Presepsin as a prognostic biomarker in COVID-19 patients: combining clinical scoring systems and laboratory inflammatory markers for outcome prediction.

BACKGROUND: There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking. METHODS: A total of 226 COVID-19 patients admitted to Beijing Youan Hospital's emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed. RESULTS: A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p < 0.001). Presepsin showed significant predictive value for 28-day mortality in COVID-19 patients, with an area under the ROC curve of 0.828 (95% CI: 0.737-0.920). Clinical scoring systems and inflammation markers also played a significant role in predicting 28-day outcomes. After Cox regression adjustment, Presepsin, qSOFA, NEWS2, PSI, CURB-65, CRP, NLR, CAR, and LCR were identified as independent predictors of 28-day mortality in COVID-19 patients (all p-values < 0.05). Combining Presepsin with clinical scoring systems and inflammation markers further enhanced the predictive value for patient prognosis. CONCLUSION: Presepsin is a favorable indicator for the prognosis of COVID-19 patients, and its combination with clinical scoring systems and inflammation markers improved prognostic assessment.

The efficacy and safety of methylprednisolone in hepatitis B virus-related acute-on-chronic liver failure: a prospective multi-center clinical trial.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe condition with high mortality due to lack of efficient therapy. Until now, the use of methylprednisolone (MP) in HBV-ACLF is still controversial. We aimed to evaluate the efficacy and safety of MP in HBV-ACLF. METHODS: Totally 171 HBV-ACLF patients from three medical centers were randomly allocated into MP group (83 patients treated with MP intravenously guttae for 7 days plus standard treatment: 1.5 mg/kg/day [day 1-3], 1 mg/kg/day [day 4-5], and 0.5 mg/kg/day [day 6-7]) and control group (88 patients treated with standard treatment). The primary endpoints were 6-month mortality and prognostic factors for 6-month survival. The survival time, cause of death, adverse events, liver function, and HBV DNA replication were analyzed. RESULTS: The 6-month mortality was significantly lower in MP group than control group [32.4% vs. 42.5%, P = 0.0037]. MP treatment was an independent prognostic factor for 6-month survival [HR (95% CI) 0.547(0.308-0.973); P = 0.040]. Factors associated with reduced 6-month mortality in MP group included HBV DNA and lymphocyte/monocyte ratio (LMR) (P < 0.05). Based on ROC curve, LMR+MELD had a better predictive value for prognosis of HBV-ACLF under MP treatment. No significant difference in HBV DNA replication was observed between groups (P > 0.05). CONCLUSIONS: MP therapy is an effective and safe clinical strategy in HBV-ACLF, increasing the 6-month survival rate. Clinical trials registered at http://www.chictr.org.cn as ChiCTR-TRC-13003113 registered on 16 March 2013.

Mitofusin2, a rising star in acute-on-chronic liver failure, triggers macroautophagy via the mTOR signalling pathway.

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome with poor prognosis. Several studies have begun to prove that mitochondria play a crucial role in liver failure. Mitofusin2 (Mfn2) plays a key role in maintaining the integrity of mitochondrial morphology and function. However, the role and underlying mechanisms of Mfn2 on cell autophagy of ACLF remain unclear. Our aim was to explore the effect of Mfn2 on several biological functions involving cell autophagy in ACLF. In this study, we constructed an ACLF animal model and a hepatocyte autophagy model, using adenovirus and lentivirus to deliver Mfn2 to liver cells, in order to assess the effect of Mfn2 on autophagy and apoptosis in ACLF. Furthermore, we explored the biological mechanism of Mfn2-induced autophagy of ACLF using Western blotting, RT-PCR and electron microscopy. We found that Mfn2 significantly attenuated ACLF, characterized by ameliorated gross appearance and microscopic histopathology of liver, and reduced serum AST, ALT, and TBIL levels. Mfn2 improved the expressions of LC3-II, Atg5 and Bcl-2 and down-regulated the expression of P62 and Bax in ACLF. Like rapamycin, Mfn2 also significantly inhibited the expressions of p-PI3K, p-Akt and p-mTOR in ACLF. In conclusion, our findings suggest that Mfn2 influences multiple biological functions of ACLF via the PI3K/Akt/mTOR signalling pathway. This study will provide a reliable theoretical basis for the application of Mfn2 as an effective target for ACLF treatment, reversing or delaying the process of ACLF.

HIF1a Inhibitor Rescues Acute-on-Chronic Liver Failure.

INTRODUCTION AND OBJECTIVES: Hypoxia-inducible factor-1α is critically involved in the pathogenesis of liver diseases. Its inhibitor genistein attenuated D-galactosamine (D-GalN)-induced liver damage. However, the role of genistein in acute-on-chronic liver failure (ACLF) is unclear. The influence of genistein on reactive oxygen species (ROS) and hepatocyte functions were evaluated in a rat model of ACLF. MATERIAL AND METHODS: Genistein [20mg/ (kg. day)]/coenzyme Q10 [10mg/ (kg. day)]/lipoic acid [20mg/ (kg. day)] was administered via the intra-gastric route daily for 6 weeks as co-treatment to the rats in the experimental groups. Then, 100µg/kg LPS combined with 0.5g/kg D-GalN was injected intraperitoneally to attack the rats. RESULTS: Genistein significantly attenuated LPS/D-GalN-induced ACLF, characterized by ameliorated gross appearance and microscopic histopathology of liver, reduced AST level in serum, whereas increased levels of ATP, ADP/O, and respiratory control ratio (RCR) in mitochondria. Genistein suppressed necrosis and ROS production. CONCLUSION: These results suggested that genistein could protect against ACLF through inhibiting cellular ROS production and necrosis, improving RCR, and decreasing permeability transition pores in mitochondrial, which was similar as mitochondrial protective agent coenzyme Q10.

Clinical performance of stem cell therapy in patients with acute-on-chronic liver failure: a systematic review and meta-analysis.

BACKGROUND: Stem cell therapy has been applied in the treatment of acute-on-chronic liver failure (ACLF). However, its clinical efficiency is still debatable. The aim of this systematic review and meta-analysis is to evaluate the clinical efficiency of stem cell therapy in the treatment of ACLF. METHODS: The Cochrane Library, OVID, EMBASE, and PUBMED were searched to December 2017. Both randomized and non-randomized studies, assessing stem cell therapy in patients with ACLF, were included. The outcome measures were total bilirubin (TBIL), alanine transaminase (ALT), international normalized ratio (INR), albumin (ALB), and the model for end-stage liver disease (MELD) score. The quality of evidence was assessed by GRADEpro. RESULTS: Four randomized controlled trials and six non-randomized controlled trials were included. The TBIL levels significantly decreased at 1-, 3-, 12-month after the stem cell therapy (p = 0.0008; p = 0.04; p = 0.007). The ALT levels decreased significantly compared with the control group in the short-term (p < 0.00001). There was no obvious change in the INR level compared with the control groups (p = 0.64). The ALB levels increased markedly as compared with the control groups (p < 0.0001). The significant difference can be found in MELD score between stem cell therapy and control groups (p = 0.008). Further subgroup analysis for 3-month clinical performance according to the stem cell types have also been performed. CONCLUSION: This study suggests that the clinical outcomes of stem cell therapy were satisfied in patients with ACLF in the short-term. MSCs may be better than BM-MNCs in the stem cells transplantation of ACLF. However, more attention should focus on clinical trials in large-volume centers.

The significance of glypican-3 expression profiling in the tumor cellular origin theoretical system for hepatocellular carcinoma progression.

BACKGROUND AND AIM: Glypican-3 (GPC3) expression is correlated with poor prognosis and progression in hepatocellular carcinoma (HCC). HCC progression can be associated with the differentiation status of tumor cell before malignant transformation. Our aim was to investigate the dynamic expression of GPC3 during tumor cells differentiation and to explore the role and theoretical significance of GPC3 in malignant essence of HCC. METHODS: The expressions of tissue GPC3 and alpha fetoprotein (AFP) were detected by immunohistochemical staining. The tumor size, lymph node involvement, and metastasis were determined by pathological and imaging studies. HepG2 cells were induced to differentiate by all-trans retinoic acid (ATRA). Differentiation was evaluated by cytokeratin 19, gamma glutamyl transferase, and AFP through reverse transcription-polymerase chain reaction and real-time polymerase chain reaction. GPC3 staining was analyzed through flow cytometry. RESULTS: Based on the immunohistochemical staining, the enrolled 316 cases were divided into two subtypes, namely, GPC3+ HCC and GPC3- HCC. Significant differences in morphology, histology variations, AFP expression, TNM staging, and overall survival curves were observed between two subtypes. During HCC differentiation induced by ATRA, the mean value of GPC3 expression treated with ATRA was much lower than the ones in placebo. There were significant differences between GPC3+ HCC and GPC3- HCC for cumulative intrahepatic and extrahepatic recurrence in early stage HCC (P = 0.009, P = 0.010). CONCLUSIONS: Glypican-3 is correlated with the clinical malignant behavior of HCC. Moreover, GPC3 phenotype changes from positive to negative during tumor cells differentiation. Meanwhile, GPC3 plays a significant role in tumor cellular origin theoretical system, which can better reflect the malignant essence of tumors.

sTREM-1 as a Predictive Biomarker for Disease Severity and Prognosis in COVID-19 Patients.

Background: Research on biomarkers associated with the severity and adverse prognosis of COVID-19 can be beneficial for improving patient outcomes. However, there is limited research on the role of soluble TREM-1 (sTREM-1) in predicting the severity and prognosis of COVID-19 patients. Methods: A total of 115 COVID-19 patients admitted to the emergency department of Beijing Youan Hospital from February to May 2023 were included in the study. Demographic information, laboratory measurements, and blood samples for sTREM-1 levels were collected upon admission. Results: Our study found that sTREM-1 levels in the plasma of COVID-19 patients increased with the severity of the disease (moderate vs mild, p=0.0013; severe vs moderate, p=0.0195). sTREM-1 had good predictive value for disease severity and 28-day mortality (area under the ROC curve was 0.762 and 0.805, respectively). sTREM-1 also exhibited significant correlations with age, body temperature, respiratory rate, PaO2/FiO2, PCT, CRP, and CAR. Ultimately, through multivariate logistic regression analysis, we determined that sTREM-1 (OR 1.008, 95% CI: 1.002-1.013, p=0.005), HGB (OR 0.966, 95% CI: 0.935-0.998, p=0.036), D-dimer (OR 1.001, 95% CI: 1.000-1.001, p=0.009), and CAR (OR 1.761, 95% CI: 1.154-2.688, p=0.009) were independent predictors of 28-day mortality in COVID-19 patients. The combination of these four markers yielded a strong predictive value for 28-day mortality in COVID-19 cases with an AUC of 0.919 (95% CI: 0.857 -0.981). Conclusion: sTREM-1 demonstrated good predictive value for disease severity and 28-day mortality, serving as an independent prognostic factor for adverse patient outcomes. In the future, we anticipate conducting large-scale multicenter studies to validate our research findings.

Study on the predictive value of laboratory inflammatory markers and blood count-derived inflammatory markers for disease severity and prognosis in COVID-19 patients: a study conducted at a university-affiliated infectious disease hospital.

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), studies have found correlations between blood cell count-derived inflammatory markers (BCDIMs) and disease severity and prognosis in COVID-19 patients. However, there is currently a lack of systematic comparisons between procalcitonin (PCT), C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR) and BCDIMs for assessing the severity and prognosis of COVID-19 patients. METHODS: A total of 1040 COVID-19 patients were included in the study. Demographics, comorbidities and laboratory results were analysed. BCDIMs refer to the following ratios: neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-C-reactive protein ratio (LCR), systemic inflammation response index (SIRI) and systemic inflammation index (SII). Disease severity and 28-day mortality are clinical outcomes of this study. Area under the curve (AUC) of receiver operating characteristic (ROC) curve was calculated for these markers, and DeLong's test compared their statistical differences. Cox regression analysis assessed their predictive value for the 28-day mortality rate. RESULTS: Among the 1040 patients, 35.3% were severe/critical, 49.6% were moderate and 15.1% were mild cases. Within 28 days, 15.1% died. The NLR had the highest predictive value for disease severity (AUC: 0.790, 95% CI: 0.762-0.818). NLR differed significantly from other markers, except LCR. LCR best predicted 28-day mortality (AUC: 0.798, 95% CI: 0.766-0.829). Some markers showed significant differences in AUC with LCR. Multivariable Cox regression identified BCDIMs, PCT, CRP and CAR as significant risk factors for 28-day mortality. CONCLUSIONS: PCT, CRP, CAR and BCDIMs, easily obtained in clinical settings, are valuable predictors of disease severity and the 28-day mortality in COVID-19 patients. The NLR is particularly effective for disease severity, while the LCR is highly predictive of 28-day mortality. These markers provide guidance for stratified management of COVID-19 patients.

Imbalance between circulating CD4+ regulatory T and conventional T lymphocytes in patients with HBV-related acute-on-chronic liver failure.

BACKGROUND & AIMS: The important pathophysiological role of immune dysfunction, especially innate immune dysfunction in patients with acute-on-chronic liver failure (ACLF), has been investigated in recent years, but dysregulation of adaptive immunity remains poorly elucidated. The aim of this study was to (i) determine the CD3(+) T-lymphocyte count and the balance between CD4(+) regulatory T (Tregs) and conventional T cells (Tconv) in hepatitis B virus (HBV)-related ACLF patients; (ii) analyse the frequencies of Tregs subpopulations; and (iii) assess the suppressive potency of CD4(+) Tregs and each fraction. METHODS: We enrolled 20 HBV-ACLF patients, 10 septic shock subjects, 20 chronic hepatitis B (CHB) patients and 20 healthy volunteers (HC). Based on flow cytometry, we performed the absolute counting of circulating T lymphocytes and phenotyping of CD4(+) Tregs and quantified the effects of Tregs and each subpopulation on Tconv proliferation by CFSE staining. RESULTS: Compared with CHB patients and HC, we observed an equal reduction in peripheral T subsets in HBV-ACLF and septic shock subjects; the number of CD4(+) Tregs remained unchanged and the Tconv count declined, promoting elevation of the Treg-to-Tconv ratio. The frequencies of Treg-II and -III were elevated in HBV-ACLF. Functional studies showed that the suppressive capacity of Tregs was preserved in the HBV-ACLF group and Treg-II came first. CONCLUSIONS: Similar to septic shock subjects, in HBV-ACLF patients there exists a reduction in CD4(+) T lymphocytes, predominantly CD4(+) Tconv, and the development of suppressive CD4(+) Tregs greatly prevails over Tconv, constituting important characteristics of adaptive immune dysfunction of HBV-ACLF.

Development and Validation of a Nomogram for 90-day Outcome in Patients with Hepatitis B Virus-related Acute-on-chronic Liver Failure.

Background and Aims: It is challenging to predict the 90-day outcomes of patients infected with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) via prevailing predictive models. This study aimed to develop an innovative model to enhance the analytical efficacy of 90-day mortality in HBV-ACLF. Methods: In this study, 149 HBV-ACLF patients were evaluated by constructing a death risk prediction nomogram. Bootstrap resampling and an independent validation cohort comprising 31 patients from June 2019 to February 2020 were assessed for model confirmation. Results: The nomogram was constructed by entering and identifying five factors (age, total bilirubin, prothrombin activity (PTA), lymphocyte (L)%, and monocyte (M)%. Healthy refinement was achieved from the nomogram analysis, where the area under the receiver operating characteristic curve was 0.864 for the training cohort and 0.874 was achieved for the validation cohort. There was admirable concordance between the predicted and true results in the equilibrium curve. The decision curve assessment revealed the useful clinical application of the nomogram. Conclusions: We constructed an innovative nomogram and validated it for the prediction of 90-day HBV-ACLF patient outcomes. This model might help develop optimized treatment protocol recommendations for HBV-ACLF patients.

The clinical parameters for the diagnosis of hepatitis B virus related acute-on-chronic liver failure with sepsis.

It is still unknown that whether sepsis with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) fit into the conventional diagnostic criteria of sepsis. Our aim was to investigate the potential clinical parameters for the diagnosis of HBV-ACLF with sepsis. A retrospective study was conducted in 43 patients with HBV-ACLF and sepsis who underwent orthotopic liver transplantation. All patients were divided into three groups according to the pathological results and laboratory test results. Immunohistochemistry (IHC) staining, hematoxylin-eosin (HE) staining and Gordon Sweet's reticulin staining were performed in this study. Alanine aminotransferase (ALT), aspartale aminotransferase (AST), total bilirubin (TBiL), cholinesterase (CHE), albumin (ALB), prothrombin activity (PTA), blood routine examination were detected. The results being chosen at admission and before transplantation were analyzed. TBiL had a significant increase (563.5 ± 191.8 umol/L vs. 383.9 ± 157.6 umol/L, 438.3 ± 154.7 umol/L, P = 0.031) and ALT significantly decreased (81.6 ± 66.4 U/L, 754.5 ± 1084.7 U/L, 120.6 ± 102.5 U/L, P = 0.005) in sepsis group before liver transplantation. When sepsis appeared in patients with HBV-ACLF, the ratio of PLT to WBC count before liver transplantation was much lower than it at admission (4.6 ± 2.0 vs. 16.1 ± 7.2, P = 0.000). In conclusion, the clinical parameters of sepsis in patients with HBV-ACLF should be reset. The ratio of PLT/WBC and (WBCBLT/WBCAA)/ (PLTBLT/PLTAA) could remind us the occurring of sepsis in patients with HBV-ACLF.

Mitofusin2, as a Protective Target in the Liver, Controls the Balance of Apoptosis and Autophagy in Acute-on-Chronic Liver Failure.

Aim: Acute-on-chronic liver failure (ACLF) is closely related to mitochondrial dysfunction. Previous studies showed the vital role of mitofusin2 (Mfn2) in the regulation of mitochondrial function. However, the effect of Mfn2 on ACLF remains unknown. As one of mitochondrial-related pathways, BNIP3-mediated pathway controls the balance between apoptosis and autophagy. However, the relationship between Mfn2 and BNIP3-mediated pathway in ACLF is still obscure. The aim of our study is to clarify the effect of Mfn2 and potential molecular mechanisms in ACLF. Methods: We collected liver tissue from ACLF patients and constructed an ACLF animal model and a hepatocyte autophagy injury model, using adenovirus and lentivirus to deliver Mfn2 and Mfn2-siRNA to liver cells, in order to assess the effect of Mfn2 on autophagy and apoptosis in ACLF. We explored the biological mechanisms of Mfn2-induced autophagy and apoptosis of ACLF through Western blotting, Quantitative Real-Time PCR (RT-PCR), transmission electron microscopy, immunofluorescence, immunohistochemical staining, and hematoxylin-eosin staining. Results: Compared with the normal liver tissue, the expressions of Mfn2, Atg5, Beclin1, and LC3-II/I were significantly decreased and the expression of P62 was much higher in patients with ACLF. Mfn2 significantly attenuated ACLF, characterized via microscopic histopathology and reduced serum AST and ALT levels. Mfn2 promoted the expressions of ATP synthase ß, Atg5, Beclin1, LC3-II/I, and Bcl2 and reduced the expressions of P62, Bax, and BNIP3. Conclusions: Mfn2 plays a protective role in the progression of ACLF. BNIP3-mediated signaling pathway is not the only factor associated with Mfn2 controlling the balance of apoptosis and autophagy in ACLF. Mfn2 will provide a promising therapeutic target for patients with ACLF.

Clinical characteristics of liver failure with hemophagocytic lymphohistiocytosis.

Liver failure with hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome with high mortality. The aim of this study was to decipher clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis after definite diagnosis of liver failure and to provide clues for early diagnosis and treatment of HLH in patients with liver failure. Eleven patients diagnosed with liver failure and HLH were retrospectively investigated in this study. All patients presented with jaundice, persistent high-grade fever, pancytopenia, splenomegaly, evidence of hemophagocytes in the bone marrow and laboratory abnormalities indicating HLH. The average interval from the earliest diagnosis of liver failure to a definitive diagnosis of HLH was 17.27 days. Six (54.55%) patients died during follow-up. For patients with liver failure after admission and subsequently definitively diagnosed with HLH, bilirubin and INR were significantly decreased. HLH is definitely diagnosed at an intermediate or late stage when patients have already suffered from liver failure. The initial dose of glucocorticoid (methylprednisolone) was decreased to 1-1.5 mg/kg/d and gradually reduced thereafter. In conclusion, for patients with liver failure, HLH should be screened as early as possible upon persistent fever, splenomegaly and unexplained pancytopenia. For patients with liver failure and HLH, the dosage of glucocorticoid should be reduced to avoid serious side effects.

The assessment of multipotent cell transplantation in acute-on-chronic liver failure: a systematic review and meta-analysis.

Acute-on-chronic liver failure (ACLF) is a serious life-threatening disease with high prevalence. Liver transplantation is the only efficient clinical treatment for ACLF. Because of the rapid progression and lack of liver donors, it is urgent to find an effective and safe therapeutic approach to ACLF. Recent studies showed that multipotent cell transplantation could improve the patients' liver function and enhance their preoperative condition. Cells such as mesenchymal stem cells, bone marrow mononuclear cells and autologous peripheral blood stem cells, which addressed in this study have all been used in multipotent cell transplantation for liver diseases. However, its clinical efficiency is still debatable. This systematic review and meta-analysis explored the clinical efficiency of multipotent cell transplantation as a therapeutic approach for patients with ACLF. A detailed search of the Cochrane Library, MEDLINE, and Embase databases was conducted from inception to November 2017. The outcome measures were serum albumin, prothrombin time, alanine aminotransferase, total bilirubin, platelets, hemoglobin, white blood cells, and survival time. The quality of evidence was assessed using GRADEpro and Jaded scores. A literature search resulted in 537 citations. Of these, 9 articles met the inclusion criteria. It was found that multipotent cell transplantation was able to alleviate liver damage and improve liver function. Multipotent cell transplantation can also enhance the short-term and medium-term survival rates of ACLF. All 9 research articles included in this analysis reported no statistically significant adverse events, side effects, or complications. In conclusions, this study suggested that multipotent cell transplantation could be recommended as a potential therapeutic supplementary tool in clinical practice. However, clinical trials in large-volume centers still needed.

[Experimental study of Qishen Yiqi Dropping Pills on liver fibrosis in rats].

OBJECTIVE: To investigate the anti-fibrotic effects of Qishen Yiqi Dropping Pills (QYDP) in rats with liver fibrosis (LF). METHODS: The LF model was induced by intraperitoneal injection with dimethylnitrosamine (DMN). Sixty Wistar rats were randomly divided into the normal group, the model group A, the QYDP intervened group , the model group B , and the QYDP treated group B. The degree of LF was evaluated according to 6-phase grading method. The expressions of collagen type I and III and tissue inhibitor of metalloproteinase-1 (TIMP-1) in liver tissues were determined by immunohistochemistry and the levels of collagen type I and III and TIMP-1 mRNA determined by semi-quantitive RT-PCR. RESULTS: Compared with the model group A and B, the degree of LF, the positive expressions of TIMP-1 mRNA and the content of collagen type I and III in liver tissue in the QYDP intervened and treated groups were significantly lower. CONCLUSION: QYDP could reduce the pathological changes and degree of LF in rats, which may be partially through inhibiting the expressions of collagen type I and III and TIMP-1.

A novel dynamic model for predicting outcome in patients with hepatitis B virus related acute-on-chronic liver failure.

AIM: It is challenging to predict the outcome of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) through existing prognostic models. Our aim was to establish a novel dynamic model to improve the predictive efficiency of 30-day mortality in HBV-ACLF patients. METHODS: 305 patients who were diagnosed as HBV-ACLF (derivation cohort, n=211; validation cohort, n=94) were included in this study. The HBV-ACLF dynamic (HBV-ACLFD) model was constructed based on the daily levels of predictive variables in 7 days after diagnosis combined with baseline risk factors by multivariate logistic regression analysis. The HBV-ACLFD model was compared with the Child-Turcotte-Pugh (CTP) score, end-stage liver disease (MELD) score, and MELD within corporation of serum sodium (MELD-Na) score by the area under the receiver-operating characteristic curves (AUROC). RESULTS: The HBV-ACLFD model demonstrated excellent discrimination with AUROC of 0.848 in the derivation cohort and of 0.813 in the validation cohort (p=0.620). The performance of the HBV-ACLFD model appeared to be superior to MELD score, MELD-Na score and CTP score (P<0.0001). CONCLUSION: The HBV-ACLFD model can accurately predict 30-day mortality in patients with HBV-ACLF, which is helpful to select appropriate clinical procedures, so as to relieve the social and economic burden.

Prognostic value of immunoscore to identify mortality outcomes in adults with HBV-related primary hepatocellular carcinoma.

This study aimed to determine if the immunoscore (IS) staging system would be a potential prognostic factor in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) in China.IS was performed in a consecutive cohort of HBV-HCC patients (n= 92). CD3+, CD8+, and CD45RO+ T cells were quantified by immunohistochemical analyses. The patients were stratified into 5 IS groups: I0, I1, I2, I3, I4 for every 2 cell phenotypes (IS1 (CD8/CD45RO, IS2 (CD3/CD8), and IS3 (CD3/CD45RO), respectively. ImagePro Plus software was used in the calculation of the paraffin-embedded tumor sections.The staining of CD3+, CD8+, and CD45RO+ cells in the HBV-HCC tissue demonstrated that there were higher density and larger area of lymphocytes in the invasive margins (IM) region than in the center (CT). Univariate analysis showed that preoperative TNM staging (P = .01), serum gamma-glutamyl transpeptidase (GGT) level (P = .03), vascular invasion (P = .00), and density of CD3+T (CT) (P = 0.01) were correlated significantly with disease-free survival (DFS); serum alpha-fetoprotein (AFP) level (P = .02), tumor size (P = .00), serum cholinesterase (CHE) (P = .04), and GGT level (P = .01), density of CD3+T(CT) (P = .00), CD8+T(CT)(P = .00), CD45RO+T(CT) (P = .00), and CD45RO+T (IM) (P = .02) were correlated with overall survival (OS). Multivariate analysis showed that TNM staging was not an independent prognostic factor of DFS and OS. Our results showed ISs did not have a significantly correlation with DFS (P = .35, .19, and .07, respectively), but it was correlated significantly with OS (P = .00, .00, and .00, respectively). There were statistical differences among the OS of every ISs subgroup except I0 and I1 by the Cox regressions analysis.The IS staging was closely related to the outcome of patients. It can compensate the TNM tumor classification system in predicting the prognosis of HBV-HCC patients.

[Dynamic evolution of MMP-2 gene expression and its enzymatic activities in experimental liver fibrosis].

OBJECTIVES: To explore the dynamic changes and interactions between MMP-2 and TIMP-2 during experimental liver fibrosis. METHODS: Wistar rats were randomly allocated into a normal group and a model group. To induce liver fibrosis, rats were injected intraperitoneally with dimethylnitrosamine (DMN) three consecutive times in the first week, then two consecutive times per week, totally for 6 weeks. In the normal control group, rats were injected with saline by the same method as the model group. Animals were sacrificed 1, 4, 10, 17, 28, 42, 56 days after starting DMN injections. Conventional histological examinations of the livers were performed with hematoxylin and eosin and Masson staining. The fibrosis was classified into 0 to 4 stages. Hydroxyproline content was determined after liver tissues were hydrolyzed in HCl at 160 degree C for 2 hrs and then measured with spectrometry at 560 nm wavelength. mRNA levels of MMP-2 and TIMP-2 were determined by semi-quantitive RT-PCR. Gelatinase activity of MMP-2 was examined by zymography using gelatin substrate. RESULTS: In the model group the hepatic MMP-2 mRNA expression started to increase 10 days after DMN administration and remained at a much higher level than in the normal group throughout the study period, while TIMP-2 mRNA expression started to be lower than in the normal group 17 days after DMN administration and reached the lowest level on the 28th day. Then it rapidly rebounded and remained higher than that in the normal group from the 42nd day to the end of the study period. TIMP-2/MMP-2 began to be lower by several days than that of the normal group after DMN administration through the remaining study period. Zymography showed that the enzymatic activities of both latent MMP-2 and active MMP-2 were increased during the process of liver fibrosis. CONCLUSION: In liver fibrosis, MMP-2 expression increases, while TIMP-2 expression relatively decreases. The enzymatic activities of MMP-2 increase as the liver fibrosis develops.