A new method to estimate the histological stage of primary biliary cholangitis.

OBJECTIVE: To analyze the diagnostic efficacy of the periportal hypoechoic band (PHB) in the histological stage of patients with primary biliary cholangitis (PBC). METHODS: We prospectively included 77 cases of PBC pathologically or clinically confirmed, and high-frequency ultrasound (HFUS) measurements of the PHB were performed in all included patients. Ludwig staging system of histopathology was used as the gold standard. RESULTS: The width of the PHB was positively correlated with histological staging (r = 0.844, p < 0.001). By area under the receiving operating characteristic curve (AUROC), the best cutoff value for PHB for advanced stage (≥ stage 3) was 2.4 mm (AUROC: 0.934; 95%CI: 0.841-0.981) and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The correct rate for early-stage PBC was 87.9% and for the progressive stage was 93.1%. After multi-factor regression analysis, the PHB (OR = 1.331, CI = 1.105-1.603, p = 0.003) and total bilirubin (OR = 1.156, CI = 1.041-1.285, p = 0.007) were independent influencing factors for progressive PBC. CONCLUSIONS: Measurement of the PHB to assess advanced PBC is a simple and effective method. This method may complement current methods for the histological staging assessment of patients with PBC. REGISTRATION: Clinical trial registration: ChiCTR 2000032053, 2020/04/19. CLINICAL RELEVANCE STATEMENT: The measurement of periportal hypoechoic band (PHB) provides a simple and easy assessment of the degree of disease progression in patients with PBC and provides an important clinical reference in predicting the histological staging of PBC from an ultrasound perspective. KEY POINTS: • The PHB is correlated with histological staging in the patient with PBC. • The area under the ROC curves of PHB for detecting advanced stage (≥ stage 3) were 0.934 and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The application of PHB can better assess the advanced PBC. • Measurement of the PHB to assess advanced PBC is a simple and effective method that can significantly reduce the need for liver biopsy.

Noninvasive prediction of insufficient biochemical response after ursodeoxycholic acid treatment in patients with primary biliary cholangitis based on pretreatment nonenhanced MRI.

OBJECTIVES: To explore the feasibility of pretreatment nonenhanced magnetic resonance imaging (MRI) in predicting insufficient biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). METHODS: From January 2009 to April 2022, consecutive PBC patients who were treated with UDCA and underwent nonenhanced MRI within 30 days before treatment were retrospectively enrolled. All MR images were independently evaluated by two blinded radiologists. Uni- and multivariable logistic regression analyses were performed to develop a predictive model for 12-month insufficient biochemical response. Model performances were evaluated by computing the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 74 patients (50.6 ± 11.9 years; 62 females) were included. Three pretreatment MRI features, including hepatomegaly (odds ratio [OR]: 4.580; p = 0.011), periportal hyperintensity on T2-weighted imaging (T2WI) (OR: 4.795, p = 0.008), and narrowing of the bile ducts (OR: 3.491; p = 0.027) were associated with 12-month insufficient biochemical response in the multivariable analysis. A predictive model based on the above indicators had an AUC of 0.781, sensitivity of 85.4%, and specificity of 61.5% for predicting insufficient biochemical response. CONCLUSIONS: A noninvasive model based on three pretreatment MRI features could accurately predict 12-month insufficient biochemical response to UDCA in patients with PBC. Early identification of PBC patients at increased risk for insufficient response can facilitate the timely initiation of additional treatment. CLINICAL RELEVANCE STATEMENT: A noninvasive predictive model constructed by incorporating three pretreatment MRI features may help identify patients with primary biliary cholangitis at high risk of insufficient biochemical response to ursodeoxycholic acid and facilitate the timely initiation of additional treatment. KEY POINTS: • Noninvasive imaging features based on nonenhanced pretreatment MRI may predict an insufficient biochemical response to UDCA in PBC patients. • A combined model based on three MRI features (hepatomegaly, periportal hyperintensity on T2-weighted imaging, and narrowing of the bile ducts) further improved the predictive efficacy for an insufficient biochemical response to UDCA in PBC patients, with high sensitivity and specificity. • The nomogram of the combined model showed good calibration and predictive efficacy for an insufficient biochemical response to UDCA in PBC patients. In particular, the calibration curve visualised the clinical applicability of the prediction model.

Ultrasound imaging findings in primary biliary cholangitis.

BACKGROUND: Our study aimed to analyze the characteristics of ultrasound images corresponding to each histological stage of primary biliary cholangitis (PBC). METHODS: We prospectively analyzed 75 confirmed cases of PBC and used liver biopsy as the gold standard to determine the disease stage. RESULTS: The typical ultrasound images of patients with PBC were characterized by a thickening of the portal vein wall (PVW) and periportal hypoechoic band (PHB) width with increasing histological stages, and significant increases in the left hepatic lobe diameter (LHLD) in stage II (by 64.0%) and stage III (by 69.2%). PHB width (r = 0.857, p < 0.001), PVW thickness (r = 0.488, p < 0.001), and spleen area (r = 0.8774, p < 0.001) were positively correlated with the histological stage. Significant changes were noted in the liver surface, echo texture, and edge between different stages. The areas under the receiver operating characteristic curve of composite indicators were 0.965 for predicting progressive PBC(≥ stage 2), and 0.926 for predicting advanced PBC(≥ stage 3). CONCLUSIONS: The ultrasound imaging characteristics of patients with PBC varied according to the histological staging. LHLD, PVW thickness, and PHB width were significantly correlated with the histological stage. A combination of high- and low-frequency ultrasound imaging can provide relevant cues regarding the degree of PBC progression and important clinical reference values. The application of all the ultrasound image findings as the composite indicators can better predict progressive and advanced PBC, providing important clinical reference values.

Systematic review and meta-analysis: Transient elastography compared to liver biopsy for staging of liver fibrosis in primary biliary cholangitis.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) is an autoimmune liver disease, with 60% of patients being asymptomatic at diagnosis and 30% progressing rapidly into liver fibrosis. Liver biopsy is standard for staging fibrosis, but performance of non-invasive methods such as transient elastography (TE) have not been evaluated. We conducted a meta-analysis of articles up to May 2022 to evaluate the performance of TE compared with liver biopsy in adult patients with PBC. MATERIALS AND METHODS: Two reviewers performed the search and assessed which articles were included. The quality of each study was evaluated according to QUADAS-2 and NOS. Meta-analysis of sensitivity and specificity was conducted with a bivariate random-effects model. The protocol was registered in PROSPERO, ID CRD42020199915. RESULTS: Four studies involving 377 patients were included. Only stages F3 and F4 were computed in the meta-analysis. TE had a pooled sensitivity of 68% and specificity of 92% for stage F3 and a pooled sensitivity of 90% and specificity of 94% for stage F4. The AUROC curves were 0.91 (95% Confidence Interval (CI) 0.88-0.93) and 0.97 (95% CI 0.96-0.98) for stages F3 and F4, respectively. The mean cut-off points of TE for stage F3 were 9.28 kPa (95% CI 4.98-13.57) and for stage F4 were 15.2 kPa (95% CI 7.02-23.37). CONCLUSIONS: TE performance compared with liver biopsy in adult patients with PBC was excellent for staging liver fibrosis and was able to rule out cirrhosis in clinical practice.

Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis.

BACKGROUND & AIMS: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. METHODS: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. RESULTS: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026-1.054) and 1.042 (1.029-1.056), respectively (p <0.0001 for both). Adjusted C-statistics (95% CI) at baseline were 0.83 (0.79-0.87) and 0.92 (0.89-0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8 kPa and 15 kPa cut-offs optimally separated low-, medium-, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM. CONCLUSIONS: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered. LAY SUMMARY: Primary biliary cholangitis (PBC) is a chronic autoimmune disease, wherein the body's immune system mistakenly attacks the bile ducts. PBC progresses gradually, so surrogate markers (markers that predict clinically relevant outcomes like the need for a transplant or death long before the event occurs) are often needed to expedite the drug development and approval process. Herein, we show that liver stiffness measurement is a strong predictor of clinical outcomes and could be a useful surrogate endpoint in PBC trials.

Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut-Off Approach.

BACKGROUND AND AIMS: Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis (AF) at disease presentation in PBC. APPROACH AND RESULTS: We collected data from 167 consecutive treatment-naïve PBC patients who underwent liver biopsy (LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and >11.0 kPa enabled to exclude and confirm, respectively, AF (negative predictive value [NPV] = 0.94; positive predictive value [PPV] = 0.89; error rate = 5.6%). These values were externally validated in an independent cohort of 91 PBC patients (NPV = 0.93; PPV = 0.89; error rate = 8.6%). Multivariable analysis found that the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. CONCLUSIONS: In a multicenter study of treatment-naïve PBC patients, we identified two cutoffs (LSM ≤6.5 and >11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.

Transverse myelitis associated with primary biliary cirrhosis: clinical, laboratory, and neuroradiological features.

PURPOSE: Only five patients diagnosed with transverse myelitis (TM) associated with primary biliary cirrhosis (PBC) have been reported in the literature to date. We report two additional patients with TM associated with PBC at our hospital and review all seven cases. MATERIALS AND METHODS: An association between neuromyelitis optic spectrum disease (NMOSD) and PBC is reported for the first time in one of our patients. The second patient was diagnosed with TM associated with PBC without Sjögren's syndrome (SS). A literature review was performed using the PubMed database. RESULTS: All patients diagnosed with TM associated with PBC were female with a median age of 53 years. TM was associated with SS in 71.4% of the patients. Complete TM and incomplete TM were diagnosed in 71.4% and 28.6% of the patients. The erythrocyte sedimentation rate was increased in 83.3% of patients. All patients were positive for anti-mitochondrial antibodies. Other autoantibodies, including anti-nuclear antibodies, rheumatoid factor, anti-SSA antibody, were detected in some patients. Cerebrospinal fluid analysis was abnormal in 83.3% of patients. The spinal cord lesions involved more than three vertebral segments in 85.7% of patients. Glucocorticoids were administered in 85.7% of patients, and good responses were observed. CONCLUSIONS: The association between TM and PBC may be missed by neurologists. More attention should be paid to the association between NMOSD and PBC. Most patients show SS and may experience relapse, and there is a good rationale for early commencement of immunosuppressive therapy.

Liver Stiffness Measured by Either Magnetic Resonance or Transient Elastography Is Associated With Liver Fibrosis and Is an Independent Predictor of Outcomes Among Patients With Primary Biliary Cholangitis.

GOALS: We aimed to describe the diagnostic and prognostic performance of transient elastography (TE) and magnetic resonance elastography (MRE) in patients with primary biliary cholangitis (PBC). BACKGROUND: The diagnostic performance of TE and MRE in detecting advanced fibrosis in PBC and in predicting outcomes independent of existing serologic prognostic markers is incompletely understood. MATERIALS AND METHODS: Five hundred thirty-eight consecutive patients with PBC at 3 centers with liver stiffness (LS) measurements by TE (n=286) or MRE (n=332) were reviewed. LS cutoffs for predicting fibrosis stages were determined by receiver operating characteristic curves among those with a liver biopsy (TE, n=63; MRE, n=98). Cox proportional hazard regression modeling was used to identify associations between covariates and hepatic decompensation. RESULTS: The optimal LS thresholds for predicting histologic stage F4 were 14.40 kPa (area under the curve=0.94) for TE and 4.60 kPa (area under the curve=0.82) for MRE. Both TE and MRE outperformed biochemical markers for the prediction of histologic advanced fibrosis. Optimal LS thresholds to predict hepatic decompensation were 10.20 kPa on TE and 4.30 kPa on MRE. LS by TE and MRE (respectively) remained predictors of hepatic decompensation after adjusting for ursodeoxycholic acid responsiveness [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.24 and HR, 1.68; 95% CI, 1.28-2.19] and the GLOBE score (HR, 1.13; 95% CI, 1.07-1.19 and HR, 2.09; 95% CI, 1.57-2.78). CONCLUSION: LS measurement with either TE or MRE can accurately detect advanced fibrosis and offers additional prognostic value beyond existing serologic predictive tools.

Liver stiffness measurements by 2-dimensional shear wave elastography compared to histological and ultrasound parameters in primary biliary cholangitis.

BACKGROUND AND AIMS: Liver stiffness measurements (LSMs) by 2-dimensional-shear-wave elastography (LSM2D-SWE) are now widely used in hepatology. However, relevant information for primary biliary cholangitis (PBC) is scant. We compare LSM2D-SWE with liver biopsy (LB) in a cohort of PBC patients in Greece. METHODS: Data of 68 LBs from 53 PBC patients were retrospectively analyzed and fibrosis stage was compared to LSM2D-SWE. Forty-six patients (86.8%) were females and at the time of LBx median (IQR) age was 62.6 (53.2-72.1). Demographic, UDCA treatment, histological and B-mode ultrasound data were tested for their influence on LSM2D-SWE estimates. RESULTS: Liver fibrosis stages F0-F4 were found in 4, 19, 19, 16 and 10 cases, respectively. Across stages F0-F4, the LSM2D-SWE was 5.6 (5.1-6.1), 7.0 (5.8-7.7), 9.1 (7.3-11.5), 10.8 (9.9-12.2) and 14.5 (11.9-25.7) kPa, respectively, with highly significant difference (p<.001). The LSM2D-SWE differed also significantly between F0 vs. F1 (p=.027), F1 vs. F2 (p=.005) and F3 vs. F4 (p=.017). The discriminatory ability of LSM2D-SWE for mild, significant, severe fibrosis and cirrhosis was highly significant in all comparisons (p<.001), with AUC2D-SWE 95.3%, 87.4%, 85.3% and 95.3% and accuracy 89.7%, 85.3%, 80.9% and 86.8%, respectively. Among 21 parameters tested, significant predictors of LSM2D-SWE by multiple linear regression were fibrosis stage, portal inflammation and parenchymal heterogeneity. The portal inflammation grade accounted for 32.2% of LSM variation with adjusted R2 0.428. CONCLUSIONS: In patients with PBC, LSM measurements by 2D-SWE can reliably discriminate between mild, significant, severe fibrosis and cirrhosis. Measurements are significantly affected by portal inflammation grade.

FibroMeter scores for the assessment of liver fibrosis in patients with autoimmune liver diseases.

INTRODUCTION AND OBJECTIVES: We assessed FibroMeter virus (FMvirus) and FibroMeter vibration-controlled transient elastography (FMVCTE) in 134 patients with autoimmune liver diseases [ALD, autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC)], in order to assess new potential non-invasive biomarkers of liver fibrosis in patients with ALD, as similar data are missing. PATIENTS AND METHODS: The following groups were included: group 1: n = 78 AIH; group 2: n = 56 PBC. FMvirus and FMVCTE were determined in all 134 patients who underwent liver biopsy and TE the same day with sera collection. In addition, APRI and FIB-4 scores were calculated. RESULTS: The AUCs for TE and FMVCTE were significantly better (0.809; p < 0.001 and 0.772; p = 0.001, respectively for AIH and 0.997; p < 0.001 and 1; p < 0.001, for PBC) than the other three markers in predicting ≥ F3 fibrosis irrespective of the biochemical activity. FMVCTE and TE had good diagnostic accuracy (75.6% and 73%, respectively) for predicting severe fibrosis in AIH and performed even better in PBC (94.6% and 96.4%, respectively). The cut-offs of TE and FMVCTE had the best sensitivity and specificity in predicting ≥ F3 fibrosis in both AIH and PBC. CONCLUSIONS: FMVCTE seems to detect severe fibrosis equally to TE in patients with ALD but with better specificity. Biochemical disease activity did not seem to affect their diagnostic accuracy in ALD and therefore, could be helpful for the assessment of fibrosis, especially if they are performed sequentially (first TE with the best sensitivity and then FMVCTE with the best specificity).

Magnetic resonance imaging features in 283 patients with primary biliary cholangitis.

OBJECTIVES: To evaluate magnetic resonance imaging (MRI) features of the liver in primary biliary cholangitis (PBC). METHODS: We conducted a multicenter retrospective review on 283 patients with PBC who underwent an MRI between 2007 and 2018. Patients with overlap syndromes were excluded. MRI studies were independently reviewed by two abdominal radiologists for liver morphology, signal intensity, postcontrast enhancement, and decompensation. Liver and spleen volumes and normalized liver apparent diffusion coefficient (nlADC) were also calculated. MRI features were correlated with fibrosis stage among a subset of patients who had a liver biopsy within 6 months (n = 72). RESULTS: The study population was comprised of 283 patients (89% females) and a mean ± SD age of 59.4 ± 11.8 years. Lymphadenopathy (78.1%), periportal hyperintensity (36.7%), and periportal halo sign (27.6%) were the most common features. A positive correlation was found between fibrosis stage and spleen size (r = 0.457, p < 0.001), spleen volume (r = 0.557, p < 0.001) and portal vein diameter (r = 0.287, p = 0.013), and a negative correlation with nlADC (r = - 0.332, p = 0.011). Fibrosis stage also correlated with the presence of surface nodularity (p < 0.001), periportal halo sign (p = 0.04), collaterals (p = 0.033), and splenomegaly (p = 0.002). No significant differences in nlADC values were found in different fibrosis stages. Spleen size and volume were significantly higher in patients with ascites and collaterals (< 0.001). The periportal halo sign was present only in patients with significant fibrosis. None of the MRI features significantly correlated with inflammation grade. CONCLUSIONS: In PBC, presence of periportal halo sign correlates with significant fibrosis. Heterogeneous T2W intensity, heterogeneous postcontrast enhancement, collaterals, spleen size, and spleen volume correlate with fibrosis stage and may be useful for predicting advanced fibrosis. KEY POINTS: • The presence of periportal halo sign is indicative for significant fibrosis in primary biliary cholangitis. • Liver parenchymal heterogeneous T2 signal intensity, heterogeneous postcontrast enhancement, collaterals, spleen size, and spleen volume correlate with fibrosis stages in PBC and may be useful for predicting advanced fibrosis.

Clinical utility of FibroScan as a non-invasive diagnostic test for primary biliary cholangitis.

BACKGROUND AND AIM: Primary biliary cholangitis (PBC) is a chronic, slowly progressive, autoimmune liver disease. Some PBC patients display disease progression regardless of medical treatment. Therefore, it is important to accurately diagnose the clinical stage of PBC. This study investigated clinical merits of vibration-controlled transient elastography using FibroScan for assessing disease stage in PBC. METHODS: A total of 74 treatment-naïve PBC patients (84% female, median age: 64 years), 69 of whom having undergone histological assessment and five clinically diagnosed as at the cirrhosis stage, were enrolled for clinical comparisons of liver stiffness measurement (LSM) with other established indices. RESULTS: The number of patients with Nakanuma stages 1, 2, 3, and 4 was 18, 33, 17, and 6, respectively. The median LSM values for Nakanuma stages 1, 2, 3, and 4 were 5.05, 5.90, 8.90, and 23.70 kPa, respectively, and correlated significantly with disease progression based on Nakanuma's classification (r = 0.501, P < 0.001). LSM was also significantly related to other non-invasive serological markers (Mac-2 binding protein glycosylation isomer: r = 0.606, FIB-4 index: r = 0.493, and aspartate aminotransferase-to-platelet ratio index: r = 0.577; all P < 0.001). The areas under the receiver operating characteristic curve for diagnosing Nakanuma stage ≥ 2, stage ≥ 3, and stage 4 were 0.744, 0.763, and 0.907, respectively. A combination of LSM ≥ 7.0 kPa and Mac-2 binding protein glycosylation isomer ≥ 1.00 cut-off index could predict late-stage PBC (i.e. moderate to advanced disease progression) with a sensitivity of 0.58, specificity of 0.82, and accuracy of 0.74. CONCLUSIONS: Liver stiffness measurement using FibroScan provided simple, accurate, and non-invasive assessment of disease stage in PBC patients.

The Complementary Value of Magnetic Resonance Imaging and Vibration-Controlled Transient Elastography for Risk Stratification in Primary Sclerosing Cholangitis.

OBJECTIVES: Magnetic resonance (MR) risk scores and liver stiffness (LS) have individually been shown to predict clinical outcomes in primary sclerosing cholangitis (PSC). The aim of this study was to assess their complementary prognostic value. METHODS: Patients with PSC from 3 European centers with a 3-dimensional MR cholangiography available for central reviewing and a valid LS measurement assessed by vibration-controlled transient elastography by FibroScan performed within a 6-month interval were included in a longitudinal retrospective study. The MR score (Anali) without gadolinium (Gd) was calculated according to the formula: (1 × dilatation of intrahepatic bile ducts) + (2 × dysmorphy) + (1 × portal hypertension). The primary end point was survival without liver transplantation or cirrhosis decompensation. The prognostic values of LS and Anali score without Gd were assessed using Cox proportional hazard models. RESULTS: One hundred sixty-two patients were included. Over a total follow-up of 753 patient-years, 40 patients experienced an adverse outcome (4 liver transplantations, 6 liver-related deaths, and 30 cirrhosis decompensations). LS and Anali score without Gd were significantly correlated (ρ = 0.51, P < 0.001) and were independently associated with the occurrence of an adverse outcome. Optimal prognostic thresholds were 10.5 kPa for LS and 2 for the Anali score without Gd. Hazard ratios (95% confidence interval) were 2.07 (1.06-4.06) and 3.78 (1.67-8.59), respectively. The use in combination of these 2 thresholds allowed us to separate patients into low-, medium-, and high-risk groups for developing adverse outcomes. The 5-year cumulative rates of adverse outcome in these 3 groups were 8%, 16%, and 38% (P < 0.001), respectively. DISCUSSION: The combined use of MRI and vibration-controlled transient elastography permits easy risk stratification of patients with PSC.

Non-Invasive Prediction of High-Risk Varices in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis.

BACKGROUND: Baveno-VI guidelines recommend that patients with compensated cirrhosis with liver stiffness by transient elastography (LSM-TE) <20 kPa and platelets >150,000/mm(3) do not need an esophagogastroduodenoscopy (EGD) to screen for varices, since the risk of having varices needing treatment (VNT) is <5%. It remains uncertain if this tool can be used in patients with cholestatic liver diseases (ChLDs): primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These patients may have a pre-sinusoidal component of portal hypertension that could affect the performance of this rule. In this study we evaluated the performance of Baveno-VI, expanded Baveno-VI (LSM-TE <25 kPa and platelets >110,000/mm(3)), and other criteria in predicting the absence of VNT. METHODS: This was a multicenter cross-sectional study in four referral hospitals. We retrospectively analyzed data from 227 patients with compensated advanced chronic liver disease (cACLD) due to PBC (n = 147) and PSC (n = 80) that had paired EGD and LSM-TE. We calculated false negative rate (FNR) and number of saved endoscopies for each prediction rule. RESULTS: Prevalence of VNT was 13%. Baveno-VI criteria had a 0% FNR in PBC and PSC, saving 39 and 30% of EGDs, respectively. In PBC the other LSM-TE-based criteria resulted in FNRs >5%. In PSC the expanded Baveno criteria had an adequate performance. In both conditions LSM-TE-independent criteria resulted in an acceptable FNR but saved less EGDs. CONCLUSIONS: Baveno-VI criteria can be applied in patients with cACLD due to ChLDs, which would result in saving 30-40% of EGDs. Expanded criteria in PBC would lead to FNRs >5%.

Impact of Microbes on the Pathogenesis of Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC).

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent the major clinical entities of chronic cholestatic liver diseases. Both disorders are characterized by portal inflammation and slowly progress to obliterative fibrosis and eventually liver cirrhosis. Although immune-pathogenic mechanisms have been implicated in the pathogenesis of PBC and PSC, neither disorder is considered to be a classical autoimmune disease, as PSC and PBC patients do not respond to immune-suppressants. Furthermore, the decreased bile flow resulting from the immune-mediated tissue assault and the subsequent accumulation of toxic bile products in PBC and PSC not only perpetuates biliary epithelial damage, but also alters the composition of the intestinal and biliary microbiota and its mutual interactions with the host. Consistent with the close association of PSC and inflammatory bowel disease (IBD), the polyclonal hyper IgM response in PBC and (auto-)antibodies which cross-react to microbial antigens in both diseases, an expansion of individual microbes leads to shifts in the composition of the intestinal or biliary microbiota and a subsequent altered integrity of epithelial layers, promoting microbial translocation. These changes have been implicated in the pathogenesis of both devastating disorders. Thus, we will discuss here these recent findings in the context of novel and alternative therapeutic options.

Non-Invasive Assessment of Liver Fibrosis Progression and Prognosis in Primary Biliary Cholangitis.

PBC (formerly known as primary biliary cirrhosis and now named primary biliary cholangitis) is a disease with a wide range of severity and variable rate of progression. The diagnosis of advanced liver fibrosis/cirrhosis portends an increased risk of liver-related morbidity and mortality. Because of its invasiveness, liver biopsy tends to be replaced by non-invasive tools for assessing liver fibrosis, making prognosis and optimising risk stratification for selection of patients, requiring new medical approaches. Many direct or indirect biomarkers have been found to correlate with the severity of liver fibrosis in PBC. They are easy to use but lack sensitivity and reproducibility in individuals with early stage disease. Three main radiologic approaches are currently proposed to assess liver fibrosis: vibration controlled transient elastography (VCTE), acoustic radiation force impulse and magnetic resonance elastography. Data using VCTE are available only for the longitudinal evaluation of liver fibrosis and prognosis in PBC. VCTE outperformed all other non-invasive current surrogate markers of liver fibrosis in PBC. Because of its high acceptability and its ability to predict hepatic decompensation, VCTE could be a useful tool to help allocate cirrhotic patients into different categories of risk. None of the radiologic and serum markers have a perfect accuracy in studies so far published. Concordance between VCTE and serum biomarkers is a prerequisite for a correct prognosis assessment in individuals in clinical practice.

Acoustic radiation force impulse elastography for non-invasive assessment of disease stage in patients with primary biliary cirrhosis: A preliminary study.

AIM: To investigate the diagnostic performance of the acoustic radiation force impulse (ARFI) elastography for the assessment of primary biliary cirrhosis (PBC) stage. MATERIALS AND METHODS: Sixty-one patients with PBC in which liver biopsy and ARFI elastography measurements were performed in the same session were included in the study. The diagnostic performance of ARFI elastography for predicting the PBC stage was determined from the area under receiver operating characteristics (AUROC) curve analysis. RESULTS: ARFI elastography correlated significantly with histological stage (r = 0.74, p < 0.001) in patients with PBC. The AUROC of ARFI elastography for predicting histological stage equal to or higher than II, III, and equal to IV were 0.83, 0.93, and 0.91, respectively. The optimal cut-off values of ARFI elastography were 1.51 m/s, 1.79 m/s, and 2.01 m/s for PBC stage equal to or higher than II, III, and equal to IV, respectively. CONCLUSION: ARFI elastography is an acceptable and powerful technique for quantitative assessment of PBC stage.

[Comparative study of transient elastography versus real-time tissue elastography for assessment of liver fibrosis in patients with chronic liver disease].

OBJECTIVE: To compare the abilities of transient elastography (TE) versus real-time tissue elastography (RTE) for assessing liver fibrosis in patients with chronic liver disease. METHODS: Ninetytwo patients with chronic liver disease were enrolled in the study, and included 77 cases of chronic hepatitis B, 4 cases of chronic hepatitis C, 4 cases of autoimmune liver disease, 2 cases of primary biliary cirrhosis, I case of abnormal bile duct development, and 4 cases of unknown etiology.All patients were assessed by both TE and RTE in a single day.The correlation coefficient of liver fibrosis level and the receiver operating characteristic (ROC) curve of S more than 2 and =4 of TE and RTE were determined.The values were compared using findings fiom pathological analysis as reference. RESULTS: The correlation coefficient of liver fibrosis level was significantly higher for TE (r =0.755, 95% CI:0.651-0.831, P =0.000) than for RTE (r=0.481, 95% CI:0.306-0.624, P =0.000) (Z=3.07, P =0.002).The areas under the ROC curves for S more than 2 and =4 were 0.903 and 0.740 for TE and 0.915 and 0.786 for RTE, respectively, indicating that the performance of TE was superior to that of RTE. CONCLUSION: TE was superior to RTE for assessment of liver fibrosis.