METAVIR Score Research Articles

A new combined predicting model using a non-invasive score for the assessment of liver fibrosis in patients presenting with chronic hepatitis B virus infection

ObjectivesSeveral non-invasive markers have recently been proposed to predict liver fibrosis without percutaneous liver biopsy (PLB). We aimed to evaluate the performance of non-invasive scores and to highlight the value of a new combined score in the prediction of liver fibrosis in chronic hepatitis B (CHB) patients. Patients and methodsWe performed a retrospective study of patients presenting with CHB who underwent PLB between 2008 and 2016. We calculated ASAT/Platelet Ratio Index (APRI), Fibrosis-4 Score (FIB4), GGT-to-platelet ratio (GPR), and ASAT/ALAT Ratio (AAR). Then, we combined APRI and FIB-4 scores into a new combined score. We assessed their performance in predicting liver fibrosis according to the Metavir score. ResultsA total of 179 patients presenting with CHB were included. Multivariate analysis showed that the APRI score was the only independent factor of significant fibrosis (OR=3.78; P=0.02), whereas the FIB-4 score was the only independent factor for severe fibrosis (OR=2.85; P<0.001) and cirrhosis (OR=2.5; P=0.001). At a threshold of severe fibrosis, APRI had the best specificity (75%) and FIB-4 had the greatest sensitivity (74%). Using the combined score, we improved the diagnostic performance of APRI and FIB-4 scores at the three thresholds of liver fibrosis. With this combined score, maximum 25.1% of patients presenting with CHB would undergo PLB. ConclusionAPRI, FIB-4, and GPR scores were well performing to predict liver fibrosis during CHB. The new combined score using APRI and FIB-4 was more accurate at the three-fibrosis thresholds.

Group 2 innate lymphoid cells exhibit progressively higher levels of activation during worsening of liver fibrosis

IntroductionThe interleukin-33/interleukin-13 pathway is involved in the immunopathology of liver fibrosis and recently characterized group 2 innate lymphoid cells (ILC2) were identified as profibrotic immune cells in the liver of mouse models. Our aim was to elucidate whether ILC2 might be present in human liver tissue and whether ILC2 contribute to liver fibrosis. Materials and methodsTo identify ILC2 in liver tissue and blood, we purified mononuclear immune cells from needle biopsies, cirrhotic explant specimen, and paired peripheral blood samples. Cell suspensions were incubated with specific markers for ILC2 and analyzed by flow cytometry. The CD69 marker was included to assess the activation level of ILC2. In addition, we determined the IL-33 plasma level. ResultsResults were correlated with the METAVIR fibrotic score of patients enrolled in this study. We detected ILC2 in a higher percentage of CD45+ cells in liver tissue than in paired peripheral blood. The number of ILC2 was significantly increased in fibrotic tissue, but only slightly increased in paired peripheral blood. A higher percentage of CD69+ ILC2 was observed in fibrotic tissue, and this increase correlates positively with aggravation of liver fibrosis measured by fibrotic METAVIR score. A higher level of plasma IL-33 was only detected in samples obtained from cirrhotic patients. ConclusionOur study indicates that ILC2 are present in the human liver and are activated in tissue contributing to the immunopathology of human liver fibrosis, independently of the etiology; which might be a potential new therapeutic target.

Investigating the Efficiency of APRI, FIB-4, AAR and AARPRI as Noninvasive Markers for Predicting Hepatic Fibrosis in Chronic Hepatitis B Patients in Bangladesh

Background and Aims:Accurate, affordable non-invasive markers are highly needed for efficient diagnosis and management of liver fibrosis caused by chronic hepatitis B. This is the first study to investigate the diagnostic efficiency of Aspartate Transaminase to Platelet Ratio (APRI), Fibrosis Index (FIB-4), Aspartate transaminase to Alanine Transaminase Ratio (AAR) and AAR/Platelet ratio index (AARPRI) as non-invasive markers to predict hepatic fibrosis caused by Chronic Hepatitis B (CHB) in Bangladesh.Methods:In this study, a training cohort of 1041 CHB patients were recruited, whereas 104 and 109 CHB patients of matched ages were recruited as internal and external validation cohort groups respectively. Histological and hematological data were analyzed. METAVIR scoring system was used to classify liver fibrosis stages. Area Under Receiver Operating Curve (AUROC), correlations and cutoff values for the four diagnostic markers were calculated and assessed.Results:92%, 81% and 84% of the patients had liver fibrosis in the training cohort, internal and external cohort groups respectively. Among the four noninvasive panels, APRI showed the best area under ROC; (0.767, CI: 0.780-0.914; 0.775) for the training cohort, (0.775, CI: 0.693-0.857), and (0.847, CI: 0.780-0.914) for the internal and external cohorts respectively. Cut-off value of APRI was 0.512 with sensitivity/specificity of 84%/67% in training cohort, 81% / 66% in the internal cohort, and 88% / 66% in an external cohort. The odds ratio for APRI was 32.95 (95%CI: 4.746-228.862,p&lt;0.001).Conclusion:Among all the four tested markers, APRI is the most accurate non-invasive test to predict major liver fibrosis (F2-3) in Bangladeshi CHB patients.

Reduced Patient-Reported Outcome Scores Associate With Level of Fibrosis in Patients With Nonalcoholic Steatohepatitis

Patient-reported outcomes (PROs) are used to measure patients' experience with their disease. However, there are few PRO data from patients with NASH. We collected data from the STELLAR clinical trials to assess PROs for NASH and advanced fibrosis. We analyzed data from 1667 patients (58 ± 9 years, 40% male, 52% with cirrhosis, 74% with diabetes) with NASH and bridging fibrosis or compensated cirrhosis (metavir scores, F3 or F4) enrolled in the phase 3 STELLAR trials of selonsertib (NCT03053050 and NCT03053063) who completed PRO questionnaires (SF-36, CLDQ-NASH, EQ-5D, or WPAI:SHP) before treatment initiation. Compared with patients with F3 fibrosis, higher proportions of patients with F4 fibrosis were female, were white, had more hematologic and gastrointestinal comorbidities, and had type 2 diabetes (P ≤ .01). Mean physical health-related PRO scores were significantly lower than thoseof the general population: patients with F4 fibrosis had score reductions of 4.4% to 12.9%in 6/8 SF-36 domains and patients with F3 fibrosis had score reductions of 3.9% to 11.7% in 4/8 domains (P < .01). Compared to patients with F3 fibrosis, those with F4 fibrosis had lower scores in all but 1 domains of CLDQ-NASH, Role Physical, Bodily Pain, and Social Functioning domains of the SF-36, and EQ-5D (P ≤ 01). In multivariate regression analysis, factors independently associated with lower PRO scores included having cirrhosis, female sex, higher body mass index, history of smoking, and diabetes or other comorbidities (P < .01). PROs are significantly lower in patients with NASH with advanced fibrosis who participated in the STELLAR clinical trials. Treatment of patients with NASH should focus on improving not only clinical outcomes but also quantifiable symptom burden and health-related quality of life.

Ultrasound Elastography-A Useful Tool in Assessment of Diffuse Liver Disease

Background: Diffuse liver diseases are commonly encountered in clinical practice and on radiological imaging .Early detection and accurate diagnosis are extremely important in the definitive management of such patients. Ultrasonography is the widely used and the first line of radiological investigation in patients suspected with diffuse liver disease. Ultrasound elastography is a recent advance in the field of ultrasonography which has reportedly improved the accuracy in the assessment of severity of liver fibrosis in diffuse liver diseases. Objectives: 1.To evaluate the role of elastography for evaluation of diffuse liver disease. 2. To evaluate the sensitivity and specificity of sonoelastography in detection and characterisation of diffuse liver disease and correlation with other clinical diagnostic modalities and histopathology as gold standard. Subjects and Methods: Study was conducted from from August 2014 to August 2016.Based on inclusion and exclusion criteria, 30 cases of diffuse liver diseases were included in the study.The ultrasound and ultrasound elastography were done in the AJ Institute of Medical Sciences. These 30 cases were subjected to FNAC/Tru-cut Biopsy for the confirmation of ultrasound and ultrasound elastography finding and establishment of final diagnosis. Results: In our study of 30 cases of diffuse liver lesions ,after Metavir scoring 13% were F1,16% were F2, 23% were F3,and 46% were F4.The sensitivity and specificity for F1 and F2 were 100% and 100%, for F3 was 71% and 91%, for F4 85 and 87%.the mean cut off value for the cirrhosis was found to be 18kPa. Conclusion: Ultrasound elastography is a recent advance in the field of ultrasound, which is a non invasive method in assessment of severity of liver fibrosis and end stage cirrhosis.

Early high levels of regulatory T cells and T helper 1 may predict the progression of recurrent hepatitis C after liver transplantation

Immune response failure against hepatitis C virus (HCV) has been associated with an increased regulatory T cell (Treg) activity. After liver transplantation (LT), 80% of patients experience an accelerated progression of hepatitis C recurrence. The aim of this work was to assess the involvement of Tregs, T helper (Th) 1, 2 and 17 cells in recurrent hepatitis C. Peripheral blood cells obtained before and one month after LT from 22 recipients were analysed. Forty-four key molecules related to Treg, Th1, 2 and 17 responses, were evaluated using qRT-PCR. Liver recipients were classified in two groups according to graft fibrosis evaluated by the METAVIR score on the biopsy performed one year after LT (mild: F ≤ 1, n = 13; severe: F > 1, n = 9). Patients developing a severe recurrence were compared with patients with a mild recurrence. mRNA levels of Treg markers obtained one month after LT were significantly increased in patients with a severe disease course when compared to patients with a mild recurrence. Markers of the Th1 response were elevated in the same group. No differences in the markers determined before LT were observed. These findings suggest that Treg, induced by a multifactorial process, which could include a strong Th1 response itself, may play a role in suppressing the early antiviral response, leading to a severe recurrence of hepatitis C.

Patients With Signs of Advanced Liver Disease and Clinically Significant Portal Hypertension Do Not Necessarily Have Cirrhosis

Patients with hepatic venous pressure gradients (HVPGs) of 10 mm Hg or greater and chronic liver disease often are assumed to have cirrhosis. We investigated the association between HVPGs and cirrhosis, using histologic findings as the reference standard. We also assessed the prevalence and characteristics of patients with HVPGs of 10 mm Hg or greater without cirrhosis. We performed a retrospective analysis of 157 consecutive patients, 89 with suspected cirrhosis and hepatic hemodynamic data collected from 2015 through 2017. Biopsy specimens collected had 10 or more portal tracts from each patient and were analyzed for features of cirrhosis. Biopsy specimens with histologic features of cirrhosis were excluded and the remaining biopsy specimens were re-reviewed by an expert pathologist. The fibrosis area was calculated digitally by image analysis. HVPG identified patients with cirrhosis with an area under the receiver operating characteristic curve of 0.879: 14 of 89 patients with HVPG of 10 mm Hg or greater (16%) had no histologic features of cirrhosis (METAVIR scores <4 and Ishak scores <6). The median HVPG was 11 mm Hg (range, 10-22 mm Hg). Based on METAVIR scores, 7 patients had fibrosis stage F3, 4 patients had fibrosis stage F2, and 3 patients had fibrosis stages F0 or F1. The mean area of fibrosis in livers was 16.2% ± 6.5%. All 14 patients had perisinusoidal fibrosis and 8 patients had hepatocyte ballooning. The most common diagnoses were nonalcoholic steatohepatitis (n= 5) and nodular regenerative hyperplasia (n= 4). An HVPG cut-off value of 12 mm Hg identified patients with cirrhosis with 92% specificity, misclassifying 5 patients with different etiologies of liver disease. In a retrospective analysis of 89 consecutive patients with chronic liver disease and an HVPG of 10 mm Hg or greater, 16% were not found to have cirrhosis upon biopsy analysis. Most of these patients had nonalcoholic steatohepatitis or nodular regenerative hyperplasia. Perisinusoidal fibrosis and hepatocyte ballooning might increase sinusoidal pressure. An HVPG cut-off value of 12 mm Hg or greater identified patients with cirrhosis with 92% specificity.

Efficiency of acoustic radiation force impulse imaging for the staging of graft fibrosis after liver transplantation

Liver biopsy is the gold standard for assessing liver fibrosis (LF) after liver transplantation (LT), but its invasiveness limits its utility. This study aimed to evaluate the usefulness of liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) imaging to assess LF after LT. Between September 2013 and January 2017, 278 patients who underwent liver biopsy after LT in Kyoto University Hospital (Kyoto, Japan) were prospectively enrolled. Liver stiffness measurement was carried out using ARFI imaging; its value was expressed as shear wave velocity (Vs) [m/s]. The LF was evaluated according to METAVIR score (F0-F4). The diagnostic performance of Vs for F2≤ and F3≤ was assessed and compared with that of laboratory tests using receiver operating characteristic (ROC) analysis. The median Vs values increased according to the progression of LF (F0, 1.18 (0.78-1.92); F1, 1.35 (0.72-3.54); F2, 1.55 (1.05-3.37); F3, 1.84 (1.41-2.97)). The Vs had the highest area under the ROC curve (AUROC) for the prediction of both F2 ≤ and F3 ≤ fibrosis (F2, 0.77; and F3, 0.85). With the cut-off value of Vs >1.31, sensitivity, specificity, positive predictive value, and negative predictive value were 89.4%, 53.3%, 37.3%, and 94.2% in predicting F2≤, respectively. Shear wave velocity diagnosed LF better than any laboratory tests regardless of the type of primary disease. Acoustic radiation force impulse helps to assess graft LF after LT. The high sensitivity suggested that ARFI might reduce the frequency of liver biopsies by detecting patients who are unlikely to have significant fibrosis after LT. (Unique trial no. UMIN R000028296.).

Value of Texture Analysis on Gadoxetic Acid-enhanced MR for Detecting Liver Fibrosis in a Rat Model.

Objective To explore the ability of texture analysis of gadoxetic acid-enhanced magnetic resonance imaging (MRI) T1 mapping images, as well as T1-weighted (T1W), T2-weighted (T2W) and apparent diffusion coefficient (ADC) maps for distinguishing between varying degrees of hepatic fibrosis in an experimental rat model.Methods Liver fibrosis in rats was induced by carbon tetrachloride intraperitoneal injection for 4-12 weeks (n=30). In the control group (n=10) normal saline was applied. The MRI protocol contained T2W, diffusion weighted imaging, pre-and post-contrast image series of T1W and T1 mapping images. METAVIR score was used to grade liver fibrosis as normal (F0), mild fibrosis (F1-2), and advanced fibrosis (F3-4). Texture parameters including mean gray-level intensity (Mean), standard deviation (SD), Entropy, mean of positive pixels (MPP), Skewness, and Kurtosis were obtained. Nonparametric Mann-Whitney U test was used to compare the average value of each texture parameter in each sequence for assessing the difference between F0 and F≥1 as well as F0-2 and F3-4. Receiver operating characteristic (ROC) curves were obtained to assess the diagnosing accuracy of the parameters for differentiating no liver fibrosis from liver fibrosis and rats with liver fibrosis grading F0-2 from those with grading F3-4. The area under ROC curve (AUC) was calculated to evaluate the diagnostic efficiency of texture parameters.Results Finally, 20 rats completed MR T1 mapping image scan. The pathologic staging of these 20 rats was no fibrosis (F0, n=6), mild fibrosis (F1-2, n=5) and advanced fibrosis (F3-4, n=9). On pre-contrast T1 mapping image, Entropy was seen to be statistically significant higher in the F≥1 group than that in the F0 group at each spatial scaling factor (SSF) setting (P=0.015, 0.015, 0.015, 0.013, 0.015 and 0.018 respectively to SSF=0, 2, 3, 4, 5, 6), and Mean of the F≥1 rats was statistically significant higher than that of the F0 rats at SSF 4, 5, 6 (P=0.004, 0.006, and 0.013, respectively). Entropy and Mean showed a moderate diagnostic performance in most SSF settings of T1 mapping pre-contrast images for differentiation of normal liver from liver fibrosis.Conclusions Certain texture features of gadoxetic acid-enhanced MR images, especially the Entropy of non-contrast T1 mapping image, was found to be a useful biomarker for the diagnosis of liver fibrosis.

Characteristics of a hepatitis C patient cohort at a specialized tertiary care facility: Identifying criteria to improve the allocation of public health resources

OBJECTIVES:Our objective was to analyze, in a population treated for hepatitis C infection at a tertiary care treatment unit, the prevalence of comorbidities and extrahepatic manifestations, the range and degree of the clinical complexity and the associations between advanced liver disease and clinical variables.METHODS:Medical records from chronically infected hepatitis C patients seen at a dedicated treatment facility for complex cases in the Infectious Diseases Division of Hospital das Clínicas in Brazil were analyzed. Clinical complexity was defined as the presence of one or more of the following conditions: advanced liver disease (Metavir score F3 or F4 and/or clinical manifestations or ultrasound/endoscopy findings consistent with cirrhosis) or hepatocellular carcinoma and/or 3 or more extrahepatic manifestations and/or comorbidities concomitantly.RESULTS:Among the 1574 patients analyzed, only 41% met the definition of being clinically complex. Cirrhosis or hepatocarcinoma was identified in 22.2% and 1.8% of patients, respectively. According to multiple logistic regression analysis, male sex (p=0.007), age>40 years (p<0.001) and the presence of metabolic syndrome (p=0.008) were independently associated with advanced liver disease.CONCLUSION:The majority of patients did not meet the criteria for admittance to this specialized tertiary service, reinforcing the need to reevaluate public health policies. Enhanced utilization of existing basic and intermediate complexity units for the management of less complex hepatitis C cases could improve care and lower costs.

ALPPS procedure in patients with locally advanced liver malignancy- single center experience

Background: ALPPS has been described as an effective strategy to induce a rapid increase in future liver remnant volume (FLRV) and widely used in patients with colo-rectal liver metastases. There is few research about the result of hepatocellular carcinoma group. This study will review our experience with ALPPS procedure dominantly in hepatocellular carcinoma patients with chronic liver fibrosis. Methods: This series is a retrospective study in patients with liver malignancies to receive the ALPPS surgery and analyze the pre-op survey, operative findings and survival outcomes. Results: Thirteen patients were enrolled (Ten with HCC, Two with colorectal cancer and liver mets, One with cholangiocarcinoma) with mean follow-up was 15.7 months. The mean hypertrophy rate of the FLRV was 48.0% (range = 14.2–82.8) in a mean of 11.6 days interval (range =8–14), which represented a mean difference between stage I and II FLRV of 170cc (P < 0.001). The mean kinetic growth rate was 15.4cc/day. Among the HCC group, 7 are BCLC A and 3 are BCLC B and the median Metavir scoring of liver fibrosis was 2.Post-operative major complication rate (Clavien-Dindo ≥ 3b) was 15.4% (2/13) and there was no 90-days mortality. The mean disease free interval was 9.3 months (range = 2-31). Conclusion: The ALPPS is feasible and safe in patients with locally advanced liver malignancy. Besides, in patients with HCC and early stage of chronic liver fibrosis can also achieve significant hypertrophy result and not inducing further liver failure.

Endothelial dysfunction and platelet function disorder in hemostasis in development of hepatic fibrosis in children with autoimmune hepatitis

The purpose is: To assess the clinical relevance of the endothelial condition and platelet aggregation in the development of hepatic fibrosis in children with autoimmune hepatitis.&#x0D; Materials and Methods. 35 patients aged from 3 to 17 years old were studied, including 19 girls - (54%) and 16 boys - (46%). The 1st group consisted of 17 children with the degree of fibrosis F 0-2 acc. to the METAVIR score; the 2nd group consisted of 18 patients with the degree of fibrosis F 3-4 (METAVIR) acc. to the METAVIR score based on the indirect elastometry data in children of the 2nd group hepatic cirrhosis was diagnosed; the control group consisted of 15 children with health group I or II. The endothelium state and the platelet aggregation activity were assessed in all the patients. To test statistical hypotheses, the Mann-Whitney U test, the Spearman correlation coefficient and the Fisher criterion were used. The critical value of the significance level is assumed to be 0.05. Quantitative data are presented as: median and the first; third quartile of Me (Q1; Q3).&#x0D; Results. In children with autoimmune hepatitis some signs of the various-degree fibrosis formation were revealed in the ¾ of the examined. Patients of the 2nd group have a more aggressive course as compared to the 1st group: in the disease debut there were mainly expressed asthenoneurotic complaints (p = 0.021), manifestations of the jaundice syndrome (p = 0.014), more frequently hepatic-cell insufficiency (p = 0.045) is diagnosed and followed by complications of the disease (hypersplenism (p = 0.014), varicose veins of the esophagus (p = 0.003)). All children with autoimmune hepatitis have the endothelial dysfunction, the enhancing platelet aggregation activity. The degree of fibrosis correlates with the concentration of endothelin-1 (r = 0.4, p = 0.004), the von Willebrand factor (vWF) activity (r = 0.5, p &lt;0.001), the platelet count (r = -0.5, p = 0.003). The determination of the endothelin-1 concentration, the von Willebrand factor activity and the platelet count may be used to assess the hepatopathy severity in children with autoimmune hepatitis.&#x0D; Conclusion. In children with autoimmune hepatitis the endothelial dysfunction and platelet disorders are revealed in the hemostasis system correlating with the severity of the pathological process.

Gadolinium Ethoxybenzyl Diethylene-triamine-pentaacetic-acid-enhanced Magnetic Resonance Imaging Perfusion and Multiple Hepatobiliary-phase Imaging for Quantitative Assessment of Liver Fibrosis in Rat Models

Objective To investigate the value of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting different stages of liver fibrosis in rats.Methods Rat models of liver fibrosis were induced by carbon tetrachloride intraperitoneal injection for 4 - 12 weeks (n=45). The control group was applied with 0.9% saline (n=15). The MRI protocol contained both dynamic contrast-enhanced sequence (60 continuous scans within 3 minutes,including three pre-contrast measurements) and multiple hepatobiliary-phase acquisitions (every 5 minutes after contrast injection,60 minutes in total). METAVIR score was used to grade liver fibrosis:normal (F0),mild fibrosis (F1 - F2),and advanced fibrosis (F3 - F4). Liver perfusion parameters [transfer constant (K trans),extravascular extracellular volume fraction (Ve),initial area under curve (iAUC),maximum relative enhancement (REmax),and time of maximum RE (Tmax)] as well as hepatobiliary-phase parameters [RE at different time point,the decrease of RE (REchange=RE3 min - RE60 min),and elimination half-life of RE (TRE1/2)] were measured and compared with ANOVA analysis and Spearman rank correlation.Results Thirty-one rats completed MRI exams and were then divided into normal (n=10),mild fibrosis (n=10),and advanced fibrosis (n=11) groups. K trans,Ve and iAUC decreased as liver fibrosis progressed (r=-0.631,P=0.002;r=-0.503,P=0.017;r=-0.446,P=0.037). K trans and Ve showed significant differences among three groups(F=7.011,P=0.005;F=4.656,P=0.023). K trans and Ve were significantly lower in advanced fibrosis group than in normal group (P=0.001,P=0.009). There were statistical significant differences of Tmax,TRE1/2 and REchange among groups(F=6.633,P=0.005;F=5.493,P=0.010;F=5.343,P=0.014). Compared to normal and mild fibrosis groups,advanced fibrosis group had significantly longer Tmax and TRE1/2 (P=0.005,P=0.004;P=0.008,P=0.008)and significantly lower REchange(P=0.007,P=0.012).Conclusion Perfusion and multi-hepatobiliary-phase parameters such as K trans,Ve,Tmax, TREI/2 and REchange obtained from Gd-EOB-DTPA-enhanced MRI,may be valuable for detecting and staging liver fibrosis.

Liver Fibrosis is Associated with NAFLD Activity Score in Chronic Hepatitis B Patients with Liver Steatosis

Background: Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are two leading hepatic diseases that cause severe public health problems. The relationship between the severity of NAFLD and liver fibrosis in CHB patients remains controversial. Objectives: This study aimed at further clarifying the association between them. Methods: A total of 272 CHB patients and 31 NAFLD patients without CHB, who underwent liver biopsies and routine blood tests were included. The NAFLD activity scores (NAS) for NAFLD patients and the METAVIR scoring system for all the patients were used to evaluate the liver pathology. The associations between steatosis or NAS score and liver fibrosis were statistically analyzed. Results: METAVIR F0-4 was identified in 10.0%, 30.5%, 36.0%, 13.2%, and 10.3% of all the CHB patients, respectively. The prevalence of hepatic steatosis in CHB patients was 39.7% (n = 108). Among them, 26.9% (n = 29) of patients had NAS ≥ 5. The severity of fibrosis was not related to the degree of steatosis nor NAS score (P > 0.05) in NAFLD patients without CHB. Similarly, the results suggested that there was no significant difference in the severity of liver fibrosis in CHB patients with varying degrees of steatosis (P > 0.05). However, the severity of liver fibrosis increased with NAS score (P = 0.004) in CHB patients with NAFLD. Conclusions: The severity of liver fibrosis in CHB patients was associated with NAS score, yet not with fat content.

SERUM LIPOPROTEINS AND CHRONIC HEPATITIS C INFECTION;

Objectives: To determine the serum lipid profile in patients with chronic HCVinfection and correlation between serum lipid levels and liver histology. Material and methods:Descriptive study was carried out in Medical Unit I of Liaquat University Hospital JamshoroHyderabad, from September 2007 to August 2009. Convenience sampling was used and 30patients were selected. Positive PCR test for HCV, non diabetic patients and non cirrhotic patientswere included in this study. All the patients were selected from the medical OPD. Clinicalexamination performed and then blood tests were done. Serum lipid profile were determined inall participants after an overnight fast of 12 h. TC, TG, and HDL-C was measured enzymaticallywith commercial kits (Olympus System Reagent, Hamburg, Germany) by the use of anautomated analyzer. The body mass index (BMI) was calculated in accordance with the formulaof weight (kg) divided by height2 (m2). Selected patients were called in the ward and biopsy wasdone via Trucut needle and the specimen was fixed in formalin. The biopsies were used tocalculate the degree of steatosis (0-3) and fibrosis by METAVIR score. Results: A total of 30patients were selected for this study. Out of these 19 were males and 11 females. The patientswere divided in three groups. Patients with chronic HCV infection were found to have significantlylower levels of serum TC, HDL-C and LDL-C than normal adults values. Steatosis was present insignificant number of patients (36.67%). However, steatosis was not correlating with fibrosis(p&gt;0.005). Conclusions: Hypolipoproteinemia and steatosis are important factors which areassociated with chronic hepatitis C

Using IVIM-MRI and R2⁎ Mapping to Differentiate Early Stage Liver Fibrosis in a Rat Model of Radiation-Induced Liver Fibrosis.

Rationale and Objectives To investigate the utility of intravoxel incoherent motion MRI (IVIM-MRI) and R2⁎ mapping in diagnosing early stage liver fibrosis in a radiation-induced rat model. Materials and Methods Thirty rats were randomly divided into three groups with 10 rats in each group. Liver fibrosis was induced by exposure of right lobe of liver in each animal to 20 Gy of radiation. MRI examination was conducted at baseline, one month, two months, and three months after radiation using T1WI, T2WI, IVIM-DWI, and R2⁎ sequences. The pathological examination included hematoxylin eosin, masson trichrome, and prussian blue staining. D, D⁎, f, and R2⁎ values were measured in both left and right lobes for quantitative analysis. Results Regarding the surviving 23 rats, eight rats were diagnosed with stage F0, ten with stage F1, and five with stage F2 liver fibrosis using METAVIR Scores. The D values of right lobes decreased (P<0.05), and R2⁎ values increased (P<0.01) significantly as fibrosis levels increased. But there was no statistical difference in D⁎ (P=0.970) and f values (P=0.079). R2⁎ value showed a strong positive correlation (r=0.819, P<0.001), while D value showed a negative correlation with fibrosis stages (r=-0.424, P<0.001). D⁎ (r=0.029, P=0.744) and f values (r=-0.055, P=0.536) were poorly correlated with fibrosis levels. Conclusion IVIM-MRI and R2⁎ mapping are useful techniques for evaluating the severity of liver fibrosis in a radiation-induced rat model, and R2⁎ value is the most sensitive parameter in detecting early stage fibrosis.

2209. Discordance Between FibroSure and FibroScan Results in Hepatitis C and Human Immunodeficiency Virus Co-infected Patients Prior to Treatment for Hepatitis C Virus Infection

BackgroundThe accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognosis and treatment decisions. FibroSure and FibroScan are commonly used to approximate fibrosis prior to HCV treatment. Both methods have been validated for their correlation to the five-level (F0–F4) METAVIR scoring system. However, the correlation between these two tests in HIV/HCV co-infected patients has not been well described. Here, we evaluated the concordance between FibroSure and FibroScan-derived METAVIR results in HIV/HCV co-infected patients.MethodsWe performed a retrospective cross-sectional study of HIV/HCV co-infected patients that were treated between 2014 and 2017 at Drexel University, Philadelphia, PA. We described patient demographics and overall METAVIR scores of treated patients. Further, we compared the concordance between FibroSure and FibroScan results among patients who had both tests before the start of HCV treatment.ResultsOne hundred and thirty-eight HIV/HCV co-infected patients were treated. Most of them (N = 134, 97%) achieved sustained virologic response after 12 weeks of treatment. One hudred and thirty-three patients underwent FibroSure testing before starting HCV treatment. Of those, 62 (47%) fell in the F0–F2 range and 71 (53%) in the F3–F4 range. Of those 133 patients, 21 also underwent FibroScan. Fourteen (67%) fell in the F0–F2 range, while seven (33%) fell in the F3–F4 range. Of the 21 patients who both had FibroSure and FibroScan testing, 12 (57%) had concordant results, while nine (42%) had discrepant results. Of the patients with discrepant results, eight had higher fibrosis scores (F3–F4) with FibroSure, while only one had a higher fibrosis score (F3–F4) with FibroScan.ConclusionIn our study, more than half of HIV/HCV co-infected patients had advanced fibrosis score at the time of HCV treatment. When FibroSure and FibroScan scores were compared, close to half of co-infected patients had discordant results, the preponderance of which had higher FibroSure scores. As early initiation of HCV treatment is crucial to co-infected patients, further studies will need to evaluate the clinical significance of the discrepancy between different non-invasive fibrosis testing systems in co-infected patients.Disclosures All authors: No reported disclosures.

Long-term histological change in chronic hepatitis C patients who had received peginterferon plus ribavirin therapy with sustained virological response

The improvement in liver histology is an important aim in the management of hepatitis C virus (HCV) infection. Previous studies suggest that antiviral treatment could reduce the progression of hepatic fibrosis, especially in patients with sustained virological response (SVR). However, most studies were limited by short-term evaluations and the liver stiffness was assessed by non-invasive methods. In our study, we performed a paired liver biopsy study aimed at analyzing the long-term histological changes in patients with SVR. We included 31 patients who had been previously treated with peginterferon plus ribavirin. All patients achieved SVR and had received pre- and post-treatment liver biopsies. The histological appearance of fibrosis and inflammation were assessed with METAVIR scoring system and Histological Activity Index (HAI) criteria. We analyzed several factors associated with the histological response. The median interval between two biopsies was 93.0 months. The percentage of patients with fibrosis regression, stable, and progression were 19%, 45%, and 36%. A total of 71% of patients achieved inflammation improvement, whereas 6% and 23% of patients had stable disease and disease-progression, respectively. We showed that the patients without baseline advanced fibrosis and those having a lower baseline HAI score had higher risk of fibrosis worsening. Baseline fibrosis and necroinflammation status did not influence HAI change significantly. The progression of hepatic fibrosis and inflammation can be reversed in some patients who had long-term virological suppression. Patients with advanced baseline fibrosis and higher inflammatory stages seemed to receive more histologic benefit from successful antiviral treatments.

In vivo confirmation of altered hepatic glucose metabolism in patients with liver fibrosis/cirrhosis by 18F-FDG PET/CT

ObjectiveThe aim of this study was to assess the value of 18F-FDG PET/CT for quantitative assessment of hepatic metabolism in patients with different stages of liver fibrosis/cirrhosis.Materials and methods18F-FDG PET/CT scans of 37 patients either with or without liver fibrosis/cirrhosis, classified according to the METAVIR score (F0-F4) obtained from histopathological analysis of liver specimen, were analyzed retrospectively and classified as follows: no liver fibrosis (F0, n = 6), mild liver fibrosis (F1, n = 11), advanced liver fibrosis (F2, n = 6), severe liver fibrosis (F3, n = 5), and liver cirrhosis (F4, n = 11). The liver-to-blood ratio (LBR, scan time corrected for a reference time of 75 min) was compared between patient groups.ResultsPatients with liver fibrosis or cirrhosis (≥ F1; LBR 1.53 ± 0.35) showed a significant higher LBR than patients with normal liver parenchyma (F0, 1.08 ± 0.23; P = 0.004). In direct comparison, LBR increased up to the advanced stage of liver fibrosis (F2; 2.00 ± 0.40) and decreased until liver cirrhosis is reached (F4, 1.32 ± 0.14).ConclusionFunctional changes in liver parenchyma during liver fibrosis/cirrhosis affect hepatic glucose metabolism and significantly differ between stages of liver fibrosis/cirrhosis, classified according to the METAVIR scoring system, as demonstrated by LBR quantification by 18F-FDG PET/CT.

Genetic variants upstream of TNFAIP3 in the 6q23 region are associated with liver disease severity in HIV/HCV-coinfected patients: A cross-sectional study

BackgroundTNFAIP3 is a crucial hepatoprotective factor due to its anti-inflammatory, anti-apoptotic, anti-oxidant and pro-regenerative functions. The aim of this study was to analyze the associations between genetic variants upstream of TNFAIP3 (rs675520, rs9376293 and rs6920220) and liver fibrosis severity and inflammation in HIV/HCV-coinfected patients. MethodsA cross-sectional study was carried out in 215 HIV/HCV-coinfected patients, who underwent a liver biopsy. TNFAIP3 polymorphisms were genotyped using GoldenGate® assay. Outcome variables were: a) liver fibrosis (Metavir score) [fibrosis stage (F0, F1, F2, F3 and F4) and advanced fibrosis and cirrhosis (F ≥ 3 and F4, respectively)]; b) non-invasive indexes [FIB-4, APRI, and their cut-offs (FIB-4 ≥ 3.25 and APRI≥1.5)]; c) inflammation-related biomarkers (leptin, HGF, NGF, sFasL, sFas, MIF, HA, Ang-2, TIMP1, MMP1 and MMP2). ResultsPatients with rs675520 AG/GG genotypes had decreased odds of having cirrhosis (F4) and advanced fibrosis (FIB-4 ≥ 3.25 and APRI≥1.5) [adjusted Odd Ratio (aOR) = 0.30 (p = 0.025), aOR = 0.20 (p = 0.014), and aOR = 0.34 (p = 0.017), respectively] and lower levels of FIB-4 and APRI [adjusted arithmetic mean ratio (aAMR) = 0.76 (p = 0.003) and aAMR = 0.72 (p = 0.006), respectively]. Patients with rs9376293 CT/CC genotypes had decreased odds of APRI≥1.5 [aOR = 0.39 (p = 0.030)] and lower levels of APRI [aAMR = 0.77 (p = 0.018)]. Patients with rs6920220 AG/AA genotypes had higher odds of having FIB-4 ≥ 3.25 [aOR = 3.72 (p = 0.043)]. Moreover, rs675520 AG/GG genotypes, compared to AA genotype, were associated with lower levels of leptin and NGF (p = 0.002 and p = 0.001, respectively) and higher levels of sFas, MIF, TIMP1 and MMP2 (p = 0.004, p = 0.007, p = 0.020 and p = 0.036, respectively). Also, rs9376293 CT/CC genotypes were related to lower leptin levels (p = 0.026) and higher sFas, MIF, TIMP1 and MMP2 levels (p = 0.029, p = 0.040, p = 0.022 and p = 0.024, respectively). ConclusionsGenetic variants upstream of TNFAIP3 were associated with the liver fibrosis severity and inflammation in HIV/HCV-coinfected patients.