Liver stiffness measurement using transient elastography and hepatocellular carcinoma

Liver fibrosis has been gaining noticeable attention because it may lead to end-stage liver cirrhosis and ultimately to hepatocellular carcinoma. Thus, a precise estimation of the degree of liver fibrosis is crucial for predicting prognosis and deciding management of patients with chronic liver diseases. Many non-invasive approaches for the evaluation of liver fibrosis have been developed. Among these procedures, transient elastography has recently drawn great attention. Transient elastography has been reported to be well correlated with the degree of liver fibrosis by many investigators and various institutions. Since the degree of liver fibrosis is considered as a strong predictor of risk for hepatocellular carcinoma development, several trials have been performed to verify the usefulness of measurement of liver stiffness to predict the emergence of hepatocellular carcinoma. From these studies, transient elastography seems to be a promising procedure to predict the risk of hepatocellular carcinoma; however, further cohorts with long-term monitoring of liver stiffness are needed to confirm the usefulness of this method.     

Feasibility of liver transient elastography with FibroScan® using a new probe for obese patients

Background & Aims: Liver stiffness measurement (LSM) failure when using transient elastography occurs in 2–10% of patients, and is generally related to obesity. The aim of this prospective study was to assess the feasibility of LSM when using a new XL probe on patients with a body mass index (BMI)≥30 kg/m². Methods: For each patient, LSM was performed using both M probe (currently available and dedicated to patients with standard morphology) and XL probe (dedicated to overweighed patients). A blood sample was taken to assess usual biological variables and simple readily available fibrosis blood tests. Results: Ninety‐nine patients were included (27 men, mean age 52 years, mean BMI 40.5 kg/m²). LSM was successful (10 valid measurements) in 45% of the cases with the M probe, vs 76% of the cases with the XL probe (P<0.001). Fifty‐nine percent of those who could not be measured (<10 valid measurements) using the M probe could successfully be measured using the XL probe. In the 44 patients successfully measured with both probes, LSM was correlated with the platelet count, prothrombin time, γ‐glutamyltransferase, aspartate aminotransferase, fasting glucose, AST platelet ratio index, Forns score and FIB‐4. Conclusion: The new XL probe allows providing a higher rate of LSM than the M probe in patients with an increased BMI and shows promising results for the evaluation of liver fibrosis.     

Interobserver discrepancy in liver fibrosis using transient elastography

Summary. Transient elastography is a useful method to assess liver fibrosis, but uncertainties still exist regarding reliability and reproducibility of the technique. We aimed to improve knowledge on interobserver variability with the procedure and tried to find factors associated with such variability. This was a cross‐sectional study to compare the results of transient elastography performed by two different operators, one test made just after the other. We assessed both results with correlation tests and with repeated parametric or nonparametric tests, as needed. We also carried out a multivariate analysis to find factors associated with discrepancy in the results obtained by the two operators. We included a total of 333 pairs of transient elastography tests, belonging to 274 different patients. A total of 325 pairs of tests (97.6%) were valid. Results of the first and the second tests were, respectively, median (and interquartile range) of direct measurement 6.2 (4.6–10.6) and 6.0 (4.4–10.1) kPa (P = 0.012), and mean ± standard deviation of log₁₀ of direct measurement 0.892 ± 0.316 and 0.871 ± 0.324 (P = 0.001). In 87 pairs of tests (26.7%), a discrepancy of at least 2 kPa between both results was found, and in 15 pairs of tests (4.6%), a discrepancy of at least 10 kPa was found. Discordance of at least one stage between both measurements was noted in 74 pairs of tests (22.8%). An association was found between higher stiffness and discrepancy between both operators (P < 0.001). Although transient elastography is a very convenient test to assess liver fibrosis in clinical practice, interobserver discrepancy in results is common and represents a significant problem with the technique. Discrepant results are more common in patients with higher values of stiffness.     

Clinical application of magnetic resonance elastography in chronic liver disease

Recent evidence highlighted that the accurate assessment of liver fibrosis is important for evaluating the progression of chronic liver disease. During the past decade, many non‐invasive methods have been developed to reduce the need for core‐needle biopsy in fibrosis staging and to overcome its limitations, such as invasiveness, high cost, low reproducibility, and poor patient consent. The diagnostic performance of magnetic resonance elastography (MRE) is promising for use in clinical practice to evaluate not only liver fibrosis, but also survival and major clinical end‐points such as liver decompensation, portal hypertension, development of hepatocellular carcinoma, and surgical outcomes. Together with other clinical markers, MRE can be used to better categorize patients with advanced fibrosis and cirrhosis, and assign them to different classes of risk for significant clinical outcomes. This review discusses clinical applications of MRE in the management strategy of patients with chronic liver disease.     

Liver stiffness measured by transient elastography is a predictor of hepatocellular carcinoma development in viral hepatitis

Aim: To investigate the value of liver stiffness in diagnosing hepatocellular carcinoma (HCC) among patients with viral hepatitis, and to prospectively investigate relationships between liver stiffness and HCC development. Methods: Liver stiffness was measured by transient elastography for 157 patients with viral hepatitis, along with various other parameters potentially associated with HCC. HCC was initially present in 41 patients and absent in 116 patients, of whom 106 patients were followed prospectively for HCC development. Diagnostic performances of liver stiffness and other clinical parameters in predicting presence of HCC were evaluated using receiver operating characteristic (ROC) curves and area under the ROC curve (AUROC). Results: Liver stiffness was significantly higher in patients with HCC (24.9 ± 19.5 kPa) than in patients without HCC (10.9 ± 8.4 kPa; P < 0.0001). Age (P < 0.0001), platelet cell count (P = 0.0001), prothrombin activity (P = 0.0009), alpha fetoprotein (P = 0.0091), and des‐gamma‐carboxy prothrombin (DCP) (P = 0.0099) also differed significantly between patients with and without HCC. The largest AUROC was for liver stiffness. Differences between liver stiffness and age, platelet cell count, prothrombin activity, and DCP were not significant, but the AUROC of liver stiffness was superior to that of alpha fetoprotein (P = 0.03850). Using a cut‐off liver stiffness of 12.5 kPa, development of HCC was identified in 10 of the 106 patients followed. Multivariate analysis identified liver stiffness ≥12.5 kPa, age ≥60 years, and serum total bilirubin ≥1.0 mg/dL as significantly correlated with development of HCC. Conclusions: Liver stiffness as measured by transient elastography is a predictor of HCC development in viral hepatitis.     

Previously unrecognized advanced liver disease unveiled by transient elastography in patients with Haemophilia and chronic hepatitis C

Summary. Before the introduction of viral inactivation procedures and viral screening of plasma‐products, haemophiliacs were at high risk of infection with HCV. Those who acquired HCV infection in the 1980s, and are still alive today, may have developed significant liver fibrosis or cirrhosis. However, liver biopsy has not routinely been utilized in the evaluation of haemophiliacs with HCV in Denmark. The aim of this study was to investigate the prevalence of significant fibrosis/cirrhosis among haemophiliacs as evaluated by transient elastography (TE). Cross‐sectional investigation of adult patients with haemophilia A or B. TE with liver stiffness measurements (LSM) ≥8 kPa were repeated after 4–6 weeks. Significant fibrosis and cirrhosis was defined as measurements ≥8 kPa or ≥12 kPa respectively. Among 307 patients with haemophilia A or B registered at the two Haemophilia centres, 141(46%) participate in this study. Forty (28.4%) had chronic hepatitis C, 33 (23.4%) past hepatitis C and 68 (48.2%) had never been infected, at screening LSM ≥8 kPa were found in 45.7%, 24.7% and 4.6% respectively. Among patients with chronic hepatitis C significant fibrosis was confirmed in 17.1% and cirrhosis in 2.9% by repeated LSM ≥8 and ≥12 kPa respectively. The median TE‐value in never HCV‐infected haemophiliacs was comparable with what has been found in healthy non‐haemophiliacs. In Danish haemophiliacs where liver biopsy has not routinely been used for assessing severity of liver fibrosis, LSM identified advanced liver disease in one‐fifth of cases that had not been recognized during clinical follow‐up.     

Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography

AIM: To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC).METHODS: Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled. Liver stiffness was obtained noninvasively by using Fibroscan (Echosens, Paris, France). The date of blood transfusion was obtained by interview. Duration of infection was derived from the interval between the date of blood transfusion and the date of liver stiffness measurement (LSM). Patients were stratified into four groups based on the duration of infection (17-29 years; 30-39 years; 40-49 years; and 50-70 years). The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness.RESULTS: A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis (225 with HCC and 291 without). The patients were 244 men and 272 women, with a mean age of 67.8 ± 9.5 years. The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in non-HCC group). The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC (r = 0.132, P = 0.024) but not in patients with HCC (r = -0.103, P = 0.123). Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001). The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001), duration of infection (P = 0.0015), and heavy alcohol consumption (P = 0.043)CONCLUSION: Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.     

Assessment of liver stiffness in patients after living donor liver transplantation by transient elastography

Objective. Recurrence of hepatitis and progression of fibrosis are major problems in liver transplantation (LT) for patients with hepatitis C. Liver stiffness measurement (LSM) by transient elastography correlates well with histologic liver fibrosis stages in chronic liver diseases. The aim of this study was to evaluate the usefulness of transient elastography for the assessment of fibrosis in patients after living donor LT. Material and methods. Seventy-nine patients who visited our institution, and in whom LSM was successfully evaluated, were enrolled in the study. The patients were divided into three groups according to positivity for hepatitis C antibody and hepatitis B surface antigen as the hepatitis C virus (HCV) group (n=37), the hepatitis B virus (HBV) group (n=10), and the NBNC (negative for both hepatitis B and C) group (n=32). The correlation between LSM and histologic fibrosis stage was assessed in 36 patients. LSM was also compared with regard to the effect of interferon therapy in HCV patients. Results. The median value for liver stiffness was 6.8 kPa and the median time from LT was 3.1 years. In patients who underwent liver biopsy, stiffness was significantly correlated with the stages of fibrosis (p<0.001, rho = 0.848). In patients who received interferon therapy after LT, the LSM decreased over time in those with a sustained virological response, whereas LSM increased in patients without a response. Conclusion. Transient elastography may be an appropriate non-invasive procedure to sequentially assess the progression of liver fibrosis in patients after LT.     

The effect of caffeine and alcohol consumption on liver fibrosis – a study of 1045 Asian hepatitis B patients using transient elastography

Background: Role of caffeine consumption in chronic hepatitis B virus (HBV)‐infected patients and the interaction with alcohol consumption is unclear. Aim: This study aimed to investigate the relationship between caffeine and alcohol consumption and liver stiffness in chronic HBV‐infected patients. Methods: Chronic HBV‐infected patients who underwent transient elastography examination in 2006–2008 were studied. Advanced fibrosis was defined as liver stiffness >9 kPa for patients with normal alanine aminotransferase (ALT) or >12 kPa for those with elevated ALT according to previous validation study. Caffeine and alcohol consumption was recorded using a standardized questionnaire. Excessive alcohol intake was defined as 30 g/day in men and 20 g/day in women. Results: The liver stiffness of 1045 patients who completed the questionnaire was 8.3 ± 6.2 kPa. Two hundred and sixteen (20.7%) patients had advanced fibrosis. Ninety‐five (19.0%) patients who drank ≥1 cup of coffee had advanced fibrosis, compared with 121 (22.2%) patients who drank <1 cup (P=0.21). The amount of caffeine intake had positive correlation with the amount of alcohol intake (r_s=0.167, P<0.001). Although 231 (22.1%) patients reported alcohol consumption, only 11 (1%) had excessive alcohol intake. The prevalence of advanced fibrosis among patients with mild to moderate alcohol intake (26, 18.8%) was comparable to that among non‐drinkers (190, 21.0%) (P=0.57). Conclusion: Caffeine intake does not affect liver stiffness in chronic HBV‐infected patients. Patients who drink coffee regularly tend to drink alcohol. Most chronic HBV‐infected patients do not have excessive alcohol consumption. The prevalence of advanced fibrosis among mild to moderate alcohol drinkers was low in this population.     

Fibrosis staging in chronic hepatitis C: analysis of discordance between transient elastography and liver biopsy

Summary. In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir ≥ F2) is variable. Constitutional and liver disease‐related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutive hepatitis C virus (HCV)‐RNA positive patients had biochemical tests, TE and a biopsy performed on the same day. The Dale model was used to identify the variables associated with discordance between biopsy and elastography results. In 97 patients (34.2%), TE and histological assessment were discordant. Seventy‐six of 286 (26.6%) had stage ≥F2 and TE < 7.1 kPa (false negative); 21 of 286 (7.3%) had stage <F2 and TE ≥ 7.1 kPa (false positive). No patient with discordant results had cirrhosis. By Dale model, aspartate aminotransferase (AST) was found to be the unique variable significantly related (P = 0.046) with discordance between biopsy and TE. Discordance rate was 43.4% (82 patients) with AST < 1.5 × UNL vs 25.8% (25 patients) with AST ≥ 1.5 × UNL (P = 0.004). False negative rate was 43.4 (82 patients) with AST < 1.5 × UNL vs 17.1% (13 patients) with AST ≥ 1.5 × UNL (P < 0.001). Areas under the receiver operating characteristic (AUROC) for F ≥ 2, according to AST < 1.5 × UNL vs ≥ 1.5 × UNL were 0.738 (95% CI: 0.683–0.812) and 0.854(95% CI: 0.754–0.907). Transient elastography is not adequate on its own to rule out or to rule in significant fibrosis, as it is influenced by major variations in biochemical activity of liver disease. Liver stiffness, at low levels of AST, can underestimate fibrosis.