Fibrosis Regression In Patients Research Articles

Regression of liver fibrosis after HBsAg loss: A prospective matched case-control evaluation using transient elastography and serum enhanced liver fibrosis test.

We assessed the effect of hepatitis B surface antigen (HBsAg) seroclearance (HBsAg-loss) on liver fibrosis regression in patients with chronic hepatitis B (CHB) infection. CHB patients with recent documented HBsAg-loss were age- and gender-matched with treatment-naïve HBeAg-negative CHB infection. Paired assessment with transient elastography and enhanced liver fibrosis (ELF) measurements were performed and repeated at 3years. Fibrosis regression was arbitrarily defined as decrease in ≥1 fibrosis stage by ELF, or combining with reduction >30% in liver stiffness. A total of 142 HBsAg-loss and 142 CHB subjects were recruited (median age 58.1years, 51.4% male). A total of 1.8% (1.4% HBsAg-loss vs 2.1% CHB) achieved combined endpoint of fibrosis regression at 3years. When ELF-only definition of fibrosis regression was used, 14.5% HBsAg-loss and 16.9% CHB subjects achieved this endpoint, which was significantly associated with baseline ELF (hazard ratio (HR) 1.827, 95% confidence interval (CI) 1.085-3.075) and time since HBsAg-loss (HR 2.688, 95% CI 1.257-5.748). While increasing time since HBsAg-loss increased the proportion of ELF-defined fibrosis regression, increasing age was also associated with significant fibrosis. Age of achieving HBsAg-loss (ageSC) was independently associated with high baseline ELF values. Up to 52.3% and 63.8% subjects with ageSC>50 had advanced fibrosis/cirrhosis at baseline and 3years, respectively, compared with 5.9% and 20.6% in subjects with ageSC<50. Fibrosis regression occurred in a minority of subjects achieving HBsAg-loss, which was not significantly different compared with subjects with persistent overt CHB. Subjects after achieving HBsAg-loss, especially among those with ageSC>50, should receive ongoing surveillance for liver-related complications.

AI Digital Pathology Using qFibrosis Shows Heterogeneity of Fibrosis Regression in Patients with Chronic Hepatitis B and C with Viral Response.

This study aimed to understand the dynamic changes in fibrosis and its relationship with the evaluation of post-treatment viral hepatitis using qFibrosis. A total of 158 paired pre- and post-treatment liver samples from patients with chronic hepatitis B (CHB; n = 100) and C (CHC; n = 58) were examined. qFibrosis was employed with artificial intelligence (AI) to analyze the fibrosis dynamics in the portal tract (PT), periportal (PP), midzonal, pericentral, and central vein (CV) regions. All patients with CHB achieved a virological response after 78 weeks of treatment, whereas patients with CHC achieved a sustained viral response after 24 weeks. For patients initially staged as F5/6 (Ishak system) at baseline, the post-treatment cases exhibited a significant reduction in the collagen proportionate area (CPA) (25-69%) and number of collagen strings (#string) (9-72%) across all regions. In contrast, those initially staged as F3/4 at baseline showed a similar CPA and #string trend at 24 weeks. For regression patients, 27 parameters (25 in the CV region) in patients staged as F3/4 and 15 parameters (three in the PT and 12 in the PP regions) in those staged as F5/6 showed significant differences between the CHB and CHC groups at baseline. Following successful antiviral treatment, the pre- and post-treatment liver samples provided quantitative evidence of the heterogeneity of fibrotic features. qFibrosis has the potential to provide new insights into the characteristics of fibrosis regression in both patients with CHB and CHC as early as 24 weeks after antiviral therapy.

The Early On-treatment Stiffness Decline Attributed to the Improved Hepatic Inflammation in Fibrotic Chronic Hepatitis B.

Hepatic inflammation, the driver of fibrosis progression in liver disease, can impact the accuracy of liver stiffness measurement (LSM). We wondered whether the decline in LSM value during the early antiviral phase was mainly attributed to the control of hepatic inflammation or the regression of fibrosis in patients with fibrotic/cirrhotic chronic hepatitis B (CHB). The study cohort was composed of 82 patients with CHB who underwent antiviral and antifibrotic therapy at the Fifth Medical Center of PLA General Hospital. All patients had liver biopsies at both baseline and 72 weeks posttherapy. Liver pathology and clinical data, including the LSM value, were collected. After 72 weeks of treatment, both the histologic activity index score and fibrosis score, as well as the LSM value, were significantly decreased (P < 0.001), compared with their baseline values. The pretreatment correlation of LSM value with either histologic activity index score (r = 0.526 vs r = 0.286) or fibrosis score (r = 0.677 vs r = 0.587) was attenuated at 72 weeks. Notably, logistic regression analysis revealed that the improvement in inflammation (odds ratio = 1.018, 95% CI: 1.002-1.031, P = 0.023) but not fibrosis (odds ratio = 0.994, 95% CI: 0.980-1.009, P = 0.414), had an impact on the change in LSM values between baseline and at 72-week treatment. The findings of this study suggest that in patients with fibrotic CHB receiving antiviral medication, the early phase reduction in LSM value was related to improved hepatic inflammation rather than fibrosis regression.

Metabolic phenotyping of patients with Advanced Chronic Liver Disease for better characterization of Cirrhosis Regression

Background & AimsRegression of cirrhosis has been observed in patients with viral and non-viral etiologies of liver disease in whom the underlying cause of liver injury was effectively suppressed. However, the understanding of the factors contributing to reversibility of fibrosis and cirrhosis is limited. Our aims were to assess clinical factors, perform genotyping of known variants, and comprehensive metabolic phenotyping to characterize the regression of fibrosis in patients with compensated advanced chronic liver disease (cACLD). MethodsIn a case-control pilot study with 81 cACLD patients, we compared individuals exhibiting histological or clinical evidence of cACLD regression ("regressors"; n=44) with those showing no improvement ("non-regressors"; n=37) after a minimum of 24 months of successful therapy of the cause of liver disease. Data were validated using an external validation cohort (n=30). ResultsRegardless of the cause of cACLD, the presence of obesity (OR 0.267 95%CI:0.072-0.882; P=0.049), high liver stiffness (OR 0.960, 95%CI:0.925-0.995; P=0.032), and carriage of GCKR variant rs1260326 (OR 0.148, 95%CI:0.030-0.773; P=0.019) are associated with a reduced likelihood of fibrosis regression in a subgroup of 60 ACLD patients genotyped for known genetic variants. Using liver tissue transcriptomics, we identified metabolic pathways differentiating regressors from non-regressors, with top pathways associated to lipid metabolism -especially fatty acids, bile acids, phospholipids, triacylglycerides (biosynthesis), and the carnitine shuttle. In the entire discovery cohort, we further measured metabolites within the defined pathways, which led to identifying 33 circulating markers differentiating regressors from non-regressors after etiological therapy. The validation cohort confirmed 14 of the differentially expressed markers. ConclusionsWe identified and validated a group of lipid biomarkers associated with regression of fibrosis that could be used as non-invasive biomarker for detecting regression of fibrosis in cACLD.

Angiopoietin-2 as a Predictor of Fibrosis Regression in Hepatitis C Virus-Patients after Direct Acting Antiviral Drugs

Abstract Background Hepatitis C virus (HCV) infection is the major cause of liver cirrhosis and hepatocellular carcinoma (HCC); thus, effective and safe treatment is crucial. Aim of the Work to evaluate the serum angiopoietin-2 as non-invasive marker of fibrosis regression in patients with Hepatitis C Virus receiving DAA drugs. Patients and Methods This study was conducted on 40 chronic HCV-patients who received DAA therapy in the Hepatic Virology Unit and the gastroenterology department of Ain Shams University hospitals. All patients were subjected to the following: Full history taking with stress concerning the hepatology system, clinical evaluation, laboratory investigations, Routine investigations: Abdominal and Pelvic ultrasonography and Transient elastography (Fibroscan) to measure liver stiffness measurement (LSM) for detection the degree of liver fibrosis in the chronic HCV-patients. Results Hematological findings, biochemical liver profile and liver fibrosis indices except hemoglobin level and platelets counts were significantly improved after DAA therapy. There was a significant improvement concerning the fibrosis stage after the treatment fibrosis staging at SVR12. The liver size, the spleen size and portal vein diameter were also significant after DAA therapy. There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant. There was a statistically significant higher mean of Ang-2 levels in higher stages of liver fibrosis stages. Overall, serum Ang-2 levels significantly decrease after DAA therapy. In F0, F1, F2 &amp; F3 fibrosis stage; the mean Ang2 levels decrease after DAA therapy but in F4 fibrosis stage; the mean Ang2 levels did not change almost. Baseline Ang-2 and WBCs, AST, ALT, total bilirubin, INR, serum albumin, alpha-fetoprotein, serum creatinine, LSM, FIB-4 index, APRI score, liver size and portal vein diameter were significantly correlated. There were also a significant correlation between Ang-2 and all the fibrosis stages (from F0 to F4) before DAA treatment. Ang-2 levels were significantly associated with LSM based liver fibrosis stage regression after successful DAA therapy. Ang-2 levels did not correlate with hemoglobin, platelets and spleen size at baseline. Ang-2 levels did not correlate with hemoglobin, platelets, WBCs, INR, spleen size and portal vein diameter after DAA therapy. Ang-2 levels did not show significant correlation with the Child-Pugh score after DAA therapy. Conclusion Liver fibrosis stage after successful HCV eradication by DAAs. But in stage F4 (cirrhosis), mean Ang-2 remained almost unchanged after DAA therapy. Significant decrease of Serum Ang-2 could suggest its use as a predictor of liver fibrosis regression in Hepatitis C Virus-patients after Direct Acting Antiviral drugs after DAA therapy.

Non-invasive Assessment of Liver Fibrosis Regression in Patients with Chronic HepatitisB: A Retrospective Cohort Study.

Non-invasive tests (NITs) have been alternative methods of liver biopsy for the cross-sectional assessment of liver fibrosis in patients with chronic hepatitisB (CHB). However, there are limited data on the longitudinal association between NITs and histological changes of liver fibrosis. This study aimed to evaluate whether NITs can be used to assess liver fibrosis regression (LFR) during anti-HBV treatment. This retrospective study included 337 patients with CHB who underwent contemporaneous NITs, such as liver stiffness measurement (LSM), the aspartate aminotransferase to platelet ratio index (APRI), the fibrosis index based on four factors (FIB-4), and the γ-glutamyl transpeptidase to platelet ratio (GPR), and liver biopsy at baseline and followed by a repeated liver biopsy and NITs assessment. The LFR was defined as fibrosis regression by at least one stage assessed by METAVIR scoring system. The median interval between the two paired liver biopsy assessment was 31months (IQR 24-45). At the first liver biopsy, the fibrosis stage was F2 in 159 (47.2%), F3 in 68 (20.2%), and F4 in 110 (32.6%) patients. At the second liver biopsy, the number of patients with fibrosis stages F0-1, F2, F3, and F4 was 102 (30.3%), 106 (31.5%), 63 (18.7%), and 66 (19.6%), respectively. At follow-up liver biopsy, 169 patients (50.1%) had LFR, 128 patients (38.0%) had no change in fibrosis stage, and 40 patients (11.9%) had liver fibrosis progression on histology. A decrease in liver stiffness measurement (LSM) by 25% is the optimal cutoff for predicting LFR. Patients with a 25% or larger decrease in LSM value had more LFR than those with a less than 25% decrease in LSM value (78.1% vs 22.9%, p < 0.001). LSM might be used to monitor regression of liver fibrosis during antiviral treatment using nucleos(t)ide analogues (NUCs) in patients with CHB.

Long-term effects of entecavir and tenofovir treatment on the fibrotic burden in patients with chronic hepatitis B.

Antiviral therapy (AVT) induces fibrosis regression in patients with chronic hepatitis B. We investigated long-term effects of entecavir (ETV) versus tenofovir (TDF) on fibrotic burden. Treatment-naïve chronic hepatitis B patients who had begun ETV or TDF were recruited from four tertiary hospitals. The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) were used to determine fibrotic burden. In the entire population (n=3277), although patients treated with ETV had higher baseline APRI (1.71 vs 1.07, P<0.001) and FIB-4 (3.60 vs 2.80, P<0.001) than those treated with TDF, significant fibrosis regression was identified during 6years of AVT in both ETV (APRI, mean 1.71→0.48, P<0.001; FIB-4, mean 3.60→2.21, P<0.001) and TDF groups (APRI, mean 1.07→0.43, P<0.001; FIB-4, mean 2.80→2.19, P<0.001). In patients without cirrhosis (n=2366), baseline APRI was significantly higher in ETV group than in TDF group (1.72 vs 0.97, P<0.001); however, they became similar after 6months. Similarly, baseline FIB-4 was significantly higher in ETV group than in TDF group (3.25 vs 2.35, P<0.001), but became similar from 4 to 6years. In patients with cirrhosis (n=911), baseline APRI (1.70 vs 1.34, P<0.001) and FIB-4 (4.62 vs 3.91, P=0.005) were higher in ETV group than in TDF, however, both parameters became statistically similar from 6months to 6years. Significant regression of APRI and FIB-4 was observed during long-term ETV and TDF treatment. Despite higher baseline fibrotic burden in ETV group, fibrotic burden between the groups eventually converged through significant fibrosis regression after 1 to 4years of AVT.

Liver fibrosis assessment by transient elastography in patients with liver cirrhosis after hepatitis C virus eradication

Direct-acting antivirals (DAAs) therapy is associated with fibrosis regression in patients with hepatitis C virus liver cirrhosis.Aim. To study the dynamic of liver fibrosis in cirrhotic patients with a DAAs-induced sustained virological response (SVR).Materials and methods. The retrospective cohort study included 80 cirrhotic patients (male — 43%, median age 54 years). Liver stiffness (LS) was measured by transient elastography before treatment and after SVR. Patients with LS improvement ≥30% were included in group 1, other patients — in group 2. Clinical, laboratory and instrumental parameters were assessed. Independent risk factors for the absence of LS improvement ≥30% were determined by binary logistic regression with the definition of odds ration (OR) and 95% confidence interval (CI).Results. LS reduced from 21.35 (15.2; 27.7) to 13.5 [10.1; 20.0] kPa (p &lt; 0.001), the median reduction was 5.1 [2.6; 11.0] kPa. Regression of fibrosis from F4 to F2 and F3 stages was observed in 16 (20%) and 19 (24%) of cases, respectively. Overall, 36 patients were included in group 1, 44 patients — in group 2. Platelet counts increased in group 1 compared to group 2 by 24.5% vs 5.2% (p = 0.014), a disappearance or reducing the size of esophageal varices were observed in 72% vs. 35% of cases (p = 0.035). Significant differences in ALT, AST, albumin, prothrombin time dynamics were not observed. Baseline albumin level ≤35 g/l is an independent risk factor for the absence of significant improvement of LS: OR 6.7 (95% CI 1.7–25.9, p = 0.006).Conclusion. SVR leads to fibrosis regression to F2-F3 stages in 44% of patients. Baseline albumin level ≤35 g/l is an independent risk factor for the absence of significant improvement of LS.

M2BPGi for assessing liver fibrosis in patients with hepatitis C treated with direct-acting antivirals.

BACKGROUNDAssessing liver fibrosis is important for predicting the efficacy of direct-acting antivirals (DAAs) and patient prognosis. Non-invasive techniques to assess liver fibrosis are becoming important. Recently, serum Mac-2 binding protein glycosylation isomer (M2BPGi) was identified as a non-invasive marker of liver fibrosis.AIMTo investigate the diagnostic accuracy of M2BPGi in assessing liver fibrosis in patients with chronic hepatitis C (CHC) treated with DAAs.METHODSFrom December 2017 to August 2018, 80 treatment-naïve adult patients with CHC who were eligible for DAAs therapy were consecutively enrolled in this observational cohort study. For 12 weeks, 65 patients were treated with sofosbuvir/daclatasvir, and 15 patients were treated with sofosbuvir/daclatasvir and a weight-based dose of ribavirin at knowledge and technology association for hepatitis C management clinic, Cairo, Egypt. We measured serum M2BPGi levels, PAPAS index, fibrosis-4 (FIB-4) score and liver stiffness measurements (LSM) at baseline and 12 weeks after the end of treatment. Serum M2BPGi levels were measured using enzyme-linked immunosorbent assay.RESULTSAll patients achieved sustained virologic response (SVR12) (100%). Serum M2BPGi levels, LSM, FIB-4 score and PAPAS index decreased significantly at SVR12 (P < 0.05). Serum M2BPGi levels correlated positively with LSM at baseline and SVR12 (P < 0.001). At baseline, compared with the FIB-4 score and PAPAS index, M2BPGi was the best marker to distinguish patients with grade F4 fibrosis (AUC = 0.801, P < 0.001), patients with grade F2 from grade F0-1 fibrosis (AUC = 0.713, P = 0.012), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.730, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.763, P < 0.001). At SVR12, M2BPGi had the greatest AUCs for differentiating patients with grade F4 fibrosis (AUC = 0.844, P < 0.001), patients with grade F3 from grade F0-2 fibrosis (AUC = 0.893, P = 0.002), patients with grade F3-4 from grade F0-2 fibrosis (AUC = 0.891, P < 0.001), and patients with grade F2-4 from grade F0-1 fibrosis (AUC = 0.750, P < 0.001).CONCLUSIONM2BPGi is a reliable marker for the non-invasive assessment and prediction of liver fibrosis regression in patients with CHC who achieved an SVR with DAAs therapy.

Histological responses of peginterferon alpha add-on therapy in patients with chronic hepatitis B with advanced liver fibrosis after long-term nucleos(t)ide analog treatment.

Although long-term antiviral treatment with nucleos(t)ide analogs (NAs) can lead to histological improvement in patients with chronic hepatitis B (CHB), a substantial proportion of patients still fail to achieve regression of fibrosis. Here, we investigated whether peginterferon alpha (Peg-IFNα） add-on therapy had benefits on fibrosis regression in patients with sustained severe fibrosis even after long-term NA treatment. We conducted a retrospective analysis of data from 50 patients with CHB receiving 48weeks of Peg-IFNα add-on therapy. All enrolled patients had advanced fibrosis or cirrhosis (S score≥3) at baseline and underwent NA treatment for at least 1year before Peg-IFNα addition. Paired liver biopsies before and after Peg-IFNα add-on treatment and laboratory tests at baseline, 24weeks of treatment, 48weeks of treatment and long-term follow-up were analysed. Of the 50 patients enrolled in this study, 34 patients (68.0%) had significant regression of fibrosis, and 42 (84.0%) showed significant remission of inflammation after Peg-IFNα add-on treatment. Compared with nonresponders, patients with significant histological improvement showed faster hepatitis B surface antigen (HBsAg) decline and tended to have higher cumulative hepatitis B e antigen (HBeAg) and HBsAg loss rates during long-term follow-up. Peg-IFNα add-on therapy led to significant regression of fibrosis and resolution of inflammation in patients with advanced fibrosis after long-term NA treatment.

Impacts of cigarette smoking on liver fibrosis and its regression under therapy in male patients with chronic hepatitis B.

The role of cigarette smoking in the development of chronic hepatitis B (CHB) remains poorly understood. We assessed the potential contributions of cigarette smoking to liver fibrosis and its regression after starting antiviral therapy in CHB patients. In this cohort study, 2144 consecutive male CHB patients under no antiviral therapy were evaluated and 206 patients with significant liver fibrosis (≥F2) initiating antiviral therapy had longitudinal follow-up. Liver fibrosis was measured by liver stiffness measurement using transient elastography. To adjust for imbalances between smoking history and never smoking groups, propensity score (PS) matching model with 1:1 ratios were performed. Cigarette smoking history and intensity (pack-years) were collected and documented using a standardized questionnaire. Before PS matching, 432/2144 patients had advanced fibrosis in prevalence cohort. Patients with smoking history (n=1002) had a greater prevalence of advanced fibrosis than those without (n=1142) (24.4% vs 16.5%, P=0.001). Multivariate logistic regression analysis demonstrated that smoking contributed to advanced fibrosis (OR, 1.458; 95% CI, 1.114-1.908). In longitudinal cohort, multivariate logistic regression analysis demonstrated retarded fibrosis regression in patients with history of smoking ≥10 pack-years (OR, 0.288; 95% CI, 0.1-0.825). After PS matching, patients with smoking history had higher prevalence of advanced fibrosis (22.8% vs 18%, P=0.024) than those non-smokers. In post-PS-matching logistic regression, the effect of smoking on advanced fibrosis persisted (OR, 1.415; 95% CI, 1.047-1.912; P=0.024). Cigarette smoking in male CHB patients aggravated liver fibrosis prior to and delayed fibrosis regression under antiviral therapy.

Declining in liver stiffness cannot indicate fibrosis regression in patients with chronic hepatitis B: A 78-week prospective study.

Little reliable data are available about the liver stiffness measurement (LSM) for fibrosis monitoring in chronic hepatitis B (CHB) patients on antiviral therapy. We aimed to assess the accuracy of LSM in fibrosis monitoring during 78-week antiviral therapy in CHB patients. Five hundred fifty-six treatment-naïve CHB patients with qualified LSM and liver biopsy at baseline were analyzed. Patients receiving entecavir-based therapy were prospectively followed to 78weeks for second LSM and liver biopsy. Serologic detection, LSM, and liver biopsy were performed on the same day. Necro-inflammatory activity was also evaluated. Areas under receiver operating characteristics curves of LSM at baseline and week 78 for significant fibrosis (≥F3), advanced fibrosis (≥F4), and liver cirrhosis (≥F5) was 0.84, 0.87, 0.83 and 0.76, 0.85, 0.88, respectively. Patients with the same fibrosis stage but higher histology activity index score tend to have higher LSM at baseline. Liver stiffness decreased rapidly (3.8 [1.6-8.6] kPa) in parallel with baseline histology activity index scores from 11.3 (7.8-16.7) kPa at baseline to 6.4 (5.1-8.8) kPa at week 78. Greater decline of LSM in patients with only inflammation improvement was observed as compared with those without inflammation improvement (5.2 [2.5-9.7] vs 1.8 [0.2-8.1] kPa, P=0.013). Baseline Ishak fibrosis score was the only predictor of 78-week fibrosis improvement (odds ratio, 1.859; P=0.000). In CHB patients receiving 78-week antiviral treatment, LSM could diagnosis different liver fibrosis stages, decrease in absolute LSM value could reflect the remission of liver inflammation, and baseline Ishak fibrosis score was the only predictor for 78-week fibrosis reversion.

Mo1426 - Regression of Liver Fibrosis in Patients with Chronic Hepatitis C Treated with Direct Anti-Viral Drugs

Mo1426 - Regression of Liver Fibrosis in Patients with Chronic Hepatitis C Treated with Direct Anti-Viral Drugs

SAT-478 - Stage-specific benefits of treatment associated fibrosis regression in patients with NASH: a Markov modeling approach

SAT-478 - Stage-specific benefits of treatment associated fibrosis regression in patients with NASH: a Markov modeling approach

Can Transient Elastography Predict Fibrosis Regression in Patients with Chronic Hepatitis B During Long-Term Antiviral Therapy?

Can Transient Elastography Predict Fibrosis Regression in Patients with Chronic Hepatitis B During Long-Term Antiviral Therapy?

Body-mass index is associated with fibrosis regression during long-term nucleoside analogue therapy in chronic hepatitis B.

Factors influencing changes in liver stiffness measurements during long-term nucleoside analogue therapy for chronic hepatitis B (CHB) have not been thoroughly investigated. To identify determinants of on-treatment fibrosis regression in CHB. We performed follow-up liver stiffness and controlled attenuation parameter measurements on nucleoside analogue-treated CHB patients with severe liver fibrosis, according to EASL-ALEH criteria, diagnosed by transient elastography in 2006-2008. Anthropometric measurements and different metabolic parameters were recorded. Among 257 patients with severe liver fibrosis by initial transient elastography, 123 (47.9%) were recruited for reassessment. Median treatment duration was 87.5 (interquartile range 75.3-102.2) months; 97.5% had undetectable HBV DNA. There was a significant reduction in median liver stiffness from 14.6 to 8.3 kPa (P < 0.001). A total of 29.3% had fibrosis regression, with lower rates of 17.9%, 14.9% and 11.5% noted in patients with body-mass index (BMI) ≥25 kg/m2 , metabolic syndrome and diabetes, respectively. Absence of BMI ≥25 kg/m2 , diabetes and metabolic syndrome, when compared with presence of any one of these three factors, was associated with increased fibrosis regression (43.1% vs. 16.9%, P = 0.001). Multivariate analysis found a lower BMI to be the only factor independently associated with fibrosis regression (P = 0.034, odds ratio 0.68, 95% CI 0.48-0.97). No association was noted between controlled attenuation parameter measurements and fibrosis regression (P > 0.05). An increased BMI hindered fibrosis regression in patients with chronic hepatitis B during nucleoside analogue treatment, suggesting that control of metabolic risk factors, in addition to virologic suppression via antiviral therapy, might be needed to halt the fibrogenic process in chronic hepatitis B.

P0812 : Impact of SVRW12 in the development of complications and fibrosis regression in patients treated with triple therapy with Boceprevir and Telaprevir

P0812 IMPACT OF SVRW12 IN THE DEVELOPMENT OF COMPLICATIONS AND FIBROSIS REGRESSION IN PATIENTS TREATED WITH TRIPLE THERAPY WITH BOCEPREVIR AND TELAPREVIR C. Perello, J. Cabezas, E. Llop, S. Menendez, J. De La Revilla, J. Crespo, J.L. Calleja. Gastroenterology, Hepatology Unit, University Hospital Puerta de Hierro, Majadahonda, Gastroenterology and Hepatology, University Hospital Marques de Valdecilla, Santander, Gastroenterology and Hepatology. CYBERehd, University Hospital Puerta de Hierro, Majadahonda, Spain E-mail: csperello@hotmail.com

Tu1045 Effect of α-Fetoprotein Levels After Interferon Therapy on Regression of Liver Fibrosis in Chronic Hepatitis C Patient Who Achieved an SVR

Objectives: Eradicating of chronic hepatitis C virus improves liver fibrosis and reduces incidence of decompensated liver disease and hepatocellular carcinoma in chronic hepatitis C patients. However, almost no reports have examined the factor associated with regression in liver fibrosis following an SVR. The aim of this study was to investigate the relationship between regression in fibrosis, as assessed by sequential biopsies, and clinical factors of patients who were achieved an SVR. Methods: 163 patients (102 men, 61 women; 59.8 ± 9.5 years) who had achieved an SVR after interferon therapy were enrolled this study. To evaluate the change in fibrosis stage over time, the enrolled patients underwent an initial biopsy before therapy, and underwent a sequential biopsy after eradicating of HCV. The clinical factor associated with regression of liver fibrosis after eradicating of HCV in patients who were achieved an SVR was analyzed. Results: The mean time interval between the sequential biopsies was 5.9 ± 1.9 years. Fibrosis stage regressed in 69 patients (39%), remained stable in 89 patients (55%) and progressed in 11 patients (6%). The mean fibrosis stage significantly decreased, from 2.15 ± 1.08 units to 1.80 ± 1.34 units (P < 0.001). Univariate analysis revealed that platelet counts, α-fetoprotein (AFP) levels, and γGTP levels at initial biopsy, ALT levels, platelet counts, AFP levels, and γGTP levels at second biopsy were significantly different between patients with regressed fibrosis and patients without regressed fibrosis. Logistic Regression analysis confirmed that lower AFP levels (Odds ratio [OR], 2.30; P=0.022), lower AST levels (OR, 2.27; P=0.019), and higher platelet levels (OR, 2.12; P=0.046) after eradicating of HCV were significant independent factor associated with regressed fibrosis after SVR. Conclusion: AFP levels after interferon therapy were significantly correlated with regression of liver fibrosis in patients who had achieved an SVR.

Négativation de l’antigène HBs : valeur pronostique pour la réponse au traitement et l’évolution à long terme

Chronic hepatitis B is a major cause of liver disease worldwide, ranking as the first cause of cirrhosis and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) is usually used as a qualitative marker for the diagnosis of hepatitis B virus (HBV) infection. HBsAg clearance is the closest to cure outcome as one can expect to achieve in hepatitis B. Support for this comes from natural history studies demonstrating increased length of survival, lower rates of hepatic decompensation, reduction in the frequency of hepatocellular carcinoma, and regression of liver fibrosis in patients who clear HBsAg. HBsAg seroclearance may occur spontaneously at a yearly incidence of 1-2%, preceded usually by a long period of inactive disease. Interferon treatment enhanced HBsAg seroclearance by approximately three-fold in western studies and sixfold in Asian studies compared with non-treated patients. Pegylated interferon induced a 10-15% yearly rate of HBsAg seroclearance in patients who developed sustained virological response in clinical trials. By contrast, treatment with nucleos (t) ides analogues did not significantly affect the rate of HBsAg seroclearance, especially in patients with hepatitis B e antigen (HBeAg) - negative disease. Recently, serum HBsAg has been shown to be a surrogate marker of covalently closed circular DNA (cccDNA) concentration in the liver. Quantification of serum HBsAg has also been recently shown to be a promising tool for monitoring virologic response in HBeAg-negative patients treated with pegylated interferon.

Decorin-mediated Transforming Growth Factor-β Inhibition Ameliorates Adverse Cardiac Remodeling

Implantation of a left ventricular assist device (LVAD) has been shown to induce regression of fibrosis in patients with congestive heart failure (CHF) and improve myocardial function. The mechanism of reverse remodeling after mechanical circulatory support (MCS), however, has not been fully characterized. In this study we examined the anti-fibrotic effects of decorin, an extracellular matrix (ECM) proteoglycan, on the transforming growth factor-beta (TGF-beta) pathway. Human myocardial tissue samples were obtained from patients undergoing LVAD implantation and again following subsequent transplantation after a sustained period of MCS. The specimens were examined by utilizing different molecular and histologic techniques, including human cardiac fibroblast in vitro studies. We assessed gene expression, mRNA and protein levels. We found a significant decrease in interstitial fibrosis after MCS, with a decrease in collagen mRNA transcription rates, serving as an indirect measurement of collagen synthesis. Both the mRNA and protein levels of decorin were significantly increased after a period of MCS. Decorin mRNA was up-regulated by 44% after MCS (p < 0.01), which paralleled the increase in interstitial decorin deposition (p < 0.001). In addition, p-SMAD2, a molecular marker downstream of the TGF-beta pathway, was found to be inactivated after MCS (p < 0.02). Moreover, cultured human cardiac fibroblasts exposed to TGF-beta demonstrated decreased collagen production when exogenous decorin was added (p < 0.03). The decorin molecule is potentially involved in reverse cardiac remodeling, by directly inhibiting the TGF-beta pathway and its pro-fibrotic effects on the failing human heart.