Elevated liver stiffness without histological evidence of liver fibrosis in rural Ugandans

Liver fibrosis may be assessed noninvasively with transient electrography (TE). Data on the performance of TE for detecting liver fibrosis in sub‐Saharan Africa are limited. We evaluated the diagnostic accuracy of TE by performing liver biopsies on persons with liver fibrosis indicated by TE. We enrolled HIV‐infected and HIV‐uninfected participants with TE scores consistent with at least minimal disease (liver stiffness measurement [LSM]≥7.1 kPa). Biopsies were performed and staged using the Ishak scoring system. A concordant result was defined using accepted thresholds for significant fibrosis by TE (LSM ≥ 9.3 kPa) and liver biopsy (Ishak score ≥ 2). We used modified Poisson regression methods to quantify the univariate and adjusted prevalence risk ratios (PRR) of the association between covariates and the concordance status of TE and liver biopsy in defining the presence of liver fibrosis. Of 131 participants with valid liver biopsy and TE data, only 5 participants (3.8%) had Ishak score ≥ 2 of whom 4 had LSM ≥ 9.3 kPa (sensitivity = 80%); of the 126 (96.2%) with Ishak score < 2, 76 had LSM < 9.3 kPa (specificity = 61%). In multivariable analysis, discordance was associated with female gender (adjPRR = 1.80, 95%CI 1.1‐2.9; P = .019), herbal medicine use (adjPRR 1.64, 95% CI = 1.0‐2.5; P = .022), exposure to lake or river water (adjPRR 2.05, 95% CI = 1.1‐3.7; P = .016), and current smoking (adjPRR 1.72, 95%CI 1.0‐2.9; P = .045). These data suggest that TE among rural Ugandans has low specificity for detection of histologically confirmed liver fibrosis. Caution should be exercised when using this tool to confirm significant liver fibrosis.     

Variability in liver stiffness values from different intercostal spaces

Aim: To investigate the variability in liver stiffness measurement (LSM) values from the fifth, sixth and seventh intercostal space (ICS) and examine whether LSM better predicts significant fibrosis (F2–4) and cirrhosis when LSM is performed at the same site as liver biopsy (LB). Methods: This study enrolled 91 consecutive patients with hepatitis B virus (HBV)‐related chronic liver disease (CLD) who underwent both LB and LSM between September 2007 and January 2009. Results: The mean age of the patients was 45.4 years (66 men and 25 women). F1 fibrosis was noted in 12 patients (13.2%), F2 in 28 (30.7%), F3 in 15 (16.5%) and F4 in 36 (39.6%). The mean LSM values from the fifth, sixth and seventh ICS were 11.6, 11.1 and 10.9 kPa respectively. The mean LSM value from the same site as LB was 11.0 kPa. An interclass correlation analysis showed no significant difference in LSM values from the fifth, sixth and seventh ICS and the same site as LB. The area under the receiver operating characteristic curves of LSM values from the fifth, sixth and seventh ICS and the same site as LB for predicting significant fibrosis were 0.815, 0.838, 0.818 and 0.837, respectively, and those for cirrhosis were 0.919, 0.916, 0.907 and 0.913, respectively, with all overlapping confidence intervals. Conclusions: Any LSM value from the fifth, sixth or seventh ICS can predict significant fibrosis and cirrhosis with considerable accuracy without statistical differences regardless of correspondence with LB site in patients with HBV‐related CLD.     

Proficiency of transient elastography compared to liver biopsy for the assessment of fibrosis in HIV/HBV‐coinfected patients

Summary. Transient elastography (TE) is a noninvasive technique to evaluate liver fibrosis. We compared the performance of TE with liver biopsy (LB) in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection. Patients prospectively underwent TE and LB. The diagnosis accuracy of TE was calculated using receiver operating characteristic (ROC) curves for different stages of fibrosis, and optimal cut‐off values were defined. A sequential algorithm combining TE with biochemical score (Fibrotest®) is proposed. Fifty‐seven patients had both TE and LB (median time: 3 days) and two with proven cirrhosis, only TE. Forty‐six (78%) were under antiretroviral therapy with anti‐HBV drugs in 98%, and 19 (32%) had elevated alanine aminotransferase (ALT). A significant correlation was observed between liver stiffness measurement (LSM) and METAVIR fibrosis stages (P < 0.0001). Patients with elevated ALT tended to have higher LSM than those with normal ALT. The areas under the ROC curves were 0.85 for significant fibrosis (≥F2), 0.92 for advanced fibrosis (≥F3) and 0.96 for cirrhosis. Using a cut‐off of 5.9 kPa for F≥2 and 7.6 kPa for F ≥ 3, the diagnosis accuracy was 83% and 86%, respectively. With an algorithm combining TE and Fibrotest®, 97% of patients were well classified for significant fibrosis. Using this algorithm, the need for LB can be reduced by 67%. In HIV/HBV‐coinfected patients, most of them with normal ALT under antiretroviral treatment including HBV active drugs, TE was proficient in discriminating moderate to severe fibrosis from minimal liver disease.     

Early steep decline of liver stiffness predicts histological reversal of fibrosis in chronic hepatitis B patients treated with entecavir

It is unknown whether dynamic changes of liver stiffness measurement (LSM) can predict the reversibility of fibrosis. Therefore, we evaluated the utility of LSM changes in predicting histological changes of fibrosis in patients with chronic hepatitis B (CHB) on antiviral therapy. In a prospective cohort of CHB patients treated with entecavir, virological measurement and biochemical measurement along with LSM were measured at baseline and every 6 months. Liver biopsies were conducted at baseline and month 18 of treatment. Fibrosis regression was defined by the following two criteria: (a) Ishak score decrease ≥1 stage, (b) Ishak score decrease ≥1 stage or predominantly regressive by post‐treatment PIR classification. The dynamic changes of LSM and its predictive value for histological reversibility were evaluated with piecewise linear mixed‐effects model and ROC analysis. We found that at month 18 of antiviral therapy, liver fibrosis was reserved in 86 of 212 (40.6%) CHB patients by Ishak reversal criterion. Overall, a decline in LSM was associated with attenuation of Ishak score. The rate of LSM decline in the first 6 months was significantly faster in patients with fibrosis reversal (ΔLSM%_Ishak = ?2.19%/month, P = 0.0025; ΔLSM%_Ishak/PIR = ?2.56%/month, P = 0.0004). The predictive model based on baseline FIB‐4 and Ishak score as well as baseline LSM, PLT, albumin and their changes during the first 6 months could predict histological reversal (AUROC_Ishak = 0.74, 95% CI: 0.67‐0.80; AUROC_Ishak/PIR = 0.81, 95% CI: 0.74‐0.87). We conclude that in CHB patients, changes in LSM during the first 6 months of entecavir therapy can predict histological reversibility of liver fibrosis at month 18 of antiviral therapy.     

Comparison of transient elastography and liver biopsy for the assessment of liver fibrosis in HIV/hepatitis C virus‐coinfected patients and correlation with noninvasive serum markers

Summary. Transient elastography (FibroScan^®) is a novel, rapid and noninvasive technique to assess liver fibrosis. Our objective was to compare transient elastography (TE) and other noninvasive serum indexes as alternatives to liver biopsy in HIV/hepatitis C virus (HCV)‐coinfected patients. The fibrosis stage (METAVIR Score), TE, the aspartate aminotransferase‐to‐platelet ratio index, the Forns fibrosis index, FIB‐4 and HGM‐2 indexes were assessed in 100 patients between January 2007 and January 2008. The diagnostic values were compared by calculating the area under the receiver operating characteristic curves (AUROCs). Using TE, the AUROC (95% CI) of liver stiffness was 0.80 (0.72–0.89) when discriminating between F ≤ 1 and F > 2, 0.93 (0.85–1.00) when discriminating between F ≤ 2 and F > 3 and 0.99 (0.97–1.00) when discriminating between F ≤ 3 and F4. For the diagnosis of F ≥ 3, the AUROCs of TE were significantly higher than those obtained with the other four noninvasive indexes. Based on receiver operating characteristic curves, three cutoff values were chosen to identify F ≤ 1 (<7 kPa), F ≥ 3 (≥11 kPa) and F4 (≥14 kPa). Using these best cutoff scores, the negative predictive value and positive predictive value were 81.1% and 70.2% for the diagnosis of F ≤ 1, 96.3% and 60% for the diagnosis of F ≥ 3 and 100% and 57.1% for the diagnosis of F4. Thus, Transient elastography accurately predicted liver fibrosis and outperformed other simple noninvasive indexes in HIV/HCV‐coinfected patients. Our data suggest that TE is a helpful tool for guiding therapeutic decisions 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.     

Prospective comparison of Fibroscan,King’s score and liver biopsy for the assessment of cirrhosis in chronic hepatitis C infection

Summary. Historically, liver biopsy (LB) was the sole method to evaluate the severity of hepatic fibrosis in patients with chronic hepatitis C infection. However, LB is expensive and associated with a risk of severe complications. Therefore, noninvasive tests have been developed to assess the severity of liver fibrosis. The accuracy of Fibroscan (FS) and King’s score (KS) was evaluated individually and in combination using liver histology as the reference standard. One hundred and eighty‐seven patients were identified who had undergone a biopsy with a diagnosis of chronic hepatitis C virus (HCV) mono‐infection (HCV RNA‐positive by RT‐PCR), attending King’s College Hospital (n = 88) or the Royal Free Hospital (n = 99) (London) between May 2006 and December 2007. Liver fibrosis was scored using the Ishak method; significant fibrosis was defined as Ishak fibrosis stage F3–F6, and cirrhosis defined as Ishak fibrosis F5–F6. The diagnostic accuracy of each test was assessed by area under receiver operator characteristic curves (AUROC). Median age was 49 years (43–54) and 115 (61%) were male. The AUROC for FS, KS and FS + KS for the diagnosis of Ishak F3–F6 were 0.83, 0.82 and 0.85, respectively and for the diagnosis of cirrhosis (≥F5) were 0.96, 0.89 and 0.93, respectively. The negative predictive values for the diagnosis of cirrhosis using the optimal cut‐off results for fibrsocan (10.05 kPa), KS (24.3) and the two combined (26.1) were 98%, 91% and 94%, respectively. The noninvasive markers and, particularly, FS were effective tests for the prediction of cirrhosis in chronic hepatitis C. Both KS and FS also had clinical utility for the prediction of Ishak fibrosis stages F3–F6.     

Noninvasive assessment of liver fibrosis via spleen stiffness measurement using acoustic radiation force impulse sonoelastography in patients with chronic hepatitis B or C

Summary. Portal hypertension and splenomegaly are common in patients with cirrhosis. However, there is limited previous in vivo research on the correlation between spleen stiffness and stages of liver fibrosis. This study aimed to evaluate the diagnostic value of spleen stiffness measurement (SSM), using acoustic radiation force impulse (ARFI) technology, for liver fibrosis assessment. Eligible patients with chronic hepatitis B or C (n = 163) underwent concurrent liver stiffness measurement (LSM), SSM and percutaneous liver biopsy. Receiver operating characteristic curves estimated the diagnostic performance of SSM, with multiple linear regression models for LSM and SSM determining the significance of explanatory factors. Results indicated significant correlation between LSM and SSM (R² = 0.574, P < 0.0001). Using SSM to classify METAVIR fibrosis (METAVIR F) scores, the areas under curves were 0.839 (95% CI: 0.780–0.898) for METAVIR F1 vs F2–4, 0.936 (95% CI: 0.898–0.975) for F1–2 vs F3–4 and 0.932 (95% CI: 0.893–0.971) for F1–3 vs F4, all P < 0.001. Multiple linear regression models identified BMI, spleen stiffness, METAVIR F3 and F4, serum alanine aminotransferase, international normalized ratio of prothrombin time, sodium and platelet count as significant independent explanatory factors for liver stiffness (adjusted R² = 0.724, P < 0.001). Male gender, liver stiffness, METAVIR F2, F3 and F4 also significantly and independently explained spleen stiffness (adjusted R² = 0.647, P < 0.001). ARFI SSM is potentially useful as a single or adjunct predictor of stages of liver fibrosis.     

Acoustic radiation force impulse imaging for non‐invasive assessment of liver fibrosis in chronic hepatitis B

Acoustic radiation force impulse (ARFI) imaging is a novel ultrasound‐based elastography method that is integrated in a conventional ultrasound machine. It might provide an alternative method to transient elastography for the noninvasive assessment of liver fibrosis. While previous studies have shown comparable diagnostic accuracy of ARFI to transient elastography in chronic hepatitis C, the aim of the present prospective multicenter study was to evaluate ARFI for the assessment of liver fibrosis in chronic hepatitis B. ARFI imaging involves the mechanical excitation of tissue using short‐duration acoustic pulses to generate localized displacements in tissue. The displacements result in shear‐wave propagation which is tracked using ultrasonic, correlation‐based methods and recorded in m/s. In the present international prospective study, patients infected with chronic hepatitis B received ARFI imaging, blood tests and if available transient elastography. The results were compared to liver biopsy as reference method analysed by a central pathologist. In 92 of 114 patients, a comparison of ARFI with transient elastography was possible. ARFI imaging and transient elastography correlated significantly with histological fibrosis stage. The diagnostic accuracy expressed as areas under ROC curves for ARFI imaging and transient elastography was 0.75 and 0.83 for the diagnosis of significant fibrosis (F ≥ 2), 0.93 and 0.94 for the diagnosis of severe fibrosis (F ≥ 3), and 0.97 and 0.93 for the diagnosis of liver cirrhosis, respectively. No significant difference was found between ARFI and transient elastography. ARFI imaging is a reliable ultrasound‐based method for the assessment of advanced stages of liver fibrosis in chronic hepatitis B.     

Hepatic steatosis leads to overestimation of liver stiffness measurement in both chronic hepatitis B and metabolic-associated fatty liver disease patients

BackgroundThe impact of hepatic steatosis on liver stiffness measurement (LSM) in both chronic hepatitis B(CHB) and metabolic-associated fatty liver disease (MAFLD) remains controversial.AimsTo determine whether LSM is affected by hepatic steatosis in CHB-MAFLD.MethodsHepatic steatosis and liver fibrosis were assessed by histological and noninvasively methods. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance of LSM.ResultsThe prevalence of MAFLD in CHB patients (n = 436)was 47.5% (n = 207). For patients with low amounts of fibrosis (F0–1 and F0–2), the median LSM was 8.8 kPa and 9.2 kPa in patients with moderate- severe steatosis,which was significantly higher than that in patients with none-mild steatosis (P < 0.05) . The positive predictive value(PPV) was lower for LSM identifying significant fibrosis (F ≥ 2) as well as severe fibrosis (F ≥ 3) in group which controlled attenuation parameter(CAP) ≥ 268 dB/m than its counterpart(68.2% vs 84.6% and 24.3% vs 45.0%). The AUROC of LSM detected F ≥ 2 was 0.833 at a cutoff of 8.8 kPa and 0.873 at a cutoff of 7.0 kPa in patients with CAP ≥ 268 and CAP < 268, respectively.ConclusionsThe presence of moderate-severe steatosis, detected by histology or CAP, should be taken into account to avoid overestimation of LSM.     

The usefulness of transient elastography by FibroScan for the evaluation of liver fibrosis

Introduction

Liver stiffness measurement (LSM) is used for the assessment of liver fibrosis. However, there is limited data in Indian patients.

Aims and Objective

The aim of this study was to find the correlation of LSM, aspartate transaminase to platelet ratio index (APRI) with fibrosis as assessed by liver biopsy (LB), and predictors of discordance between LB and LSM.

Methods

One hundred and eighty-five consecutive patients who underwent liver biopsy and transient elastography (TE) were enrolled. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) was used to evaluate the accuracy of transient elastography and APRI in diagnosing significant fibrosis (F>2) and cirrhosis (F4).

Results

Predominant etiologies were hepatitis B (46 %) and hepatitis C (26 %). LSM was unsuccessful in ten patients (5 %) because of small intercostal space (n?=?3) and obesity (n?=?7). Fibrosis is significantly correlated with LSM (r?=?0.901, p?=?0.001) and APRI (r?=?0.736, p?=?0.001). There was a significant difference in median LSM value in patients with no fibrosis (F0) in comparison to patients having mild fibrosis [mild portal fibrosis (F1)?+?fibrosis with few septa (F2)] (4.5 vs. 7.5 kPa, p?=?0.001) and advanced fibrosis [bridging fibrosis that is spreading and connecting to other areas that contain fibrosis (F3)?+?cirrhosis or advanced scarring of the liver (F4)] (4.5 vs. 19.4 kPa, p?=?0.001). Similarly, there was a significant difference in mean APRI value in patients with F0 in comparison to patients having mild fibrosis (F1?+?F2) (0.55?±?0.31 vs. 1.09?±?0.81, p?=?0.001) and advanced fibrosis (F3?+?F4) (2.3?±?1.3, p?=?0.001). AUROC for diagnosis of significant fibrosis was 0.98 (95 % confidence interval (CI) 0.963–0.999) for TE and 0.865 (95 % CI 0.810–0.920) for APRI. Optimal TE value was 10.0 kPa for diagnosis of significant fibrosis and 14.7 kPa for cirrhosis with specificity and sensitivity of 89 %, 98 % and 96 %, and 97 %, respectively. On multivariate analysis, total bilirubin and histological activity index (HAI) were identified as an independent predictor of TE inaccuracy.

Conclusion

LSM is a reliable predictor of hepatic fibrosis in Indian patients. LSM is superior to APRI for noninvasive diagnosis of hepatic fibrosis and cirrhosis, and high bilirubin (10.5 mg/dL) and Ishak HAI grade (>11) were independent predictors of discordance between LB and LSM.     

Liver stiffness measurement using FibroScan® is influenced by serum total bilirubin in acute hepatitis

Background: Liver stiffness measurement (LSM) using FibroScan^® is accepted as a highly reproducible and accurate technique for assessment of liver fibrosis. However, several studies have indicated that the LSM value can be significantly influenced by major changes in aminotransferases in patients with chronic viral hepatitis and LSM is unreliable for diagnosing underlying liver cirrhosis in patients with acute liver damage. We aimed to determine biochemical factors influencing the LSM value in patients with acute hepatitis. Methods: From July to December 2007, a total of 60 patients with acute hepatitis of varying aetiologies were recruited prospectively. LSM and biochemical tests were performed at diagnosis and recovery from acute hepatitis. Results: The mean age of the patients (38 men and 22 women) was 40.7±15.4 years. The aetiology of acute hepatitis included hepatitis A virus in 31 patients, drug induced in 19 and hepatitis B virus in 10. The mean LSM value was 19.6 kPa at diagnosis and 15.9 kPa at recovery. Correlation analysis showed that the LSM value at diagnosis was significantly associated with platelet count (P=0.023), alanine aminotransferase (P=0.045), albumin (P<0.001), total bilirubin (P=0.004) and prothrombin time (P=0.005). However, additional correlation analysis between the changes in LSM value and biochemical factors from diagnosis to recovery showed that the change in total bilirubin was found to be the only factor associated with the change in the LSM value (P<0.001). Conclusions: Our data suggest that the LSM value might be influenced by serum total bilirubin in patients with acute hepatitis without pre‐existing underlying chronic liver disease.     

Diagnosis of advanced fibrosis in HIV and hepatitis C virus-coinfected patients via a new noninvasive index: the HGM-3 index

Background

Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F≥3) in HIV/hepatitis C virus (HCV)‐coinfected patients.

Methods

We carried out a cross‐sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM‐3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase‐1 and hyaluronic acid.

Results

In the EG, the area under the receiver operating characteristic curve (AUC‐ROC) of HGM‐3 for identification of F≥3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC‐ROC of the HGM‐2, FIB‐4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM‐3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM‐3 >0.570 in the EG for F≥3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F≥3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG.

Conclusions

HGM‐3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV‐coinfected patients.     

Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B

Summary.  The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.     

Usefulness of FibroScan for Detection of Early Compensated Liver Cirrhosis in Chronic Hepatitis B

Background It is difficult to differentiate early compensated cirrhosis from chronic hepatitis solely by clinical features. The aim of this study was to assess the usefulness of liver stiffness measurement (LSM) for detection of early compensated liver cirrhosis in chronic hepatitis B (CHB). Methods Ninety-one consecutive CHB patients who underwent liver biopsy (LB) and LSM were recruited. All patients did not fulfill the clinical criteria for cirrhosis. The cutoff of LSM for cirrhosis was 10.3 kPa. Results All patients were divided into either group A (cirrhosis) or group B (CHB) according to LB result. The median LSM values of groups A and B were 11.8 and 7.6 kPa, respectively (P < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of LSM in predicting cirrhosis were 0.59, 0.78, 0.68, and 0.72, respectively. The area under the receiver operating characteristics curve (AUROC) of LSM was 0.803, whereas the AUROCs of aspartate to alanine aminotransferase ratio (AAR) and aspartate aminotransferase to platelet ratio index (APRI) were 0.488 and 0.723, respectively. Conclusions LSM showed an acceptable diagnostic accuracy for detecting early compensated cirrhosis in CHB. Do Young Kim and Seung Up Kim have contributed equally to this work.     

Non-invasive assessment of liver fibrosis by transient elastography in post transfusional iron overload

Background: Liver fibrosis, assessed by biopsy, is the main complication of post transfusional liver iron overload. Transient elastography (TE) is a new, non invasive method able to measure liver stiffness (LS) caused by fibrosis. Method: We prospectively evaluated the predictive value of LS measurement for liver fibrosis evaluation in 15 chronically transfused patients and compared these results with the METAVIR histological fibrosis stage from liver biopsies. Results: Mean TE values significantly differed in patients with severe fibrosis (METAVIR F3, F4): 9.1 (±3.7 SD) kPa from those with mild or no fibrosis (METAVIR F0, F1, F2): 5.9 (±1.8 SD) kPa (P = 0.046). TE value above 6.25 kPa (Se = 80%; Sp = 70%; AUROC = 0.820) identified patients at risk for severe fibrosis (Negative Predictive Value 88%; Positive Predictive Value 57%). Conclusion: Transient elastography appears to be a reliable tool to evaluate liver fibrosis in post‐transfusional iron overload.     

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.     

Transient elastography compared to liver biopsy and morphometry for predicting fibrosis in pediatric chronic liver disease: Does etiology matter?

AIM: To evaluate transient elastography(TE) as a noninvasive tool in staging liver fibrosis compared with liver biopsy and morphometry in children with different chronic liver diseases.METHODS: A total of 90 children [50 with chronic hepatitis C virus(HCV), 20 with autoimmune hepatitis(AIH) and 20 with Wilson disease] were included in the study and underwent liver stiffness measurement(LSM) using TE. Liver biopsies were evaluated for fibrosis, qualitatively, by Ishak score and quantitatively by fibrosis area fraction(FAF) using digital image analysis(morphometry). LSM was correlated with fibrosis and other studied variables using spearman correlation. A stepwise multiple regression analysis was alsoperformed to examine independent factors associated with LSM. Different cut-off values of LSM were calculated for predicting individual fibrosis stages using receiveroperating characteristic curve. Cut-off values with optimal clinical performance(optimal sensitivity and specificity simultaneously) were selected.RESULTS: The majority of HCV group had minimal activity(80%) and no/mild fibrosis(72%). On the other hand, the majority of AIH group had mild to moderate activity(70%) and moderate to severe fibrosis(95%) and all Wilson disease group had mild to moderate activity(100%) and moderate to severe fibrosis(100%). LSM correlated significantly with both FAF and Ishak scores and the correlation appeared better with the latter(r = 0.839 vs 0.879, P 0.0001 for both). LSM discriminated individual stages of fibrosis with high performance. Sensitivity ranged from 81.4% to 100% and specificity ranged from 75.0% to 97.2%. When we compared LSM values for the same stage of fibrosis, they varied according to the different etiologies. Higher values were in AIH(16.15 ± 7.23 k Pa) compared to Wilson disease(8.30 ± 0.84 k Pa) and HCV groups(7.43 ± 1.73 k Pa). Multiple regression analysis revealed that Ishak fibrosis stage was the only independent variable associated with higher LSM(P 0.0001).CONCLUSION: TE appears reliable in distinguishing different stages of liver fibrosis in children. However, its values vary according to the disease type. For that, a disease-specific estimation of cut-off values for fibrosis staging is worthy.     

Fibrosis evolution in chronic hepatitis B e antigen‐negative patients across a 10‐year interval

The degree of liver fibrosis in chronic hepatitis B (CHB) infection influences outcome and management. Existing data describing the long‐term dynamic changes of liver fibrosis are limited. This study aimed to evaluate the evolution of liver fibrosis in CHB across a 10‐year period. CHB patients with liver stiffness measurement (LSM) by transient elastography 10 years ago were recruited for follow‐up LSM. Fibrosis stages were classified according to EASL‐ALEH guidelines. Fibrosis progression/regression was arbitrarily defined as ≥1 fibrosis stage change from baseline. A total of 459 hepatitis B e antigen (HBeAg)‐negative patients (224 untreated, 235 treated with nucleos(t)ide analogues [NAs]) were recruited. The mean age at baseline LSM was 41.7 ± 9.0 years (56.2% male). Over 10 years, the proportion of patients with advanced fibrosis/cirrhosis significantly reduced from 16.3% to 5.7% (P < 0.001). Fibrosis progression and regression were observed in 8.7% and 37.5%, respectively. No treatment with NAs (OR 2.259, 95% confidence interval [CI]: 1.032‐4.945), metabolic syndrome (OR 4.379, 95% CI: 1.128‐16.999) and hepatic steatosis (OR 7.799, 95% CI: 2.271‐26.776) was associated with fibrosis progression. Liver stiffness decline demonstrated positive correlation with the time after HBsAg seroclearance (r = ?0.50, P < 0.001). Median liver stiffness was higher both at baseline (14.0 vs 6 kPa, P < 0.001) and 10 years (9.1 vs 4.9 kPa, P < 0.001) in patients with cirrhosis‐related complications/hepatocellular carcinoma compared with those without. In conclusion, CHB‐related liver fibrosis changed dynamically across 10 years. Metabolic syndrome and hepatic steatosis were associated with fibrosis progression, while antiviral therapy was associated with fibrosis regression. Patients with HBsAg seroclearance demonstrated time‐dependent decline in liver stiffness.     

Clinical noninvasive markers for antiviral therapy decision in chronic hepatitis B with alanine aminotransferase less than two times upper limit of normal

Liver biopsy is the reference method for antiviral therapy decision‐making in chronic hepatitis B (CHB) when alanine aminotransferase (ALT) is less than two times of upper limit of normal (<2ULN). Our aim was to explore noninvasive markers for antiviral therapy decision in CHB with ALT <2ULN. A total of 452 treatment‐naïve CHB patients with ALT < 2ULN who had undergone liver biopsy were analysed in this prospective multi‐centre study. If liver biopsy showed moderate or severe inflammation (histology activity index ≥ 5) or significant fibrosis (Ishak fibrosis score ≥ 3), antiviral treatment was recommended. We analysed data using univariate and multivariate analyses and receiver operating characteristic curves (ROC). Two hundred and sixty‐nine (59.5%) of 452 cases with ALT < 2ULN had moderate, severe or significant inflammation. Aspartate aminotransferase (AST) (P = 0.03), anti‐hepatitis B virus core antibody (anti‐HBc) (P = 0.003) and liver stiffness measurement (LSM) (P = 0.000) were independent variables for antiviral therapy decision‐making, with area under the ROC curve (AUROC) of 0.718, 0.703 and 0.819, respectively. Our novel AAF index, which combined AST, anti‐HBc and LSM, showed better performance with AUROC of 0.876, 0.877 and 0.876 in estimation, validation and total set. Finally, 247 (54.6%) of 452 patients could avoid liver biopsy based on AAF index. Furthermore, performances of 23 noninvasive models were unsatisfactory for antiviral therapy decision with AUROC < 0.800, which were inferior to AAF index. In conclusion, AST, anti‐HBc and LSM were related to antiviral therapy decision‐making among CHB patients with ALT < 2ULN. Thus, the novel AAF index was a more reliable noninvasive model for antiviral therapy decision‐making.