Non-invasive Measures Of Liver Fibrosis Research Articles

Effectiveness of fenofibrate in treatment-naïve patients with primary biliary cholangitis: A Randomized Clinical Trial.

Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease, and patients with inadequate response to ursodeoxycholic acid (UDCA) treatment show reduced long-term survival. Recent studies have shown that fenofibrate is an effective off-label therapy for PBC. However, prospective studies on biochemical response including timing of fenofibrate administration are lacking. This study is aimed to evaluate the efficacy and safety of fenofibrate in UDCA treatment- naïve patients with PBC. A total of 117 treatment-naïve patients with PBC were recruited from the Xijing Hospital for a 12-month randomized, parallel and open-label clinical trial. Study participants were assigned to receive either UDCA standard dose (UDCA-only group) or fenofibrate at a daily dose of 200 mg in addition to UDCA (UDCA-Fenofibrate group). Primary outcome was biochemical response percentage in patients according to the Barcelona criterion at 12 month. In the UDCA-Fenofibrate group, 81.4% [69.9-92.9%] of the patients achieved the primary outcome and 64.3% [51.9-76.8%] in the UDCA-only group achieved (p = 0.048). There was no difference between two groups in noninvasive measures of liver fibrosis and biochemical markers other than alkaline phosphatase at 12 months. Creatinine and transaminases levels in the UDCA-Fenofibrate group increased within the first month, then returned to normal, and remained stable thereafter until the end of the study, even in patients with cirrhosis. In this randomized clinical trial in treatment-naïve patients with PBC, the combination of fenofibrate and UDCA resulted in a significantly higher biochemical response rate. Fenofibrate seemed to be well-tolerated in patients.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial

Ethnopharmacological relevanceThe AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). Aim of the studyWe aimed to investigate whether monotherapy with AHP improves liver histology in these patients. Materials and methodsIn this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. ResultsPer-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. ConclusionsTreatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

Study of the effect of direct acting antivirals (DAAs) on fibrosis in chronic hepatitis C patients using transient elastography

Back ground: As DAA agents are leading to enormous cure rates, so identifying and monitoring patients who remain at a high complication risk after achieving SVR continue to be a critical issue. Numerous validated methods for noninvasive measurement of liver fibrosis can be used in the management of HCV infection. Methods study: A total of 50 Egyptian chronic HCV patients eligible for treatment with DAAs were enrolled in this prospective study. All subjects selected from Virology Unit of Tropical Medicine Department, Faculty of Medicine, Beni-Suef University received DAAs (SOV DCV) the endpoint was a sustained virologic response at 12 (SVR12) weeks post-treatment. All participants were evaluated non-invasively by Liver Stiffness Measurement (LSM) by Fibro Scan before DAAs treatment, and 6 months post-treatment. Results: SVR achieved by DAAs therapy was 96 % and was associated with significant improvement (p ˂0.05) of non-invasive fibrosis markers (FIB-4, APRI score, and LSM by Fibro Scan) from baseline compared to 6 months post-treatment. Using fibro scan regression of fibrosis in 30/45 patients (66%). Liver inflammation and synthetic functions also improved on follow up 12w and 6m post treatment. Conclusion: Regression of Liver inflammation and fibrosis in chronic hepatitis C patients post treatment with SOF DCV.

NS34A resistance-associated substitutions in chronic hepatitis C in Upper Egypt and regression of liver fibrosis after direct-acting antiviral therapy

BackgroundViral resistance-associated substitutions (RASs) can develop in the setting of DAAs therapy (i.e., emerging RASs). Long-term monitoring of fibrosis regression after achieving SVR to simiprevir (SMV)/sofosbuvir (SOF) is essential. The aim of this study was to determine the prevalence of baseline and emerging NS34A RASs in chronic HCV patients in Upper Egypt and to assess the impact of SMV/SOF therapy on liver stiffness.ResultsThe enrolled 59 patients had HCV genotype 4a without any baseline RASs in the NS34A region. 96.6% (57/59) of patients achieved sustained virological response (SVR12). Of the two patients who failed to achieve SVR12, one of them developed emerging RASs Q80K in the NS34A region. Seventy-two weeks after SMV/SOF therapy, the percentage of patients with liver fibrosis stage (F2, F3, and F4) decreased from 75.4% before treatment to 42.1% after treatment. The combination of SOF and SMV appeared to be well tolerated.ConclusionsAll patients had HCV genotype 4a without any baseline RASs in the NS34A region. In addition, there was improvement of non-invasive measures of liver fibrosis in patients who achieved SVR, 72 weeks after SMV/SOF therapy.

Diagnostic Accuracy of FibroScan and Factors Affecting Measurements.

Evaluating liver steatosis and fibrosis is important for patients with non-alcoholic fatty liver disease. Although liver biopsy and pathological assessment is the gold standard for these conditions, this technique has several disadvantages. The evaluation of steatosis and fibrosis using ultrasound B-mode imaging is qualitative and subjective. The liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) determined using FibroScan are the evidence-based non-invasive measures of liver fibrosis and steatosis, respectively. The LSM and CAP measurements are carried out simultaneously, and the median values of more than ten valid measurements are used to quantify liver fibrosis and steatosis. Here, we demonstrate that the reliability of the LSM depends on the interquartile range to median ratio (IQR/Med), but CAP values do not depend on IQR/Med. In addition, the LSM is affected by inflammation, congestion, and cholestasis in addition to fibrosis, while CAP values are affected by the body mass index in addition to steatosis. We also show that the M probe provides higher LSM values but lower CAP values than the XL probe in the same population. However, there was no statistically significant difference between the diagnostic accuracies of the two probes. These findings are important to understand the reliability of FibroScan measurements and the factors influencing measurement values for all patients.

A Liver Biopsy Validation Pilot Study of Shear Wave Elastography, APRI, FIB-4, and Novel Serum Biomarkers for Liver Fibrosis Staging in Children With Chronic Viral Hepatitis.

As liver biopsy in children poses inherent risks, noninvasive measures of liver fibrosis are needed. This was a cross-sectional, liver biopsy validation pilot study of 16 participants evaluating the ability of shear wave elastography, aspartate transaminase to platelet ratio index (APRI), fibrosis index based on the 4 factors, and novel serum biomarkers to stage liver fibrosis in children with chronic hepatitis B or C. There was very high intrasegmental shear wave speed variation in our participants and little correlation with fibrosis. APRI and monocyte chemoattractant protein (MCP-1) were higher in fibrosis stage F2-3 versus F0-1 (P = .02, P = .06, respectively). Soluble Fas (sFas) was lower in F2-3 versus F0-1 (P = .046). A logistic regression analysis calculated by (APRI × MCP-1)/sFas demonstrated an area under the receiver operating characteristic curve of 0.92 (P < .001), suggesting that this combination can differentiate fibrosis stage F0-1 from F2-3 in children with chronic viral hepatitis.

New treatments/targets for primary biliary cholangitis.

SummaryPrimary biliary cholangitis (PBC) is an autoimmune, cholestatic, chronic liver disease that ultimately progresses towards cirrhosis and liver failure if untreated. While ursodeoxycholic acid has been established as standard of care for PBC in the last few decades, significant advances in second-line treatment options have recently been made and new therapeutic developments are currently under evaluation. The purpose of this article is to provide the clinician with an overview of the current treatment options and future opportunities for patients with PBC.

Short-term changes observed in multiparametric liver MRI following therapy with direct-acting antivirals in chronic hepatitis C virus patients

MethodsWe applied multiparametric MRI to assess changes in liver composition, perfusion and blood flow in 17 patients before direct-acting antiviral (DAA) therapy and after treatment completion (within 12 weeks of last DAA tablet swallowed).ResultsWe observed changes in hepatic composition indicated by a reduction in both liver longitudinal relaxation time (T1, 35 ± 4 ms), transverse relaxation time (T2, 2.5 ± 0.8 ms; T2* 3.0 ± 0.7 ms), and liver perfusion (28.1 ± 19.7 ml/100 g/min) which we suggest are linked to reduced pro-inflammatory milieu, including interstitial oedema, within the liver. No changes were observed in liver or spleen blood flow, splenic perfusion, or superior mesenteric artery blood flow.ConclusionFor the first time, our study has shown that treatment of HCV with DAAs in patients with cirrhosis leads to an acute reduction in liver T1, T2 and T2* and an increase in liver perfusion measured using MR parameters. The ability of MRI to characterise changes in the angio-architecture of patients with cirrhosis after intervention in the short term will enhance our understanding of the natural history of regression of liver disease and potentially influence clinical decision algorithms.Key Points• DAAs have revolutionised the treatment of hepatitis C and achieve sustained virological response in over 95% of patients, even with liver cirrhosis.• Currently available non-invasive measures of liver fibrosis are not accurate after HCV treatment with DAAs, this prospective single-centre study has shown that MRI can sensitively measure changes within the liver, which could reflect the reduction in inflammation with viral clearance.• The ability of MRI to characterise changes in structural and haemodynamic MRI measures in the liver after intervention will enhance our understanding of the progression/regression of liver disease and could potentially influence clinical decision algorithms.

A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis

BackgroundPatients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator–activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition.MethodsIn this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid. The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months.ResultsThe primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P<0.001). Normal levels of alkaline phosphatase were observed in 67% of the patients in the bezafibrate group and in 2% in the placebo group. Results regarding changes in pruritus, fatigue, and noninvasive measures of liver fibrosis, including liver stiffness and Enhanced Liver Fibrosis score, were consistent with the results of the primary outcome. Two patients in each group had complications from end-stage liver disease. The creatinine level increased 5% from baseline in the bezafibrate group and decreased 3% in the placebo group. Myalgia occurred in 20% of the patients in the bezafibrate group and in 10% in the placebo group.ConclusionsAmong patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy. (Funded by Programme Hospitalier de Recherche Clinique and Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731.)

Prevalence and Characteristics of Liver Fibrosis Detected by Elastography: Results from the Cameron County Hispanic Cohort

Abstract Mexican Americans in south Texas have among highest rates of hepatocellular carcinoma (HCC) in the US. Non-invasive measures of liver fibrosis are needed to identify those at high risk of HCC. The purpose of the study was to determine the prevalence of and factors associated with liver fibrosis using acoustic radiation force impulse (ARFI) elastography, an accurate and non-invasive modality, in the Cameron County Hispanic Cohort (CCHC). Methods. The CCHC is a well characterized population-based cohort in south Texas. Liver stiffness was measured by ARFI in 404 participants in the CCHC by two separate operators. Median liver stiffness &amp;gt; 1.34 m/s was considered significant (F2-F4) fibrosis. Ultrasound was used to determine presence of steatosis. Absence of HCV and HBsAg antigen, and absence of heavy drinking, was considered non-alcoholic fatty liver disease (NAFLD). We calculated design-based prevalence of fibrosis and determined clinical associations with (1) significant fibrosis and (2) simple steatosis using multinomial logistic regression. Results. Mean age was 51.1 years, 44.6% were male, and 29.1% had diabetes. The prevalence of significant fibrosis was 16.5%. In the fibrosis group, most (47/57, 84%) had NAFLD. We excluded participants with etiologies other than NAFLD for further analyses. After adjustment for age and sex, hypertension [Odds Ratio (OR) 3.0, 95% confidence interval (CI) 1.1–8.1), platelet count (OR 0.6, 95% CI, 0.5–1.0), and potassium level (OR 1.5, 95% CI, 1.1–2.0) were significantly associated with fibrosis, but not steatosis. HDL cholesterol (OR 0.5, 95% CI, 0.4–0.7), obesity (OR 2.2, 95% CI, 1.2–4.0) and insulin level (OR 2.1, 95% CI, 1.2–3.7) were significantly associated with steatosis, but not fibrosis. Elevated fasting glucose, diabetes, and elevated ALT levels were significantly associated with both steatosis and fibrosis. Conclusion. This is the first population-based application of liver elastography in the US. We find a high prevalence of fibrosis in Mexican Americans, dominated by NAFLD. Our results indicate a higher burden of fibrosis than population-based studies of liver fibrosis conducted elsewhere. We urge community intervention for the early detection of liver disease and prevention of NAFLD-related HCC.

A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis

BackgroundPrimary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease.MethodsIn this 12-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 217 patients who had an inadequate response to ursodiol or who found the side effects of ursodiol unacceptable to receive obeticholic acid at a dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with adjustment to 10 mg if applicable (the 5–10-mg group), or placebo. The primary end point was an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a normal total bilirubin level.ResultsOf 216 patients who underwent randomization and received at least one dose of obeticholic acid or placebo, 93% received ursodiol as background therapy. The primary end point occurred in more patients in the 5–10-mg group (46%) and the 10-mg group (47%) than in the placebo group (10%; P<0.001 for both comparisons). Patients in the 5–10-mg group and those in the 10-mg group had greater decreases than those in the placebo group in the alkaline phosphatase level (least-squares mean, −113 and −130 U per liter, respectively, vs. −14 U per liter; P<0.001 for both comparisons) and total bilirubin level (−0.02 and −0.05 mg per deciliter [−0.3 and −0.9 μmol per liter], respectively, vs. 0.12 mg per deciliter [2.0 μmol per liter]; P<0.001 for both comparisons). Changes in noninvasive measures of liver fibrosis did not differ significantly between either treatment group and the placebo group at 12 months. Pruritus was more common with obeticholic acid than with placebo (56% of patients in the 5–10-mg group and 68% of those in the 10-mg group vs. 38% in the placebo group). The rate of serious adverse events was 16% in the 5–10-mg group, 11% in the 10-mg group, and 4% in the placebo group.ConclusionsObeticholic acid administered with ursodiol or as monotherapy for 12 months in patients with primary biliary cholangitis resulted in decreases from baseline in alkaline phosphatase and total bilirubin levels that differed significantly from the changes observed with placebo. There were more serious adverse events with obeticholic acid. (Funded by Intercept Pharmaceuticals; POISE ClinicalTrials.gov number, NCT01473524; Current Controlled Trials number, ISRCTN89514817.)

Hepatitis por el virus C

EpidemiologyHepatitis C affects 180 million people worldwide. It is the first leading indication for a liver transplantation. Natural history. In our country. Natural history of this disease is the development of cirrhosis and an increase of hepatocellular carcinoma risk. Clinical manifestationsIt is an asymptomatic disease, thus when the patient shows some clinical signs, this situation indicates an advanced disease stage, therefore it is very important the encouragement of screening programs. DiagnosisThe first diagnostic tool is the detection of antibodies against HCV and then, the confirmation study must be done demonstrating viral replication. Indication of treatmentThe indication to receive treatment is performed after fibrosis evaluation. New tools for a non-invasive measurement of liver fibrosis and newest ultrasound machines allows for an accurate and quickly disease staging. Direct acting antiviralsNewest direct-acting antivirals incorporated to HCV treatment options have made a great increase in cure rates avoiding the use of interferon and ribavirin.

Enhanced liver fibrosis marker as a noninvasive predictor of mortality in HIV/hepatitis C virus-coinfected women from a multicenter study of women with or at risk for HIV.

Coinfection with hepatitis C virus (HCV) is a major cause of morbidity and mortality among individuals with HIV. Our objective was to assess the prognostic performance of noninvasive measures of liver fibrosis in predicting all-cause mortality in women with HIV/HCV coinfection. We studied HCV/HIV coinfected women enrolled in the prospective, multicenter Women's Interagency HIV Study. Aspartate aminotransferase to platelet ratio and FIB-4 were used to identify women without fibrosis at all visits and women who progressed to severe fibrosis. Enhanced liver fibrosis (ELF), which utilizes direct measures of fibrosis, hyaluronic acid, procollagen III aminoterminal peptide and tissue inhibitor of matrix metalloproteinase was performed. Included were 381 women with 2296 ELF measurements, with mean follow-up 8.3 ± 3.3 years. There were 134 deaths (60% with severe liver fibrosis). Receiver operator characteristic curves at fixed time windows prior to death or at end of follow-up showed that ELF was best at predicting mortality when tested within a year of death (area under the curve for ELF 0.85 vs. APRI 0.69, P < 0.0001 and vs. FIB-4 0.75, P = 0.0036); and 1-3 years prior (ELF 0.71 vs. APRI 0.61, P = 0.005 and vs. FIB-4 0.65, P = 0.06). Use of all three measures did not improve on ELF alone. In multivariate logistic regression models controlling for CD4 cell count, HIV viral load, antiretroviral use and age, ELF continued to perform better than APRI and FIB-4. ELF predicted all-cause mortality and was superior to APRI and FIB-4 in HIV/HCV coinfected women.

Noninvasive Measurement of Liver Fibrosis Using Transient Elastography in Pediatric Patients with Major Thalassemia Who Are Candidates for Hematopoietic Stem Cell Transplantation

Although liver biopsy is an invasive procedure, it remains the gold standard technique for the evaluation of hepatic fibrosis in different patients, including those with major thalassemia (MT). Recently, noninvasive imaging techniques, such as transient elastography, have emerged. We investigated the effectiveness of TE, in comparison to liver biopsy, for the evaluation of liver fibrosis in pediatric patients with MT who were candidates for hematopoietic stem cell transplantation (HSCT). Eighty-three pediatric MT patients (48 boys and 35 girls), who were candidates for HSCT, were included in this study. The median age was 8 years. Liver stiffness was assessed for all patients, before transplantation, using both TE, measured in kilopascals (kPa) and liver biopsy, based on the Metavir score. The diagnostic accuracy of TE and liver biopsy were estimated using linear discriminated analysis (the area under the receiver operating characteristic curves [AUROCs]). The median TE score was 4.3 kPa (range, 3.5 to 5.2). The TE value did not differ among patients with different ferritin levels (P = .53). TE increased proportionally to Metavir fibrosis stages (P < .001) and the necro-inflammatory grade (P < .001). The TE score also correlated to liver iron content (P < .001), liver size (P < .003), and Lucarelli risk classification (LRC) (P < .001). ROC curve analysis revealed moderate accuracy of the TE score for the diagnosis of fibrosis (AUROC = 73%) and for distinguishing individuals with a LRC III from those classified as I and II (AUROC = 82%). The TE score was also superior to Fibrosis-4 (AUROC = 61%) for the assessment of liver fibrosis and LRC differentiation. The results of this study demonstrated that TE can be a valuable method for assessing liver fibrosis and differentiating LRC III from the other 2 classes in pediatric patients with MT who have been selected for HSCT.

CD4/CD8 ratio is a promising candidate for non-invasive measurement of liver fibrosis in chronic HCV-monoinfected patients

The extent of liver fibrosis is an important factor in prognosis and clinical decision-making in chronic hepatitis C virus (HCV) infection. We investigated CD4/CD8 ratio in HCV-monoinfected and HIV/HCV-coinfected patients, in order to reveal its relation with liver fibrosis. CD4/CD8 ratio in the peripheral blood was assessed by flow cytometry in a cohort of 19 HCV-monoinfected, 14 HIV/HCV-coinfected, ten HIV-monoinfected patients and 15 healthy controls. Liver fibrosis was assessed by transient elastography (n = 25) or by liver biopsy (n = 8). Coinfection with HIV was associated with decreased CD4/CD8 ratios in chronic HCV-infected patients, despite adequate antiretroviral treatment. Furthermore, HCV-monoinfected patients with F3-F4 liver fibrosis demonstrated much lower CD4/CD8 ratios than patients with F0-F2 fibrosis (1.4 versus 2.5, p = 0.023). Similarly, we observed a strong negative correlation between the CD4/CD8 ratio and liver stiffness measured by transient elastography (R = -0.78, p = 0.0006). ROC analysis revealed that CD4/CD8 ratio as a non-invasive marker for fibrosis is very promising (area under the curve 0.8). Although our study was performed with a relatively small number of patients, our findings suggest that the CD4/CD8 ratio is a promising candidate for non-invasive evaluation of liver fibrosis in HCV-monoinfected patients.

Noninvasive measurement of liver fibrosis by transient elastography and influencing factors in patients with chronic hepatitis B—A single center retrospective study of 466 patients

The noninvasive measurement of liver stiffness (LS) was evaluated by transient elastography (FibroScan) and the possible influencing factors from the patients' clinical situations including age, gender, liver inflammation represented by alanine transaminase (ALT) and total billirubin (TBIL) level, HBV replication (HBV DNA loads), portal vein pressure (portal vessel diameter, PVD), splenic thickness (SPT) and body mass index (BMI) were analyzed in patients with chronic hepatitis B (CHB). A total of 466 patients including 31 patients with acute-on-chronic liver failure (ACLF), and 435 patients with chronic hepatitis B (CHB) among which 82 patients were diagnosed with liver cirrhosis (LC) by clinical manifestations and liver B-type ultrasonic inspection were enrolled at Tongji Hospital from April to December 2009. LS was measured by a FibroScan device (EchoSens, France). Simultaneously, ALT and TBIL levels, HBV DNA loads, PVD, SPT and BMI in all patients were also tested. Forty-one healthy volunteers served as controls. The values of LS were correlated positively with ages of CHB patients and significantly higher in males than in females. In patients with BMI>28 kg/m(2) (obesity) and abnormal levels of ALT and TBIL, LS values were significantly increased as compared with those having normal levels of ALT and TBIL. The patients with ACLF had the highest LS value. Furthermore, LS values in the patients with LC were significantly higher than those in patients without LC. It is concluded that noninvasive measurement of liver fibrosis by FibroScan provides an alternative method to evaluate liver fibrosis of patients with CHB. In order to properly illustrate the stiffness value taken by transient elastography, patients' gender should be taken into consideration and it is also suggested to avoid possible influencing factors including liver inflammation (high levels of ALT and TBIL) and obesity (high BMI).

Estimating Complex Multi-State Misclassification Rates for Biopsy-Measured Liver Fibrosis in Patients with Hepatitis C

For both clinical and research purposes, biopsies are used to classify liver damage known as fibrosis on an ordinal multi-state scale ranging from no damage to cirrhosis. Misclassification can arise from reading error (misreading of a specimen) or sampling error (the specimen does not accurately represent the liver). Studies of biopsy accuracy have not attempted to synthesize these two sources of error or to estimate actual misclassification rates from either source. Using data from two studies of reading error and two of sampling error, we find surprisingly large possible misclassification rates, including a greater than 50% chance of misclassification for one intermediate stage of fibrosis. We find that some readers tend to misclassify consistently low or consistently high, and some specimens tend to be misclassified low while others tend to be misclassified high. Non-invasive measures of liver fibrosis have generally been evaluated by comparison to simultaneous biopsy results, but biopsy appears to be too unreliable to be considered a gold standard. Non-invasive measures may therefore be more useful than such comparisons suggest. Both stochastic uncertainty and uncertainty about our model assumptions appear to be substantial. Improved studies of biopsy accuracy would include large numbers of both readers and specimens, greater effort to reduce or eliminate reading error in studies of sampling error, and careful estimation of misclassification rates rather than less useful quantities such as kappa statistics.

A review of the natural history of chronic hepatitis B in the era of transient elastography

Understanding the natural history of chronic hepatitis B is important in order to predict the prognosis, to stratify the risk of hepatocellular carcinoma and to select appropriate candidates for antiviral treatment. Liver fibrosis is the pathogenic process that leads to liver cirrhosis. The study of liver fibrosis in the past has largely been hampered by the invasive nature of a liver biopsy. Most liver biopsy series represent biased populations with more active disease. Transient elastography is a reliable and non-invasive measurement of liver fibrosis that allows the study of liver fibrosis among patients without clinical indication for liver biopsy. Large studies using transient elastography in patients with predominantly normal alanine aminotransferase levels have been reported recently. The different roles of patient age, hepatitis B virus DNA and alanine aminotransferase levels in the risk stratification for advanced liver fibrosis have been defined in hepatitis B e antigen-positive and hepatitis B e antigen-negative chronic hepatitis B patients. The relationship between metabolic syndrome and chronic hepatitis B is also explored. In this review, new insights from studies using transient elastography on the natural history of chronic hepatitis B with special focus on liver fibrosis will be summarized and discussed.

Diagnosis and Quantitation of Fibrosis

Hepatic fibrosis is the final common pathway for many different liver insults. Originally considered to be irreversible, hepatic fibrosis is now known to be a dynamic process with a significant potential for resolution. The diagnosis and quantitation of fibrosis have traditionally relied on liver biopsy. However, there are a number of drawbacks including the invasive nature of the procedure, sampling error, and interobserver variability. This article reviews the current role of liver biopsy in the assessment of hepatic fibrosis and discusses the role of the newer noninvasive methods including serum markers and radiologic tests.

Noninvasive assessment of liver fibrosis in patients with Fontan circulation using transient elastography and biochemical fibrosis markers

Studies have shown that patients with failing Fontan circulation may develop liver cirrhosis with its sequelae. Therefore, early detection of fibrosis is essential to identify patients at risk. Transient elastography has been evaluated for noninvasive staging of liver fibrosis in a multitude of studies. A total of 39 patients who underwent the Fontan procedure were included in the study. All patients underwent an abdominal ultrasound, transient elastography, and detailed laboratory testing. Conventional echocardiography assessment of inflow and outflow and ventricular function were performed. Significant signs of liver fibrosis were found in 36 of 39 children according to the elastography method and in 28 of 39 children according to the measured biochemical fibrosis markers. The Spearman correlation coefficient between the liver stiffness measured with transient elastography and the time interval since the Fontan operation was highly significant (0.514, P = 0.001). The present study shows that patients who undergo the Fontan procedure are at increased risk of developing liver fibrosis and liver cirrhosis. The risk increases with the age of the patient and the time interval since the Fontan procedure. The noninvasive measurement of liver fibrosis using transient elastography and fibrosis marker scores can be a useful tool to identify patients at risk and for noninvasive surveillance.