and cirrhosis who had undergone liver biopsy at our hospital. Serum WFA+ -M2BP levels were significantly related with liver fibrosis (r = 0.3725, P = 0.001). Fibrosis stage F2, F3, and F4 had a cut-off index of 0.94, 1.26, and 1.26, respectively. For diagnosing F ≥ 2 fibrosis, the area under the receiver-operating characteristic curve for WFA+ -M2BP was 0.713 and comparable with those of other non-invasive fibrosis markers, such as hyaluronic acid, type IV collagen 7S, aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, serum albumin, and platelet count. Multivariate analysis identified male, WFA+ -M2BP ≥0.71, alanine aminotransferase ≥80IU/L, and platelet count <14.5 × 109 /L as independent risk factors for the development of HCC in patients with HBV infection. Serum WFA+ -M2BP values appear to be useful for assessing liver fibrosis stage and are independently associated with HCC development in patients with chronic HBV infection.

Liver Fibrosis in HCV Monoinfected and HIV/HCV Coinfected Patients: Dysregulation of Matrix Metalloproteinases (MMPs) and Their Tissue Inhibitors TIMPs and Effect of HCV Protease Inhibitors.

An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to liver fibrosis in patients with hepatitis C (HCV) infection. We measured the circulating levels of different MMPs and TIMPs in HCV monoinfected and HIV/HCV coinfected patients and evaluated the potential for anti-HCV therapy to modulate MMP and TIMP levels in HCV subjects. We analyzed 83 plasma samples from 16 HCV monoinfected patients undergoing dual or triple anti-HCV therapy, 15 HIV/HCV coinfected patients with undetectable HIV load, and 10 healthy donors (HD). Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, TIMP-1, and TIMP-2 were measured by a SearchLight Multiplex Immunoassay Kit. MMP-2 and MMP-9 were the highest expressed MMPs among all the analyzed samples and their levels significantly increased in HCV monoinfected and HIV/HCV coinfected subjects compared to HD. TIMP-1 levels were significantly higher in HCV and HIV/HCV subjects compared to HD and were correlated with liver stiffness. These findings raise the possibility of using circulating TIMP-1 as a non-invasive marker of liver fibrosis in HCV infection. A longitudinal study demonstrated that MMP-9 levels significantly decreased (40% reduction from baseline) in patients receiving dual as well as triple direct-acting antivirals (DAA) anti-HCV therapy, which had no effect on MMP-2, TIMP-1, and TIMP-2. As the dysregulation of MMP-2 and MMP-9 may reflect inflammatory processes in the liver, the decrease of MMP-9 following HCV protease inhibitor treatment suggests a positive effect on the reduction of liver inflammation.

The predictive value of noninvasive serum markers of liver fibrosis in patients with chronic hepatitis C.

This study aims to show the predictive value of noninvasive serum markers on the hepatic fibrosis level. This cross sectional study involves 120 patients with chronic hepatitis C. The noninvasive markers used were as follows: age-platelet index (AP index), cirrhosis discriminant score (CDS), aspartate aminotransferase (AST)-alanine aminotransferase (ALT) ratio (AAR), fibrosis-4 (FIB-4) index, AST-platelet ratio index (APRI), Goteborg University Cirrhosis Index (GUCI), FibroQ, King's score, platelet count. Concurrent liver biopsies were evaluated using the modified Ishak and Knodell scoring systems. In accordance with the Knodell scores, F3-F4 scores were defined as "severe fibrosis," and the modified Ishak scores stage of ≥3 (F3-F6) were defined as "clinically significant fibrosis." Receiver Operating Characteristic (ROC) curve analyses were carried out to compare the noninvasive markers with hepatic fibrosis level. Mean age of the patients was 51.7±11.6. A total of 10 patients (8.3%) with Knodell scores and 24 patients (20%) with modified Ishak scores were evaluated to have ≥F3 hepatic fibrosis. ROC analyses with the Knodell and modified Ishak scores were as follows: AP index=0.61-0.57, CDS=0.66-0.55, AAR=0.60-0.49, FIB-4=0.70-0.68, APRI=0.67-0.72, GUCI=0.66-0.72, FibroQ=0.64-0.54, King's score=0.68-0.54, platelet count=0.61-0.55. We found that APRI, FIB-4, King's score, and GUCI can be used to determination patients with mild fibrosis with a high negative predictive value and in the differentiation of severe/significant fibrosis from mild to moderate fibrosis.