Worse Response to Ursodeoxycholic Acid in Primary Biliary Cholangitis Patients with Autoimmune Hepatitis Features.

BACKGROUND: There is limited evidence on the treatment response of primary biliary cholangitis (PBC) with autoimmune hepatitis (AIH) features but not meet the criteria of PBC-AIH syndromes. The aim of this study was to elucidate the clinical characteristics of PBC patients with features of AIH. METHODS: We included patients with diagnostic criteria of PBC. All patients were treated with ursodeoxycholic acid (UDCA) and without immunosuppressive agents for >1 year. The biochemical response was evaluated at 1 year after the treatment of UDCA. RESULTS: Among 432 patients with PBC, 166 (38.4%) patients did not achieve biochemical response within 1 year of UDCA treatment. Nonresponders had a lower albumin level and higher immunoglobulin G, alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase, glutamyl transpeptidase and total bilirubin levels (p < 0.05). The response rates were significantly lower in patients with elevated level of IgG or ALT or AST. Moreover, the higher the IgG or AST level was, the lower the response rate was in patients with PBC, regardless of cirrhosis. For patients with cirrhosis, there was no differences among patients with different levels of ALT. Patients in the PBC with AIH features group had a significant lower response rate than patients in the PBC-only group. Among the 139 patients who underwent liver biopsy, 54 were nonresponsive to UDCA and 48 (88.9%) shown mild interface hepatitis. CONCLUSION: In conclusion, PBC patients with AIH features had a worse response to UDCA therapy.

Comparison of Concanavalin a-Induced Murine Autoimmune Hepatitis Models.

BACKGROUND/AIMS: Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver whose pathogenic mechanisms have not yet been elucidated. Moreover, the current treatment used for the vast majority of AIH patients is largely dependent on immunosuppressant administration and liver transplantation. However, research on the pathogenesis of AIH and effective new treatments for AIH have been hampered by a lack of animal models that accurately reproduce the human condition. METHODS: AIH models created by concanavalin A (ConA) injections at different times and doses. The levels of ALT, AST, LDH and inflammatory cytokines were examined at various times after 20 mg/kg ConA was administered by ELISA using commercially available kits. Moreover, liver pathological changes were observed by flow cytometry (FCM) and H&E staining. RESULTS: Our experiments demonstrated that the levels of ALT, AST, LDH and several inflammatory cytokines, including TNF-α, IFN-γ, and IL-6, were higher in the 20 mg/kg 12 h ConA group than in the other groups. Importantly, the numbers of activated CD4+ and CD8+ T lymphocytes in the blood, spleen and liver were calculated. These results showed that ConA (20 mg/kg for 12 h)-induced hepatitis was similar to that in clinical AIH patients. Furthermore, we found that the number of MDSCs in the blood was significantly increased in the ConA (20 mg/kg for 12 h) group compared with controls. Our findings indicated that ConA (20 mg/kg for 12 h)-induced hepatitis could be used as an experimental murine model that mirrors most of the pathogenic properties of human type I AIH. CONCLUSION: This model [ConA (20 mg/kg for 12 h)] provides a valuable tool for studying AIH immunopathogenesis and rapidly assessing novel therapeutic approaches.

Sequential Therapy or Standard Triple Therapy for Helicobacter pylori Infection: An Updated Systematic Review.

The effectiveness of standard triple therapy (STT) for the eradication of Helicobacter pylori has decreased recently. Sequential therapy (SQT) is a new regimen proposed to address this problem. The aim of this study was to compare the efficacy of SQT versus STT for H. pylori eradication. We searched The Cochrane Library, MEDLINE, Web of Science, and EMBASE databases up to July 2014. The risk ratios (RRs) of eradication rate were pooled, with a 95% confidence interval (CI). Thirty-six randomized clinical trials including a total of 10,316 patients met the inclusion criteria. The RR for eradication of H. pylori with SQT compared with STT was 1.14 (95% CI: 1.09-1.17), the eradication rates were 84.1% and 75.1%, respectively. There was significant heterogeneity between trial results (I = 73%; P < 0.00001). Subgroup analyses showed that SQT was superior to both 7- and 10-day STT, but not significantly better than 14-day STT. This superiority existed when patients were treated with either metronidazole or tinidazole. Patients with single clarithromycin-resistant strain showed a greater benefit of SQT over STT (eradication rates 80.9% vs. 40.7%), RR = 1.98 (95% CI: 1.33-2.94). There was no significant difference between groups in terms of the risk of adverse effects. In conclusion, SQT is more efficacious than STT (7 days and 10 days) in the eradication of HP, but the pooled rate seemed suboptimal. Further research is needed to develop more effective therapeutic approaches. Surveillance of resistance rates should be performed to guide treatment.

[Clinical Characteristics of Wilson's Disease: a Retrospective Analysis of Admission Data among 126 Patients].

OBJECTIVE: To investigate the clinical features of Wilson's disease (WD) for the purpose of avoiding misdiagnosis and therefore improving the prognosis of this rare disease. METHODS: This study enrolled all the patients diagnosed as WD who were admitted to West China Hospital, Sichuan University from Jan 2008 to Dec 2014. Their clinical manifestations, head and abdominal images data were extracted and analyzed. RESULTS: There were a total of 126 patients of WD, male female ratio was 75 : 51, median age was 21-years old. 10.3% (13/126) of them had family history, 87.3% (109/126) patients presented with neuropsychiatric symptoms, 14.3% (18/126) patients manifested as chronic liver disease. All patients had decreased serum ceruloplasmin level < 200 mg/L, 121 (96.9%) patients had serum ceruloplasmin level < 100 mg/L. Magnetic resonance imaging and abdominal ultrasound detected structural abnormalities in 92.7% (102/110) and 88.9% (97/109) patients respectively. Kayser-Fleischer rings on slit-lamp ophthalmologic examination was found in 98.3% (115/117) patients. One patient underwent liver biopsy and the result of rhodanine stain was positive. The time from onset to diagnosis varied from 3 d to 19 years [(1.59 ± 2.66) years]. 20 (15.9%) patients were initially misdiagnosed. CONCLUSION: The patients presenting with neurological signs or unexplained liver disease should be assessed carefully for WD. Serum ceruloplasmin, 24-h urinary copper, Kayser-Fleischer rings and sometimes even liver biopsy could be helpful for the diagnosis.

Nogo-B: A potential indicator for hepatic cirrhosis and regulator in hepatic stellate cell activation.

AIM: To evaluate plasma Nogo-B levels in liver cirrhotic patients and declare a novel molecular basis by which Nogo-B modulates hepatic stellate cell (HSC) activation. METHODS: Plasma Nogo-B levels from liver cirrhotic patients were detected by enzyme-linked immunosorbent assay. Rat primary HSC were culture activated or stimulated with transforming growth factor (TGF)-ß. Activated HSC were transfected for 48 h with Nogo-B shRNA to inhibit Nogo-B expression. Gene expressions of Nogo-B, α-smooth muscle actin (SMA), collagen type I, TGF-ß, endoplasmic reticulum (ER) stress key molecules, including C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), activating transcription factor (ATF)4, ATF6, X-box binding protein 1 (Xbp-1) and calnexin, and the marker of autophagy beclin 1, were detected by quantitative reverse transcription polymerase chain reaction. The protein expressions of Nogo-B, α-SMA, collagen type I, CHOP, GRP78 and the marker of autophagy LC3B were evaluated by western blot. RESULTS: Liver cirrhotic patients showed a much higher level of plasma Nogo-B compared with the healthy controls. Nogo-B expression and ER stress could be induced during the process of cultured HSC activation. TGF-ß treatment increased Nogo-B expression time- and dose-dependently. Knockdown of Nogo-B in HSC reduced the activation of HSC. After Nogo-B gene knockdown, there was a decline of expression of ER stress markers and autophagic markers. Agonist or antagonist of ER stress could regulate autophagy level. CONCLUSION: Circulating Nogo-B may be an effective indicator for liver cirrhosis. Nogo-B inhibition could diminish HSC activation, in which alleviating ER stress may be one of the mechanisms, suggesting a potential approach to interference Nogo-B in liver fibrosis.

[Effect of hypoxia on the activation and visfatin expression in rat hepatic stellate cells].

OBJECTIVE: To investigate the effect of hypoxia on the visfatin and the expression of smooth muscle-actin (alpha-SMA) and hypoxia-inducible factor-1alpha (HIF-1alpha) in rat hepatic stellate cells (HSCs). METHODS: Rat primary HSCs were isolated from SD rats by in situ perfusion of collagenase and pronase and single-step Nycodenz density gradient centrifugation, and then cultured and activated. Completely activated primary HSCs were exposed to hypoxic conditions (37 degrees C, 5% CO2, 1% O2, 94% N2), or normoxic conditions (37 degrees C, 5% CO2, 21% O2, 74% N2), for 3, 6, 12 or 24 h respectively. The expression of alpha-SMA, the marker of HSC activation, and visfatin were assessed by Real time-PCR and Western blot. The Expression of HIF-1alpha was detected by Real time-PCR. RESULTS: HIF-1alpha mRNA in rat HSCs was induced after exposed to hypoxia for 3 h, and maintained elevated status up to 24 h. HSCs exposed to 1% O2 hypoxic conditions for 6 h increased alpha-SMA mRNA and protein expression. Visfatin mRNA expression was up-regulated after subjected to hypoxia for 12 h, and protein level was elevated after 6 h hypoxia. A positive linear correlation existed between alpha-SMA and visfatin expression in responsible to hypoxia (r = 0.991 (genes) and r = 0.968 (proteins), P < 0.05). CONCLUSION: Microcirculation impairment could significantly induce alpha-SMA and visfatin expression in rat HSCs, which might potentate the activation process of HSCs.

[Construction of shRNA expressing plasmid targeted rat NogoB and observation of the effection about NogoB on hepatic stellate cells].

OBJECTIVE: To construct shRNA expressing plasmid inhibiting rat NogoB and to observe its possible effect on rat primary hepatic stellate cells (HSCs) contraction. METHODS: Three pairs of shRNAs targeting different sequence of rat NogoB were designed and constructed into pSuper plasmid by DNA recombination technique. Culture-activated HSCs were transfected with NogoB-shRNA plasmids to scan the effective plasmid which could inhibit NogoB gene expression by Real-time PCR. And this depressant effect was also confirmed with Western blot. After NogoB was knocked-down effectively, ETA and ETB mRNA expression were assessed by Real-time PCR. RESULTS: Among the three pairs of recombinant plasmids, NogoB-shRNA2 plasmid could inhibit NogoB expression specifically. In HSCs, NogoB knockdown decreased the ratio of ETA and ETB. CONCLUSION: We constructed specific NogoB-shRNA expression plasmid successfully which might be involved in contraction of HSCs.

[Association between acid reflux and esophageal dysmotility in patients with gastroesophageal reflux disease].

OBJECTIVE: To investigate the association between esophageal motility and acid reflux in patients with gastroesophageal reflux disease (GERD). METHODS: A total of 94 patients with typical reflux symptoms such as heartburn, regurgitation and chest pain, whose score (Sc) of reflux diagnostic questionnaire (RDQ) was greater than or equal to 12 were enrolled in the study. Each participant was evaluated by upper gastrointestinal endoscopy, high resolution manometry (HRM) of esophagus and 24 h esophageal pH monitoring. The participants were divided into groups of reflux esophagitis (RE) and non-erosive reflux disease (NERD) on the basis of endoscopy findings. The 24 h esophageal pH monitoring categorized participants into physiologic reflux (pH) and pathologic reflux (pH+). The characteristics of esophageal motility and acid reflux were compared between the two groups of participants. RESULTS: Lower but non-significant differences (P > 0.05) were found in pressure of lower esophageal sphincter (LESP), length of lower esophageal sphincter (LESL), esophageal contraction amplitude (CA), distal contractile integral (DCI) and effective peristalsis proportion (EPP) in the participants in the RE group compared with those in the NERD group. Participants in the RE group had significantly higher prevalence of reduced LESP (63.0% vs. 31.7%, P < 0.01) and hiatus hernia (HH) (37.0% vs. 14.3%, P < 0.05) than those in the NERD group, pH+ was more prevalent in the RE group than in the NERD group (63.0% vs. 17.5%, P < 0.01). Indicators of 24 h esophageal pH monitoring were significantly higher in participants in the RE group compared with those in the NERD group (P < 0.05). Participants with pH+ had significantly lower LESP, CA and higher HH and prevalence of reduced LESP compared with those with pH (P < 0.05). LESL, DCI and EPP were lower in those with pH+ compared with those with pH-, but without statistical significance (P > 0.05). CONCLUSION: RE is closely associated with acid reflux and hiatus hernia. Esophageal dysmotility is more likely to appear in patients with pH+. The interaction of acid reflux and esophageal dysmotility may play a role in GERD.

Helicobacter pylori infection prevalence declined among an urban health check-up population in Chengdu, China: a longitudinal analysis of multiple cross-sectional studies.

Objectives: The efficacy of updated health policy in improving the generalization of Helicobacter pylori screening and eradication in southwest China was assessed in a longitudinal analysis of multiple cross-sectional studies from an institution. Methods: In the periods 2009-2010, 2013-2014, and 2019-2021, 8,365, 16,914, and 18,281 urban observations from health check-ups at West China Hospital were analyzed, respectively. The 14C-urea or 13C-urea breath test was consistently used for H. pylori detection. The protocol has been reported elsewhere (PROSPERO Registration number: CRD42019120764). Results: The overall prevalence of H. pylori dramatically decreased from 53.1% to 30.7% over the past decade (OR = 0.39, 95% CI 0.37-0.41), with a similar decline in all sex-specific and age-specific subgroups. The age-specific prevalence consistently increased before 40 years of age and always peaked at 50-59 years. Longitudinal clearance increased along with aging, and prevalence dropped to 22.6%, 25.1%, and 23.6% in the 40-49, 50-59, and 60-69 years initial age groups, respectively. Conclusion: The generalization of H. pylori screening and eradication could greatly contribute to the control of H. pylori infection among urban health check-up populations and lower gastric cancer incidence.

Twist1-induced miR-199a-3p promotes liver fibrosis by suppressing caveolin-2 and activating TGF-ß pathway.

The activation of hepatic stellate cells (HSCs) participates in liver fibrosis, and emerging evidences indicate that microRNAs (miRNAs) are abnormally expressed during HSC activation. However, the potential roles of miRNAs in liver fibrosis still remain elusive. Therefore, this study aimed to investigate the role of miR-199a-3p in liver fibrosis and its underlying mechanism. We found that miR-199a-3p expression was dramatically upregulated during HSC activation in vitro, and during liver fibrogenesis in CCl4-treated rats, and its liver expression was increased in the patients with cirrhosis. By the luciferase assay and RT-qPCR, we revealed that the expression of miR-199a-3p in HSCs was driven by the transcription factor Twist1 which could be further induced by TGF-ß treatment. Functional studies showed that inhibition of miR-199a-3p in both human LX2 cells and rat HSCs significantly decreased the expression of fibrotic markers, such as fibronectin and connective tissue growth factor (CTGF), whereas the forced expression of miR-199a-3p exhibited opposite effects, demonstrating the role of miR-199a-3p in promoting HSC activation. Mechanistically, miR-199a-3p plays an important role in TGF-ß signalling pathway activation through targeting CAV2 that negatively regulates the expression of transforming growth factor-beta receptor type I (TGFßRI). Importantly, administration of antagomiR-199a-3p in the CCl4-treated mice significantly ameliorated hepatic fibrosis. In conclusion, Twist1-induced miR-199a-3p mediates the activation of HSCs by suppressing CAV2 expression and subsequently increasing TGFßRI expression to promote TGF-ß pathway. Our findings highlight the therapeutic potential of miR-199a-3p for hepatic fibrosis.

Efficacy and Safety of Immunosuppressive Therapy for PBC-AIH Overlap Syndrome Accompanied by Decompensated Cirrhosis: A Real-World Study.

Aim: To explore the efficacy and safety of immunosuppressive therapy for the treatment of primary biliary cirrhosis-autoimmune hepatitis (PBC-AIH) overlap syndrome accompanied by decompensated cirrhosis. Methods: A cohort study was performed to evaluate the usefulness of immunosuppressive therapy in this unique group. This cohort study was performed between October 2013 and June 2017 and included 28 biopsy-proven patients diagnosed according to the Paris criteria. The therapies included ursodeoxycholic acid (UDCA) alone (N=14) or in combination with immunosuppression (IS) therapy (N=14). The primary endpoints were biochemical remission, liver-related adverse events, transplant-free survival, and drug side-effects. Results: The frequency of biochemical remission for the AIH features was significantly higher in the UDCA+IS group than in the UDCA-only group (60.0 versus 9.1%, P=0.024) after 12 months of therapy but not after 3 and 6 months (28.6 versus 0%, P=0.165; 35.7 versus 7.1%, P=0.098). The rates of liver-related adverse events were lower in the combined group (2/14 versus 9/14, P=0.018). The Kaplan-Meier estimate showed that the transplant-free survival was distinct between the two groups (P=0.019). In the UDCA+IS group, mild and transient leukopenia occurred in two patients receiving azathioprine (AZA), and an infection was observed in one patient receiving mycophenolate mofetil (MMF). Conclusions: PBC-AIH patients with decompensated cirrhosis receiving a combination of UDCA and immunosuppressors presented with higher biochemical remission rates and experienced fewer liver-related adverse events, implying that the combined treatment might be a better therapeutic option for strictly defined decompensated PBC-AIH overlap syndrome.

MicroRNA-214 promotes hepatic stellate cell activation and liver fibrosis by suppressing Sufu expression.

MicroRNAs (miRNAs) have been demonstrated to modulate cellular processes in the liver. However, the role of miRNAs in liver fibrosis is poorly understood. Because the activation of hepatic stellate cells (HSCs) is a pivotal event in the initiation and progression of hepatic fibrosis, we investigate the differential expression of miRNAs in activated and quiescent rat HSCs by microarray analysis and find that miR-214 (miR-214-3p) is significantly upregulated during HSC activation. Moreover, the robust induction of miR-214 is correlated with liver fibrogenesis in carbon tetrachloride (CCl4)-treated rats and mice, high-fat diet-induced non-alcoholic steatohepatitis in mice, and cirrhosis in humans. We identify that miR-214 expression is driven by the helix-loop-helix transcription factor Twist1 via the E-box element. The increased miR-214 inhibits the expression of suppressor-of-fused homolog (Sufu), a negative regulator of the Hedgehog signaling pathway, thereby contributing to HSC activation to promote the accumulation of fibrous extracellular matrix and the expression of profibrotic genes in HSCs and LX2 cells. Furthermore, miR-214 expression is inversely correlated with the expression of Sufu in clinical cirrhosis samples. To explore the clinical potential of miR-214, we inject antagomiR-214 oligos into mice to induce hepatic fibrosis. The knockdown of miR-214 in vivo enhances Sufu expression and reduces fibrosis marker expression, which ameliorates liver fibrosis in mice. In conclusions, the Twist1-regulated miR-214 promotes the activation of HSC cells through targeting Sufu involved in the Hedgehog pathway and participates in the development of hepatic fibrosis. Hence, the knockdown of miR-214 expression may be a promising therapeutic strategy for liver fibrosis.

MiR-142-3p blocks TGF-ß-induced activation of hepatic stellate cells through targeting TGFßRI.

AIM: To understand the contribution of miR-142-3p in the activation of hepatic stellate cells (HSCs) and liver fibrosis, and the underlying mechanism. MATERIALS AND METHODS: We detected microRNAs expression profiles in quiescent and activated HSCs by microRNA-array, and performed qRT-PCR to validate these data in HSCs and plasma of cirrhosis patients. In vitro, the 3rd-5th passage HSCs was transfected with mir-142-3p mimics or stimulated with TGF ß. The markers of HSCs activation (i.e. FN and α-SMA) were examined by qRT-PCR and western blotting, and cell viability was detected by MTT, colony formation assays respectively. KEY FINDING: In our study, we identified miR-142-3p as a novel regulator of HSCs activation and indicator of hepatic cirrhosis. We found that miR-142-3p was significantly reduced in activated HSCs, while TGFßRI was distinctly up-regulated in activated HSCs. Ectopic expression of miR-142-3p in activated HSCs inhibited cell viability as well as cell growth, and blocked HSCs activation, concomitant with decreased transdifferentiation markers (i.e. FN and α-SMA). Further, we confirmed that miR-142-3p was reduced upon TGF-ß exposure, while diminishing TGF-ß-Smad signaling pathway in turn by reducing TGFßRI expression in HSCs. Besides, the plasma level of miR-142-3p declined significantly in patients with hepatic cirrhosis. SIGNIFICANCE: In conclusion, we demonstrated that miR-142-3p repressed TGF-ß-Smad signaling pathway to prevent HSCs activation through directly targeting TGFßRI in HSCs.

MircoRNA-145 promotes activation of hepatic stellate cells via targeting krüppel-like factor 4.

Krüppel-like Factor 4 (KLF4), a target gene of miR-145, can negatively regulate lung fibrosis. However, the potential role of KLF4 and miR-145 in hepatic stellate cells (HSCs) activation or in hepatic fibrosis keeps unclear. This study aims to characterize miR-145 and KLF4 in activated HSCs and liver cirrhotic, and the underlying molecular basis. miR-145 was significantly up-regulated, while KLF4 was dramatically down-regulated during the activation of rat primary HSCs and TGF-ßtreated HSCs. Furthermore, miR-145 mimics induced and inhibition of miR-145 reduced α-SMA and COL-I expression in primary HSCs. Additionally, the mRNA and protein levels of KLF4 in the liver of cirrhotic patients and rats were significantly down-regulated. α-SMA and COL-I were increased after inhibition of KLF4 by specific shRNA in primary HSCs. Forced KLF4 expression led to a reduction of α-SMA and COL-I expression in HSCs. miR-145 promotes HSC activation and liver fibrosis by targeting KLF4.

Involvement of miR-30c in hepatic stellate cell activation through the repression of plasminogen activator inhibitor-1.

AIMS: This study aimed to determine the role of miR-30c in the process of hepatic stellate cells (HSCs) activation and liver fibrosis/cirrhosis and to explore the underlying mechanism. MAIN METHODS: A microarray analysis of miRNAs in HSCs was performed, and quantitative RT-PCR analyses were conducted to validate the results in HSCs, cirrhotic liver tissues and plasma. Rat HSCs were stimulated with angiotensin II (AngII) and transfected with miR-30c mimics/inhibitor to elucidate the underlying mechanism. KEY FINDINGS: miR-30c was down-regulated during HSCs activation and in cirrhotic liver tissues and plasma. This miRNA was found to be involved in HSCs activation by repressing the expression of one of its target genes-plasminogen activator inhibitor-1 (PAI-1), and AngII stimulation decreased the expression of miR-30c. However, the up-regulation of miR-30c by specific mimics could down-regulate the mRNA and protein expression of α-SMA, a marker of HSCs activation, in AngII-stimulated HSCs and attenuate the AngII-induced activation of HSCs. SIGNIFICANCE: miR-30c is involved in HSCs activation and might be a novel biomarker of liver fibrosis/cirrhosis.

Does adding variceal status to the Child-Turcotte-Pugh score improve its performance in predicting mortality in cirrhosis?

The Child-Turcotte-Pugh (CTP) score is widely used worldwide to predict outcomes across a broad spectrum of liver diseases, mainly cirrhosis. Portal hypertension and variceal bleed are significant causes of morbidity and mortality in cirrhotic patients, although the variceal status is not incorporated into the classical CTP score. We sought to determine whether the inclusion of variceal status, specifically the Child-Turcotte-Pugh-Kumar (CTPK) score, would improve the utility of the classical CTP score to predict the clinical outcomes of cirrhotic patients in a single but high-volume center in China.We retrospectively analyzed the records of 253 patients from January 1, 2014 to December 31, 2014 and performed follow-up for at least 12 months. The CTPK score and the CTP score were obtained as soon as possible after the patient's admission. Telephone follow-up was performed to assess survival situations.At 3 and 12 months, the cumulative number of deaths was 9.1% (n = 23) and 13.8% (n = 35), respectively. In the multivariate Cox proportional hazards models, the CTPK score was independently associated with death within 3 and 12 months after adjusting for potential confounders. The predictive ability related to the 2 scores was evaluated by the area under the receiver operating characteristic curve (AUC-ROC) respectively. At 3 months of enrollment, the AUCs of CTPK and CTP were 0.814 and 0.838, respectively. At 12 months of enrollment, the AUCs of CTPK and CTP were 0.825 and 0.840, respectively. No significant difference between time points was observed. Both the CTPK score and the CTP score displayed prognostic value in cirrhotic patients, as the Kaplan-Meier analysis showed that the CTPK score could clearly discriminate patients in the intermediate term (P < 0.001).The CTPK score provides reliable prediction of mortality in Chinese cirrhotic patients for both short-term and medium-term prognoses, although it is not superior to the CTP score. Therefore, the CTP score remains an excellent tool for outcome prediction in patients with cirrhosis, and greater attention to variceal status may be in veins, even for patients with a history of variceal bleed or medium/large varices.

The Value of Circulating Nogo-B for Evaluating Hepatic Functional Reserve in Patients with Cirrhosis.

OBJECTIVE: To examine Nogo-B in liver tissues and plasma of patients with liver cirrhosis and associate them with various clinical parameters. MATERIALS AND METHODS: Nogo-B protein expression was examined by immunohistochemistry in 24 human fibrotic/cirrhotic liver specimens and 10 healthy controls. We determined plasma Nogo-B levels by enzyme-linked immunosorbent assay in 301 patients with liver cirrhosis and 153 healthy controls, and then analyzed various clinical parameters. RESULTS: Nogo-B was mainly expressed in nonparenchymal cells in the liver and was marked increased in liver with significant fibrosis/cirrhosis compared to controls. Moreover, Metavir F4 showed a higher level of expression than F2. Plasma Nogo-B levels were significantly higher in cirrhotic patients than in healthy controls and were the highest in Child-Pugh class C patients. Plasma Nogo-B levels were positively correlated with Child-Pugh scores. However, there was no relationship between plasma Nogo-B levels and etiology of liver diseases, ALT, AST, platelet counts, and the severity of esophagogastric varices. CONCLUSIONS: Nogo-B is mainly expressed in hepatic nonparenchymal cells and is present in plasma. Abnormally high plasma levels of Nogo-B are associated with hepatic cirrhosis and Child-Pugh score, but not correlated with the grade of liver inflammation or portal hypertension. Plasma Nogo-B may be a novel surrogate marker to reflect liver function reserve.