Non-invasive Markers Of Liver Fibrosis Research Articles

Long-term native liver fibrosis in biliary atresia: Development of a novel scoring system using histology and standard liver tests

Although liver fibrosis is an important predictor of outcomes for biliary atresia (BA), postsurgical native liver histology has not been well reported. Here, we retrospectively evaluated postsurgical native liver histology, and developed and assessed a novel scoring system - the BA liver fibrosis (BALF) score for non-invasively predicting liver fibrosis grades. We identified 259 native liver specimens from 91 BA patients. Of these, 180 specimens, obtained from 62 patients aged ≥1 year at examination, were used to develop the BALF scoring system. The BALF score equation was determined according to the prediction of histological fibrosis grades by multivariate ordered logistic regression analysis. The diagnostic powers of the BALF score and several non-invasive markers were assessed by area under the receiver operating characteristic curve (AUROC) analyses. Natural logarithms of the serum total bilirubin, γ-glutamyltransferase, and albumin levels, and age were selected as significantly independent variables for the BALF score equation. The BALF score had a good diagnostic power (AUROCs=0.86-0.94, p<0.001) and good diagnostic accuracy (79.4-93.3%) for each fibrosis grade. The BALF score revealed a strong correlation with fibrosis grade (r=0.77, p<0.001), and was the preferable non-invasive marker for diagnosing fibrosis grades ⩾F2. In a serial liver histology subgroup analysis, 7/15 patients exhibited liver fibrosis improvement with BALF scores being equivalent to histological fibrosis grades of F0-1. In postsurgical BA patients aged ⩾1year, the BALF score is a potential non-invasive marker of native liver fibrosis.

Thrombocytopenia, Liquor Use and Marijuana are Associated with Noninvasive Markers of Liver Fibrosis in People Living with HIV

Objective and aims: Liver disease is currently one of the leading causes of death among people living with HIV. Although platelets alterations are well recognized in the course of liver disease, the impact of thrombocytopenia (TCP: platelet counts <150,000 per microliter), which is highly prevalent among Hazardous Alcohol Users (HAU), is unclear. This lack of information limits the possibility to identify those at risk and to create targeted interventions. Methods: In this study, a total of 400 people living with HIV underwent laboratory assessments to determine if in addition to alcohol, TCP or its related factors (i.e., serotonin) were associated with non-invasive markers of liver fibrosis. The FIB-4 and the APRI scores were calculated using the Sterling’s and the Wai’s formulas, respectively. Results: Liver fibrosis was present in almost half of the study population (47%). As expected, APRI values of Hepatitis C co-infected subjects were higher than in HIV mono-infected patients (0.96 ± 0.18 vs. 0.5 ± 0.45, p=0.01). Notably, the risk was higher among marijuana users (OR= 9 95% CI 1.3-9.5, p=0.02). The risk of moderate fibrosis was also higher in the HAU (OR = 1.3; 95% CI, 1-2.5, p=0.04) when compared to non-HAU. Additional analyses indicated that consumption of liquor even 1-2 drinks per day, and high daily intakes of beer or wine (> 3 drinks per day) increases the risk of liver fibrosis. Thrombocytopenia, which is still prevalent (HAU=15% versus Hep C=22%) significantly increased the odds of moderate fibrosis (OR = 9; 95% CI, 3.6-23; p=0.0001). The odds of having severe fibrosis were 52% higher in the TCP group (95% CI, 13-97; p=0.0000). Serotonin, which is stored in the platelets, was also reduced among subjects with liver fibrosis levels (55.7 ± 6.7 vs. 87.3 ± 7.8 ng/mL, p=0.003). Multivariate analysis identified gender, hepatitis C, liquor use, TCP, marijuana and serotonin alterations as risk factors associated with liver fibrosis. Conclusion: Liver fibrosis is a condition that was associated with modifiable risk factors such as HAU, marijuana, TCP and viral hepatitis C. These results indicated that health care providers must be attentive for signs of these conditions to avert the risk of this terminal liver disease. From the clinical perspectives, analyses suggest that platelet-based interventions and serotonin agonist could be potential therapeutic targets.

Baseline Values and Changes in Liver Stiffness Measured by Transient Elastography Are Associated With Severity of Fibrosis and Outcomes of Patients With Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that leads to extensive liver fibrosis and cirrhosis, which are associated with poor outcome. However, there are no validated noninvasive markers of liver fibrosis in patients with PSC. We assessed the diagnostic performance, reproducibility, longitudinal changes, and prognostic value of liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE). In a prospective study, we analyzed percutaneous liver biopsy specimens from 73 consecutive patients with PSC from January 2005 to December 2010. Patients underwent VCTE no more than 6 months after the biopsy specimens were collected. The biopsy specimens were analyzed by a pathologist blinded to the results of VCTE for the stage of fibrosis, and LSM was associated with the stage of fibrosis and other variables using the Kruskal-Wallis and Spearman correlation tests. The cutoff values of LSM were selected based on the accuracy with which they identified the stage of fibrosis on receiver-operating characteristic analysis. The rates of LSM progression were assessed using a linear mixed model, and the association between LSM values and clinical outcomes were evaluated using Cox regression analysis in 168 patients with PSC treated with ursodeoxycholic acid and followed up from November 2004 to July 2013 (mean follow-up period, 4 years). LSM was independently linked to the stage of fibrosis. Cutoff values for fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 7.4 kPa, 8.6 kPa, 9.6 kPa, and 14.4 kPa, respectively. The adjusted diagnostic accuracy values for severe fibrosis and cirrhosis were 0.83 and 0.88, respectively. The diagnostic performance of LSM was comparable to that of hyaluronic acid measurement but superior to the aspartate aminotransferase/platelet ratio index, FIB-4 score, and Mayo risk score in differentiating patients with significant or severe fibrosis from those without. LSM had a high level of reproducibility between operators for the same measurement site and for the same operator between 2 adjacent sites. LSM increased significantly and exponentially over time. Baseline measurements and rate of LSM progression were strongly and independently linked with patients' outcomes. VCTE is able to differentiate severe from nonsevere liver fibrosis with high levels of confidence in patients with PSC. Baseline measurements of LSM and longitudinal changes are prognostic factors for PSC.

Can Biomarkers Predict Significant Fibrosis In Patients With Chronic Hepatitis C (CHC)?

Purpose: CHC causes significant morbidity and mortality related to progressive fibrosis and associated complications. Histological details, including degree of fibrosis, are best described by liver biopsy; however, it is invasive, and has other limitations. Emerging blood tests target assessment of fibrosis, which is critical in making management decisions and predicting prognosis. Comprehensive prospective validation of these tests in a U.S. population is lacking. The aim of our study is to compare and validate the performance of aspartate aminotransferase/platelet ratio index (APRI), FIB4, and HCV FibroSURETM scores as predictors of significant hepatic fibrosis in HCV treatment-naive patients. Methods: One hundred ninety seven consecutive, treatment-naive patients with CHC undergoing liver biopsy were studied over a calendar year. Routine hematological, biochemical, and serological tests were performed, and demographics recorded. APRI, FIB4, and HCV FibroSURETM scores were calculated. Liver biopsy was interpreted and staged according to the Metavir system, by a pathologist blinded to other clinical information. AUROC were calculated on various parameters to determine the performance of the non-invasive scores when compared with the biopsy. Results: Only 196 patients' data could be included for the calculation of the APRI and FIB4 models. Demographics of the study cohort were: mean age 49.31 ± 9.96 years, 70% male, 79.7% Caucasians, 8.1% Hispanic, and 6.1% African Americans. The genotype distribution of study cohort was GT1-139 (70.55%), GT2-20 (10.15%), GT3-26 (13.19%), GT4-8 (4.06%), and GT6-4 (2.03%). Mean AST, ALT, and platelet counts were 61.86, 82.27, and 207.99, respectively. Significant fibrosis was defined based on histology (stage F2 and above), APRI score (>1.5), FIB4 index (>3.25), and HCV FibroSURETM (F2 and above). Based on liver histology, significant fibrosis was identified in 124 patients. The AUROC calculated for FibroSURETM was 0.712, APRI = 0.77, and FIB4 = 0.80. The PPV and NPV for FibroSURETM was 79.2% and 62.3%, respectively. The PPV/NPV for APRI and FIB4 were 100% /45.6% and 100%/ 44.5%, respectively. Additionally, the specificity for APRI and FIB4 were 100%. Conclusion: The APRI and FIB4 correlated better than FibroSURETM in identifying significant fibrosis. However, in the absence of significant fibrosis, none of these markers demonstrated satisfactory correlation, and therefore, a liver biopsy may still need to be performed. In conclusion, although non-invasive markers of liver fibrosis are easier to obtain than a biopsy, they are most useful when there is significant fibrosis, and thus cannot be used in lieu of a biopsy to accurately predict the stage of hepatic fibrosis. Further studies are needed to evaluate biomarkers that might demonstrate better correlation.

Non-invasive Liver Fibrosis Markers Are Associated with Liver-Related Death in the Multicenter AIDS Cohort Study

Non-invasive Liver Fibrosis Markers Are Associated with Liver-Related Death in the Multicenter AIDS Cohort Study

Liver biopsy for parenchymal liver disease—Is routine real time image guidance unnecessary?

Liver biopsy even today remains the standard of care for grading and staging chronic hepatitis despite advances in noninvasive markers of liver fibrosis. Literature suggests an expanding role for real-time image guided liver biopsy and declining trend for blind liver biopsies. In our center, where we perform around 400 liver biopsies per year, we performed a prospective clinical audit of our practice of blind outpatient percutaneous liver biopsies. Patients requiring histological grading and staging of chronic hepatitis routinely undergo blind outpatient percutaneous liver biopsies in our endoscopy unit unless there is a definite indication for real-time image guidance. All procedures were assessed for safety, and all specimens were evaluated by a specimen quality grading score for adequacy for grading and staging of chronic hepatitis. Of the 446 patients referred for histological grading and staging of chronic hepatitis C by liver biopsy, only 42 patients (9.5 %) required real-time ultrasound for liver biopsy. The remaining 404 patients underwent blind outpatient percutaneous liver biopsies which were found to be extremely safe with no major complications, yielding adequate liver tissue with high specimen quality score allowing optimal grading and staging of chronic hepatitis.

Interleukin-6 Is Associated with Noninvasive Markers of Liver Fibrosis in HIV-Infected Patients with Alcohol Problems

Both HIV and hepatitis C virus (HCV) cause chronic inflammation and alterations in serum inflammatory cytokines. The impact of inflammatory cytokines on liver fibrosis is not well understood. We studied the association between interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α and liver fibrosis in HIV-infected patients with current or past alcohol problems (CAGE ≥2 or physician investigator diagnosis). Liver fibrosis was estimated with FIB-4 (FIB-4 <1.45 defined the absence of liver fibrosis and FIB-4 >3.25 defined advanced fibrosis). Logistic regression was used to assess the association between cytokines and fibrosis, adjusting for age, sex, CD4, HIV RNA, current antiretroviral therapy, body mass index, and HCV. Secondary analyses explored whether the association between HCV and liver fibrosis was mediated by these cytokines. Participants (n=308) were all HIV-infected; 73% were male with a mean age of 42 years; half had detectable HCV-RNA, 60.7% had an absence of liver fibrosis, and 10.1% had advanced fibrosis. In models that adjusted for each cytokine separately, higher levels of IL-6 were significantly associated with an absence of fibrosis [adjusted OR (95% CI): 0.43 (0.19, 0.98), p=0.05] and were borderline significant for advanced fibrosis [adjusted OR (95% CI): 8.16 (0.96, 69.54), p=0.055]. In the final model, only higher levels of IL-6 remained significantly associated with advanced liver fibrosis [adjusted OR (95% CI): 11.78 (1.17, 118.19), p=0.036]. Adjustment for inflammatory cytokines attenuated the adjusted OR for the association between HCV and fibrosis in the case of IL-6 [for the absence of fibrosis from 0.32 (0.17, 0.57) p<0.01 to 0.47 (0.23, 0.96) p=0.04; and for advanced fibrosis from 7.22 (2.01, 25.96) p<0.01 to 6.62 (1.20, 36.62) p=0.03], suggesting IL-6 may be a partial mediator of the association between HCV and liver fibrosis. IL-6 was strongly and significantly associated with liver fibrosis in a cohort of HIV-infected patients with alcohol problems. IL-6 may be a useful predictive marker for liver fibrosis for HIV-infected patients.

Commentary: prognostication of chronic hepatitis B – are Fibrotest and Fibroscan the final answers? Authors' reply

We read with great interest the commentary by Wong et al.1 We completely agree that further large clinical studies with long-term follow-up should be conducted to predict the prognosis of patients with chronic liver diseases. For this reason, in France, a large cohort, named HEPATHER, started at the end of 2012. In this prospective study, 25 000 hepatitis C (HCV) or hepatitis B (HBV) patients will be followed up for 8 years. This cohort is supported by ANRS (Agence Nationale de Recherche sur le SIDA et les hépatites). Our study confirms that non-invasive markers of liver fibrosis (blood markers or liver stiffness) are excellent methods for the prognosis of HBV patients,2 as published before in HCV patients,3 or more recently in non-alcoholic fatty liver disease patients.4 The role of serial or combination of non-invasive tests should be also explored in chronic liver diseases. The authors' declarations of personal and financial interests are unchanged from those in the original article.2

Serum cystatin C: a non-invasive marker of liver fibrosis or of current liver fibrogenesis in chronic hepatitis C?

Background. Serum levels of cystatin C, an endogenous inhibitor of cysteine proteases, provide an alternative method to creatinine-based criteria for measuring glomerular filtration rate. Preliminary data suggested that serum cystatin C levels parallel with the stage of liver fibrosis in chronic liver disorders. Our aim has been to evaluate the possible role of serum cystatin C as a marker of liver fibrosis in hepatitis C virus (HCV)-induced chronic liver disease. Material and methods. 100 consecutive patients (56 men, mean age 51.2 ± 9.5 yrs) with HCV-induced chronic liver disease, scheduled for their first liver biopsy and naive for antiviral therapy were included. Liver fibrosis was evaluated with the METAVIR score. Serum cystatin C and standard laboratory tests were measured simultaneously. Patients with ethanol abuse (> 50 g/day), HBV or HIV coinfection or plasma creatinine ≥ 1.20 mg/dL were excluded. In addition, a second group of 16 patients fulfilling the same requisites and diagnosed with HCV-induced compensated cirrhosis by clinical evidence of portal hypertension was included. Results. Serum cystatin C levels significantly increase from F0 to F2 fibrosis stages, remained stable in F3 and F4 stages and increased again in the group of non-biopsied compensated cirrhosis. Serum cystatin C levels were higher in patients with moderate-advanced necroinflammation in the liver biopsy. Conclusion. Serum cystatin C level may reflect current fibrogenic and necroinflammatory activities in chronic HCV-induced liver disease with normal renal function but can not be considered as a non-invasive marker of liver fibrosis.

Course of Liver Fibrosis in HIV-Hepatitis C Virus-Coinfected Patients Depending on the Response to Hepatitis C Therapy

To evaluate the course of liver fibrosis, 328 HIV-hepatitis C virus (HCV)-coinfected patients (210 HCV treated and 118 HCV untreated) were followed-up for 38-42 months. Liver fibrosis was assessed by biopsy or elastometry at baseline and by elastometry afterward, in addition to other noninvasive indexes. A combined liver stiffness stage (LSS) was established and evaluated over time. Eighty patients had sustained virological response (SVR) and 130 had treatment failure (TF) after a standard course of peginterferon-ribavirin therapy. LSS decreased significantly in all fibrosis indexes during HCV therapy in treated patients, but the improvement persisted only in those with SVR. At the end of study, median elastometry values suffered variations of -29%, -5.0%, and +15.4% in SVR, TF, and untreated patients, respectively. Likewise, LSS worsened in 2.5%, 33.1%, and 39% of these groups, respectively: [OR (95% CI) 19.3 (4.4-119), p<0.001] for TF vs. SVR; [24.9 (5.6-154), p<0.001] for no therapy vs. SVR; and [1.29 (0.74-2.3), p=0.40] for no therapy vs. TF. LSS improved in 53.8%, 19.2%, and 5.9% of these groups, respectively: [4.88 (2.51-9.53), p<0.001] for SVR vs. TF; 18.4 (7.17-49.4), p<0.001 for SVR vs. no therapy; and 3.78 (1.47-10.1), p=0.003 for TF vs. no therapy. Independent predictive factors of LSS improvement or worsening were as follows: alcohol abuse [OR (95% CI) 0.48 (0.20-0.99), p=0.047] and [2.45 (1.19-5.03), p=0.016], respectively; SVR [27.7 (6.41-168), p<0.001] and [0.15 (0.07-0.31), p<0.001], respectively; and lower baseline CD4 counts [1.92 (1.08-3.45), p=0.026] and [0.31 (0.15-0.63), p=0.001], respectively. SVR was usually associated with regression of noninvasive liver fibrosis markers, whereas TF and HCV-untreated patients experienced poorer outcomes.

PMO-172 Direct non-invasive serum markers of liver fibrosis predict fibrosis evolution in chronic hepatitis C but are increased by interferon-based therapy

IntroductionLiver biopsy remains the reference standard for the detection of liver fibrosis. While non-invasive markers of liver fibrosis have been validated in chronic hepatitis C, their performance during interferon-based therapy...

PWE-272 Concordance of non-invasive markers of liver fibrosis in a mixed population of liver diseases

IntroductionThe enhanced liver fibrosis (ELF) test, a panel of liver fibrosis biomarkers, accurately assesses fibrosis in a range of chronic liver disease (CLD) aetiologies. We evaluated concordance of ELF and...

Non-invasive markers of liver fibrosis in chronic liver disease in a group of Mexican children. A multicenter study

Identifying liver fibrosis is important to evaluate the severity of liver damage and to establish a prognosis. Utility of non-invasive markers of liver fibrosis has been proved in adults but there are few reports in children. The aim of this study was to evaluate Fibrotest® score and APRI suitability to identify children with liver fibrosis. 68 children with chronic liver disease requiring liver biopsy were prospectively included from three 3rd-level pediatric hospitals. The same pathologist evaluated all liver biopsies; fibrosis degree was determined by METAVIR score. Serum samples were obtained to determine Fibrotest® and APRI. AUROC were used to determine cut-off and differentiate between advanced fibrosis (METAVIR F3, F4) and no fibrosis (F0). 68 biopsies were evaluated; METAVIR > F3 was identified in 26 (38%). Non invasive liver fibrosis markers to differentiate between advanced and no fibrosis were: Fibrotest® AUROC = 0.90 (95% CI 0.77-1.00) (cut-off value 0.35) sensitivity 88.00% (95% CI 68-96) and specificity 80% (95% CI 29-98); and for APRI AUROC = 0.97 (95% CI 0.92-1.00) (cut-off value 0.82), sensitivity 88% (95% CI 68-96) and specificity = 100% (95% CI 46-100). These results suggest the utility of Fibrotest® and APRI to identify advanced fibrosis; they can be recommended to select patients for liver biopsy and during patient follow-up.

1075 DIRECT NON-INVASIVE SERUM MARKERS OF LIVER FIBROSIS PREDICT FIBROSIS EVOLUTION IN CHRONIC HEPATITIS C BUT ARE INCREASED BY INTERFERON-BASED THERAPY

Introduction Liver biopsy remains the reference standard for the detection of liver fibrosis. While non-invasive markers of liver fibrosis have been validated in chronic hepatitis C, their performance during interferon-based therapy is not established. Methods 70 previous non-responders to interferon based therapy for chronic hepatitis C (40 male, age range 24–67, mean 48.7) were recruited from five centres. Patients were randomised to receive pegylated interferon with or without silymarin for 24 months as an exploratory antifibrotic therapy. All patients underwent a liver biopsy and ELF tests (HA, P3NP, TIMP-1) prior to, and after treatment (month 0 and 24). Changes in histological fibrosis stages before and after therapy (0 to 24 months) were compared with changes in marker scores before, during and after therapy (0 to 24 months). Results Mean ELF score prior to therapy was 9.32 (SD 1.10), during therapy 9.91 (SD1.18) and after therapy 9.53 (SD 1.27). ELF scores were significantly higher during therapy than when compared to both before therapy (p Conclusion During interferon-based therapy, levels of HA and P3NP and the ELF score rise globally and subsequently fall to values similar to those seen prior to therapy regardless of fibrosis evolution, while TIMP1 levels remained unaffected. However, ELF scores pre and post therapy did accurately reflect changes in histology. This suggests that ELF scores and non-invasive panels incorporating HA and P3NP should be interpreted with caution during interferon-based therapy. Competing interests None declared.

Soluble Urokinase Plasminogen Activator Receptor is Associated With Progressive Liver Fibrosis in Hepatitis C Infection

Progressive liver fibrosis is the main predictor of disease outcome in chronic hepatitis C viral (HCV) infection. Although the importance of the coagulation cascade has been suggested in liver fibrogenesis, the role of the fibrinolytic pathway is yet unclear. We evaluated the association of serum levels of the fibrinolysis-associated soluble urokinase plasminogen activator receptor (suPAR) with the severity of liver fibrosis in HCV infection. suPAR serum levels were assessed in 146 chronically HCV-infected patients of 2 independent cohorts (64 subjects in the screening cohort, 82 in the validation cohort) by enzyme-linked immunosorbent assay and correlated with biopsy-proven histologic stage of liver fibrosis and noninvasive liver fibrosis markers (aspartate transaminase to platelets ratio index score, transient elastography). suPAR serum levels were strongly associated with the histologic stage of liver fibrosis in both cohorts (P<0.0001). Although mean suPAR levels in patients with F1 and F2 fibrosis were not different from healthy control subjects, they were significantly increased at higher stages of liver fibrosis (F3 and F4, P<0.0001). suPAR values had a high diagnostic specificity and sensitivity to differentiate mild/moderate fibrosis (F1/F2) from severe fibrosis (F3/F4) with an area under curve of 0.774 (P=0.0001) and for the differentiation of noncirrhosis from cirrhosis (F1/F2/F3 vs. F4, area under curve 0.791, P=0.0001). SuPAR serum levels were also strongly correlated to the noninvasive fibrosis markers aspartate transaminase to platelets ratio index score (r=0.52) and transient elastography (r=0.44, both P<0.0001). Serum suPAR levels were robust markers of liver fibrosis in 2 cohorts with a comparable diagnostic accuracy for prediction of severe liver fibrosis as established noninvasive marker.

Lack of short-term increase in serum mediators of fibrogenesis and in non-invasive markers of liver fibrosis in HIV/hepatitis C virus-coinfected patients starting maraviroc-based antiretroviral therapy

The aim of this study was to analyze serum changes in mediators of fibrogenesis and in non-invasive markers of liver fibrosis among HIV/HCV-coinfected patients starting maraviroc (MVC)-based antiretroviral therapy. Patients included in this prospective pilot study met the following criteria: (1) HIV-infection, (2) detectable serum HCV-RNA, and ((3) started MVC. Transforming growth factor-β1 (TGF-beta1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured in serum samples at baseline and 6 months after starting MVC. AST-to-platelet ratio index (APRI) was assessed at the same time points. Twenty-four patients were analyzed. Median (IQR) serum levels at baseline and after 6 months on MVC of TGF-beta1 were 27,295 (20,562-36,844) and 33,753 (18,973-46,130) pg/mL (p=0.116), of MMP-2 were 216 (186-274) and 241 (194-306) ng/mL (p=0.247), and of TIMP-1 were 237 (170-284) and 216 (171-271) ng/mL (p=0.415). APRI levels were 0.99 (0.53-3.46) at baseline and 0.83 (0.48-2.34) at 6 months (p=0.16). Serum mediators of liver fibrogenesis and fibrosis do not change significantly in HIV/HCV-coinfected patients in the short-term after starting MVC. As TGF-beta1 levels have been shown to increase over time in HCV infection and liver fibrosis worsens rapidly in HIV/HCV coinfection, these parameters seem to evolve in a different way in MVC-treated patients.

Change in Fibrosis Score as a Predictor of Mortality Among HIV-Infected Patients with Viral Hepatitis

Noninvasive markers of liver fibrosis, measured at baseline, have been shown to predict liver-related mortality. It remains unknown if a change in the value of the scores over time predicts mortality in patients with HIV and viral hepatitis. In this retrospective study, survival in HIV/hepatitis B virus (HBV; n = 67), HIV/hepatitis C virus (HCV; n = 43), and HIV/HBV/HCV (n = 41) patients was examined using Kaplan-Meier life table analysis. Aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and FIB-4 scores, two noninvasive markers of liver fibrosis, were calculated at baseline and at last available clinical follow-up to determine the change in fibrosis score. Factors associated with mortality were assessed by Cox proportional hazards, including the change in the noninvasive marker score between the two time points. All-cause mortality was determined by Social Security Death Index and chart review. Sixty-seven were coinfected with HIV/HBV, 43 with HIV/HCV, and 41 were triply infected (HIV/HBV/HCV). Kaplan-Meier analysis showed similar survival for the three groups at 7 years of follow-up (p = 0.10). However, median length of follow-up was lower in HIV/HCV (60.5; range 0-102) compared to HIV/HBV (75.7; 12.3-126.5) and HIV/HBV/HCV (80.0; 2.7-123) months, respectively, p = 0.02. Baseline fibrosis score (p = 0.002), an increase in the value for noninvasive measurements for fibrosis (p < 0.001), and the presence of HIV/HCV coinfection (p = 0.041) were each associated with higher risk for mortality. Baseline fibrosis score (p = 0.03) and an increase in FIB-4 score (p = 0.05) were independent predictors of all-cause mortality, but liver-related mortality was not evaluated. In this study, baseline fibrosis score was predictive of 7-year all-cause mortality. Further studies are needed in a prospective cohort to evaluate the predictive value of monitoring changes in fibrosis scores over time to predict mortality in patients with viral hepatitis.

Serum Hyaluronic Acid (HA) and Soluble Intercellular Adhesion Molecule-1(Sicam-1) as Non-Invasive Markers of Liver Fibrosis in Viral Hepatitis, Schistosomiasis mansoni and Co-infected Patients

Background: This study aimed to correlate serum Hyaluronic Acid (HA) and soluble intercellular adhesion molecule-1 (sICAM-1), with severity of liver fibrosis as clinically and histologically assessed in viral hepatitis, schistosomiasis mansoni and co-infected patients. Methods: The study was performed on 4 groups: Group 1 (G1) 15 chronic hepatitis patients; Group 2 (G2) 15 chronic schistosomiasis mansoni co-infected with chronic hepatitis patients; Group 3 (G3) 15 chronic schistosomiasis mansoni without hepatitis patients; Group 4 (G4) 15 active schistosomiasis mansoni without hepatitis patients. Results:The results showed a significant high level of HA and sICAM-1 in all groups compared to G4, while a significantly high level of HA in G2 compared to G3. There was a highly significant positive correlation between the level of HA and sICAM-1 and between both of them, and Child-Pugh clinical classification of patients with higher levels in Child-Pugh C. Also, serum level of both HA and sICAM-1 was positively correlated to the severity of liver fibrosis assessed by biopsy, with a highly significant higher level in advanced stages 4 and 5. Conclusions: HA and sICAM-1 showed good diagnostic performance and could discriminate severe from mild liver fibrosis, enabling them to be used as valuable non-invasive markers to identify and follow up patients with liver fibrosis.

Diagnostic and therapeutical role of vitamin D in chronic hepatitis C virus infection

Although initially identified as a calcium homeostatic hormone, vitamin D is now known to have pleiotropic functions, dealing with both innate and adaptative immunity. Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is expressed not only by intestine, bone and kidney but also on cell membranes of T lymphocytes, B lymphocytes, dendritic cells and macrophages. Vitamin D plays a role on the degree of liver damage in patients with chronic hepatitis C (CHC): low vitamin D levels have been associated with high hepatic necroinflammatory activity and progression of liver fibrosis. Vitamin D, in CHC patients, could also affect the response to antiviral therapy: in fact, recent studies have shown a relationship between low responsiveness to IFN-based therapy and low vitamin D serum levels. Further studies are required to better assess if vitamin D could work as a reliable noninvasive marker of liver fibrosis and whether vitamin D supplementation could be given to all CHC patients together with standard antiviral treatment, in order to improve the rate of sustained virological response (SVR).

Diagnostic and therapeutical role of vitamin D in chronic hepatitis C virus infection

Although initially identified as a calcium homeostatic hormone, vitamin D is now known to have pleiotropic functions, dealing with both innate and adaptative immunity. Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is expressed not only by intestine, bone and kidney but also on cell membranes of T lymphocytes, B lymphocytes, dendritic cells and macrophages. Vitamin D plays a role on the degree of liver damage in patients with chronic hepatitis C (CHC): low vitamin D levels have been associated with high hepatic necroinflammatory activity and progression of liver fibrosis. Vitamin D, in CHC patients, could also affect the response to antiviral therapy: in fact, recent studies have shown a relationship between low responsiveness to IFN-based therapy and low vitamin D serum levels. Further studies are required to better assess if vitamin D could work as a reliable noninvasive marker of liver fibrosis and whether vitamin D supplementation could be given to all CHC patients together with standard antiviral treatment, in order to improve the rate of sustained virological response (SVR).