Non-invasive Fibrosis Markers Research Articles

Factors Associated With Increased Risk of De Novo or Recurrent Hepatocellular Carcinoma in Patients With Cirrhosis Treated With Direct-Acting Antivirals for HCV Infection

Patients with cirrhosis and hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC). We aimed toidentify features of de novo or recurrent HCCs in these patients, and factors associated withHCC development, in a large cohort of patients with cirrhosis who received treatment with DAAs. In a retrospective study, we collected data from 565 patients with cirrhosis (median age, 64years; range, 28-87 years; 60% male, 49% infected with HCV genotype 1; median liver stiffness measurement [LSM], 19.1 kPa; 87% Child-Pugh-Turcotte score A) treated with DAAs at a single center in Italy, from December 2014 through 2016. Cirrhosis was defined based on clinical features, histologic factors (METAVIR F4), or LSM >11.9 kPa. Patients were assessed (complete blood analysis and HCV-RNA quantification) every 4 weeks during treatment; at weeks 4, 12, and 24 afterward; and at 6-month intervals thereafter. HCC surveillance was performed by ultrasound or CT scans every 3-6 months, based on history of HCC. Non-invasive markers of fibrosis, such as ratio of aspartate aminotransferase to platelets, fibrosis-4 (FIB-4) score, and LSMs were assessed. During a median 25 months of follow up (range, 3-39 months), HCC developed in 28/505 patients without a history of HCC (de novo HCC); the 3-year estimated cumulative probability for HCC was 6% (95% CI, 4%-9%). Of patients with de novo HCC, 75% had a single tumor and82% of these were Barcelona liver cancer stage 0-A; the median level of alpha-fetoprotein was 6 ng/mL (range, 1.0-9240 ng/mL). Male sex (hazard ratio [HR], 6.17; 95% CI, 1.44-26.47; P= .01), diabetes (HR, 2.52; 95% CI, 1.08-5.87; P= .03), LSM (HR, 1.03; 95% CI, 1.01-1.06; P= .01), and FIB-4 score (HR, 1.08; 95% CI, 1.01-1.14; P= .01) were independently associated with de novo HCC. HCC developed in 20/60 patients with a history of HCC (HCC recurrence); the 3-year cumulative probability for recurrence was 43% (95% CI, 20%-61%). In the 20 patients with HCC recurrence, 11 had a single tumor and 90% were Child-Pugh-Turcotte score A. Diabetes was independently associated with HCC recurrence (HR, 4.12; 95% CI, 1.55-10.93; P=.004). In a large, single-center cohort of consecutive patients with cirrhosis and who received DAA treatment for HCV infection, most liver tumors were identified at early stages. Male sex, diabetes, and non-invasive markers of liver fibrosis can be used to identify patients at increased risk for HCC following DAAs therapy.

Identification of liver fibrosis using the hepatic vein waveform in patients with Fontan circulation.

Liver fibrosis caused by congestive hepatopathy has emerged as an important complication after Fontan procedure. We evaluated the utility of the hepatic vein (HV) waveform using Doppler ultrasound for identification of liver fibrosis in Fontan patients. We investigated the HV waveforms in 41 Fontan patients and assessed correlations with clinical parameters, liver fibrosis markers, and hemodynamic data. Based on our preliminary analysis of 64 adult patients with chronic liver disease who underwent liver biopsy, we classified HV waveforms into five types with reference to the degree of flattening (from type 1, normal triphasic waveform; to type 5, a monophasic waveform indicating cirrhosis), and confirmed a significant correlation between waveform pattern and fibrosis stage. Notably, we detected HV waveforms in all of the Fontan patients and classified them into five types. The HV waveform pattern positively correlated with γ-glutamyl transferase and hyaluronic acid levels, and negatively correlated with albumin level and platelet count, but did not correlate with central venous pressure or brain natriuretic peptide level, suggesting that HV waveform could reflect pathophysiological changes in the liver without being affected by hepatic congestion. The highest area under the receiver operating characteristic curve of the HV waveform for detecting advanced liver fibrosis, as defined by ultrasonic findings and clinical features, was 0.829 (81.8% sensitivity, 73.3% specificity), which was higher than that of other non-invasive fibrosis markers. Hepatic vein waveforms change in accordance with liver fibrosis progression in Fontan patients, and can be a useful indicator of liver fibrosis after the Fontan procedure.

Utility and limitations of noninvasive fibrosis markers for predicting prognosis in biopsy-proven Japanese non-alcoholic fatty liver disease patients.

The fibrosis stage of non-alcoholic fatty liver disease (NAFLD) is closely associated with long-term prognosis, including liver-related mortality. However, it is not yet clear whether noninvasive fibrosis markers can predict the incidence of non-liver-related complications in Japanese NAFLD. In this study, we clarified the prognosis of NAFLD patients, including non-liver-related diseases, based on hepatic pathology and noninvasive fibrosis markers. A total of 246 Japanese patients with NAFLD diagnosed by liver biopsy were enrolled. We investigated their prognosis based on hepatic pathology and noninvasive fibrosis markers. When these patients were categorized based on the severity of liver fibrosis as F0-2 (n=196) and F3-4 (n=50), the patients with F3-4 had significantly poorer prognosis in overall survival rates and all complications (P<0.05). The fibrosis-4 (FIB-4) index was useful to predict overall survival and the incidence of hepatocellular carcinoma and liver cirrhosis (LC)-related complications but not extrahepatic malignancies. Multiple logistic regression analyses revealed the following risk factors: total bilirubin ≥1.2 (hazard ratio [HR] 6.362, 95% confidence interval [CI] 1.393-29.052) and severe liver fibrosis (HR 6.512, 95% CI 1.433-29.592) for overall survival; liver fibrosis (F3-4) (HR 13.370, 95% CI 2.775-64.427) for hepatocellular carcinoma; FIB-4 index (HR 26.560, 95% CI 3.320-212.494) for LC-related complications, and liver inflammation (A2-3) (HR 4.214, 95% CI 1.354-13.116) for extrahepatic malignancies. Severe liver fibrosis was associated not only with the hepatocarcinogenesis and LC-related complications but also with extrahepatic malignancies. The FIB-4 index was useful for predicting liver-related diseases but had limitations in predicting extrahepatic malignancies.

Serum leptin and homeostasis model assessment-IR as novel predictors of early liver fibrosis in chronic hepatitis B virus infection

ABSTRACTBackground: The relationship between hepatitis B virus (HBV) infection, leptin and insulin resistance remains unclear. We hypothesised links between serum leptin and insulin resistance in non-diabetic patients with chronic viral hepatitis B infection and their relation to liver fibrosis.Methods: We recruited 190 untreated patients with chronic HBV infection and 72 healthy controls. Serum leptin, fasting glucose, insulin, liver function tests (LFTs), C-peptide and Homeostasis model assessment-IR (HOMA-IR) were measured/calculated by ELISA and standard techniques.Results: Serum leptin, C-peptide (both P < 0.001), HOMA-IR (P = 0.021) and several LFTs were increased in patients with chronic HBV-infection. In multivariate regression analysis, both HOMA-IR (P = 0.003) and leptin (P = 0.002) were significant independent predictors of HBV infection. There were significant positive correlations (P < 0.01) between leptin and HOMA-IR (r = 0.81), between serum leptin and METAVIR activity (r = 0.95), and between HOMA-IR and BMI (r = 0.75), fasting glucose (r = 0.005), and fasting insulin (r = 0.81). Several LFTs, glucose and insulin correlated modestly (r = 0.61–0.69, P < 0.05) with leptin.Conclusion: Serum leptin may be related to the rate of fibrosis progression in nondiabetic patients with chronic HBV infection. Follow-up by serial measurement of serum leptin and HOMA-IR in non diabetic HBV-infected patients may be used as a non-invasive marker of early liver fibrosis.

PMD36 - Maximising Diagnoses of Advanced Fibrosis in Primary Care with Non-Invasive Markers of Liver Fibrosis and Minimising Unnecesary Referals to Secondary Care

PMD36 - Maximising Diagnoses of Advanced Fibrosis in Primary Care with Non-Invasive Markers of Liver Fibrosis and Minimising Unnecesary Referals to Secondary Care

Usefulness of aspartate aminotransferase to platelet ratio index as a prognostic factor following hepatic resection for hepatocellular carcinoma.

Liver function is a major prognostic factor following hepatic resection for hepatocellular carcinoma (HCC), which is well correlated with the degree of fibrosis. On the other hand, the presence of liver cirrhosis itself leads to a higher incidence of HCC than chronic hepatitis. Therefore, preoperative noninvasive markers of fibrosis are important for the assessment of prognosis for treatment of HCC. The present study aimed to analyze whether aspartate aminotransferase to platelet ratio index (APRI) could predict prognosis following hepatic resection for HCC. The subjects were 162 patients who underwent hepatic resection for HCC between January 2000 and December 2011. The relationship between APRI and disease-free and overall survival were retrospectively investigated. In multivariate analysis, indocyanine green at 15 min (ICG-R15) ≥15% (P=0.0306), APRI ≥0.45 (P=0.0184), perioperative blood transfusion of red cell concentrates (RCC; P=0.0034) and TNM stage II, III or IV (P=0.0184) were significant predictors in disease-free survival. For overall survival, ICG-R15 ≥15% (P=0.0454), APRI ≥0.45 (P=0.0417), perioperative blood transfusion of RCC (P=0.0036) and TNM stage II, III or IV (P=0.0033) were significant predictors. In addition, higher APRI values were positively correlated with hepatitis C virus infection and preoperative liver function. In conclusion, APRI is an independent risk factor for disease-free and overall survival following hepatic resection for HCC.

Evaluation of serum procollagen C-proteinase enhancer 1 level as a fibrosis marker in patients with chronic hepatitis B.

Although liver biopsy has long been considered the gold standard for staging fibrosis, because of the disadvantages and risks of biopsy, several noninvasive processes such as serum biomarkers have been introduced for the assessment of liver fibrosis. The aim of this study was to assess the diagnostic value of serum procollagen C-proteinase enhancer 1 (PCPE-1) as a noninvasive fibrosis marker in treatment-naive chronic hepatitis B patients. This study included 126 patients with biopsy-proven hepatitis B and 50 healthy controls. Fibrosis stage was determined using the Ishak scoring system. The PCPE-1 level was measured using the enzyme-linked immunosorbent assay assay, and the aspartate aminotransferase to platelet ratio index and the FIB-4 index were calculated using the formulas described in Appendix 1 (Supplemental digital content 1, http://links.lww.com/EJGH/A277). Serum PCPE-1 levels of chronic hepatitis B patients were found to be significantly lower than those of the healthy control group (4.49±2.74 vs. 42.9±59.6 pg/ml, respectively, P<0.001). There was a statistically significant negative correlation between serum PCPE-1 level and fibrosis stage (P=0.011; r=-0.226). A statistically significant negative correlation was found between serum PCPE-1 level and necroinflammatory activity (P=0.030; r=-0.194). PCPE-1 levels of patients with liver fibrosis scores of F1-2 were statistically significantly lower than those of the healthy control group (P<0.001) (area under the receiver operating characteristic: 0.955). The area under the receiver operating characteristic of the PCPE-1 level was 0.615 for the prediction of fibrosis (F0 vs. F1-6) (P=0.039). Serum PCPE-1 might be used as a noninvasive marker of liver fibrosis. Further animal and human studies are needed to assess the utility of this marker.

Lysosomal Acid Lipase: Can it be a New Non-Invasive Serum Biomarker of Cryptogenic Liver Fibrosis and Cirrhosis?

Introduction and aim. The association between lysosomal acid lipase (LAL) activity and liver steatosis or fibrosis is poorly studied. The aim of our study was to determine the predictive power of LAL for cryptogenic liver steatosis and cryptogenic significant fibrosis/ cirrhosis. Material and methods. Cross-sectional observational study of 101 adult patients with unexplained elevated liver enzymes/hepatomegaly with or without dyslipidemia submitted to the determination of LAL activity and LIPA gene (E8SJMC. 894G→A) mutation. Seventy-one patients underwent liver biopsy or FibroScan®. Patients with an identifiable liver dysfunction cause and well-stablished NAFLD/NASH risk factors were excluded. Predictors for liver steatosis, significant fibrosis (≥ F2) or cirrosis (F4) were evaluated. Results. Liver steatosis and fibrosis were mainly assessed by liver biopsy (74.6%; n = 53). Steatosis was present in 62.0% (n = 44), significant fibrosis in 47.9% (n = 34) and cirrhosis in 39.4% (n = 28). The median LAL was 0.36 (0.21-0.46)nmol/spot/h (vs. 0.29 (0.20-0.47); p = 0.558) for liver steatosis, 0.22 (0.11-0.29) nmol/spot/h (vs. 0.40 (0.34-0.51); p &lt; 0.001) for significant fibrosis and 0.21 (0.11-0.27) nmol/spot/h (vs. 0.40 (0.32-0.52); p &lt; 0.001) for cirrhosis. No LIPA gene mutations were found. LAL activity was the strongest predictor of significant fibrosis (AUROC: 0.833; p &lt; 0.001) with a cut-off of 0.265 (sensitivity: 85.9%; specificity: 75.0%) and cirrhosis (AUROC: 0.859; p &lt; 0.001) with a cut-off of 0.235 (sensitivity: 86.2%; specificity: 75.0%), being higher than FIB4, GUCI or APRI. However, LAL activity was not associated with liver steatosis (AUROC: 0.536; p = 0.558). Conclusion. LAL activity can be considered a non-invasive new marker of cryptogenic liver fibrosis with higher accuracy than other known biomarkers. LAL activity &lt; 0.265 nmol/spot/h was strongly associated with cryptogenic significant fibrosis and &lt; 0.235 nmol/spot/h with cryptogenic cirrhosis. LAL activity was not associated with cryptogenic liver steatosis.

Index serum hyaluronic acid independently and accurately predicts mortality in patients with liver disease.

Hyaluronic acid is a recognised noninvasive marker of liver fibrosis. However, its prognostic ability has not been extensively studied. To investigate the ability of an index serum hyaluronic acid measurement to independently predict transplant-free survival in patients with liver disease of varying aetiology and severity. This was a retrospective single-centre cohort study. Serum hyaluronic acid was measured at the discretion of the attending clinicians, in patients attending the liver clinic, to assess disease severity. Patients with a hyaluronic acid measurement between 1995 and 2010 were identified. Patient characteristics at the point of hyaluronic acid measurement were recorded from medical records. Follow-up was from date of index hyaluronic acid measurement to date of death, date of transplant or censor date (July 01, 2015). Primary outcomes were all-cause and liver-related mortality. Kaplan-Meier analysis was used to compare survival in 3 patient groups with hyaluronic acid levels of <100μg/L, 100-300μg/L and >300μg/L. Survival models were constructed using Cox proportional hazard and prediction accuracy was assessed by Harrell's C-statistic. Five hundred and eighty nine patients fulfilled inclusion criteria. Median follow-up was 5.6years (range 0.1-19.7). Transplant-free survival was significantly different between patients with hyaluronic acid <100μg/L, 100-300μg/L and >300μg/L for liver-related as well as all-cause mortality (P<0.001). Hyaluronic acid level was an independent predictor of survival (liver-related: HR 1.39, 95% CI 1.20-1.60, P<0.001; all-cause: HR 1.04, 95% CI 1.02-1.06, P=0.001). The liver-related prediction accuracy of hyaluronic acid was 0.74 (Standard error 0.03). Index hyaluronic acid measurement can accurately and independently predict liver-related and all-cause mortality in patients with liver disease.

1. Impact of direct acting antiviral drugs in treatment naïve HCV cirrhosis on fibrosis and severity of liver disease: a real life experience from a tertiary care center of North India

Background and Aims: Treatment of chronic hepatitis C infection with direct-acting antiviral (DAA) drugs has been highly effective, but data regarding benefit in advanced liver disease is relatively scarce in Indian patients. The aim of this study was to determine the effects of DAA in patients with HCV related cirrhosis (compensated/decompensated) that achieved sustained virological response post therapy at 12 weeks (SVR12). Methods: 63 patients with HCV related cirrhosis treated with Sofosbuvir based regimen were evaluated. The primary end point was to evaluate the effect of treatment (SVR12) on the severity of liver disease with the secondary end point being to observe for any adverse events related to treatment. Results: Treatment naïve patients with HCV cirrhosis either due to genotype 1 or genotype 3 were divided into two groups: group A (compensated cirrhosis), group B (decompensated cirrhosis). SVR12 in group A was 91.66% (33/37) and in group, B was 73.17% (30/41). Baseline mean liver stiffness measurement (LSM) in group A was 16.81 ± 3.57 kPa which decreased to 11.19 ± 1.75 kPa at SVR12 (p-value < 0.0001). Baseline mean APRI and FIB-4 Score in group A were 1.228 ± 0.499 & 2.61 ± 1.06 and in group B were 2.156 ± 1.10 & 5.71 ± 2.06 respectively which decrease to 0.415 ± 0.115 & 1.25 ± 0.46 in group A, to 0.759 ± 0.275 & 2.60 ± 1.12 in group B following SVR12 (p value < .0001). Mean MELD-Na improved from baseline 9.93 ± 2.04, 20.70 ± 4.52 to 7.21 ± 0.92, 14.23 ± 4.51 respectively in group A and B at SVR12 (p-value < .0001). CTP Score improved by 1 in 27.27% (9/33) and ≥2 in 76.67% (23/30) of patients in group A and group B respectively. Conclusions: There was a significant improvement in severity of liver disease as depicted by the decrease in LSM and other noninvasive marker of fibrosis in patients who achieved SVR12 on DAA therapy. The authors have none to declare.

52. Performance of non-invasive markers of liver fibrosis

52. Performance of non-invasive markers of liver fibrosis

Non-invasive aspartate aminotransferase to platelet ratio index correlates well with invasive hepatic venous pressure gradient in cirrhosis.

Hepatic venous pressure gradient (HVPG) is the best recommended tool to measure portal pressure, but is invasive. HVPG helps in prognosticating cirrhosis and predictits complications. Aminotransferase to platelet ratio index (APRI) is a simple non-invasive marker of hepatic fibrosis. We aimed to correlate APRI with HVPG and to determine the usefulness of APRI in predicting complication of cirrhosis. APRI and HVPG were measured in consecutive patients of cirrhosis aged 18 to 70 years. Spearman's rho was used to estimate their correlation; acut-off valueof APRI topredict severe portal hypertension (HVPG > 12mmHg) was determined. This study, conducted between August 2011 and December 2014, included 277 patients, median age 51 (range: 16-90) years, 84% males. Etiology of cirrhosis was alcohol in 135 (49%), cryptogenic/nonalcoholic steatohepatitis (NASH) in 104 (38%), viral in 34 (12%), and others in 4 (1%). Median Child-Turcott-Pugh (CTP) and model for end-stage liver disease (MELD) scores were 7 (5-11) and 11 (6-33), respectively. Median HVPG was 17.0 (1.5-33) mmHg and median APRI was 1.09 (0.21-12.22). There was positive correlation between APRI andHVPG (Spearman's rho 0.450, p < 0.001). The area under the receiver operating characteristic (ROC) curve of APRI for predicting severe portal hypertension was 0.763 (p < 0.01). Youden's index defined the cut-off of APRI for predicting HVPG > 12mmHg was 0.876 with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 71%, 78%, 94%, 38%, and 73%, respectively. APRI also correlated well with CTP, variceal size, bleeding status, ascites but not with MELD. APRI score of 0.876 has an acceptable accuracy topredictsevere portal hypertension (HVPG > 12mmHg). High APRI also correlated with severity of cirrhosis and its complications. Thus, APRI may be used as a simple, bedside, non-invasive, and inexpensive tool for evaluating portal hypertension and complications of cirrhosis.

APRI score non-invasive marker of metabolic syndrome in breast carcinoma patients

BackgroundBreast carcinoma is one of the commonest cancer in women accounting for major health burden worldwide. Metabolic syndrome is a known risk factor of non-alcoholic steatohepatitis (NASH) as well as breast carcinoma. APRI (Aspartate aminotransferase to platelet ratio index), a known non-invasive marker of liver fibrosis and steatohepatitis has never been studied in patients of metabolic syndrome with breast carcinoma. Breast carcinoma has various modifiable risk factors such as obesity and alcohol consumption. Hence, we compared APRI score in patients with breast carcinoma in order to establish a possible correlation. Aims and ObjectivesOur primary objective was to study APRI (Aspartate aminotransferase to platelet ratio index) score in patients of breast carcinoma with and without metabolic syndrome. The secondary objective was to study APRI score in post-menopausal women with breast carcinoma. Material and MethodThis prospective observational study included 151 patients of breast carcinoma, these patients were sub grouped into two, with and without metabolic syndrome and pre and post-menopausal women. Multiple demographic and biochemical parameters including APRI score were studied in these groups. The sensitivity and specificity of APRI score was calculated in these groups. ResultsA total of 151 patients of breast carcinoma were included in the study group.53.64% patients with breast carcinoma had metabolic syndrome. The mean values of AST (Aspartate aminotransferase), BMI (Body mass index), FBS (Fasting blood sugar) and APRI score were significantly higher in the patients with metabolic syndrome. More than 50% patients of breast carcinoma belonged to the post-menopausal age group. Mean values of AST (aspartate aminotransferase), BMI (body mass index), FBS (fasting blood sugar) and APRI were higher in this group. The area under the receiver operating characteristics (ROC) curve of APRI score of metabolic syndrome patients was 0.93 and that of post-menopausal women was 0.82. ConclusionAPRI score can be used as a surrogate marker of metabolic syndrome in patients with breast carcinoma. It is also useful in planning preventive strategies in patients with breast carcinoma especially in post-menopausal age group.

Improvement of liver stiffness measurement, acoustic radiation force impulse measurements, and noninvasive fibrosis markers after direct-acting antivirals for hepatitis C virus G4 recurrence post living donor liver transplantation: Egyptian cohort.

Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct-acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single-center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir-based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir-based treatment resulted in an early improvement in parameters of liver fibrosis in post-LT patients with hepatitis C recurrence.

Molecular profiling of subclinical inflammatory lesions in long-term surviving adult liver transplant recipients

Subclinical inflammatory changes are commonly described in long-term transplant recipients undergoing protocol liver biopsies. The pathogenesis of these lesions remains unclear. The aim of this study was to identify the key molecular pathways driving progressive subclinical inflammatory liver allograft damage. All liver recipients followed at Hospital Clínic Barcelona who were >10 years post-transplant were screened for participation in the study. Patients with recurrence of underlying liver disease, biliary or vascular complications, chronic rejection, and abnormal liver function tests were excluded. Sixty-seven patients agreed to participate and underwent blood and serological tests, transient elastography and a liver biopsy. Transcriptome profiling was performed on RNA extracted from 49 out of the 67 biopsies employing a whole genome next generation sequencing platform. Patients were followed for a median of 6.8 years following the index liver biopsy. Median time since transplantation to liver biopsy was 13 years (10-22). The most frequently observed histological abnormality was portal inflammation with different degrees of fibrosis, present in 45 biopsies (67%). Two modules of 102 and 425 co-expressed genes were significantly correlated with portal inflammation, interface hepatitis and portal fibrosis. These modules were enriched in molecular pathways known to be associated with T cell mediated rejection. Liver allografts showing the highest expression levels for the two modules recapitulated the transcriptional profile of biopsies with clinically apparent rejection and developed progressive damage over time, as assessed by non-invasive markers of fibrosis. A large proportion of adult liver transplant recipients who survive long-term exhibit subclinical histological abnormalities. The transcriptomic profile of these patients' liver tissue closely resembles that of T cell mediated rejection and may result in progressive allograft damage. A large proportion of adult liver transplant recipients who survive for a long time exhibit subclinical histological abnormalities. The expression profile (a measurement of the activity of genes) of liver tissue from a large fraction of these patients closely resembles the profile of T cell mediated rejection. Liver allografts showing the highest expression levels of rejection-related genes developed progressive damage over time.

Changes in serum levels of autotaxin with direct-acting antiviral therapy in patients with chronic hepatitis C.

Sustained virological response (SVR) rates have increased remarkably since the introduction of direct-acting antiviral agents (DAAs) for chronic hepatitis C. Autotaxin (ATX) is a secreted enzyme converting lysophosphatidylcholine to lysophosphatidic acid and a newly established biomarker for liver fibrosis. Interferon-free DAA regimens for chronic hepatitis C could improve liver stiffness in SVR patients according to several non-invasive evaluation methods, but the clinical response and significance of ATX in this context have not yet been defined. We therefore investigated sequential serum ATX levels at baseline, 4 weeks after the start of treatment, and 24 weeks after treatment in 159 hepatitis C virus (HCV)-infected patients who received DAA therapy. Other non-invasive fibrosis markers (aspartate aminotransferase-to-platelet ratio and FIB-4 index) were examined as well. Baseline median ATX levels were comparable between the 144 patients who achieved a SVR and the 15 who did not (1.54 vs. 1.62 mg/L), but median ATX levels became significantly decreased during and after DAA therapy in the SVR group only (from 1.54 to 1.40 and 1.31 mg/L, respectively; P < 0.001). ATX was significantly decreased between baseline and 4 weeks of treatment in overall, male, and female SVR patients (all P < 0.001). In subjects with low necroinflammatory activity in the liver (i.e., alanine aminotransferase < 30 U/L), ATX levels were significantly reduced from baseline to 4 weeks of treatment and remained low (P < 0.001) in patients with a SVR. Thus, interferon-free DAA therapy was associated with a significant decrease in serum ATX levels in patients achieving a SVR, suggesting early regression of liver fibrosis in addition to inflammation treatment.

Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is defined by the pathologic accumulation of fat in more than 5% of hepatocytes in the absence of significant alcohol consumption (daily intake &lt; 20 g in women and &lt; 30 g in men) and by excluding secondary causes of hepatic steatosis. NAFLD can be categorized into two principal phenotypes: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is defined by the presence of macrovesicular steatosis without inflammation, whereas NASH sees inflammation and hepatocyte ballooning injury, is associated with varying degrees of fibrosis, and can progress to cirrhosis and end-stage liver disease. This review addresses the epidemiology, etiology, pathophysiology, diagnosis, treatment, and prognosis of NAFLD. Figures show the spectrum of fatty liver disease, hepatic consequences of insulin resistance, role of liver biopsy in evaluation of NAFLD, histologic features of NASH, and principles of NAFLD. Tables list risk factors and clinical manifestations for NAFLD, physical examination findings in NAFLD, comparison of imaging modalities, and noninvasive fibrosis markers. This review contains 6 figures, 5 tables and 166 references Key words: Nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, non-invasive assessment, vibration controlled transient elastography, magnetic resonance elastography, diet and lifestyle treatment

Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is defined by the pathologic accumulation of fat in more than 5% of hepatocytes in the absence of significant alcohol consumption (daily intake &lt; 20 g in women and &lt; 30 g in men) and by excluding secondary causes of hepatic steatosis. NAFLD can be categorized into two principal phenotypes: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is defined by the presence of macrovesicular steatosis without inflammation, whereas NASH sees inflammation and hepatocyte ballooning injury, is associated with varying degrees of fibrosis, and can progress to cirrhosis and end-stage liver disease. This review addresses the epidemiology, etiology, pathophysiology, diagnosis, treatment, and prognosis of NAFLD. Figures show the spectrum of fatty liver disease, hepatic consequences of insulin resistance, role of liver biopsy in evaluation of NAFLD, histologic features of NASH, and principles of NAFLD. Tables list risk factors and clinical manifestations for NAFLD, physical examination findings in NAFLD, comparison of imaging modalities, and noninvasive fibrosis markers. This review contains 6 figures, 5 tables and 166 references Key words: Nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, non-invasive assessment, vibration controlled transient elastography, magnetic resonance elastography, diet and lifestyle treatment

Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is defined by the pathologic accumulation of fat in more than 5% of hepatocytes in the absence of significant alcohol consumption (daily intake &lt; 20 g in women and &lt; 30 g in men) and by excluding secondary causes of hepatic steatosis. NAFLD can be categorized into two principal phenotypes: nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is defined by the presence of macrovesicular steatosis without inflammation, whereas NASH sees inflammation and hepatocyte ballooning injury, is associated with varying degrees of fibrosis, and can progress to cirrhosis and end-stage liver disease. This review addresses the epidemiology, etiology, pathophysiology, diagnosis, treatment, and prognosis of NAFLD. Figures show the spectrum of fatty liver disease, hepatic consequences of insulin resistance, role of liver biopsy in evaluation of NAFLD, histologic features of NASH, and principles of NAFLD. Tables list risk factors and clinical manifestations for NAFLD, physical examination findings in NAFLD, comparison of imaging modalities, and noninvasive fibrosis markers. This review contains 6 figures, 5 tables and 166 references Key words: Nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, non-invasive assessment, vibration controlled transient elastography, magnetic resonance elastography, diet and lifestyle treatment

THU-201 - VCAM-1 and soluble CD-163 as novel non-invasive markers of liver fibrosis in patients with autoimmune hepatitis – a prospective study

THU-201 - VCAM-1 and soluble CD-163 as novel non-invasive markers of liver fibrosis in patients with autoimmune hepatitis – a prospective study