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.     

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.     

瞬时弹性扫描检测慢性乙型肝炎病情严重程度的研究

目的 探讨瞬时弹性扫描(TE)诊断慢性乙型肝炎(CHB)肝纤维化状态的临床价值.方法 969例CHB患者纳入研究,均接受TE检查,其中258例还接受肝活检,117例接受胃镜检查食管静脉曲张情况.结果 35例患者因TE检查成功率低于60%或肝脏弹性值(LSM)四分位偏差值/LSM比值高于0.3而被剔除.影响LSM的因素包括胆红素、AST、肝纤维化分期、炎症分级、超声波评分及血白蛋白水平.TE预测肝硬化Child-PughC级、B/C级、肝纤维化分期S4、≥S3、≥S2的接受者操作特征(ROC)曲线下面积分别为0.907、0.920、0.871、0.852及0.807.LSM＜32.2 kPa时排除Child-Pugh C级的可能性为99.4%,LSM≥35.3 kPa时诊断Child-Pugh B/C级的可能性为82.0%.对于代偿性CHB,LSM临界值23.3、15.2及10.8 kPa诊断肝硬化、肝纤维化分期≥S3及≥S2的阳性似然比均接近10.0;LSM临界值8.8、6.6 kPa排除肝硬化、肝纤维化分期≥S3的阴性似然比接近0.1.LSM与食管静脉曲张分期的等级相关系数仅为0.180,TE预测食管静脉曲张的ROC曲线下面积似无临床意义.结论 TE可较准确预测CHB患者肝纤维化严重性及Child-Pugh等级,LSM≥10.8 kPa的患者应考虑抗病毒治疗.

Abstract：

Objective To evaluate the value of transient elastography (TE) for predicting severity of liver fibrosis in patients with chronic hepatitis B (CHB).Methods A total of 969 patients with CHB was enrolled and recruited for analysis,which had been received TE scan,including 258 patients of liver biopsy,and 117 patients of gastric endoscopy.Results A total of 35 patients was excluded from analysis due to TE failure or unreliable TE.Liver stiffness measurement (LSM) was independently influenced by bilirubin,AST,liver fibrosis and inflammation,ultrasonic score and albumin.TE predicted Child-Pugh C,B/C,liver fibrosis S4,≥S3 and ≥ S2 with respective area under receiver operating characteristics curves (AUROC)0.907 (95% CI 0.886-0.928 ),0.920 ( 95% CI 0.899-0.940 ),0.871 ( 95% CI 0.819-0.923 ),0.852(95%CI0.805-0.899) and 0.807(95% CI0.749-0.865),respectively.While LSM ＜32.2 kPa excluded Child-Pugh C with 99.4% probability,LSM ≥35.3 kPa determined Child-Pugh B/C with positive predictive value (PPV) 0.820.For compensated CHB,cut-offs of LSM 23.3,15.2 and 10.8 kPa diagnosed cirrhosis,liver fibrosis ≥S3 and ≥S2 with positive likelihood ratio nearly 10.0 and PPV 0.692,0.882 and 0.980,respectively; and cut-offs 8.8 kPa,6.6 kPa excluded cirrhosis,liver fibrosis ≥ S3 with negative likelihood ration nearly 0.1 and negative predictive value 0.977 and 0.903,respectively.Correlation coefficient between LSM and grades of esophageal varices was only 0.180,and AUROC for TE predicting EV was of no clinical value.ConclusionTE relatively make accurate prediction in the severity of liver fibrosis and classification of Child-Pugh.Patients with LSM ≥ 10.8 kPa should be considered for receiving antivirus treatment.     

A prospective evaluation of the role of transient elastography for the detection of hepatic fibrosis in type 2 diabetes without overt liver disease

Abstract

Background. Type 2 diabetes mellitus (T2DM) is a major risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and subsequently hepatic fibrosis. Transient elastography (TE) is a rapid, reproducible non-invasive test that may be appropriate as a screening tool for the presence of hepatic fibrosis. AIM: Assess the utility of TE as a screening tool for the presence of hepatic fibrosis in a T2DM population with no known liver disease. Methods. T2DM patients without known liver disease were included. Patients were assessed with TE in addition to biochemical parameters. Results. A successful TE evaluation could be obtained in 74 of 81 (91%) included subjects. Of these, 26 (35%) had a liver stiffness measurement (LSM) ≥7.65 kPa. Sixteen of these subjects had confirmatory liver biopsies with significant (≥F2 fibrosis) present in 12 (75%) and cirrhosis diagnosed in 2 subjects. 15/16 (94%) had histological steatohepatitis. Compared with those with a lower LSM, subjects with an LSM ≥ 7.65 kPa had higher ALT levels (38.0 ± 21.7 vs 26.1 ± 11.1 U/L, p = 0.021) and increased prevalence of hepatic steatosis by ultrasound (85% vs 63%, p = 0.005). Conclusion. Significant hepatic fibrosis in the T2DM population is frequently under-recognized. TE may be a feasible tool for the screening of T2DM patients for the presence of hepatic fibrosis.     

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.     

Efficacy of transient elastography in screening for large esophageal varices in patients with suspicious or proven liver cirrhosis

OBJECTIVE: To evaluate the liver stiffness measurement (LSM) using transient elastography (TE) to predict the risk of esophageal varices (EVs) in Chinese patients. METHODS: In total, 46 patients with suspicious or proven liver cirrhosis underwent TE and liver biopsy. All participants were endoscopically screened for the presence of EVs and large EVs by two endoscopists who were blinded to the LSM status. Large EVs were defined as more than 5 mm in diameter. Receiver operating characteristic (ROC) curves for both TE and the platelet count/spleen diameter (PC/SD) ratio in predicting the presence of EVs or large EVs were calculated. RESULTS: Of the 46 patients, 30 (65%) had EVs including 19 (41%) with large EVs. The area under the ROC curve (AUROC) of LSM was 0.85 for the presence of EVs and 0.83 for large EVs, respectively. The cut‐off values of LSM were ≥13.4 kPa for the presence of EVs and ≥14.6 kPa for large EVs. Notably, the AUROC of the PC/SD ratio was 0.92 for the presence of EVs but only 0.69 for large EVs. CONCLUSION: LSM using TE can predict the presence of EVs or large EVs in Chinese patients with suspicious or proven cirrhosis and may identify patients who require endoscopic surveillance.     

Transient elastography for the noninvasive assessment of liver fibrosis: a multicentre Canadian study

BACKGROUND

Liver stiffness measurement (LSM) using transient elastography (TE) is a promising tool for the noninvasive assessment of hepatic fibrosis.

OBJECTIVES

To determine the feasibility and performance of TE in a North American cohort of patients with chronic liver disease.

METHODS

LSMs were obtained using TE in 260 patients with chronic hepatitis B or C, or nonalcoholic fatty liver disease from four Canadian hepatology centres. The accuracy of TE compared with liver biopsy for the prediction of significant fibrosis (Metavir fibrosis score of F2 or greater), bridging fibrosis (Metavir fibrosis score of F3 or greater) and cirrhosis (Metavir fibrosis score of F4 ) was assessed using area under ROC curves (AUROCs), and compared with the aspartate aminotransferase-to-platelet ratio index. The influence of alanine aminotransferase (ALT) levels and other factors on liver stiffness was determined using linear regression analyses.

RESULTS

Failure of TE occurred in 2.7% of patients, while liver biopsies were inadequate for staging in 0.8%. Among the remaining 251 patients, the AUROCs of TE for Metavir fibrosis scores of F2 and F3 or greater, and F4 were 0.74 (95% CI 0.68 to 0.80), 0.89 (95% CI 0.84 to 0.94), and 0.94 (95% CI 0.90 to 0.97), respectively. LSM was more accurate than the aminotransferase-to-platelet ratio index for bridging fibrosis (AUROC 0.78) and cirrhosis (AUROC 0.88), but not significant fibrosis (AUROC 0.76). At a cut-off of 11.1 kPa, the sensitivity, specificity, and positive and negative predictive values for cirrhosis (prevalence 11%) were 96%, 81%, 39% and 99%, respectively. For significant fibrosis (prevalence 53%), a cut-off of 7.7 kPa was 68% sensitive and 69% specific, and had a positive predictive value of 70% and a negative predictive value of 65%. Liver stiffness was independently associated with ALT, body mass index and steatosis. The optimal LSM cut-offs for cirrhosis were 11.1 kPa and 11.5 kPa in patients with ALT levels lower than 100 U/L and 100 U/L or greater, respectively. For fibrosis scores of F2 or greater, these figures were 7.0 kPa and 8.6 kPa, respectively.

CONCLUSIONS

The major role of TE is the exclusion of bridging fibrosis and cirrhosis. However, TE cannot replace biopsy for the diagnosis of significant fibrosis. Because liver stiffness may be influenced by significant ALT elevation, body mass index and/or steatosis, tailored liver stiffness cut-offs may be necessary to account for these factors.     

Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients

Failure of liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) and unreliable results occur in ≈ 5% and 15% of patients, respectively, mainly due to obesity. In this multicenter study, we evaluated the feasibility and performance of the novel FibroScan XL probe in 276 patients with chronic liver disease (42% viral hepatitis, 46% nonalcoholic fatty liver disease [NAFLD]) and a body mass index (BMI) ≥ 28 kg/m(2) . Patients underwent liver biopsy and TE with the standard M and XL probes. TE failure was defined as no valid LSMs and unreliable examinations as <10 valid LSMs or an interquartile range (IQR)/LSM >30% or success rate <60%. Probe performance for diagnosing ≥ F2 fibrosis and cirrhosis (F4) versus biopsy were examined using areas under receiver operating characteristic curves (AUROC). FibroScan failure was less frequent with the XL probe than the M probe (1.1% versus 16%) and the XL probe was more often reliable (73% versus 50%; both P < 0.00005). Reliable results with the XL probe were obtained in 61% of patients in whom the M probe was unreliable. Among 178 patients with ≥ 10 valid LSMs using both probes, liver stiffness was highly correlated between probes (ρ = 0.86; P < 0.0005); however, median liver stiffness was lower using the XL probe (6.8 versus 7.8 kPa; P < 0.00005). The AUROC of the XL and M probes were similar for ≥ F2 fibrosis (0.83 versus 0.86; P = 0.19) and cirrhosis (0.94 versus 0.91; P = 0.28). CONCLUSION: Compared with the M probe, the FibroScan XL probe reduces TE failure and facilitates reliable LSM in obese patients. Although the probes have comparable accuracy, lower liver stiffness cutoffs will be necessary when the XL probe is used to noninvasively assess liver fibrosis.     

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.     

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.     

Larger biopsies evaluation of transient elastography for detecting advanced fibrosis in patients with compensated chronic hepatitis B

Background and Aim: Although larger biopsies sample had been recommended for the study of non‐invasive liver fibrosis assessment, few studies with larger biopsies for transient elastography (TE) detecting liver fibrosis had been reported. The present study tries to re‐evaluate the performance of TE for detecting advanced fibrosis (≥F3) with larger biopsies in patients with compensated chronic hepatitis B. Methods: A total of 375 compensated patients were analyzed, who had undergone liver biopsy, reliable TE and routine blood tests. Results: The area under the receiver operating characteristic curve (AUC) was influenced by liver biopsy sample: 0.873 (95% confidence interval 0.838–0.909) in total patients, 0.880 (0.844–0.917) in length ≥ 15 mm, 0.897 (0.863–0.932) in length ≥ 20 mm and 0.911 (0.874–0.949) in length ≥ 25 mm. In patients with sample length ≥ 20 mm, the cutoffs to exclude and confirm advanced fibrosis were 7.1 kPa and 12.7 kPa, respectively. Stratified by alanine aminotransferase of two times the upper limit of normal (ALT 2 × ULN), transient elastography detecting advanced fibrosis with the most efficiency by 72.5% of patients obviated from liver biopsy. In patients with normal bilirubin and ALT < 2 × ULN, the area was 0.921 (0.860–0.982), and cutoffs for excluding and confirming diagnosis were 7.4 kPa and 10.6 kPa, respectively; 80% of patients could be classified with or without advanced fibrosis (AF). In patients with normal bilirubin and ALT ≥ 2 × ULN, the corresponding numbers were 0.885 (0.824–0.947), 7.5 kPa, 12.7 kPa and 79.2%, respectively. Conclusions: Inadequate sample study would underestimate the efficiency of TE on detecting advanced fibrosis. With ALT 2 × ULN stratified cutoffs, TE determined nearly 80% of patients with normal bilirubin as AF or non‐AF and obviated them from liver biopsies.     

Transient elastography: Kill two birds with one stone?

Assessment of liver fibrosis and steatosis is crucial in chronic liver diseases in order to determine the prognosis, the need of treatment, as well as monitor disease progression and response to treatment. Liver biopsy is limited by its invasiveness and patient acceptability. Transient elastography (TE, Fibroscan ) is a non-invasive tool with satisfactory accuracy and reproducibility to estimate liver fibrosis and steatosis. TE has been well validated in major liver diseases including chronic hepatitis B and C, non-alcoholic fatty liver disease, alcoholic liver disease, primary biliary cirrhosis, and primary sclerosing cholangitis. As alanine aminotransferase (ALT) is one of the major confounding factors of liver stiffness in chronic hepatitis B, an ALT-based algorithm has been developed and higher liver stiffness measurements (LSM) cutoff values for different stages of liver fibrosis should be used in patients with elevated ALT levels up to 5 times of the upper limit of normal. Otherwise falsely-high LSM results up to cirrhotic range may occur during ALT flare. TE is also useful in predicting patient prognosis such as development of hepatocellular carcinoma (HCC), portal hypertension, post-operative complications in HCC patients, and also survival. Unfortunately, failed acquisition of TE is common in obese patients. Furthermore,obese patients may have higher LSM results even in the same stage of liver fibrosis. The new XL probe, a larger probe with lower ultrasound frequency and deeper penetration, increases the success rate of TE in obese patients. The median LSM value with XL probe was found to be lower than that by the conventional M probe, hence cutoff values approximately 1.2 to 1.3 kPa lower than those of M probe should be adopted. Recent studies revealed a novel ultrasonic controlled attenuation parameter (CAP) of the machine is a useful parameter to detect even low-grade steatosis noninvasively. CAP may also be used to quantify liver steatosis by applying different cutoff values. As both LSM and CAP results are instantly available at same measurement, this makes TE a very convenient tool to assess any patients who are suspected or confirmed to suffer from chronic liver diseases.     

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.     

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.     

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.     

Prevalence in vulnerable population of liver fibrosis identified by transient elastography

Background. Transient elastography (TE) is a useful tool for the assessment of hepatic fibrosis as an alternative to liver biopsy, but it has not been validated as a screening procedure in apparently healthy people.Aim. To determine the prevalence of advanced liver fibrosis diagnosed by TE in a socioeconomically challenged rural population.Material and methods. We enrolled 299 participants aged over 18 years old from a vulnerable population in Mexico who responded to an open invitation. All participants had their history recorded and underwent a general clinical examination and a liver stiffness measurement, performed by a single operator according to international standards.Results. Overall, 7.35% participants were found to be at high risk for cirrhosis. Three variables correlated with a risk for a TE measure ≥ 9 kPa and significant fibrosis: history of alcohol intake [7.95 vs. 92.04%, odds ratio (OR) 4.47, 95% confidence interval (CI) 1.45-13.78, P = 0.0167], body mass index (BMI) ≥ 30 kg/m² (30.87 vs. 69.12%, OR 4.25, 95%CI 1.04-6.10, P = 0.049), and history of diabetes mellitus (14.87 vs. 85.12%, OR 2.76, 95%CI 1.002-7.63, P = 0.0419). In the multivariate analyses BMI ≥ 30 kg/m² was the only significant risk factor for advanced liver fibrosis or cirrhosis (OR 2.54, 95%CI 1.02-6.3, P = 0.0460).Conclusion. TE could be useful as a screening process to identify advanced liver fibrosis in the general and apparently healthy population.     

Is transient elastography a useful tool for screening liver disease？

Transient elastography （TE） is a new non invasive tool for measuring liver stiffness, which is correlated to the histologic stage of liver fibrosis. Several studies in chronic liver disease （CLD） have determined a good accuracy of TE in predicting significant fibrosis and an optimal accuracy in predicting cirrhosis. Normal liver stiffness ranges between 3.3-7.8 KPa and using a cut off of 7.1 KPa, significant fibrosis and cirrhosis can be excluded with a very high negative predictive value （NPV）. Positive predictive value （PPV） for the diagnosis of cirrhosis is lower using just a single scan but increases to 90% if high stiffness values are confirmed by a second independent scan. However the presence of fatty liver and metabolic syndrome slightly increases the readings and may reduce the accuracy of the test. it is uncertain if this increase is related to the presence of steatofibrosis or if it is caused by steatosis itself. TE can be used in screening patients attending the liver clinics to identify those with significant fibrosis or cirrhosis and may be particularly useful in discriminating HBV inactive carriers from chronic hepatitis B patients. TE, however, is not reliable in predicting the presence of esophageal varices in cirrhotics. Another potential indication for TE is the systematic screening of populations at high risk for CLD, such as intravenous drug users and alcoholics, but further studies are needed to determine its diagnostic accuracy in these settings.     

Prevalence,risk factors and causes of discordance in fibrosis staging by transient elastography and liver biopsy

Background and aims: Liver stiffness measurement (LSM) by transient elastography (TE) is widely used for the noninvasive assessment of fibrosis. Our objectives were to examine the prevalence, risk factors and causes of discordance between fibrosis estimated by TE and liver biopsy. Methods: Two hundred and fifty‐one patients with hepatitis B, C and nonalcoholic fatty liver disease underwent LSM by TE and liver biopsy. Predictors of discordance (≥2 fibrosis stages) between measures, which occurred in 14% of patients (n=35), were identified by comparing patient, TE and biopsy characteristics of discordant and nondiscordant cases. Results: According to predefined criteria, 40% of discordances were attributed to TE error and 23% to biopsy error; 37% were indeterminate. In multivariate analysis, mild fibrosis (F0–2 vs. F3–4), and higher body mass index (BMI), ALT and LSM variability [assessed by the ratio of the interquartile range to median LSM (IQR/M)] were independently associated with discordance. Discordance was three‐fold more common in patients with obesity (28 vs. 9%), ALT≥60 U/L (20 vs. 7%) and IQR/M ≥0.17 (22 vs. 7%; all P<0.005). Based on these variables, a discordance risk score assigning 1 point to each factor was developed. The prevalence of discordance in patients with 0, 1, 2 and 3 factors were 2, 7, 20, and 55% respectively (P<0.0005). Conclusions: Discordance between liver fibrosis estimated by TE and biopsy occurs in one in seven patients. In assessing the validity of TE results, clinicians must recognize risk factors for discordance and in at‐risk patients, consider alternative measures including biomarkers and possibly biopsy.     

Prevalence and factors associated with significant liver fibrosis assessed by transient elastometry in HIV/hepatitis C virus‐coinfected patients

Summary. Transient elastometry (TE) could provide a more accurate evaluation of the frequency and risk factors of liver fibrosis in hepatitis C virus (HCV) infection than that based on biopsy. The aim of this study was to assess the prevalence of and factors associated with significant liver fibrosis in a large population of HIV/HCV‐coinfected patients. HIV/HCV‐coinfected patients, who had participated in a cross‐sectional, multicenter, retrospective study of liver fibrosis using noninvasive markers and in whom a determination of liver stiffness (LS) by TE was available, were included in this analysis. Factors potentially associated with significant fibrosis (LS ≥ 9 kPa) were analyzed. One thousand three hundred and ten patients fulfilled the inclusion criteria, 526 (40%) of them showed LS ≥ 9 kPa and 316 (24%) cirrhosis (LS ≥ 14 kPa). The factors independently associated with significant fibrosis [adjusted odds ratio (95% confidence interval, P value) were the following: older age [1.04 (1.01–1.07), 0.002], daily alcohol intake > 50 g/day [1.58 (1.10–2.27), 0.013] and the length of HCV infection [1.03 (1.00–1.06), 0.023]]. A CD4 cell count lower than < 200 per mm³ [1.67 (0.99–2.81), 0.053] and HCV genotype 4 [0.66 (0.42–1.02), 0.066] were marginally associated with LS ≥ 9 kPa. In conclusion, the prevalence of cirrhosis in HIV/HCV‐coinfected patients seems to be higher than previously reported in studies based on liver biopsy. Older age, alcohol consumption and lower CD4 cell counts are related with significant fibrosis. The latter association supports an earlier starting of antiretroviral therapy in this setting.     

Liver stiffness measured by transient elastography in patients with acute pancreatitis

BackgroundAlcohol abuse constitutes a risk factor for acute pancreatitis and liver cirrhosis, and cirrhosis in turn may delay the recovery from pancreatitis. We evaluated the occurrence and significance of liver fibrosis or cirrhosis in patients with acute pancreatitis by applying transient elastography (TE).MethodsTE was carried out in 78 patients with acute pancreatitis. Comparisons were made to the severity and recurrence of pancreatitis, to biological markers for fibrosis (APRI test), alcohol intake (AST/ALT ratio, AUDIT), and prothrombin time (TT-SPA). A cut-off value of ≥7.5 kilopascals (kPa) was set for increased liver stiffness, and ≥10 kPa for significant fibrosis.ResultsThe aetiology of pancreatitis was alcohol intake in 62 patients, gallstones in 11, idiopathic in 3, tumour in 1 and medication in 1. TE was successful in 64 out of 78 patients. The median TE value was 6.5 kPa (range 2.5–61.1); 22 (35%) had values ≥7.5 kPa and 7 (11%) ≥10 kPa. Values ≥7.5 were associated with older age, higher APRI ratio, and lower TT-SPA. It did not predict the length of hospitalization or the recurrence of pancreatitis. Increased AST/ALT ratio was associated with high TE values, whereas AUDIT values were not. Values ≥10 kPa seemed to indicate manifest cirrhosis, hepatitis or subsequent development of diabetes.ConclusionsTE values ≥7.5 kPa did not predict the length of hospital stay or recurrence of pancreatitis but there were some findings of impaired liver function. Values ≥10 kPa may indicate subsequent development of diabetes and a more severe course of acute pancreatitis.