Serial Liver Stiffness Measurement Research Articles

Successful therapy with tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) does not guarantee amelioration of liver damage assessing by transient elastography. A retrospective - prospective multicenter study

BackgroundPreventing disease progression and viral suppression are the main goals of antiviral therapy in chronic hepatitis B (CHB). Liver stiffness measurement (LSM) by transient elastography is a reliable non-invasive method to assess liver fibrosis in patients with CHB. Our aim was to explore factors that may affect changes in LSMs during long term tenofovir (TDF) monotherapy in a well characterized cohort of patients with compensated CHB.MethodsWe analyzed serial LSMs in 103 adult patients with CHB who were on TDF monotherapy and had at least three LSMs over a period of 90 months.ResultsTwenty-five (24%) patients had advanced fibrosis at baseline. A significant decline in mean LSM between baseline and last visit (8.7 ± 6.2 kPa vs. 6.7 ± 3.3, p = 10− 3) was observed. Twenty-four (23%) patients had progression of liver fibrosis with mean increase in liver stiffness of 2.8 kPa (range: 0.2–10.2 kPa). Multivariate analysis showed that BMI ≥ 25 (OR, 0.014; 95% CI, 0.001–0.157; p = 0.001) and advanced fibrosis (OR, 5.169; 95% CI, 1.240–21.540; p = 0.024) were independently associated with a fibrosis regression of > 30% of liver stiffness compared to baseline value.ConclusionsIn CHB patients TDF monotherapy resulted in liver fibrosis regression, especially in patients with advanced fibrosis. Despite the successful antiviral effect of TDF, 1 out of 4 patients had liver fibrosis progression. Obesity and advanced fibrosis at baseline were independently associated with significant liver fibrosis regression.

FibroScan Predicts Liver Fibrosis Progression in Chronic HBV Infection Patients with No Clear Indication for Antiviral Therapy: A Retrospective Cohort Study.

Chronic hepatitis B virus (HBV) infection patients who do not fulfill the typical treatment indications should be followed up. This study aimed to evaluate the risk of liver fibrosis progression (LFP) and assess the role of noninvasive tests (NITs) of liver fibrosis in monitoring LFP in these patients. A total of 116 patients with active HBV replication, persistently normal or minimally elevated alanine aminotransferase (ALT) levels, and no or mild hepatic necroinflammation or fibrosis based on liver biopsy tests at baseline and followed by a repeated liver biopsy assessment during follow-up. LFP was defined as increase in METAVIR fibrosis score by 1 score or more. Among 116 patients, 40 (34.5%) progressed by at least one fibrosis stage, 16 (13.8%) progressed by at least two fibrosis stages at a median follow-up interval of 27 months (IQR: 12-36). Multivariate analysis confirmed the significant association of an increase in liver stiffness measurement (LSM) value with LFP on histology (p =0.005). The AUROC of LSM value increase rate is significantly higher than that of serum-based NITs of liver fibrosis for the prediction of LFP (p < 0.05). An increase in LSM by 20% is the optimal cutoff for the prediction of LFP. LFP is non-negligible in patients with active HBV replication, persistently normal or minimally elevated ALT, and initially no or minimal hepatic necroinflammation or fibrosis. Serial LSM tests would be more reliable in identifying LFP than serum-based NITs, and easier to obtain than serial liver biopsy tests.

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Change in serial liver stiffness measurement by magnetic resonance elastography and outcomes in NAFLD.

The impact of disease progression in NAFLD on liver outcomes remains poorly understood. We aimed to investigate NAFLD progression using longitudinal liver stiffness measurements (LSM) by serial magnetic resonance elastography (MRE) and the association with liver outcomes. All adult patients with NAFLD who underwent at least two serial MREs for clinical evaluation at Mayo Clinic, Rochester, between 2007 and 2019 were identified from the institutional database. Progression and regression were defined based on LSM change of 19% above or below 19% of initial LSM, respectively, based on Quantitative Imaging Biomarker Alliance consensus. The association between change in LSM and liver-related outcomes occurring after the last MRE was examined using time-to-event analysis. A total of 128 participants underwent serial MREs (53% female, median age 59 years). The median time between paired MREs was 3.4 (range 1-10.7) years. NAFLD progression (LSM = +0.61 kPa/year) was identified in 17 patients (13.3%). NAFLD regression (-0.40 kPa/year) occurred in 35 patients (27.3%). Stable LSM was noted in 76 participants (59.4%). In NAFLD without cirrhosis at baseline ( n = 75), cirrhosis development occurred in 14% of LSM progressors and 2.9% of non-progressors ( p = 0.059) over a median 2.7 years of follow-up from the last MRE. Among those with compensated cirrhosis at baseline MRE ( n = 29), decompensation or death occurred in 100% of LSM progressors and 19% of non-progressors ( p < 0.001) over a median 2.5 years of follow-up after the last MRE. Noninvasive monitoring of LSM by conventional MRE is a promising method of longitudinal NAFLD monitoring and risk estimation of liver-related outcomes in NAFLD.

Longitudinal monitoring of liver fibrosis status by transient elastography in chronic hepatitis B patients during long-term entecavir treatment.

The correlation between improvement in longitudinal liver stiffness and fibrosis regression has not been properly evaluated during long-term antiviral therapy in chronic hepatitis B (CHB) patients. In this study, liver stiffness was serially performed by FibroScan® every 26weeks in a prospective cohort of CHB patients receiving entecavir. Results were compared with liver biopsies at baseline and week 78. A total of 120 treatment-naïve CHB patients were analyzed, in which 54 (45%) patients had fibrosis regression at 78weeks of antiviral therapy. Liver stiffness measurement presented as a rapid-to-slow decline pattern and decreased more significantly in patients with fibrosis regression than those without improvement in fibrosis at week 78 (-46.4 vs. -28.6%, P < 0.001). Multivariate analysis revealed that percentage decline of 52-week and 78-week liver stiffness from baseline was independent predictive factors for fibrosis regression (OR = 46.6, P < 0.001; OR = 17.8, P = 0.002, respectively). Moreover, percentage decline of 78-week liver stiffness was moderately predictive of fibrosis regression (AUROC = 0.694, P < 0.001), while the optimal cutoff values were different between non-cirrhosis and cirrhosis patients (38 vs. 45%). Fibrosis regression could be predicted with a high positive predictive value (96%) in non-cirrhosis patients and could be excluded with a high negative predictive value (94%) in cirrhosis patients. In conclusion, serial liver stiffness measurement could be applied for longitudinal monitoring of fibrosis status in CHB patients. Continuous decline of liver stiffness after effective antiviral treatment could partially reflect fibrosis regression at an optimal cutoff value.

FRI-069 - Risk of hepatocellular carcinoma recurrence is changing according to serial liver stiffness measurement follow-up in patients who underwent radiofrequency ablation for hepatocellular carcinoma

FRI-069 - Risk of hepatocellular carcinoma recurrence is changing according to serial liver stiffness measurement follow-up in patients who underwent radiofrequency ablation for hepatocellular carcinoma

Serial Liver Stiffness Measurements and Monitoring of Liver-Transplanted Patients in a Real-Life Clinical Practice.

BackgroundLiver transplanted patients need close surveillance for early signs of graft disease.ObjectivesTransient elastography can safely be repeated over time, offering serial liver stiffness measurement values. Serial stiffness measurements were compared to single baseline stiffness measurements in predicting the appearance of liver-related clinical events and guiding subsequent clinical decisions.MethodsOne hundred and sixty liver transplanted patients were observed for three years in our real-life practice.ResultsLiver stiffness measurements were stable in 75% of patients, decreased in 4% of patients, and increased in 21% of patients. The pattern of increased stiffness measurements was associated with both HCV-RNA positive status and the presence of an active biliary complication of liver transplantation and was more predictive of a clinically significant event resulting from any disease of the transplanted liver when compared to a stable pattern or to a single liver stiffness measurement. The procedures that were consequently performed were often diagnostic for unexpected situations, both in HCV-RNA positive and HCV-RNA negative patients.ConclusionsThe pattern of longitudinally increased liver stiffness measurements efficiently supported clinical decisions for individualized management strategies. Repeated transient elastography in real-life clinical practice appears to have a practical role in monitoring liver transplanted patients.

Baseline and serial liver stiffness measurement in prediction of portal hypertension progression for patients with compensated cirrhosis

Liver stiffness measurement (LSM) using transient elastography is useful in prediction of significant portal hypertension (PHT). To evaluate the usefulness of baseline and serial LSM in predicting clinical disease progression (CDP) for patients with compensated hepatic cirrhosis. Consecutive patients with compensated cirrhosis and without hepatocellular carcinoma (HCC) were prospectively enrolled. Baseline LSM was assessed at enrolment, then at a 6- to 12-month interval. Esophagogastroduodenoscopy and ultrasonography were performed regularly for surveillance of varices and HCC, while CDP including HCC development and PHT progression was recorded. Two hundred and twenty patients were enrolled. In a median follow-up of 36.9 months, CDP were detected in 49 patients including 30 PHT progression and 19 HCC developments. The cumulative incidence of CDP, PHT progression and HCC development at 3 years was 20.7%, 12.8% and 9.1% respectively. Multivariate analyses showed that baseline LSM was an independent predictor of PHT progression and CDP, however, not of HCC occurrence. The performance of baseline LSM in predicting PHT progression, varices growth/development and hepatic decompensation was 0.744, 0.638 and 0.929. With 17, 12 and 21.1 kPa as the cut-off, the negative predictive value was 92, 94 and 99% respectively. Patients with baseline LSM ≧17 kPa without serial changes had higher risk of PHT progression. For patients with compensated cirrhosis, LSM was an independent predictor of PHT progression and CDP, but not of HCC occurrence. Baseline LSM was useful to exclude PHT progression. Patients with baseline and serial LSM ≧17 kPa had higher risk of PHT progression.

Longitudinal change of liver stiffness by transient elestography in chronic hepatitis B patients treated with nucleos(t)ide analogue

Liver stiffness measurement (LSM) by transient elastography is a non-invasive method to assess liver fibrosis. Decline in LSM value has been reported after antiviral treatment (AVT) using nucleos(t)ide analogues (NUCs) in chronic hepatitis B (CHB) patients, however, factors associated with changes in LSM during AVT remains unclear. A total of 76 CHB patients who received AVT with NUCs and had serial LSM (median duration: 16 months, range: 12 to 35 months) during AVT were analyzed. Complete virological response (CVR) was defined when hepatitis B virus DNA level was undetectable by real-time PCR assay (< 50 copies/mL). LSM value had significantly decreased after AVT with NUCs [median (quartile): 6.5 (4.7-9.2) to 5.3 (3.9-6.7), P<0.001]. The median change of LSM value/year was -0.8 (range: -9.5∼4.9). The annual change of LSM value was associated with baseline total bilirubin levels, HBeAg status and achievement of CVR during follow-up in univariable analysis, and achievement of CVR during follow-up was an only independent factor associated with the annual change of LSM value [beta coefficients (95% confidence interval)=-0.29 (-2.81∼-0.26), P=0.02]. The annual LSM change was significantly different between those who achieved and did not achieve CVR (median change: -1.08/year vs. 0.26/year, P<0.01), and more patients with CVR had decrease in LSM value (89% (47/53) vs. 35% (8/23), P<0.01). A significant decrease in LSM value was observed in CHB patients after AVT with NUCs. Achievement of CVR was significant factor associated with change in LSM value. Achieving CVR might be a key to decrease LSM value during AVT with NUCs.

Optimal Time for Restoring the Reliability of Liver Stiffness Measurement in Patients With Chronic Hepatitis B Experiencing Acute Exacerbation

Liver stiffness measurement (LSM) using transient elastography (FibroScan) is influenced by major changes in aminotransferase. We aimed to determine the optimal time for restoring the reliability of LSM for assessing liver fibrosis in patients with chronic hepatitis B experiencing acute exacerbation. Twenty-one patients with acute exacerbation of chronic hepatitis B [alanine aminotransferase (ALT)>5× upper limit of normal (ULN)] were prospectively recruited. Serial LSM and biochemical tests were performed at the time of admission and after 1, 3, 6, 9, and 12 months. The ULN of ALT was defined as 40 IU/L. The cutoff LSM value for cirrhosis was defined as 10.3 kPa. The median age (9 male) was 49 years. The median ALT and LSM in the baseline were 522 IU/L and 15.1 kPa, respectively. Three months after acute exacerbation, ALT had decreased significantly below 2× ULN and stabilized (median: 522, 43, 21, 19, 18, and 16 IU/L at baseline, 1, 3, 6, 9, and 12 mo, respectively). However, LSM needed 3 more months (6 mo after exacerbation) for stabilization (median: 15.1, 10.0, 7.4, 7.1, 6.3, and 5.8 kPa at baseline, 1, 3, 6, 9, and 12 mo, respectively). LSM should be postponed for at least 3 months after stabilization of ALT below 2× ULN to restore the reliability of LSM in assessing liver fibrosis.

Liver stiffness measurements to assess progression of fibrosis in HCV‐infected patients with inherited bleeding disorders

Hepatitis C is a major co-morbidity in patients with inherited bleeding disorders, leading to progressive liver fibrosis and eventually cirrhosis. Liver stiffness measurement (LSM) is a non-invasive way of assessing the extent of liver fibrosis. This article describes our experience with serial LSM to assess prospectively progression of fibrosis in a cohort of patients with inherited bleeding disorders and chronic hepatitis C. A total of 84 patients underwent serial LSMs, with a median interval of 3.7 years. The change in LSM results over time was assessed. Overall, there was no significant difference between the median results of LSM 1 and LSM 2. The median result of LSM 2 was low (6.6 kPa), after a median duration of infection of 37 years. On the individual level, deterioration of LSM results of more than 2 kPa was seen in 13 patients (16%), 44 patients (52%) remained stable and 27 patients (32%) showed improvement of LSM results of more than 2 kPa. These results are comparable with those of paired liver biopsy studies. LSM appears to be a good alternative for liver biopsies in patients with hepatitis C and inherited bleeding disorders, although the interpretation of the unexpected improvement we found in some of our patients is not straightforward. LSMs will be repeated in our patient population in a few years to be able to better assess the value of serial LSM.