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.     

Outreach screening of drug users for cirrhosis with transient elastography

Aims Transient elastography (TE) is a non‐invasive sensitive tool for diagnosing cirrhosis in hospital‐based cohorts. This study aimed to evaluate TE as a screening tool for cirrhosis among drug users. Design Cross‐sectional study. Setting All treatment centres in the county of Funen, Denmark. Participants Drug users attending treatment centres during the presence of the study team. Measurements Liver stiffness measurements (LSM) by transient elastography using the Fibroscan device; blood tests for viral hepatitis, HIV infection and hyaluronic acid (HA) levels; and routine liver tests. Individuals with LSM ≥ 8 kPa were referred to the hospital for treatment evaluation. Individuals with LSM ≥ 12 kPa were recommended a liver biopsy. Findings Among 175 drug users negative for hepatitis C, 13% had LSM = 8–11.9 kPa and 4% had LSM ≥ 12 kPa; elevated LSM was associated with a body mass index (BMI) > 30. Among 128 drug users with chronic hepatitis C, 19.5% had LSM = 8–11.9 kPa and 21.1% had LSM ≥ 12 kPa (P < 0.001). Repeat LSM at liver biopsy performed a median 3 months after screening showed a significant decrease (<12 kPa) among 30% (six of 20), and this was independent of alcohol consumption, BMI, age and gender. In 29 patients where liver biopsy was performed a LSM ≥ 16 kPa predicted cirrhosis with 88.9% sensitivity and 90% specificity. Conclusions Transient elastography is a feasible screening tool for cirrhosis among drug users. Transient elastography identifies severe liver fibrosis in a significant proportion of drug users with hepatitis C infections but management should not be based on a single elevated liver stiffness measurement.     

Food intake increases liver stiffness in patients with chronic or resolved hepatitis C virus infection

Background and aims: Transient elastography is increasingly being used in patients with chronic liver disease. It has proven particularly useful to identify patients with advanced fibrosis or cirrhosis, while classification of no or little fibrosis appears to be difficult. In general, stiffness values <6 kPa are considered normal, whereas patients with higher levels are candidates for a disease‐specific treatment or further diagnostic evaluation. Parameters influencing liver stiffness may include food intake that increases liver blood flow. Methods: In a pilot study, transient elastography was performed in eight patients with chronic hepatitis C at fasting and serially for 180 min after intake of a standardized breakfast. Confirmatory, 56 patients and 19 controls underwent liver stiffness determination at fasting, directly after meal intake and 1 h after breakfast. Results: Liver stiffness significantly increased immediately after food intake for up to 60 min (P=0.01) before normalizing after 180 min. An intraindividual analysis showed a significant increase in 22 out of 43 patients with an initial liver stiffness ≤10 kPa. An increase of at least 1 kPa after food intake was found in 24 out of 43 (56%) patients with initial stiffness ≤10 kPa. Notably, nine out of 23 (39%) patients with normal initial liver stiffness (<6 kPa) had a value of >6 kPa after food intake, potentially leading to unnecessary treatment or diagnostic procedures. Conclusion: Food intake increases liver stiffness in patients with hepatitis C virus infection and healthy controls. To standardize liver stiffness evaluation, we suggest measurement in the fasting condition.     

Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis

Transient elastography (FibroScan [FS]) is a novel non-invasive tool to assess liver fibrosis/cirrhosis. However, it remains to be determined if other liver diseases such as extrahepatic cholestasis interfere with fibrosis assessment because liver stiffness is indirectly measured by the propagation velocity of an ultrasound wave within the liver. In this study, we measured liver stiffness immediately before endoscopic retrograde cholangiopancreatography and 3 to 12 days after successful biliary drainage in patients with extrahepatic cholestasis mostly due to neoplastic invasion of the biliary tree. Initially elevated liver stiffness decreased in 13 of 15 patients after intervention, in 10 of them markedly. In three patients, liver stiffness was elevated to a degree that suggested advanced liver cirrhosis (mean, 15.2 kPa). Successful drainage led to a drop of bilirubin by 2.8 to 9.8 mg/dL whereas liver stiffness almost normalized (mean, 7.1 kPa). In all patients with successful biliary drainage, the decrease of liver stiffness highly correlated with decreasing bilirubin (Spearman's rho = 0.67, P < 0.05) with a mean decrease of liver stiffness of 1.2 +/- 0.56 kPa per 1 g/dL bilirubin. Two patients, in whom liver stiffness did not decrease despite successful biliary drainage, had advanced liver cirrhosis and multiple liver metastases, respectively. The relationship between extrahepatic cholestasis and liver stiffness was reproduced in an animal model of bile duct ligation in landrace pigs where liver stiffness increased from 4.6 kPa to 8.8 kPa during 120 minutes of bile duct ligation and decreased to 6.1 kPa within 30 minutes after decompression. Conclusion: Extrahepatic cholestasis increases liver stiffness irrespective of fibrosis. Once extrahepatic cholestasis is excluded (e.g., by liver imaging and laboratory parameters) transient elastography is a valuable tool to assess liver fibrosis in chronic liver diseases.     

Liver stiffness values in apparently healthy subjects: influence of gender and metabolic syndrome

BACKGROUND/AIMS: Liver stiffness measurement by transient elastography is a very promising non-invasive method for the diagnosis of fibrosis in chronic liver diseases. However, studies on normal values of liver stiffness in healthy subjects are still lacking. The aim of the present study was to prospectively assess liver stiffness values in the general population and to determine potential factors, which may influence these values. METHODS: Liver stiffness measurements were performed in 429 consecutive apparently healthy subjects, without overt cause of liver disease and normal liver enzymes, undergoing a free medical check-up. RESULTS: Mean liver stiffness value was 5.49+/-1.59 kPa. Transient elastography failure was observed in 4.6% of the cases. The failure rate increased with BMI, reaching 88% for values above 40 kg/m2. Liver stiffness values were higher in men than in women (5.81+/-1.54 vs 5.23+/-1.59 kPa, p=0.0002) and in subjects with BMI>30 kg/m2 (6.26+/-1.89 vs 5.37+/-1.51 kPa, p=0.0003). Metabolic syndrome was diagnosed in 59 (13.7%) subjects. After adjustment for gender and BMI, liver stiffness values were higher in subjects with metabolic syndrome than in those without (6.51+/-1.64 vs 5.33+/-1.51 kPa, p<0.0001). CONCLUSIONS: Liver stiffness values in the general population are influenced independently by gender, BMI and metabolic syndrome.     

Performance and utility of transient elastography and noninvasive markers of liver fibrosis in primary biliary cirrhosis

Background

The performance of transient elastography in primary biliary cirrhosis has yet to be fully established.

Aim

To assess: (1) the performance of transient elastography in identifying significant fibrosis in primary biliary cirrhosis by comparison with surrogate markers (AST platelet ratio index (APRI), FIB-4, Fibroindex, Forns, aspartate aminotransferase/alanine aminotransferase ratio); (2) the correlation between liver stiffness and Mayo score prognostic index.

Methods

One hundred and twenty patients with primary biliary cirrhosis were consecutively enrolled. The performance of each marker and of liver stiffness was compared with histological staging and METAVIR at time of liver biopsy.

Results

The area under receiver operating characteristic (ROC) of liver stiffness were 0.87, 0.88, 0.99 for histological stage ≥II, ≥III and =IV and 0.89, 0.92, 0.99 for METAVIR ≥2, ≥3 and =4. Transient elastography alone proved better able in identifying any grade of fibrosis or cirrhosis than noninvasive markers. Combining each surrogate marker with transient elastography did not improve the area under ROC. Transient elastography correlated positively with the Mayo score (P < 0.001). Logistic regression analysis showed that transient elastography was associated with an advanced fibrosis (P < 0.001).

Conclusions

Transient elastography proved a simple, reliable and useful method for assessing liver fibrosis in primary biliary cirrhosis, whereas noninvasive surrogate markers proved unsatisfactory in predicting significant fibrosis.     

Comparison of transient elastography,serum markers and clinical signs for the diagnosis of compensated cirrhosis

Background and Aims: Non‐invasive diagnosis of compensated cirrhosis is important. We therefore compared liver stiffness by transient elastography, APRI score, AST/ALT ratio, hyaluronic acid and clinical signs to determine which modality performed best at identifying compensated cirrhosis. Methods: Patients undergoing evaluation at a single center were recruited and had clinical, serological, endoscopy, radiological imaging, liver stiffness measurement and liver biopsy. Patients were stratified into cirrhotic and non‐cirrhotic. Results: In 404 patients (124 cirrhosis), transient elastography was diagnostically superior to the other modalities yielding an AUC 0.9 ± 0.04 compared with hyaluronic acid (AUC 0.81 ± 0.04: P < 0.05), clinical signs (AUC 0.74 ± 0.04: P < 0.05), APRI score (AUC 0.71 ± 0.03: P < 0.05) and AST/ALT ratio (AUC 0.66 ± 0.03: P < 0.05). The optimum cut‐off for transient elastography was 12 kPa giving a sensitivity of 89% and specificity of 87% for cirrhosis. In 238 hepatitis C patients (87 cirrhosis), transient elastography yielded an AUC 0.899 ± 0.02 for cirrhosis and in 166 non‐HCV patients (37 cirrhosis) the results were similar with an AUC 0.928 ± 0.03; with transient elastography being superior to HA, APRI, AST/ALT and clinical signs for all etiologies of cirrhosis (P < 0.05 for all). Importantly, transient elastography was statistically superior at identifying cirrhosis in 38 biopsy proven Childs Pugh A cirrhotics with no clinical, biochemical or radiological features of cirrhosis or portal hypertension (AUC 0.87 ± 0.04). Conclusion: Transient elastography accurately identified compensated cirrhosis; a liver stiffness of >12 kPa represents an important clinical measurement for the diagnosis of cirrhosis.     

Transient elastography and other noninvasive tests to assess hepatic fibrosis in patients with viral hepatitis

Summary. The limitations of liver biopsy (invasive procedure, sampling errors, inter‐observer variability and nondynamic fibrosis evaluation) have stimulated the search for noninvasive approaches for the assessment of liver fibrosis in patients with viral hepatitis. A variety of methods including the measurement of liver stiffness, using transient elastography, and serum markers, ranging from routine laboratory tests to more complex algorithms or indices combining the results of panels of markers, have been proposed. Among serum indices, Fibrotest has been the most extensively studied and validated. Transient elastography appears as a promising method but has been mostly validated in chronic hepatitis C with performance equivalent to that of serum markers for the diagnosis of significant fibrosis. The combination of both approaches as first‐line assessment of liver fibrosis could avoid the performance of liver biopsy in the majority of patients with chronic hepatitis C, a strategy that deserves further evaluation in patients with hepatitis B or HIV‐HCV coinfection. Transient elastography also appears to be an excellent tool for early detection of cirrhosis and may have prognostic value in this setting. Guidelines are now awaited for the use of noninvasive methods in clinical practice.     

Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C

Liver fibrosis is the main predictor of the progression of chronic hepatitis C, and its assessment by liver biopsy (LB) can help determine therapy. However, biopsy is an invasive procedure with several limitations. A new, noninvasive medical device based on transient elastography has been designed to measure liver stiffness. The aim of this study was to investigate the use of liver stiffness measurement (LSM) in the evaluation of liver fibrosis in patients with chronic hepatitis C. We prospectively enrolled 327 patients with chronic hepatitis C in a multicenter study. Patients underwent LB and LSM. METAVIR liver fibrosis stages were assessed on biopsy specimens by 2 pathologists. LSM was performed by transient elastography. Efficiency of LSM and optimal cutoff values for fibrosis stage assessment were determined by a receiver-operating characteristics (ROC) curve analysis and cross-validated by the jack-knife method. LSM was well correlated with fibrosis stage (Kendall correlation coefficient: 0.55; P < .0001). The areas under ROC curves were 0.79 (95% CI, 0.73-0.84) for F > or =2, 0.91 (0.87-0.96) for F > or =3, and 0.97 (0.93-1) for F=4; for larger biopsies, these values were, respectively, 0.81, 0.95, and 0.99. Optimal stiffness cutoff values of 8.7 and 14.5 kPa showed F > or =2 and F=4, respectively. In conclusion, noninvasive assessment of liver stiffness with transient elastography appears as a reliable tool to detect significant fibrosis or cirrhosis in patients with chronic hepatitis C.     

Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage

Transient elastography [FibroScan (FS)] is a rapid, noninvasive, and reproducible method for measuring liver stiffness, which correlates with the degree of liver fibrosis in patients with chronic hepatitis. Whether FS is useful in the detection of preexisting liver fibrosis/cirrhosis in patients presenting with acute liver damage is unclear. Patients with acute liver damage of different etiologies were analyzed. Liver stiffness was measured during the acute phase of the liver damage and followed up to the end of the acute phase. A total of 20 patients were included in the study. In 15 of the 20 patients, initial liver stiffness values measured by FS during the acute phase of the liver damage were suggestive of liver cirrhosis. However, none of these 15 patients showed any signs of liver cirrhosis in the physical examination, ultrasound examination, or liver histology [performed in 11 of 15 (73%) patients]. A significant difference was observed in the initial bilirubin levels (5.8 +/- 6.5 mg/dL versus 15.7 +/- 11.8 mg/dL; P = 0.042) and age (32.4 +/- 17.5 years versus 49.7 +/- 15.8 years; P = 0.042) between patients with liver stiffness below or above 12.5 kPa. Six patients with initially high liver stiffness were followed up to abatement of the acute hepatitic phase; in all of them, liver stiffness values decreased to values below the cutoff value for liver cirrhosis. CONCLUSION: Transient elastography frequently yields pathologically high values in patients with acute liver damage and is unsuitable for detecting cirrhosis/fibrosis in these patients.     

The use of transient elastography in the management of chronic hepatitis B

There has been increasing interest in noninvasive methods of assessing liver fibrosis over the last decade. The use of transient elastography in measuring liver stiffness has become the forefront of a wide range of noninvasive tools. Most of the other methods are based on measurements of biomarkers associated with fibrosis. There are several reasons for its wide acceptance, including the ease of performing a scan, the short procedure time, the results being immediately available on completion of the examination, and its reproducibility. For chronic hepatitis B (CHB), the cut-off values for F3 and F4 fibrosis range between 7.5–12.0 and 11.0–13.4 kPa, respectively, although the cut-offs may be slightly lower in those with normal ALT. In addition to measuring liver fibrosis, recent studies have demonstrated several other roles for transient elastography, including selecting patients who will benefit from antiviral therapy, monitoring response to antiviral therapy, and predicting long-term outcomes. However, there are limitations associated with transient elastography, including the confounding effects of inflammatory activity, and to a lesser extent, steatosis, on liver stiffness. There is also reduced accuracy observed in lower fibrosis stages (F0–F2). Furthermore, the incidences of failed and unreliable scan have been reported to be ~ 3 and 16%, respectively. Although liver biopsy can be avoided in an estimated 50–60% using transient elastography, in situations where liver stiffness measurement is nondiagnostic or inconsistent with the clinical picture, a biopsy is still recommended. Further studies are needed to consolidate the role of transient elastography in the management of CHB, and for incorporation of this method into current treatment guidelines.     

Transient elastography: Applications and limitations

Transient elastgraphy with use of FibroScan is one of most accurate methods for assessment of liver fibrosis. FibroScan can be readily used with an operator with a short training. In many different studies, liver stiffness measured by transient elastgraphy correlates well with fibrosis stages, and cutoff values of liver stiffness for fibrosis staging are similar even among different diseases. However there is wide variation of stiffness values in the same fibrosis stage, and some overlap between the adjacent stages. In addition, inflammatory activity and size of nodule of cirrhosis affect the liver stiffness values. The reproducibility may be reduced by age, obesity, steatosis, narrow intercostal space and lower degrees of hepatic fibrosis in patients. Thus the estimation of fibrosis stages from liver stiffness should be cautiously done. To improve the accuracy of liver fibrosis staging, the combination of transient elastography with other noninvasive methods such as FibroTest should be required.     

Assessment of biliary fibrosis by transient elastography in patients with PBC and PSC

Noninvasive measurement of liver stiffness with transient elastography has been recently validated for the evaluation of hepatic fibrosis in chronic hepatitis C. The current study assessed the diagnostic performance of liver stiffness measurement (LSM) for the determination of fibrosis stage in chronic cholestatic diseases. One hundred one patients with primary biliary cirrhosis (PBC, n=73) or primary sclerosing cholangitis (PSC, n=28) were prospectively enrolled in a multicenter study. All patients underwent liver biopsy (LB) and LSM. Histological and fibrosis stages were assessed on LB by two pathologists. LSM was performed by transient elastography. Efficiency of LSM for the determination of histological and fibrosis stages were determined by a receiver operating characteristics (ROC) curve analysis. Analysis failed in six patients (5.9%) because of unsuitable LB (n=4) or LSM (n=2). Stiffness values ranged from 2.8 to 69.1 kPa (median, 7.8 kPa). LSM was correlated to both fibrosis (Spearman's rho= 0.84, P < .0001) and histological (0.79, P < .0001) stages. These correlations were still found when PBC and PSC patients were analyzed separately. Areas under ROC curves were 0.92 for fibrosis stage (F) > or =2, 0.95 for F > or =3 and 0.96 for F=4. Optimal stiffness cutoff values of 7.3, 9.8, and 17.3 kPa showed F > or =2, F > or =3 and F=4, respectively. LSM and serum hyaluronic acid level were independent parameters associated with extensive fibrosis on LB. In conclusion, transient elastography is a simple and reliable noninvasive means for assessing biliary fibrosis. It should be a promising tool to assess antifibrotic therapies in PBC or PSC.     

Quality criteria for the measurement of liver stiffness

Liver elastography offers the possibility of a quick, non-invasive, and painless evaluation of the liver with immediate results at bedside. Transient elastography is the most validated technology, and many others such as point shear wave elastography, 2D-shear wave elastography, or magnetic resonance elastography have been developed. To ensure the best evaluation, several conditions of examination must be respected for liver stiffness measurement. Indeed, patient, operator and examination characteristics have all been shown to influence the result of liver stiffness measurement. Food intake increases liver stiffness, whereas withdrawal in alcoholics is associated with a decrease in elastography results. Inter-observer reproducibility of the measurement seems suboptimal, and the influence of the operator experience is still being debated. The measurement site and the FibroScan® probe must be correctly chosen. Finally, the intrinsic characteristics and quality criteria of the measurement, especially the interquartile range/median ratio, must be carefully checked to avoid overestimation of liver stiffness. Most of the results come from studies which have evaluated transient elastography, with less data available for the other technologies. Liver stiffness measurement could appear as a simple way to explore the liver, but several conditions must be met before deciding the patient management according to its result.     

Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD)

BACKGROUND: Liver fibrosis is the main predictor of the progression of nonalcoholic fatty liver disease. Transient elastography (FibroScan), which measures liver stiffness, is a novel, noninvasive method to assess liver fibrosis. AIM: We investigated the usefulness of liver stiffness measurement in the evaluation of liver fibrosis in nonalcoholic fatty liver disease patients. STUDY POPULATION: A total of 97 nonalcoholic fatty liver disease patients. METHODS: Transient elastography was performed for liver stiffness measurement in 97 nonalcoholic fatty liver disease patients. And the relationship between histological parameters and liver stiffness measurement was studied by multivariate analysis. Moreover, we investigated the relationship between liver stiffness measurement and the serum levels of hyaluronic acid and type IV collagen 7s domain. RESULTS: The liver stiffness was well correlated with the stage of liver fibrosis (Kruskal-Wallis test p < 0.0001). The areas under the receiver-operating characteristic curves were 0.927 for > or = F1, 0.865 for > or = F2, 0.904 for > or = F3, 0.991 for > or = F4. Only fibrosis stage was correlated significantly with liver stiffness measurement by multiple regression analysis. Liver stiffness was also strongly correlated with the serum levels of type IV collagen 7s domain (r = 0.525, p < 0.0001) and hyaluronic acid (r = 0.457, p < 0.0001). CONCLUSIONS: Our results show a significant correlation between liver stiffness measurement and fibrosis stage in nonalcoholic fatty liver disease patients, as confirmed by the results of liver biopsy, which remains the gold standard for evaluation of the severity of liver fibrosis in patients with nonalcoholic steatohepatitis.     

Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia

AIM: To analyze plasma osteopontin levels and liver stiffness using transient elastography in postoperative biliary atresia (BA) children compared with healthy controls. METHODS: Thirty children with postoperative BA and 10 normal controls were enrolled. The patients were categorized into two groups according to their jaundicestatus. Plasma levels of osteopontin were determined using commercially available enzyme-linked immunosorbent assay. Liver stiffness was measured by using transient elastography (Fibroscan). Ten validated Fibroscan measurements were performed in each patient and control with the result expressed in kilopascals (kPa). RESULTS: Plasma osteopontin was significantly elevated in BA children compared with that of healthy controls (47.0 ± 56.4 ng/mL vs 15.1 ± 15.0 ng/mL, P = 0.01). The liver stiffness measurement was markedly elevated in the patients with BA compared with that of controls (26.9 ± 24.6 kPa vs 3.9 ± 0.7 kPa, P = 0.001). Subgroup analysis showed that the BA patients with jaundice had more pronounced plasma osteopontin levels than those without jaundice (87.1 ± 61.6 ng/mL vs 11.9 ± 6.1 ng/mL, P = 0.001). Furthermore, the mean liver stiffness was significantly greater in the jaundiced BA patients compared with non-jaundiced patients (47.7 ± 21.8 kPa vs 8.7 ± 3.0 kPa, P = 0.001). Additionally, plasma osteopontin was positively related to serum total bilirubin (r = 0.64, P < 0.001). There was also a correlation between plasma osteopontin and liver stiffness values (r = 0.60, P < 0.001). CONCLUSION: High plasma osteopontin positively correlated with degree of hepatic fibrosis and could be used as a biochemical parameter reflecting disease severity in postoperative BA children.     

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.     

Prognostic significance of liver stiffness for hepatocellular carcinoma and mortality in HBeAg‐negative chronic hepatitis B

Summary. The prognostic value of liver stiffness measurements for chronic hepatitis B (CHB) is not known. The present study aimed to investigate the use of transient elastography in predicting hepatocellular carcinoma (HCC) development and mortality in patients with CHB. Five hundred and twenty‐eight patients with HBeAg‐negative CHB underwent liver stiffness measurements and were prospectively followed up every 3–6 months for a median length of 35 months. The patients were divided into those with liver stiffness <10 kPa (group 1) and ≥10 kPa (group 2). Of the 528 patients, 324 (61%) were men. The median age was 42 years. Compared with group 1, group 2 had a higher percentage of men, with higher median levels of age, liver biochemistry, and viral load. At the third year of follow‐up, the cumulative incidence of HCC was higher in group 2 compared with group 1 (9%vs 0%, respectively, P < 0.001). The cumulative liver‐related mortality was also higher in group 2 compared to group 1 (4%vs 0%, respectively, P < 0.001). After multivariate analysis, only liver stiffness measurement (LSM) was significantly associated with HCC development and mortality. There was also a higher cumulative incidence of hepatitis flares in group 2 compared to group 1 (46%vs 14%, respectively, P = 0.001) in patients with normal ALT, with higher LSM and AST being significantly associated with subsequent flares. In HBeAg‐negative CHB patients, a liver stiffness measurement of ≥10 kPa was associated with a significantly increased risk of subsequent HCC development and mortality.     

Close correlation of liver stiffness with collagen deposition and presence of myofibroblasts in non‐alcoholic fatty liver disease

Aim: Transient elastography is known as a rapid, objective, and highly reliable technique for staging hepatic fibrosis caused by hepatitis C virus infection; however, the relationship between degree of fibrosis and the collagen deposition or the accumulation of myofibroblasts in non‐alcoholic fatty liver disease (NAFLD) remains to be further elucidated. Methods: The subjects were 36 patients with NAFLD who received liver biopsy and liver stiffness measurement using transient elastography. Their clinical data and laboratory values were collected. Morphometric analyses of liver fibrosis indicated by collagen deposition and the relative numbers of myofibroblasts were performed. Results: Liver stiffness measured by transient elastography correlated with histopathological fibrosis staging of NAFLD determined by Brunt's scoring system (P = 0.000149). The fibrosis staging correlated with the ratios of the Sirius red‐positive area (P = 0.000032) and α‐smooth muscle actin‐positive area (P = 0.000898). Finally, liver stiffness significantly correlated with the ratios of the Sirius red‐positive area (r = 0.390, P = 0.0184) and α‐smooth muscle actin‐positive area (r = 0.333, P = 0.0471). Conclusions: Liver stiffness measurement by transient elastography is valuable for evaluating fibrotic progression in NAFLD.     

瞬时弹性成像技术在慢性肝病肝纤维化诊断中的应用进展

肝脏纤维化程度及进展与慢性肝脏疾病的诊断与治疗密切相关。早期诊断肝纤维化程度有助于避免代偿期患者向肝硬化失代偿期发展,也有助于降低肝细胞癌的发生率。目前,临床上评估肝纤维化程度的“金标准”仍为肝脏穿刺活检,但是由于其操作的有创性,以及穿刺后可能出现的多种并发症等多种因素的影响,限制了它在临床研究中的使用。瞬时弹性成像技术无创、安全、有利于动态监测肝纤维化进展、客观评价肝脏纤维化程度,使其在国内外得到了广泛的认同,在临床上具有良好的应用前景。