Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase.

BACKGROUND: Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B (CHB) patients were not previously conducted. AIM: To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy. METHODS: The clinical and laboratory data of 1532 untreated CHB patients were collected, and all patients had least once liver biopsy from January 2015 to December 2021. The significant differences among different phases of CHB infection were compared with t-test, and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis. RESULTS: Among 1532 untreated CHB patients, 814 (53.13%) patients were in the indeterminate phase. Significant liver histological changes (defined as biopsy score ≥ G2 and/or ≥ S2) were found in 488/814 (59.95%) CHB patients in the indeterminate phase. Significant liver histological changes were significant differences among different age, platelets (PLTs), and alanine aminotransferase (ALT) subgroup in indeterminate patient. Multivariate logistic regression analysis indicated that age ≥ 40 years old [adjust odd risk (aOR), 1.44; 95% confidence interval (CI): 1.06-1.97; P = 0.02], PLTs ≤ 150 × 109/L (aOR, 2.99; 95%CI: 1.85-4.83; P < 0.0001), and ALT ≥ upper limits of normal (aOR, 1.48; 95%CI: 1.08, 2.05, P = 0.0163) were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase. CONCLUSION: Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase, and additional strategies are urgently required for the management of these patients.

The Challenging Path to Diagnosing Extraintestinal Amoebiasis: A Case Report of an HIV-Infected Patient.

Background: Amoebiasis, an infectious disease caused by the parasitic protozoan E. histolytica, is easily misdiagnosed due to its declining incidence and atypical symptoms. Case Presentation: A 31-year-old male presented to the hospital with dyspnea and inability to lie flat. Imaging studies indicated a large amount of pleural effusion on the right side and multiple huge cysts in the liver. The patient underwent liver tumor resection surgery at another hospital due to suspected malignancy, but no evidence of relevant malignant tumors was found in the pathological examination. Subsequently, we performed metagenomic next-generation sequencing on the liver drainage fluid and obtained liver pathology slides from the hospital where the surgery was performed at that time. Both of them confirmed the diagnosis of amoebic infection. Empirical treatment with metronidazole was initiated before the diagnosis was confirmed, along with symptomatic treatments such as thoracic drainage and liver drainage. Eventually, the patient's condition improved and he was discharged smoothly. Conclusion: In order to avoid misdiagnosis of amoebiasis, thoroughly inquiring about the patient's medical history, shifting perspectives and continuing investigating are necessary when one diagnostic approach proves ineffective. Besides, interdisciplinary collaboration and persistent efforts are crucial for accurate diagnosis.

Corticosteroid plus glycyrrhizin therapy for chronic drug- or herb-induced liver injury achieves biochemical and histological improvements: a randomised open-label trial.

BACKGROUND: Treatment of chronic drug-induced liver injury (DILI) or herb-induced liver injury(HILI) is an important and unresolved challenge. There is no consensus regarding the indications for corticosteroids for chronic DILI/HILI. AIMS: To investigate the efficacy and safety of corticosteroid plus glycyrrhizin for patients with chronic DILI/HILI. METHODS: This was a randomised open-label trial. Eligible patients with causality assessment using the updated RUCAM were randomly assigned (1:1) either to the steroid treatment group (48-week stepwise dose reduction of methylprednisolone plus glycyrrhizin) or control group (glycyrrhizin alone). Liver biopsies were performed at baseline and at the end of the 48-week treatment period. The primary outcome was the proportion of patients with sustained biochemical response (SBR). The secondary outcomes were improvement in liver histology, time to biochemical normalisation and safety. RESULTS: Of 80 participants, 70 (87.5%) completed the trial. The patients were predominantly female (77.5%), aged >40 years (77.5%) and had a hepatocellular injury pattern of DILI (71.2%). Compared to the control group, the treatment group showed a higher proportion of SBR (94.3% vs. 71.4%, p = 0.023), shorter biochemical normalisation time and histological improvements in both histological activity and fibrosis. The DILI and HILI subgroups, as well as the autoimmune hepatitis (AIH)-like DILI and non-AIH-like subgroups, showed comparable responses. No severe adverse events were observed during the trial. CONCLUSION: This study provides the first clinical evidence that corticosteroid plus glycyrrhizin therapy for chronic DILI with or without AIH-like features can achieve both biochemical response and histological improvements with good safety. (ClinicalTrials.gov, NCT02651350).

Gd-EOB-DTPA-enhanced MRI-a noninvasive and short-term assessment method for liver necroinflammation after direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C.

PURPOSE: To assess liver necroinflammation in HCV patients undergone antiviral therapy by Gd-EOB-DTPA-enhanced MRI with histopathologic analyses as reference. METHODS: HCV patients were enrolled in this prospective study before antiviral treatment between 09-2016 and 07-2017. Unenhanced MR, Gd-EOB-DTPA-enhanced MR, and liver biopsy were performed before and 24 weeks after treatment of daclatasvir with asunaprevir (DAA). DWI was obtained using a breath-hold single-shot echo planar spin-echo sequence. Twenty minutes after administration of Gd-EOB-DTPA, the relative enhancement (RE) and the contrast enhancement index (CEI) were recorded. Liver necroinflammatory activity grades (G0-18) were categorized on the Ishak Scoring systems. CEI, RE, and DWI of baseline and 24 weeks after treatment were compared by paired t test. Relationship between MR parameters and histologic scores was evaluated by Pearson's correlation. Receiver operating characteristic analysis evaluated the measurements' diagnostic performance. MRI variability between two readers was assessed using the intraclass correlation coefficient.Results RESULTS: A decrease of liver necroinflammatory activity grade (p < 0.0001) was detected in final cohort (n = 21; mean age 44 years; 23 to 67 years; 11 F, 10 M). Statistical results of 42 person-times in 21 patients at baseline and follow-up showed CEI and ADC were significantly different (p = 0.006 and 0.036) across histologic grades of liver necroinflammation. Significant increase of CEI, RE, and ADC (p = 0.0004, 0.0032, 0.0110) 24 weeks after DAA treatment was seen. Additionally, CEI was correlated to necroinflammatory grade (r = - 0.596, p = 0.006). AUROC for CEI, ADC, and CEI combined with ADC to differentiate patients with none and mild (G0-6) from patients with moderate and severe necroinflammation (G7-18) was 0.834 (95% CI 0.712-0.956, 0.724(95% CI 0.565-0.884) and 0.837(95% CI 0.717-0.956). CONCLUSION: Gd-EOB-DTPA-enhanced MRI by CEI could be used as a noninvasive imaging biomarker to distinguish grades of necroinflammatory activity in patients with HCV after DAAs therapy at early stage and CEI combined with ADC could get a better diagnostic accuracy.

Prediction of biochemical nonresolution in patients with chronic drug-induced liver injury: A large multicenter study.

BACKGROUND AND AIMS: To clarify high-risk factors and develop a nomogram model to predict biochemical resolution or biochemical nonresolution (BNR) in patients with chronic DILI. APPROACH AND RESULTS: Retrospectively, 3655 of 5326 patients with chronic DILI were enrolled from nine participating hospitals, of whom 2866 underwent liver biopsy. All of these patients were followed up for over 1 year and their clinical characteristics were retrieved from electronic medical records. The endpoint was BNR, defined as alanine aminotransferase or aspartate aminotransferase >1.5× upper limit of normal or alkaline phosphatase >1.1× ULN, at 12 months from chronic DILI diagnosis. The noninvasive high-risk factors for BNR identified by multivariable logistic regression were used to establish a nomogram, which was validated in an independent external cohort. Finally, 19.3% (707 of 3655) patients presented with BNR. Histologically, with the increase in liver inflammation grades and fibrosis stages, the proportion of BNR significantly increased. The risk of BNR was increased by 21.3-fold in patients with significant inflammation compared to none or mild inflammation (p < 0.001). Biochemically, aspartate aminotransferase and total bilirubin, platelets, prothrombin time, sex, and age were associated with BNR and incorporated to construct a nomogram model (BNR-6) with a concordance index of 0.824 (95% CI, 0.798-0.849), which was highly consistent with liver histology. These results were successfully validated both in the internal cohort and external cohort. CONCLUSIONS: Significant liver inflammation is a robust predictor associated with biochemical nonresolution. The established BNR-6 model provides an easy-to-use approach to assess the outcome of chronic DILI.

Adult diffuse hepatic hemangiomatosis: A case report and review of the literature.

Diffuse hepatic hemangiomatosis (DHH) is an extremely rare disease, especially in adults. We present a case of DHH involving the entire liver in a 62-year-old male with a giant hemangioma next to the superior mesenteric vein. Based on what we could find in PubMed with pathological evidence, there are only seventeen cases of adult DHH reported in the literature. The female-to-male ratio is 2.4:1. Most patients consult for abdominal pain or distension. Radiographic examination shows multiple diffuse liver nodules. On MRI, these lesions show hypointense T1 and hyperintense T2. Some lesions may show peripheral rim enhancement in the arterial phase but no portovenous washout. In total, 47% of patients with DHH have one or more giant hemangioma(s). Pathology shows that the lesions are lined with flat endothelial cells without cellular atypia, which are stained positive for vascular endothelial markers. Liver failure is the main cause of death. Some patients can be improved by partial hepatectomy. However, there is no effective treatment for most patients. Liver transplantation should be considered in patients with liver failure or congestive heart failure caused by DHH. We attempt to classify DHH into two types based on the distribution of DHH and their treatment.

TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection.

Limited understanding of T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impeded vaccine development and drug discovery for coronavirus disease 2019 (COVID-19). We found that triggering receptor expressed on myeloid cells 2 (TREM-2) was induced in T cells in the blood and lungs of patients with COVID-19. After binding to SARS-CoV-2 membrane (M) protein through its immunoglobulin domain, TREM-2 then activated the CD3ζ/ZAP70 complex, leading to STAT1 phosphorylation and T-bet transcription. In vitro stimulation with M protein-reconstituted pseudovirus or recombinant M protein, and TREM-2 promoted the T helper cell 1 (TH1) cytokines interferon-γ and tumor necrosis factor. In vivo infection of CD4­TREM-2 conditional knockout mice with murine coronavirus mouse hepatitis virus A-59 showed that intrinsic TREM-2 in T cells enhanced TH1 response and viral clearance, thus aggravating lung destruction. These findings demonstrate a previously unidentified role for TREM-2 in SARS-CoV-2 infection, and suggest potential strategies for drug discovery and clinical management of COVID-19.

The LAC Score Indicates Significant Fibrosis in Patients With Chronic Drug-Induced Liver Injury: A Large Biopsy-Based Study.

Currently, there are no satisfactory noninvasive methods for the diagnosis of fibrosis in patients with chronic drug-induced liver injury (DILI). Our goal was to develop an algorithm to improve the diagnostic accuracy of significant fibrosis in this population. In the present study, we retrospectively investigated the biochemical and pathological characteristics of consecutive patients with biopsy-proven chronic DILI, who presented at our hospital from January 2013 to December 2017. A noninvasive algorithm was developed by using multivariate logistic regression, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) to diagnose significant fibrosis in the training cohort, and the algorithm was subsequently validated in the validation cohort. Totally, 1,130 patients were enrolled and randomly assigned into a training cohort (n = 848) and a validation cohort (n = 282). Based on the multivariate analysis, LSM, CHE, and APRI were independently associated with significant fibrosis. A novel algorithm, LAC, was identified with the AUROC of 0.81, which was significantly higher than LSM (AUROC 0.78), CHE (AUROC 0.73), and APRI (AUROC 0.68), alone. The best cutoff value of LAC in the training cohort was 5.4. When the LAC score was used to diagnose advanced fibrosis and cirrhosis stages, the optimal cutoff values were 6.2 and 6.7, respectively, and the AUROC values were 0.84 and 0.90 in the training cohort and 0.81 and 0.83 in the validation cohort. This study proved that the LAC score can contribute to the accurate assessment of high-risk disease progression and the establishment of optimal treatment strategies for patients with chronic DILI.

Serum Golgi Protein 73 as a Potential Biomarker for Hepatic Necroinflammation in Population with Nonalcoholic Steatohepatitis.

AIMS: Persistent hepatic necroinflammatory damage almost always results in fibrosis/cirrhosis or even hepatocellular carcinoma. Therefore, the presence of active necroinflammation in the liver suggests that nonalcoholic fatty liver disease (NAFLD) patients are in urgent need of treatment. Unfortunately, alanine transaminase (ALT), a routine indicator of liver inflammatory damage, showed a poor performance in nonalcoholic steatohepatitis (NASH) patients. Thus, it will be valuable to find an alternative indicator to identify patients with hepatic necroinflammatory damage. In this study, we evaluated the diagnostic value of serum Golgi protein 73 (GP73) for hepatic necroinflammatory damage in patients with NASH. METHODS: The clinical data of 201 patients with NASH diagnosed by liver biopsy according to the Brunt staging system were collected retrospectively. The in situ expression of GP73 protein was measured by immunohistochemistry. The receiver operating characteristic (ROC) curve was used to calculate the area under the ROC curve (AUROC) of serum GP73 for diagnosing hepatic necroinflammatory damage. RESULTS: The serum GP73 levels of NASH patients increased with the aggravation of liver necroinflammation. The median levels significantly increased from 49.98 ng/ml (31.49, 75.05) for G0-1 to 76.61 ng/ml (48.68, 110.03) for G2 and to 116.44 ng/ml (103.41, 162.17) for G3 patients (G0-1 vs. G2, P < 0.0001; G2 vs. G2, P < 0.0001; G2. CONCLUSIONS: GP73 is a valuable alternative serum marker reflecting the severity of hepatic necroinflammation in NASH patients.

Emperipolesis mediated by CD8+ T cells correlates with biliary epithelia cell injury in primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell-in-cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty-six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early-stage PBC (stages I and II, n = 39) and late-stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin-eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R2  = 0.318, P < .001; R2  = 0.060, P < .05). The cell numbers of TUNEL-positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R2  = 0.236, P < .001; R2  = 0.267, P < .001). We conclude that emperipolesis mediated by CD8+ T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts.

Nonalcoholic fatty liver disease is associated with lower hepatitis B viral load and antiviral response in pediatric population.

BACKGROUND: The interaction between nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B infection (CBI) was unclear. We aimed to investigate the association between NAFLD and CBI and the effect of NAFLD on response to antiviral therapy in pediatric population. METHODS: All children aged 0-18 years with liver biopsy-proven NAFLD, CBI, and co-existing NAFLD and CBI were consecutively collected. Children with co-existing CBI and NAFLD were considered as cases and n:m matched with simple NAFLD and simple CBI patients in the same cohort, respectively. In longitude study, the role of NAFLD in antiviral response was further analyzed in children with CBI who received antiviral treatment. Logistic or Cox regression models were used appropriately for analysis. RESULTS: 765 subjects were finally enrolled with 62 co-existing patients, 560 CBI patients, and 143 NAFLD patients. Multivariate analysis showed that HBV DNA level was negatively associated with NAFLD in CBI children (OR 0.376, 95% CI 0.173-0.818). Conversely, the severity of steatosis and levels of serum lipid profile were found to be inversely associated with CBI in NAFLD subjects. Then, in longitude study, we found that HBsAg loss at 96 weeks of antiviral treatment was independently associated with NAFLD (aHR 3.245, 95% CI 1.288-8.176). CONCLUSIONS: An inverse association between CBI and NAFLD reciprocally existed in pediatric population. In longitude study, HBsAg loss was associated with NAFLD at week 96 of antiviral therapy.

CXC Motif Ligand 16 Promotes Nonalcoholic Fatty Liver Disease Progression via Hepatocyte-Stellate Cell Crosstalk.

Context: Nonalcoholic fatty liver disease (NAFLD) is a focus of attention because of its prevalence. CXC motif ligand 16 (CXCL16) has been studied in inflammatory and metabolic diseases. Objective: To investigate the role of CXCL16 in steatosis and fibrosis in patients with NAFLD. Design: Liver specimens and sera of patients with NAFLD were collected from 2012 to 2017. Setting: Beijing 302 Hospital. Participants: 117 patients with NAFLD and 15 healthy controls. Interventions: None. Main Outcome Measures: The main outcome measures were CXCL16 levels in sera and biopsy specimens of patients with NAFLD. Results: CXCL16 serum level was markedly elevated in patients with NAFLD, especially in those at the S3 steatosis level according to the steatosis, activity, and fibrosis (SAF) scoring system. The different serum levels of CXCL16 between groups were due to data in patients with A or F scores ≥2, according to the SAF scoring system. CXCL16 accumulated around steatotic hepatocytes in biopsy specimens. In vitro, CXCL16 treatment led to severe steatosis of hepatocytes in the hepatocyte-stellate cell coculture system and suppressed the respiration rate of hepatocytes. Lipogenic gene expression and hepatic stellate cell activation indexes were increased in a CXCL16 overexpression system. In addition, ligands in the Hedgehog pathway cascade were downregulated in hepatocytes. Conclusions: CXCL16 was highly expressed in patients with NAFLD, suggesting that it may contribute to steatotic and fibrotic progression. CXCL16 may be a potential noninvasive marker of NAFLD and a future potential therapeutic target to treat NAFLD.

The Clinical Significance of GP73 in Immunologically Mediated Chronic Liver Diseases: Experimental Data and Literature Review.

There is significant void in establishing validated non-invasive surrogate biomarkers of liver fibrosis/cirrhosis in chronic liver diseases (CLD). Golgi protein 73 (GP73) has been suggested as a potential serum marker for the diagnosis of hepatocellular carcinoma (HCC). However, significant background of cirrhosis could have accounted for the elevation of serum GP73 in HCC. In this study, we have taken advantage of a well-defined extensive cohort of 3044 patients with either compensated cirrhosis (n = 1247), decompensated cirrhosis (n = 841) or pre-cirrhotic CLD (n = 956) and our ability to quantify serum GP73 to define the potential of serum GP73 as a biomarker of liver cirrhosis/fibrosis in CLD. The diagnostic value of GP73 was compared with aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on four factors (FIB-4) and liver stiffness measurement (LSM). Immunohistochemical analysis was performed to measure hepatic GP73 expression. Receiver operating characteristic curve analysis demonstrated that serum GP73 had a good diagnostic potential for compensated cirrhosis regardless of etiology. The diagnostic performance of GP73 is better than APRI, FIB-4 and similar with LSM, especially in patients with severe inflammation, steatosis and cholestasis. Notably, in patients of autoimmune liver diseases, non-alcoholic fatty liver disease and viral hepatitis, serum GP73 also exhibited diagnostic value for advanced fibrosis as well as cirrhosis. Furthermore, there is also a gradual increase in GP73 expression with disease progression from mild fibrosis to cirrhosis. In conclusion, GP73 is an effective and reliable serological marker for the diagnosis of advanced fibrosis and prediction of appearance of cirrhosis.

CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice.

The p53 mutation and altered Pten expression are two most common genetic events in Hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC). To confirm the causative role of p53 and Pten somatic mutation in HCC development, we established CRISPR/Cas9-mediated somatic gene disruption via hydrodynamic tail vein injection, allowing for in vivo targeting p53 and Pten simultaneously in adult HBV transgenic mice. Here we demonstrated that the utility of this approach resulted in macroscopic liver tumors as early as 4 months' post injection and most tumors harbored both p53 and Pten loss-of-function alterations. Immunohistochemical (IHC) and histopathology analysis demonstrated that the tumors were positive for Glutamine synthetase (GS), a marker of HCC and accompanied with prominent lipid accumulation. The study here indicated that CRISPR/Cas9-mediated p53 and Pten somatic mutation accelerated hepatocarcinogenesis in adult HBV transgenic mice. This method also provides a fast and convenient system for generating mouse model of HCC with HBV infection characteristics.

Myeloproliferative Neoplasm or Reactive Process? A Rare Case of Acute Myeloid Leukemia and Transient Posttreatment Megakaryocytic Hyperplasia with JAK-2 Mutation.

Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies characterized by unchecked proliferation of differentiated myeloid cells. The most common BCR-ABL1-negative MPNs are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The discovery of JAK2 V617F mutation has improved our understanding of the molecular basis of MPN. The high frequency of JAK2 mutation in MPN makes JAK2 mutation testing an essential diagnostic tool and potential therapeutic target for MPN. Here, we present a rare case of a 34-year-old patient who was initially diagnosed with acute myeloid leukemia (AML) with mutated NPM1. After chemotherapy treatment followed by granulocyte colony stimulating factor administration, the patient achieved complete remission of AML. However, the bone marrow showed hypercellularity with granulocytic hyperplasia, markedly increased atypical megakaryocytes (50.2/HPF) with focal clustering, and reticulin fibrosis (3/4). JAK2 V617F mutation was also detected. Considering the possibility of AML transformed from a previous undiagnosed MPN, patient underwent peripheral blood allogenic stem cell transplant. This case illustrates the diagnostic challenges of firmly establishing a diagnosis between similar, but distinct, disease entities and an accurate clinicopathological differentiation is crucial.

Lipid rafts promote liver cancer cell proliferation and migration by up-regulation of TLR7 expression.

Hepatocellular carcinoma (HCC) occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Toll-like receptors (TLRs) play an important role in innate immune responses and TLR signaling has been associated with various chronic liver diseases. Lipid rafts provide the necessary microenvironment for certain specialized signaling events to take place, such as the innate immune recognition. The purpose of this study was to determine the pattern of TLR7 expression in HCC, how to recruit TLR7 into lipid rafts responded to ligands and whether targeting TLR7 might have beneficial effects. The study group was comprised of 130 human liver tissues: 23 chronic hepatitis B (CHB), 18 liver cirrhosis (LC), 68 HCC and 21 normal livers. The expression of TLR7 was evaluated using immunohistochemistry, western blotting, and flow cytometry. Proliferation and migration of human HepG2 cells were studied following stimulation of TLR7 using the agonist gardiquimod and inhibition with a specific antagonist 20S-protopanaxadiol (aPPD). The activation of lipid raft-associated TLR7 signaling was measured using western blotting, double immunohistochemistry and immunoprecipitation in liver tissues and HepG2 cells. TLR7 expression was up-regulated in human HCC tissues and hepatoma cell line. Proliferation and migration of HepG2 cells in vitro increased significantly in response to stimulation of TLR7. TLR7 inhibition using aPPD significantly reduced HepG2 cell migration in vitro. The lipid raft protein caveolin-1 and flotillin-1 were involved with enhanced TLR7 signaling in HCC. CONCLUSIONS: The data suggest that inhibiting TLR7 with antagonists, like aPPD, could potentially be used as a novel therapeutic approach for HCC.

[Value of serum osteoprotegerin in noninvasive diagnosis of nonalcoholic steatohepatitis].

OBJECTIVE: To investigate the correlation of serum osteoprotegerin (OPG) with the progression of nonalcoholic fatty liver disease (NAFLD) and the noninvasive prediction and diagnosis of nonalcoholic steatohepatitis (NASH). METHODS: A total of 136 patients with NAFLD were enrolled, and their tissue samples for liver biopsy and serum samples obtained at 1 week after liver biopsy were collected; 83 healthy subjects without the symptoms of fatty liver disease proved by ultrasound examination were enrolled as controls. The physiological indicators including height, body weight, and waist circumference were measured, and body mass index was calculated. The biochemical parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, alkaline phosphatase, gamma-glutamyl transferase, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. Double-antibody sandwich enzyme-linked immunosorbent assay was used to determine the serum level of OPG. The rank sum test, chi-square test, t-test, one-way analysis of variance, Spearman correlation analysis, least significant difference test, and receiver operating characteristic (ROC) curve were applied for statistical analysis of various data. RESULTS: Serum OPG level was correlated with AST and TG (P < 0.05), and was highly correlated with hepatocyte fatty degeneration, ballooning degeneration, intralobular inflammation, portal inflammation, and fibrosis degree (P < 0.01). With the increasing NAFLD activity score (NAS), serum OPG level decreased, and there was a highly negative correlation between them (r = -0.928, P < 0.01). Serum OPG level was significantly lower in NASH patients than non-NASH patients. The area under the ROC curve of serum OPG level was 0.963, and according to the Youden index, its optimal sensitivity and specificity were 96.1% and 97.4%, respectively, at an optimal cut-off value of 242.96 ng/L, which suggested a high diagnostic power. CONCLUSION: In NASH patients, serum OPG level decreases significantly. Serum OPG level can be used as an independent predictive factor to evaluate NASH and its severity, as well as a noninvasive diagnostic index for NASH.

Comparison of acoustic radiation force impulse imaging and transient elastography for non-invasive assessment of liver fibrosis in patients with chronic hepatitis B.

The aims of this study were to compare the performance of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) in the assessment of liver fibrosis in patients with chronic hepatitis B and to evaluate the impact of elevated alanine transaminase levels on liver stiffness assessment using ARFI elastography. One hundred eighty consecutive patients with chronic hepatitis B were enrolled in this study and evaluated with respect to histologic and biochemical features. All patients underwent ARFI elastography and TE. ARFI elastography and TE correlated significantly with histologically assessed fibrosis (r = 0.599, p < 0.001, for ARFI elastography; r = 0.628, p < 0.001, for TE) and necro-inflammatory activity (r = 0.591, p < 0.001, for ARFI elastography; r = 0.616, p < 0.001, for TE). Areas under the receiver operating characteristic curves for ARFI elastography and TE were 0.764 and 0.813 (p = 0.302, ≥stage 2), 0.852 and 0.852 (p = 1.000, ≥stage 3) and 0.825 and 0.799 (p = 0.655, S = 4), respectively. The optimum cutoff values for ARFI elastography were 1.63 m/s for stage ≥2, 1.74 m/s for stage ≥3 and 2.00 m/s for stage 4 in patients for whom alanine transaminase levels were evaluated. The cutoff values decreased to 1.24 m/s for ≥ stage 2, 1.32 m/s for ≥ stage 3 and 1.41 m/s for stage 4 in patients with normal alanine transaminase levels. ARFI elastography may be a reliable method for diagnosing the stage of liver fibrosis with diagnostic performance similar to that of TE in patients with chronic hepatitis B. In addition, liver stiffness values obtained with ARFI elastography, like those obtained with TE, may be influenced by alanine transaminase levels.

[Clinical value of acoustic radiation force impulse imaging for quantitative evaluation of degree of liver fibrosis in chronic hepatitis C patients].

OBJECTIVE: To investigate the diagnostic value of acoustic radiation force impulse (ARFI) imaging technology for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients. METHODS: One-hundred-and-eight CHC patients were examined by real-time ultrasound elastography using the Acuson S2000 ARFI instrument (Siemens Healthcare) and underwent liver biopsy for pathohistological analysis. The correlation between liver fibrosis grades determined by the two approaches was analyzed. The cut-off values for diagnosis by ARFI (S more than 2, S more than 3 and S = 4) were determined by generating a receiver operating characteristic (ROC) curve. RESULTS: The spectrum of liver stiffness detected by ARFI sonoelastography included S1 at (1.26+/-0.27) m/s (n = 36), S2 at (1.45+/-0.51) m/s (n = 31), S3 at (2.01+/-0.54) m/s (n = 27), and S4 at (2.28+/-0.82) m/s (n = 14). The ARFI values were significantly different among the four different stages of liver fibrosis (P less than 0.001). The liver stiffness detected by ARFI sonoelastography was significantly correlated with the liver fibrosis stage determined by the gold standard pathohistological analysis (Spearman's rank coefficient: 0.61, P less than 0.001). Using the ARFI technology for assessment of liver fibrosis gave areas under the ROC curve of 0.779 for S more than 2 patients, of 0.863 for S more than 3 patients, and of 0.0880 for S = 4 patients. CONCLUSION: The real-time ultrasound elastography ARFI technology can show the elasticity modulus of liver, and its data values positively correlate with the patho-histology grade of liver fibrosis in CHC patients. ARFI technology is easy to operate, non-invasive, and quantitative, and has potential clinical value for assessing liver fibrosis in CHC.