Improvement Of Liver Stiffness Research Articles

Mo1398 - Improvement of Liver Stiffness After Treatment for HCV is Independent of Changes in Aminotransferases

Mo1398 - Improvement of Liver Stiffness After Treatment for HCV is Independent of Changes in Aminotransferases

Changes in liver stiffness and its associated factors during oral antiviral therapy in Chinese patients with chronic hepatitis B.

The present study aimed to assess improvements in liver stiffness determined by transient elastography and associated factors in Chinese patients with chronic hepatitis B (CHB) during long-term treatment with oral antiviral drugs. A total of 334 consecutive Chinese patients with CHB who underwent oral antiviral therapy and received at least two liver stiffness measurements (LSMs) at the First Hospital of Jilin University (Changchun, China) from December 2012 to February 2015 were enrolled in the present study. The cohort included 201 patients without liver cirrhosis (group 0) and 133 patients with liver cirrhosis (group 1). Each patient was subjected to LSM twice with an interval of 6 months. The mean initial liver stiffness values were 14.01±9.37 and 21.59±10.25 kPa for patients in group 0 and group 1, respectively (P<0.001). Multivariate analysis revealed that higher aspartate aminotransferase and lower alanine aminotransferase levels at baseline as well as higher α-fetoprotein levels at follow-up (24 weeks) were associated with a greater decline of liver stiffness in group 0. Furthermore, a higher liver stiffness at baseline and a longer course of antiviral therapy prior to the initial LSM were significantly correlated with a reduction of liver stiffness, whereas higher total bilirubin levels at follow-up contributed to increased liver stiffness in group 1. In conclusion, LSM at the beginning and the end of a 24-week observation period showed that antiviral drug therapy significantly improved in group 1, while a marked decreasing trend was also observed in group 0. In group 0, the reduction of liver stiffness was correlated with liver inflammation, whereas in group 1, it was correlated with the treatment duration prior to the initial LSM and serum levels of hepatitis B virus DNA. Furthermore, a higher liver stiffness at baseline was associated with a greater reduction of liver stiffness in each group.

Ursodeoxycholic acid treatment is associated with improvement of liver stiffness in cystic fibrosis patients

BackgroundUrsodeoxycholic acid (UDCA) might prevent progression of cystic fibrosis liver disease, but objective parameters for its effect are lacking. MethodsWe used liver stiffness measurements to evaluate the effect of Ursodeoxycholic acid. ResultsPaired measurements of liver stiffness were done in 73 patients without UDCA and in 32 patients with UDCA. In the latter group, 6 patients had cirrhosis; in 15 patients, UDCA was started based on Colombo criteria, and in 11 patients for other reasons. In patients without UDCA, liver stiffness increased: 0.19 (−0.03 to 0.59)kPa/year. Liver stiffness also increased in patients with cirrhosis: 4.6 (0.67–12.4)kPa/year. In patients who had UDCA based on Colombo criteria, a decrease of liver stiffness was observed: 0.70 (−1.6 to 0.55)kPa/year (P=0.01). In patients on UDCA for other reasons, liver stiffness increased: 0.23 (−0.20 to 0.51)kPa/year. ConclusionUDCA reduced liver stiffness in patients with well-defined, mild liver disease.

100% Virological Response with 3D Regimen and Significant Short-term Liver Stiffness Improvement in Patients with Recurrent Hepatitis C Following Liver Transplantation

Introduction: Over recent years, interferon-free regimens offer the prospect of treating the high risk patient groups (liver cirrhosis/liver transplant recipients) with high SVR rates across all genotypes. Aim: To present our experience with DAA agents in LT recipients, as well as to compare pre and posttreatment liver stiffness (LS). Methods: Our cohort consisted of 72 patients with recurrent hepatitis C after LT. All patients received associated ribavirin. The 3D regimen was administered 24 weeks. Fibroscan® and Fibromax® were performed in all patients before DAA therapy. At EOT and at time of SVR12 evaluation only Fibroscan was performed. Results: There were analyzed 32 females and 40 males with a mean age of 55.2±7.0 years. Median time since LT was 26.6 months (range 4.6-176.9 months). At baseline 56.4% of patients had severe necroinfl ammation at Fibromax, cirrhosis (F4) was encountered in 34.5% of LT recipients and grade 3 steatosis in 43.6% of transplanted patients. On treatment virologic response was 100%. End of therapy in this cohort of LT patients was 100%. However, at week 2 after beginning of therapy, only 13.9% of LT recipients were HCV RNA undetectable. Undetectable HCV RNA at 4 weeks of therapy was present in 66.7% of patients with recurrent hepatitis C, but at week 8 all patients were HCV RNA undetectable. Viral load positivity at week 4 was not influenced by baseline HCV RNA or stage of fibrosis. Liver stiffness differed statistically significant according to the activity grades (p=0.02) and fibrosis stages (p < 0.0001) at Fibromax. There was a significant improvement in LS between antiviral therapy start and EOT: 11.9±1.8kPa vs 9.5±1.0kPa (p=0.02) in LT recipients. Conclusion: Conclusions: Virological response was 100% at EOT. LS can reliably assess both inflammation and fibrosis in LT recipients and can be used to follow these patients after HCV eradication. LS significantly decreased after EOT and suggests improvement in liver damage. Data regarding LS at SVR12 will be available at the meeting.

Regression of fibrosis and portal hypertension in HCV-associated cirrhosis and sustained virologic response after interferon-free antiviral therapy.

It is still controversial, whether and to what amount cirrhosis and portal hypertension are reversible in patients with hepatitis C virus (HCV)-associated cirrhosis and sustained virologic response (SVR) after interferon-free antiviral therapy. In this study, we prospectively evaluated dynamics of liver and spleen stiffness in HCV-infected patients with advanced liver disease and SVR after interferon-free treatment. A total of 54 patients with HCV-associated cirrhosis and SVR were included. Liver and spleen stiffness was measured at therapy baseline (BL), end of treatment (EOT) and 24weeks after EOT (FU24) by transient liver elastography (L-TE) as well as by acoustic radiation force impulse of the liver (L-ARFI) and spleen (S-ARFI), as well as biochemical, virologic and clinical data. Improvement of liver and spleen stiffness was found in 44 of 50 (88%), 31 of 54 (57%) and 25 of 54 (46%) of patients assessed by L-TE, L-ARFI and S-ARFI between baseline and FU24. Liver stiffness assessed by L-TE improved between BL [median (range), 32.5 (9.1-75) kPa] and EOT [median (range), 21.3 (6.7-73.5) kPa; (P<.0001)], and between BL and FU24 [median (range), 21.2 (5.4-70) kPa; (P<.0001)]. Liver stiffness assessed by L-ARFI improved between BL [median (range), 2.7 (1.2-4.1) m/s] and FU24 [median (range), 2.4 (1.2-3.9) m/s; P=.002), while spleen stiffness remained unchanged. Our data suggest that improvement of liver stiffness may be rather due to reduced necroinflammation and may be due to a less extent to regression of cirrhosis, as dynamics of liver stiffness improvement was more pronounced between BL and EOT than BL and FU24.

Evaluation of advanced fibrosis measured by transient elastography after hepatitis C virus protease inhibitor-based triple therapy.

Few studies have investigated the course of liver stiffness after treatment with protease inhibitors. We evaluated the impact of this therapy on liver fibrosis measured by transient elastography. This multicenter observational, cohort, prospective study included 90 patients with hepatitis C genotype 1 treated with telaprevir or boceprevir who had advanced fibrosis evidenced by liver stiffness (≥9.5 kPa). Liver stiffness was measured at baseline and 24 weeks after treatment ended, and was compared with virological responses at week 12. Liver stiffness decreased in 89% of patients who achieved sustained virological response. The median intrapatient liver stiffness value at the end of follow-up decreased by 5.1 kPa (35%) from baseline compared with 0.1 kPa (0.5%) in those who did not achieve a sustained virological response (P<0.001). The liver stiffness level fell below 9.5 kPa in 58% of patients with sustained virological response, and 71% of those with sustained virological response and cirrhosis evidenced by liver stiffness at baseline achieved regression below 12.5 kPa by the end of follow-up. Sustained virological response was the only variable associated with improved liver stiffness in multivariate analysis (odds ratio: 17.3; 95% confidence interval: 4.4-67.6; P<0.001). In patients with advanced fibrosis measured by transient elastography at the beginning of protease inhibitor-based therapy with sustained virological response, liver stiffness was significantly reduced 24 weeks after treatment. This suggests the possibility of liver cirrhosis evidenced by liver stiffness regression after sustained virological response in a significant proportion of patients.

SAT-473 - Liver Stiffness Improvement in Subjects with Advanced Chronic Hepatitis C Treated with Direct Antiviral Agents

SAT-473 - Liver Stiffness Improvement in Subjects with Advanced Chronic Hepatitis C Treated with Direct Antiviral Agents

FRI-473 - Lack of Improvement of Liver Stiffness during Sofosbuvir-Treatment in Decompensated Cirrhotic Patients Listed for Liver Transplant Seems to be Associated with more Severe Histological Damage in the Native Liver

FRI-473 - Lack of Improvement of Liver Stiffness during Sofosbuvir-Treatment in Decompensated Cirrhotic Patients Listed for Liver Transplant Seems to be Associated with more Severe Histological Damage in the Native Liver

Regression of liver stiffness after sustained hepatitis C virus (HCV) virological responses among HIV/HCV-coinfected patients.

We assessed the impact of a sustained virological response (SVR) on liver stiffness among HIV/hepatitis C virus (HCV)-coinfected patients enrolled in the ANRS CO13 HEPAVIH cohort. We studied HIV/HCV-coinfected patients who received at least one dose of any anti-HCV treatment and who had documented SVR status, a pretreatment FibroScan value of at least 7.1 kPa, and at least one posttreatment FibroScan value. The time required to achieve at least a 30% decrease in liver stiffness was analyzed by constructing Kaplan-Meier curves and using Cox proportional hazards models. Among 98 patients treated for HCV infection with either pegylated interferon along with ribavirin (n = 89) or protease inhibitor-based triple therapy (n = 9), 53 patients (54%) had an SVR. Median follow-up was 44.6 (interquartile range: 28.8-58.9) months. The probability of achieving a 30% decrease in FibroScan values was 51% [95% confidence interval (CI): 39-66] in patients with an SVR and 21% in nonresponders (95% CI: 11-36) at 1 year, and 74% (61-86) and 28% (17-44) at 2 years, respectively. In the subgroup of 35 cirrhotic patients (pretreatment liver stiffness ≥12.5 kPa), 14 of 18 patients with an SVR and three of 17 nonresponders had a fibrosis score below 12.5 kPa at the last follow-up examination. Multivariable analysis showed that SVR was independently associated with a ≥30% reduction in liver stiffness, both in the overall study group (hazard ratio: 5.77; 95% CI: 2.00-16.62; P = 0.0012) and in cirrhotic patients (hazard ratio: 8.21; 95% CI: 2.15-31.34; P = 0.0021). Robustness analyses using FIB4 values showed similar results. SVR is significantly associated with improvement in liver stiffness in HIV/HCV-coinfected patients, including those with cirrhosis.

Interferon-free regimens for chronic hepatitis C overcome the effects of portal hypertension on virological responses.

Portal hypertension is the strongest predictor of virological response to pegylated interferon (IFN)/ribavirin in patients with chronic hepatitis C (CHC)-related cirrhosis. To investigate the effects of portal pressure assessed by hepatic venous pressure gradient (HVPG) measurement on virological responses in patients treated with IFN-free regimens outside of clinical trials. Fifty-six patients with CHC and cirrhosis who underwent HVPG measurement before starting an IFN-free therapy were retrospectively studied. Patients were treated with sofosbuvir in combination with daclatasvir (n = 32), ribavirin (n = 12) or simeprevir (n = 11), or the combination of simeprevir/daclatasvir (n = 1), for 12-24 weeks. Hepatic venous pressure gradient values ≥10 mmHg and ≥16 mmHg were observed in 41 (73%) and 31 (55%) patients respectively. The distributions of treatment regimens and durations were comparable between patients with or without portal hypertension. Patients with portal hypertension had lower platelet counts and albumin levels, while bilirubin levels, INR, MELD and Child-Pugh scores were higher than in patients without portal hypertension. Importantly, rates of on-treatment virological response and viral kinetics, as well as the rates of sustained virological response 12 weeks after the end of therapy [96% (54/56)] were not affected by portal hypertension. Anti-viral therapy improved liver stiffness, platelet count, serum albumin and bilirubin levels, as well as prothrombin time. This is the first study to demonstrate that IFN-free regimens overcome the negative effect of portal hypertension on virological responses and viral kinetics. Improvements in liver stiffness and platelet count might reflect an anti-portal hypertensive effect of IFN-free treatments.

Sa1114 Early Improvement of Liver Stiffness Measured by ARFI During Protease Inhibitor Based Triple Therapy for Chronic Hepatitis C

Sa1114 Early Improvement of Liver Stiffness Measured by ARFI During Protease Inhibitor Based Triple Therapy for Chronic Hepatitis C

Sa1318 Improvement of Liver Stiffness Measured by ARFI During Telaprevir-Based Triple Therapy for Chronic Hepatitis C

Sa1318 Improvement of Liver Stiffness Measured by ARFI During Telaprevir-Based Triple Therapy for Chronic Hepatitis C

Assessment of hepatic fibrosis regression by transient elastography in patients with chronic hepatitis B treated with oral antiviral agents.

Transient elastography (TE) has been used as a non-invasive method for liver stiffness measurement (LSM) in patients with chronic liver disease. This study was performed to assess the change of LSM by TE and to assess its clinical usefulness during long-term oral antiviral therapy in patients with chronic hepatitis B (CHB). We retrospectively reviewed 83 CHB patients. The mean interval between two LSM was 411.5 ± 149.5 days. Initial and follow-up LSM was 16.15 ± 12.41 kPa and 11.26 ± 7.36 kPa, respectively (P < 0.001). The degree of regression of liver stiffness was -2.03 ± 0.36% per month. The fibrosis stage classified by LSM value improved in 37 (44.6%) patients during oral antiviral therapy. Of the 30 (36.1%) patients with LSM ≥ 14.1 kPa (cirrhosis) at 1st LSM, 12 (40%) proved to no longer have cirrhosis (≥ 1 decrease in fibrosis stage) at 2nd LSM. LSM significantly decreased in both baseline high (> upper limit of normal [ULN] × 2) and low (≤ ULN × 2) alanine aminotransferase groups during antiviral therapy (P < 0.001; P = 0.001, respectively). Long-term oral antiviral therapy resulted in the improvement of liver stiffness in a substantial portion of patients with CHB. TE may be used a useful clinical tool to assess disease progression in CHB patients.

Sa1045 Factors That Affect the Improvement of Liver Stiffness in Patients With Chronic Hepatitis B

Background and aims Long term suppression of Hepatitis B virus (HBV) replication with nucleos(t)ide analogues (NA) is associated with biochemical improvement and viral suppression. However the factors affecting this response remain unclear. Method A cohort of 107 HBV infected patients undergoing treatment with NA at Royal North Shore Hospital (20002011) was studied. Demographic, viral, biochemical and histological data were collected prospectively during treatment and subjected to univariate and multivariate analysis. Result Seventy-eight percent of the total cohort were Asian, 70% were males and 47% had advanced fibrosis (F≥3) at baseline. Mean HBV DNA PCR was 5.62 log IU/mL and mean ALT was 129 IU/L at baseline. Mean duration of treatment was 66 months. There were 42 eAg positive and 65 eAg negative patients. In the combined cohort, 64% had undetectable DNA at week 48. Negative eAg at baseline, lower DNA at baseline, no interferon use (before or during the therapy), normalised ALT at week 48 and older age were associated with undetectable DNA at week 48. (p<0.05) However, logistic regression analysis identified baseline eAg negativity as the only significant predictor of undetectable DNA at week 48. (p=0.02) Sixtytwo percent had normalised ALT at week 48, and associated factors were undetectable DNA at week 48, shorter time to undetectable DNA and higher ALT at baseline. (p<0.05) Logistic regression identified shorter time to lowest DNA as the only predictor of normalised ALT at week 48. (p=0.02) In patients with positive eAg at baseline, 55% and 7% achieved eAg seroconversion (or loss) and sAg seroconversion (or loss) respectively. Older age and advanced fibrosis were significantly associated with eAg seroconversion and/or eAg loss. (p≤0.05) No patients developed progressive liver failure while on treatment in the absence of hepatocellular cancer. Conclusion NA therapy in the clinic setting is associated with effective long term viral suppression with improved eAg seroconversion in older patients and those with advanced fibrosis. Higher rates of sAg seroconversion or loss were observed in patients with positive eAg at baseline.

Liver stiffness diminishes with antiviral response in chronic hepatitis C

Transient elastography measures liver stiffness, which correlates with the hepatic fibrosis stage and has excellent accuracy for the diagnosis of cirrhosis in patients with chronic hepatitis C. To assess prospectively the kinetics of liver stiffness in treated patients with chronic hepatitis C and compare them with the viral kinetics on treatment and with the final outcome of therapy. 91 patients with chronic hepatitis C with significant fibrosis (>7.0kPa) at baseline were included. They received therapy with pegylated interferon-α and ribavirin. The kinetics of liver stiffness were characterized during therapy and thereafter by means of Fibroscan, and compared with the virological responses at weeks 4, 12, 24, end of treatment and 12 and 24weeks after. A significant liver stiffness decrease was observed during therapy, which continued after treatment only in patients who achieved a sustained virological response. In this group, the median intra-patient decrease relative to baseline at the end of follow-up was -3.4kPa, vs-1.8kPa in the patients who did not achieve an SVR. Similar dynamics were observed in cirrhotic and non-cirrhotic patients. In multivariate analysis, only the SVR was associated with long-term improvement of liver stiffness (odds ratio: 3.10; 95% confidence interval: 1.20-8.02, P=0.019). In patients with advanced fibrosis at the start of therapy, liver stiffness is significantly reduced during treatment, but improvement continues off treatment only in patients who achieve a sustained virological response. Liver stiffness assessment earlier than 6months after the end of therapy does not appear to be clinically meaningful.