Scheuer's Classification Research Articles

Novel noninvasive indices for the assessment of liver fibrosis in primary biliary cholangitis.

The present study aimed to investigate the accuracy of new noninvasive markers in predicting liver fibrosis among individuals with primary biliary cholangitis (PBC). This retrospective analysis included subjects with PBC who had liver biopsies. Scheuer's classification was used to determine the fibrosis stage. The bilirubin to albumin (Alb) ratio (BAR), fibrosis index based on the four factors (FIB-4), γ-glutamyl transpeptidase to platelet (PLT) ratio (GPR), red cell distribution width to PLT ratio (RPR), aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR), AST to PLT ratio index (APRI) and total bilirubin to PLT ratio (TPR) were calculated based on the laboratory parameters. A novel index called BARP was conceived as BAR x RPR. A total of 78 individuals with PBC were included in the study, 84.6% of whom had significant fibrosis, 30.8% had advanced fibrosis and 15.4% had cirrhosis. In the multivariate analysis, Alb was determined to be an independent predictor of advanced fibrosis (odds ratio=0.823, P=0.034). The area under the receiver operating characteristic curves (AUROCs) of the BAR, GPR, TPR and BARP were statistically significant in predicting severe fibrosis (P<0.05) and were 0.747, 0.684, 0.693 and 0.696, respectively. In assessing advanced fibrosis, the AUROCs for the AAR, APRI, BAR, FIB-4, RPR, TPR and BARP were 0.726, 0.650, 0.742, 0.716, 0.670, 0.735 and 0.750, respectively. The AUROCs for the APRI, BAR, FIB-4, RPR, TPR and BARP for cirrhosis prediction were 0.776, 0.753, 0.821, 0.819, 0.808 and 0.832, respectively. By comparing the AUROCs, it was demonstrated that the diagnostic capabilities of the BARP (P=0.021) and TPR (P=0.044) were superior to those of the APRI in predicting advanced fibrosis. In conclusion, the BAR, BARP and TPR were of predictive value for the grade of liver fibrosis in PBC and Alb had a diagnostic value in identifying early fibrosis. The aforementioned noninvasive indices may be used for predicting histologic stages of PBC.

Serum Alpha-Fetoprotein as a Predictor of Liver Fibrosis in HBeAg-Positive Chronic Hepatitis B Patients.

Background and Objectives: Non-invasive methods for evaluating liver fibrosis have been a crucial focus of clinical research. The aim of the current study is to assess the accuracy of serum alpha-fetoprotein (AFP) in determining the stage of liver fibrosis in patients with chronic hepatitis B (CHB) who are positive for HBeAg. Materials and Methods: The current study included a total of 276 HBeAg-positive CHB patients who underwent liver biopsy. The levels of serum AFP were measured in these patients using electrochemiluminescence immunoassays. The correlations between serum AFP levels and other laboratory parameters were analyzed using Spearman's correlation analysis. Binary logistic regression analysis was performed to determine the independent associations between serum AFP levels and liver fibrosis. The diagnostic performance of serum AFP and other non-invasive markers was evaluated using receiver operating characteristic (ROC) curves. Results: A total of 59 (21.4%) patients were found to have elevated levels of serum AFP (>7 ng/mL). These patients displayed a significantly higher proportion of both advanced fibrosis and cirrhosis compared to those with normal serum AFP levels (0-7 ng/mL). The level of serum AFP was positively associated with levels of serum globulin (GLB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL), as well as the AST-to-platelet ratio (APRI), fibrosis-4 (FIB-4), and Scheuer's classification, and negatively correlated with platelet (PLT) counts. Furthermore, serum AFP was found to be independently associated with significant fibrosis, advanced fibrosis, and cirrhosis. The results of the ROC analysis showed that serum AFP was an effective predictor of significant fibrosis, advanced fibrosis, and cirrhosis, with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95% CI: 0.721-0.821), 0.889 (95% CI: 0.847-0.923), and 0.925 (95% CI: 0.887-0.953), respectively. These values are higher than those of the APRI and FIB-4. Conclusions: Serum AFP could serve as a valuable supplemental biomarker for determining the severity of liver fibrosis in HBeAg-positive patients with chronic hepatitis B.

Prognostic utility of albumin-bilirubin grade in Japanese patients with primary biliary cholangitis

The albumin-bilirubin (ALBI) score is calculated using serum levels of total bilirubin and albumin as a simple method to assess liver function. This study investigated the ability of baseline ALBI score/grade measurements to assess histological stage and disease progression in individuals with primary biliary cholangitis (PBC) in a large Japanese nationwide cohort. A total of 8,768 Japanese patients with PBC were enrolled between 1980 and 2016 from 469 institutions, among whom 83% received ursodeoxycholic acid (UDCA) only, 9% received UDCA and bezafibrate, and 8% were given neither drug. Baseline clinical and laboratory parameters were retrospectively retrieved and reviewed from a central database. Associations of ALBI score/grade with histological stage, mortality, and need for liver transplantation (LT) were evaluated using Cox proportional hazards models. During the median follow-up period of 5.3 years, 1,227 patients died (including 789 from liver-related causes) and 113 underwent LT. ALBI score and ALBI grade were significantly associated with Scheuer's classification (both p <0.0001). ALBI grade 2 or 3 had significant associations with all-cause mortality or need for LT as well as liver-related mortality or need for LT according to Cox proportional hazards regression analysis (hazard ratio 3.453, 95% CI 2.942-4.052 and hazard ratio 4.242, 95% CI 3.421-5.260, respectively; both p <0.0001). Cumulative LT-free survival rates at 5 years in the ALBI grade 1, 2, and 3 groups were 97.2%, 82.4%, and 38.8%, respectively, while respective non-liver-related survival rates were 98.1%, 86.0%, and 42.0% (both p <0.0001, log-rank test). This large nationwide study of patients with PBC suggested that baseline measurements of ALBI grade were a simple non-invasive predictor of prognosis in PBC. Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by progressive destruction of intrahepatic bile ducts. This study examined the ability of albumin-bilirubin (ALBI) score/grade to estimate histological findings and disease progression in PBC by means of a large-scale nationwide cohort in Japan. ALBI score/grade were significantly associated with Scheuer's classification stage. Baseline ALBI grade measurements may be a simple non-invasive predictor of prognosis in PBC.

Feasibility, safety and tolerability of the CREB-binding protein/β-catenin inhibitor OP-724 in patients with advanced primary biliary cholangitis: an investigator-initiated, open-label, non-randomised, two-centre, phase 1 study

ObjectiveThis study aimed to evaluate the safety and tolerability of OP-724, a CREB-binding protein/β-catenin inhibitor, in patients with advanced primary biliary cholangitis (PBC).DesignAn open-label, non-randomised, phase 1 trial was conducted...

Is serum ferritin level or T2-sequence magnetic resonance imaging more effective in predicting liver iron in transfusion-dependent thalassemia cases?

Amaç: Transfüzyon bağımlı talasemi hastalarında aşırı demir yüklenmesi, sürekli şelasyon tedavisi ve demir düzeyi izlemini gerektiren bir durumdur. Serum ferritin düzeyinin tayini, demir yükünü takip etmek için basit bir yöntem olarak kabul edilmektedir. Bununla birlikte, karaciğer demir düzeyi tayininde manyetik rezonans görüntüleme (MRG) gibi yöntemlerin daha kesin olduğunu vurgulamaktadır.&#x0D; Gereç ve Yöntem: Talasemide demir yükünün anlaşılmasına katkıda bulunmak amacıyla, kök hücre transfüzyonuna hazırlık amacıyla karaciğer biyopsisi yapılan 14 transfüzyon bağımlı talasemi hastasının karaciğer demir düzeyi sonuçlarını karaciğer T2 MRG ve serum ferritin sonuçları ile karşılaştırıldı.&#x0D; Bulgular: Serum ferritin değeri ortalaması 2488,43±1520,18 mg/L idi. T2*MRG sonuçlarına göre karaciğer demir yükü değerlendirildiğinde sekiz hastada hafif düzey, beş hastada orta düzey, bir hastada ileri düzey demir birikimi saptandı. Modifiye Scheuer sınıflamasına göre biyopsilerde demir düzeyi iki hastada derece 1; yedi hastada derece 2; üç hastada derece 3 ve iki hastada derece 4 olarak değerlendirildi. Ferritin düzeyi arttıkça karaciğer demir biyopsi skoru da istatistiksel anlamlı olarak artmaktaydı (r=0,544 ve p=0,044). Karaciğer T2 MRG düzeyi ile karaciğer demir biyopsi skoru arasında ise istatistiksel olarak anlamlı ve ters yönlü korelasyon mevcuttu (r=-0,724 ve p=0,003). Karaciğer biyopsi demir skoruna göre demir düzeyini ayırt etmede ferritin düzeyi istatistiksel olarak anlamlı bulunmazken (p=0,096); T2*MRG ölçümlerine ilişkin ROC eğrisi altında kalan alan istatistiksel olarak anlamlı bulundu (AUC=0,967; 95% CI: 0,880-1,000 ve p=0,005).&#x0D; Sonuç: Çalışmamızda serum ferritin ve T2 MRG sonuçlarının karaciğer biyopsisi demir düzeyi ile korele olduğunu saptadık. Ancak ferritin düzeyinin karaciğer biyopsisi demir düzeyini göstermede sensitivite ve spesifitesinin düşük olduğu, T2 MRG ise sensitivite ve spesifitesinin yüksek olduğunu saptadık.

Clinical impact of antibodies to Sp100 on a bacterial infection in patients with primary biliary cholangitis.

BackgroundA specific antinuclear antibody for primary biliary cholangitis (PBC) is anti‐Sp100, which was recognized as a serological marker of concurrent urinary tract infection. We sought to determine the clinical characteristics of PBC patients who had anti‐Sp100.Patients and MethodsFifty‐one patients with PBC and 10 healthy controls (HCs) were enrolled. Anti‐Sp100 were determined with an ELISA method. Lipopolysaccharide‐binding protein (LBP) was measured as a serological hallmark for bacterial infection. The correlations of anti‐Sp100 with demographic, laboratory, and pathological parameters were investigated.ResultsSix of the 51 (11.8%) PBC patients had anti‐Sp100, whereas none of the HCs did. There was no significant difference in the frequency of antimitochondrial antibodies (AMAs) between PBC patients with and without anti‐Sp100 (67% vs. 82%, p = 0.5839). Biochemical and immunological parameters were not associated with the emergence of anti‐Sp100 in these patients. The clinical stage by Scheuer classification was not correlated with the existence of anti‐Sp100. No significant difference in the serum LBP levels was found between PBC patients with and without anti‐Sp‐100, although serum LBP levels were significantly higher in PBC patients with anti‐Sp100 than in HCs (8.30 ± 2.24 ng/ml, vs. 5.12 ± 2.48 ng/ml, p = 0.0022). The frequency of granuloma formation was higher in the liver specimens of PBC patients with anti‐Sp100 than in those without anti‐Sp100 (67% vs 29%, p = 0.0710).Conclusionanti‐Sp100 does not become a complementary serological marker for PBC in AMA‐negative patients. A bacterial infection may trigger the production of anti‐Sp100. Another factor is required to initiate the autoantibody production.

Enhanced liver fibrosis score as a surrogate of liver-related complications and mortality in primary biliary cholangitis.

The presence of bridging fibrosis predicts survival of primary biliary cholangitis (PBC). This study aimed to compare serum parameters for the estimation of liver fibrosis and prediction of clinical outcomes in PBC.Out of 392 patients with PBC, 102 who underwent liver biopsy and in whom fibrosis indices, platelet count, hyaluronic acid, type IV collagen 7 second domain, procollagen type III amino-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer, N-terminal type III collagen propeptide levels; fibrosis index based on 4 factors, aspartate aminotransferase-to-platelet ratio index, and enhanced liver fibrosis (ELF) score were determined, were included. The correlation of histological stages based on both Scheuer and Nakanuma classifications with fibrosis indices was investigated. The Nakanuma system comprises grading for liver fibrosis and bile duct loss. Diagnostic performances of 10 fibrosis indices were evaluated to identify patients with poor prognosis. Moreover, correlations of those with PBC clinical manifestation and survival were also investigated.Enhances liver fibrosis (ELF) score had the highest correlation coefficient for liver fibrosis evaluated according to either the Scheuer or Nakanuma classification among 10 serum fibrosis indices. It also had the highest diagnostic performance in estimating Scheuer stage III and Nakanuma fibrosis score 2, both of which represent portal-bridging fibrosis. Patients with an ELF score of ≥10.0 had shorter survival and presented more frequently clinical complications than those with an ELF score of <10.0.ELF score determines the severity of liver fibrosis and predicts the occurrence of complications and survival in patients with PBC.

Intrahepatic Expression of C-C Motif ligand 5 in Patients with Chronic Hepatitis B.

C-C motif ligand 5 (CCL5) is reported to play a key role in acute and chronic liver diseases. However, the association between CCL5 and chronic hepatitis B (CHB) remains to be explored. We aimed to investigate the CCL5 expression in the liver tissues of CHB patients and compared the CCL5 expression among CHB patients with different stages of liver inflammation and fibrosis. Liver tissue specimens from 51 CHB patients who underwent liver biopsy and twelve healthy liver donors were included in the present study. CCL5 expression in the liver tissues was analyzed using immunohistochemistry. The hepatic inflammation grades and fibrotic stages of CHB patients were assessed by the Scheuer classification system. Livers of CHB patients exhibited significantly accumulated CCL5+ cells when compared to those of healthy controls (42.80 ± 4.37 vs. 7.25 ± 0.99/HPF, P < .001). CHB patients with higher hepatic inflammation grades had more CCL5+ cells in their livers than those with lower grades (P < .05). However, the numbers of CCL5+ cells were not correlated with the fibrotic stages in CHB patients (r = .073, P = .61). The number of CCL5+ cells in the liver tissues of CHB patients was positively correlated with alanine transaminase levels (r = .278, P = .041) and aspartate aminotransferase levels (r = .328, P = .009). CHB patients have a significant accumulation of CCL5+ cells in the liver, and CCL5 may play a pathological role in hepatic inflammation of CHB.

The ursodeoxycholic acid response score predicts pathological features in primary biliary cholangitis.

The ursodeoxycholic acid response score (URS) can predict the biochemical response to 12months of ursodeoxycholic acid (UDCA) treatment in patients with primary biliary cholangitis (PBC). We investigated the relationship between the URS and the histopathological features before and after UDCA treatment. Patients with PBC (n = 126) were examined for the association between the probability of response (POR) to UDCA based on the URS formulas and clinicopathological features. Furthermore, 30 patients were examined for the association between the POR and pathological changes. The POR area under the receiver operating characteristic curve (AUROC) for predicting the biochemical response to UDCA was 0.861. The PORs of stage 1 in the Nakanuma system and grade 0 in the CK7 grading in hepatocytes were significantly higher than those of stage 3 and grade 3, respectively. The AUROCs for the prediction of stage ≥2, stage ≥3 and stage 4 in the Nakanuma system at pretreatment were 0.592, 0.710 and 0.817, respectively. The AUROCs for the prediction of grade ≥1, grade ≥2 and grade 3 in the CK7 hepatocyte grading were 0.741, 0.824 and 0.970, respectively. Furthermore, the AUROC for predicting the histological stage progression after UDCA treatment in the Scheuer classification and the Nakanuma system were 0.712 and 0.799, respectively. The URS not only predicts the biochemical response, but also reflects the Nakanuma system and the CK7 hepatocyte grading at pretreatment. This scoring system can identify an inadequate histological response to UDCA treatment in the Scheuer classification and the Nakanuma system.

Prediction of Transplant-Free Survival through Albumin-Bilirubin Score in Primary Biliary Cholangitis.

Albumin–bilirubin (ALBI) grade is defined using the ALBI score, which is calculated based on total serum bilirubin and albumin. This study aimed to evaluate the diagnostic ability of the ALBI score for determining hepatic fibrosis stage and transplant-free survival in primary biliary cholangitis (PBC) patients. A total of 181 Japanese patients with biopsy-proven or serologically diagnosed PBC were enrolled. The pathological stage was assessed using the Scheuer classification. The ALBI score differentiated fibrosis in stage 4 from that of 3 in the biopsy-proven cohort (p < 0.05). With an ALBI score cut-off value of −1.679, the sensitivity and specificity were 100% and 91.1%, respectively, with a likelihood ratio of 12.3 to differentiate stage 4 from stages 1–3. The ALBI score at the beginning of ursodeoxycholic acid (UDCA) prescription correlated with the two prognostic scores calculated after 1-year UDCA treatment. Kaplan–Meier analysis showed that the baseline ALBI score differentiated liver transplant-free survival (p < 0.05). The ALBI score presented a greater hazard ratio for transplant-free survival than aspartate aminotransferase-to-platelet ratio index (APRI) in Cox proportional hazard model. In conclusion, ALBI score indicates pathological stage in Japanese PBC patients and scores before UDCA prescription predict better liver transplant-free survival, which correlated well with the two major prognostic scores. The prognosis-predicting ability of the ALBI score might surpass that of APRI.

Serum alkaline phosphatase levels as a simple and useful test in screening for significant fibrosis in treatment-naive patients with hepatitis B e-antigen negative chronic hepatitis B.

BackgroundStaging of liver fibrosis is critical in guiding the treatment of chronic hepatitis B (CHB) virus. Many efforts have been made toward the research of noninvasive techniques, mostly focusing on hepatitis B e-antigen (HBeAg)-positive [HBeAg(+)] CHB patients, whereas HBeAg(+) and HBeA-negative [HBeAg(−)] represent different stages of hepatitis B virus infection. Thus, in this study, we aimed to search for routinely available clinical noninvasive liver fibrosis markers and separately analysed the markers in HBeAg(+) and HBeAg(−) CHB patients.MethodsPatients with CHB who were treatment naive and who underwent a liver biopsy at our hospital from 1 January 2016 to 31 April 2017 were enrolled. Liver histology was scored using the Scheuer classification system. The area under the receiver operator curve was used to determine the diagnostic accuracy.ResultsA total of 191 patients, including 104 HBeAg(+) and 87 HBeAg(−) treatment-naive CHB patients, were enrolled in this study. Serum alkaline phosphatase (ALP) levels increased gradually in all patients and separately in HBeAg(−) CHB patients, but not in HBeAg(+) CHB patients. ALP was an independent factors predicting significant fibrosis (S≥2) in all of the patients and separately in HBeAg(−) patients, with area under the receiver operator curves of 0.651 and 0.717, respectively. Further, the optimal cut-off value of ALP (>69.5 IU/l) for distinguishing HBeAg(−) CHB patients with significant fibrosis was determined (S≥2).ConclusionSerum ALP levels can identify significant fibrosis (S≥2) in treatment-naive HBeAg(−) CHB patients and could potentially reduce the need for liver biopsies and help to guide the clinical treatment of CHB.

Clinical utility of FibroScan® as a noninvasive diagnostic test for primary biliary cholangitis

Background/Aims Primary biliary cholangitis (PBC) is a chronic, slowly progressive, liver-specific autoimmune liver disease. Some patients with PBC display disease progression regardless of ursodeoxycholic acid therapy. Therefore, it is important to accurately diagnose the clinical stage of PBC. This study investigated the utility and clinical advantages of vibration-controlled transient elastography (VCTE) using FibroScan® for assessing disease status in PBC. Methods Forty-five treatment naive PBC patients (80% female, median age: 63 years), all of whom had undergone liver biopsy for histological assessment, were enrolled. Relationships between clinical indices and VCTE were compared with those for other noninvasive markers (FIB4 index and AST-to-platelet ratio index [APRI]) as well as platelet count (PLT) and several clinical features. Results The numbers of patients with histologically-assessed clinical stage I+II (early stage) and III+IV (late stage) PBC as defined by Scheuer or Nakanuma classification were 33 and 12 and 31 and 14, respectively. The median VCTE and controlled attenuation parameter (CAP) of FibroScan® were respectively 5.9 kPa and 205 dB/m. Respective median VCTE values in early- and late-stage PBC patients were 5.1 and 8.3 (p = 0.003). VCTE was significantly correlated with Scheuer (r = 0.48, p = 0.0008) and Nakanuma (r = 0.49, p = 0.0006) classification disease stage, whereas CAP was not but was associated with body weight (r = 0.38, p = 0.011). VCTE was also significantly related to FIB4 index (r = 0.39, p = 0.0082) and APRI (r = 0.51, p = 0.0003), but not with PLT (-0.25, p = 0.10). The areas under the receiver operating characteristic curve (AUROC) for diagnosing PBC stage II or more for VCTE, FIB4 index, and APRI were 0.75, 0.66, and 0.73, respectively (p > 0.05 for each comparison). The AUROCs for diagnosing late-stage PBC for VCTE, FIB4 index, and APRI were 0.78, 0.71, and 0.70, respectively (p > 0.05 for each comparison). A combination of VCTE > 6.0 kPa and FIB4 > 2.0 could predict late-stage PBC with a sensitivity of 0.8, specificity of 0.8, and accuracy of 0.8. Conclusions VCTE using FibroScan®provided comparable results to established markers for the assessment of liver fibrosis in patients with PBC. Further validation and better detection strategies are needed to more accurately identify PBC disease stage.

Association of CCL11, CCL24 and CCL26 with primary biliary cholangitis

BackgroundCCL11, CCL24 and CCL26 are potent chemokines for eosinophils. Since there has been no study reporting the association serum CCL11, CCL24 and CCL26 with fibrotic progression of PBC, the aim of this study is to explore the association. MethodsOne hundred and eight PBC patients, 52 patients with chronic hepatitis B (CHB) and 50 healthy controls (HC) were recruited. The sera were detected for CCL11, CCL24 and CCL26 using multiplex immunoassay. Other laboratory indicators were routinely measured. PBC was divided into four stages according to Scheuer's classification. ResultsSerum CCL11, CCL24 and CCL26 levels were significantly higher in PBC patients than those with CHB and HC (P < 0.05). The ROC analyses showed that all of the three CCLs performed well for identification of PBC (all P< or =0.001). The multiple linear regression analysis showed an independent relationship of CCL26 with APRI and FIB-4 in PBC patients, but no relationship of CCL11 and CCL24 with fibrotic indicators. Additionally, serum CCL11 and CCL26 were negatively correlated with histological stage of PBC, while serum CCL24 showed no statistical correlation. ConclusionSerum CCL11, CCL24 and CCL26 are upregulated in PBC. CCL11 and CCL26 are associated with fibrotic progression of PBC, but CCL24 is not.

Correlations between serum hepatitis B surface antigen and hepatitis B core antibody titers and liver fibrosis in treatment-naïve CHB patients

BackgroundPrevious studies have revealed that quantitative hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (qAnti-HBc) levels can be used as predictors of treatment response in both interferon-α and nucleoside analogue therapies. Few data have been published regarding the relationship between quantitative HBsAg or Anti-HBc levels and liver fibrosis stages in patients with chronic hepatitis B (CHB). MethodsWe conducted a cross-sectional study of treatment-naïve CHB patients. A total of 624 CHB patients were recruited. We assessed the serum HBsAg and qAnti-HBc levels, HBV DNA levels, HBV genotypes, BCP/PC mutations, histological fibrosis staging by Scheuer classification. ResultsIn HBeAg (+) patients, the S0-1 subjects had significantly higher serum HBsAg and lower qAnti-HBc levels than the S2-4 subjects (both p < 0.001). A moderate inverse correlation was present between serum HBsAg levels and fibrosis scores (r = −0.381, p < 0.001), and a moderate positive correlation was found between qAnti-HBc levels and fibrosis scores (r = 0.408, p < 0.001). In the HBeAg (−) patients, the S0-1 subjects also had significantly lower qAnti-HBc levels than the S2-4 subjects (p < 0.001); however, no significant difference in the HBsAg levels was observed between the S0-1 and S2-4 subjects (p > 0.05). Serum qAnti-HBc levels showed a moderate positive correlation with fibrosis scores (r = 0.383, p < 0.001), while serum HBsAg levels exhibited a low inverse correlation with fibrosis scores (r = −0.171, p < 0.001). Multiple logistic regression analysis showed that the parameters for predicting significant fibrosis (S ≥ 2) included age, PLT, qAnti-HBc levels, HBV genotype and BCP/PC mutations in HBeAg (+) group, and age, PLT, qAnti-HBc levels in HBeAg (−) group (all p < 0.05). The AUC of qAnti-HBc levels associated with the diagnosis of significant fibrosis abnormalities in HBeAg (+) and HBeAg (−) patients were 0.734 (95%CI 0.689 to 0.778) and 0.707 (95%CI 0.612 to 0.801), respectively. ConclusionOur study found an association between high serum qAnti-HBc levels and significant fibrosis in both HBeAg (+) and HBeAg (−) treatment-naïve CHB patients. However, low serum HBsAg levels were correlated with moderate to severe fibrosis in HBeAg (+) subjects only.

Implication of increased serum stromal cell-derived factor-1 for primary biliary cholangitis

BackgroundStromal cell-derived factor-1 (SDF-1), also called chemokine (C-X-C motif) ligand 12 (CXCL12), as a chemokine for premature B cells, T cells and monocytes, is detected in liver, pancreas, spleen and heart. However, its diagnostic value for primary biliary cholangitis (PBC) as well as the association of SDF-1 with inflammatory and fibrotic progression is unclear. The aim of this study was to determine serum stromal cell-derived factor-1 (SDF-1) level and to explore its diagnostic value for primary biliary cholangitis (PBC) as well as the association of SDF-1 with inflammatory and fibrotic progression of PBC. MethodsA total of 60 PBC patients who received liver biopsy, 32 age- and sex-matched patients with chronic hepatitis B (CHB) and 30 age- and sex-matched healthy controls (HC) were recruited. The sera were measured for SDF-1, interleukin-4 (IL-4), interferon gamma (IFN-γ) and IL-17 using multiplex immunoassay. PBC was divided into four histologic stages according to Scheuer's classification. ResultsThe results showed significantly higher median level of serum SDF-1 (median, interquartile (IQR), 1186.96, 1002.05–1471.33 pg/mL) in PBC patients than those with CHB (median, IQR, 740.69,600.30–1239.27 pg/mL) and HC (median, IQR, 738.44, 687.65–879.33 pg/mL) (P < 0.001). There was no significant difference between CHB patients and HC (P = 0.526). The receiver operating characteristic curves (ROC) showed good diagnostic performance of serum SDF-1 for PBC, AMA-positive and -negative PBC. In particular for AMA-negative PBC, the area under ROC was 0.817, with optimal cutoff value of 802.64 pg/mL and the sensitivity of 100%. Serum SDF-1 level was not associated with other immune, inflammatory and fibrotic indicators, including AMA, ANA, anti-gp210, sp100 and centromere antibodies, bilirubin, ALT, AST, ALP, GGT, WBC, neutrophil, lymphocyte, platelet, Neutrophil- (NLR) and platelet-lymphocyte (PLR), AST to ALT ratio, AST to platelet ratio index (APRI) and FIB-4 index (P > 0.05). Also, there was no significant difference for serum SDF-1 among histological stages (P = 0.091). However, Serum SDF-1 level was significantly correlated with serum IL-17 (r = 0.373, P = 0.004), but not with IL-4 (r = 0.110, P = 0.407) and IFN-γ (r = 0.215, P = 0.098) in those with PBC. ConclusionSerum SDF-1 is increased in and may be a potential useful marker for PBC. Moreover, it may be associated with Th17 recruitment and differentiation in PBC. However, serum SDF-1 may not be associated with the progression of PBC.

Serum Monocyte Chemoattractant Protein-1 Predicts Liver Inflammation of Patients with Chronic Hepatitis B.

The usefulness of serum markers for predicting liver necroinflammation is limited in chronic hepatitis B (CHB) patients with normal or slightly elevated alanine aminotransferase (ALT). Monocyte chemoattractant protein-1 (MCP-1) is an important inflammatory mediator in liver disease. Our study was to investigate the expression of MCP-1 and its diagnostic value in patients with HBV-related liver necroinflammation. One hundred and six patients with hepatitis B virus (HBV) infection were recruited. All were positive for hepatitis B e antigen (HBeAg) and underwent liver biopsy. Significant inflammation was defined as inflammatory grade ≥ 2 according to Scheuer's classification scoring system. Enzyme-linked immunosorbent assay (ELISA) was used to detect expression of MCP-1 in the peripheral blood of all patients, and receiver operating characteristics (ROC) analysis was used to evaluate diagnostic accuracy of MCP-1 and liver inflammation. MCP-1 level in patients with HBV infection was higher than in healthy controls (p < 0.05). Moreover, MCP-1 level in the ALT ≥ two times of upper limits of normal (2 ULN) group was higher than that of the ALT < 2 ULN group (p < 0.05). In the ALT < 2 ULN group, the MCP-1 level in patients whose inflammatory activity was grade ≥ 2 was higher than in patients with grade < 2 (p < 0.05). ROC curve analysis showed that the area under the curve of MCP-1 in diagnosis of liver inflammation was 0.842. MCP-1 could be used as a serological marker for non-invasive evaluation of liver inflammation in CHB patients with normal or slightly elevated ALT.

Value of susceptibility weighted imaging in hepatic fibrosis staging by using MR in a rabbit model

To assess the feasibility of susceptibility weighted imaging (SWI) in staging hepatic fibrosis(HF). Sixty healthy rabbits were divided into three groups: HF group(n=32), control group(n=16), supplementary group(n=12). Rabbits in HF group and supplementary group were injected subcutaneously with 50% CCl4 oil solution to establish hepatic fibrosis model. On the basis of preliminary test, eight rabbits from HF group and four rabbits from control group underwent liver conventional MR scans and SWI once a time at 4, 5, 6, 10 weeks after CCl4 administration.After MR scans at each time point, rabbits were killed to detect pathological staging with Scheuer staging.The liver signal intensity (SI) and liver-to-muscle SI ratios (SIR) were measured. According to the Scheuer classification of histological fibrosis stages, the correlation about the SI value, SIR value and the histological fibrosis stages was investigated by using the Spearman correlation test. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of SWI for staging HF on the basis of the histopathologic analysis of HF. There were fifteen rabbits in pathological staging F0, the value of SIR and SI was 0.974 ± 0.018, 374±44, SIR values of pathological staging from F1 to F4 were 0.963 ± 0.018, 0.796 ± 0.023, 0.786 ± 0.025, 0.512±0.024 respectively. SI values of pathological staging from F1 to F4 were 372±18, 376±22, 346±15, 288±19 respectively. In the early period of liver fibrosis, there were no statistical differences in the SI value between F0 and F1, F1 and F2 stage.With progression of hepatic fibrosis, from F2 to F4, SI value decreased, the difference was statistically significant (P<0.05). With the progress of liver fibrosis, SIR value was reduced. It was negatively correlated with the HF stages and SIR value(r=-0.896, P<0.05). ROC curve analysis showed that the efficiency of SI value diagnosis in liver fibrosis was high in the late stage of liver fibrosis, but it was low in the early stage.The performance of liver-to-muscle SI ratio on SWI was high in the early stage. Liver-to-muscle SI ratio had a higher diagnostic performance than SI in the diagnosis of liver fibrosis stages. SWI can be a safe, reliable method for staging hepatic fibrosis and provide quantitative imaging basis for clinical treatment.

An experimental study on the assessment of rabbit hepatic fibrosis by using magnetic resonance T1ρ imaging

ObjectiveTo explore the correlation between the T1ρ values of liver and liver fibrosis by using magnetic resonance (MR) T1ρ imaging. Materials and methodsThe study consisted of the control group and the hepatic fibrosis (HF) group. Carbon tetrachloride (CCl4) injection was performed once a week for 10weeks (week 1–10) in the HF group which was divided into 5 subgroups and underwent MR examinations at weeks 4, 5, 6, 10, and 15 respectively post the first CCl4 injection (week 1). According to Scheuer Classification, the stage of HF of all rabbits was classified as S0–S4. Mann–Whitney U test was performed to compare the T1ρ values, and p<0.05 was considered statistically significant. ResultsThe control group included 11 rabbits and the HF group included 46 rabbits. The T1ρ values in the HF group tended to increase with the increase of CCl4 injection duration or in higher HF stages. The T1ρ values were significantly lower (p=0.036) in the control group (or the stage S0 group) (23.5±4.0ms) compared to the whole HF group (or S1–S4 group) (26.1±3.7ms), and dropped at week 15 (p=0.043) after the CCl4 injection was stopped at week 10. ConclusionT1ρ imaging is closely associated with the severity of HF and may play an important role in the early diagnosis of HF.

Hematological Complications in chronic Hepatitis C Virus Infection

The course of chronic hepatitis C virus infection (c-HCVI) is often asymptomatic at onset; If becomes symptomatic extrahepatic complications may dominate. Among them, hematological complications occur quite frequently including mainly mixed cryoglobulinemia and thrombocytopenia, less common non-Hodgkin’s lymphomas (NHL) and monoclonal gammopathy of unknown significance (MGUS). The incidence of hematological complications in c-HCVI varies from 36-76% and is geographically dependent. The aim of this retrospective study was to evaluate the frequency, co-occurrence and risk factors for hematological complications in 1237 untreated patients (pts) diagnosed with c-HCVI in Pomerania region of Poland in the years 1998-2010.The data included complete blood count (CBC), proteinogram and results of liver biopsy, performed at the time when patients were evaluated for antiviral treatment. Declines for hemoglobin (HGB), leukocyte count (WBC) and platelet count (PLT) were graded as mild//moderate if HGB was not lower than 10//8g/dl, WBC than 3//2G/l and PLT than 100//50G/l. Liver fibrosis was assessed using Scheuer classification. Detection of cryoglobulins was performed only in patients with symptoms of cryoglobulinemia. Data were analyzed using univariate and multivariate logistic regression and ROC curves.Mixed cryoglobulinemia was confirmed in 5.3% of pts. No cases of MGUS were detected; NHL were diagnosed in 0.3% of pts. Hypoalbuminemia (<3.75 g/dl) was found in 20.9% and hypergammaglobulinemia (>1.69 g/dl) in 29% of pts. CBC abnormalities were found in 33% of patients: the most common was thrombocytopenia (PLT<150 G/l) in 23.8%, leucopenia (WBC<4 G/l) in 8.4% and neutropenia (ANC<1.5 G/l) in 4.5% of patients. Anemia (HGB≤11.5 g/dl), lymphopenia (ALC<1 G/l) were rare (about 3% of patients). The CBC declines were generally mild; Thrombocytopenia, anemia and leucopenia were mild in 63%, 75% and 78% of pts, respectively. Thrombocytopenia more often (66%) occurred as a single CBC change. Leucopenia, conversely, more often coexisted (68%) with other CBC abnormalities, especially with thrombocytopenia (96%). In univariate analysis pts with thrombocytopenia had a significantly (p<0.05) 5.1 times higher risk of co-occurrence of other hematological complication, of which the highest (7.3) risk related to leucopenia (table 1). Moreover, the more severe thrombocytopenia the higher risk of co-existence of leucopenia was observed: in patients with PLT≤100 G/l risk of leucopenia increased 14.6 times. Hypergammaglobulinemia more often (56%) occurred as a solitary abnormality. If not solitary, it co-existed mainly with thrombocytopenia (82%). Additionally, incidence of thrombocytopenia and leucopenia increased with advancement of liver fibrosis: In pts with stage>3 fibrosis the incidence of thrombocytopenia and leukocytopenia was 73% and 34%, respectively. In multivariate analysis the risk of thrombocytopenia and leucopenia increased significantly from stage 2 and 3 of liver fibrosis, respectively compared to pts without fibrosis: patients with stage>3 had 16.5 times higher risk of thrombocytopenia and 8.2 higher risk of leucopenia comparing to pts without liver fibrosis. The risks of hypergammaglobulinemia and hypoalbuminemia increased significantly only in patients with stage>3, 2.3 and 4.4 times, respectively. Among PLT, albumin and gamma- globulin concentration, PLT was the strongest predictor of lack of advanced liver fibrosis (grade ≥3) (area under ROC curve- 0.8122). For patients with PLT≥155 G/l sensitivity was 74.2%, specificity 75.7% (figure 1). We conclude that in patients with c-HCVI, CBC abnormalities mainly CBC declines occur often and usually are mild and isolated. The most often is thrombocytopenia. Normal PLT count is a strong predictor of lack of advanced liver fibrosis. Coexistence of thrombocytopenia, leucopenia and presence of hypergammaglobulinemia and hypoalbuminemia may indicate advanced liver fibrosis.Table 1Odds ratios for additional hematological complications in patients with thrombocytopenia in univariate analysis.complicationodds ratioP>|z|95% CI:additional hematological complication5.580.0003.95- 7.87leucopenia7.520.0004.89- 11.56anemia2.480.0061.31- 4.71mixed cryoglobulinemia2.430.0011.46- 4.06 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Mean Platelet Volume, Red Cell Distribution Width to Platelet Count Index, Globulin Platelet Index, and Twelve Other Simple Non-invasive Fibrosis Scores: How Much Do Routine Blood Tests Tell About Liver Fibrosis?: ACG Governors Award for Excellence in Clinical Research

Introduction: There are many simple non-invasive scores to predict liver fibrosis that can be calculated from routine blood parameters. We aim to compare these simple non-invasive scores for evaluation of liver fibrosis with liver biopsy in patients with chronic hepatitis C (HCV). Methods: In 1,602 HCV patients who underwent liver biopsy, we compared the liver biopsy (Scheuer classification) fibrosis scores with APRI (AST/Platelet ratio), Fibrosis-4 (FIB-4), Lok score, GUCI score, Fibro-alpha score, Forns’ score, King score, AAR (AST/ALT ratio), Fibrosis index (FI), Pohl score, Fibro-Q score, FCI (Fibrosis cirrhosis index), and 3 new scores: mean platelet volume (MPV), RPR (red cell distribution width/platelet count ratio), and globulin/platelet count index (GPI). Results: Mean age of patients was 41.8±9.6 years (1,365 males); genotype 4 (65.6%) was the most common, followed by genotype 1 (10.9%). Liver biopsy showed stage 0 fibrosis (F0) in 1.9%, stage 1(F1) in 32.9%, stage 2(F2) in 39.5%, stage 3(F3) in 19%, and stage 4(F4) in 6.6% of patients. Of the baseline parameters, AST (adjusted odds ratio [OR] 1.015; confidence interval [CI] 1.008-1.022; p=0.001), albumin (adjusted OR 0.842; CI 0.742-0.915; p=0.001) and platelet count (adjusted OR 0.981; CI 0.974-0.989; p=0.001) were independent predictors of cirrhosis. We derived a study score (8.5 -0.2 [albumin, g/dl] + 0.01[AST, IU/l] - 0.02 [platelet count, 109/l]) at a cut-off of >4.7; it had high predictive accuracy (AUROC=0.868; CI 0.833-0.904) for cirrhosis. All the scores except AAR and Pohl score showed high predictive accuracy for cirrhosis (Table 1). Of the new scores, MPV and RPR had relatively low, and GPI had high, predictive accuracy for cirrhosis. GUCI score (cut-off >1.1) had the highest predictive accuracy for cirrhosis, followed by APRI (cut-off >1.5). King’s score had highest predictive accuracy for significant (F2-F4) and advanced fibrosis (F3-4), AUROC of 0.771 and 0.860, respectively.Table 1: Performance of Non-invasive Scores Compared to Cirrhosis(F4-Fibrosis) in Liver BiopsyConclusion: Excluding AAR, Pohl score, MPV, and RPR, all the non-invasive scores including the study score we derived, and GPI showed high predictive accuracy for cirrhosis. GUCI score and APRI for cirrhosis and King’s score for significant and advanced fibrosis seem to have the highest predictive accuracy.