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Background: Although patients with liver failure exhibit a generalized inflammatory-imbalance status, substantial evidence indicates that this immunosuppressive or anti-inflammatory state may be deleterious. Increased expression of CD163 (known to be involved in several anti-inflammatory functions of the immune system) in patients with liver failure is significantly correlated with a fatal outcome. However, little is known of the regulatory mechanisms that influence the expression of CD163., Methods: We assessed the expression of CD163 on monocytes from both circulating cells and the liver tissues of patients with hepatitis B induced liver failure using flow cytometry and isolated the myofibroblasts from diseased livers. The ability of human liver myofibroblasts to regulate CD163 expression on monocytes was studied in vitro., Results: We showed that CD163⁺ monocytes were enriched primarily in diseased livers and that they were associated with liver myofibroblasts in the same area. Accordingly, liver myofibroblasts were significantly superior to normal skin fibroblasts in inducing the expression of CD163 on monocytes in vitro. Moreover, we found that liver myofibroblasts triggered the activation of monocytes by secreting PGE2. Inhibition of PGE2 production in liver myofibroblasts using NS-398 markedly reduced CD163 expression in vitro., Conclusion: These results suggest that liver myofibroblasts play a direct role in regulating the expression of CD163 on monocytes in human liver tissues and thereby may regulate monocyte function during hepatitis B induced liver failure.

Background and Aim: Although regulatory T cells (Treg) and interleukin-17-producing CD4 T cells (Th17) have been demonstrated to play opposing roles in inflammation-associated diseases, their frequency and balance in different stages of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remain unknown., Methods: Fourteen patients with HBV-associated ACLF were studied and defined into different stages according to disease activity. Circulating Th17 cells and Treg cells were analyzed by flow cytometry, and the cytokines were quantitated by enzyme-linked immunosorbent assay. Results were correlated with temporal changes in viral load, disease progression and compared with 30 chronic hepatitis B (CHB) subjects and 18 healthy subjects., Results: We showed a significantly higher frequency of circulating Th17 cells in the remission stage of ACLF when compared with the progression stage, the CHB group, or normal controls. However, the frequency of circulating Treg cells was significantly lower in the remission stage of ACLF when compared with the progression stage or the CHB group. The increase in Th17 cells and concomitant decrease in Treg cells created an imbalance in the remission stage of ACLF patients, which negatively correlated with disease progression. In addition, we showed that ACLF patients in the remission stage had an altered profile of cytokines that regulated the induction of Th17 cells and Treg cells., Conclusions: ACLF patients in the remission stage had an imbalance of Th17 to Treg cells, which could be used as a prognostic marker to predict disease progression. This imbalance could play a role in the immunopathogenesis of HBV-related ACLF., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Unlabelled: Our study aimed to investigate the short-term efficacy and long-term prognosis of liver failure patients caused by hepatitis B after a single transplantation with autologous marrow mesenchymal stem cells (MMSCs). A total of 527 inpatients with liver failure caused by hepatitis B were recruited and received the same medical treatments, among whom 53 patients underwent a single transplantation with autologous MMSCs. A total of 105 patients matched for age, sex, and biochemical indexes, including alanine aminotransferase (ALT), albumin, total bilirubin (TBIL), prothrombin time (PT), and Model for End-Stage Liver Disease (MELD), comprised the control group. A total of 120 mL of bone marrow was obtained from each patient and then diluted and separated. Then, the MMSC suspension was slowly transfused into the liver through the proper hepatic artery. The success rate of transplantation was 100%, without serious side effects or complications. Levels of ALB, TBIL, and PT and MELD score of patients in the transplantation group were markedly improved from 2-3 weeks after transplantation, compared with those in the control group. At 192 weeks of follow-up, there were no dramatic differences in incidence of hepatocellular carcinoma (HCC) or mortality between the two groups. Additionally, there were no significant differences in the incidence of HCC or mortality between patients with and without cirrhosis in the transplantation group., Conclusion: Autologous MMSC transplantation is safe for liver failure patients caused by chronic hepatitis B. Short-term efficacy was favorable, but long-term outcomes were not markedly improved. In respect to several parameters, this method is preferable for patients with liver cirrhosis and may have potential for reducing their incidence of HCC and mortality., (Copyright © 2011 American Association for the Study of Liver Diseases.)

To investigate the prognostic value of Model for End-Stage Liver Disease (MELD) score and Hepatic Encephalopathy (HE) for short-term prognosis of Hepatitis B virus-related Acute-on-Chronic Liver Failure (HBV-ACLF) patients treated with plasma exchange (PE). A total of 108 patients with HBV-ACLF treated with PE were retrospectively enrolled between January 2014 to December 2020. Based on survival at 28 days, patients were divided into survival (N = 87) and death groups (N = 21). Clinical data and laboratory indicators were analyzed. Compared with the survival group, the death group was associated with higher ACLF grade and incidence of HE. The levels of total bilirubin, prothrombin time, creatinine, blood urea nitrogen, MELD score, and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH II) score were significantly higher in the death group than in the survival group (p <.05). Grade 1 ACLF and the MELD score after PE treatment at one week were independent risk factors for 28-day liver transplantation-free mortality (OR = 0.062, 95%CI: 0.005–0.768; OR = 1.328, 95%CI: 1.153–1.531). A MELD score at one week of at least 25.5 was associated with a poor short-term prognosis. Of note, HE was a strong independent risk factor for a decline in MELD score at one week. (OR = 11.815, 95%CI: 3.187–43.796, p < 0.001). We found patients with HE at admission and MELD score of at least 25.5 at one week after PE treatment had a poor short-term prognosis and should prompt preparation for liver transplantation. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565). Registered 13 May 2020. [ABSTRACT FROM AUTHOR]

Tenofovir alafenamide (TAF) has been available in China for a short time, little is known about its safety and efficacy in patients with hepatitis B virus (HBV)–related acute‐on‐chronic liver failure (HBV‐ACLF). We conducted this study to further verify the safety and efficacy of TAF in these patients. Eighty‐eight eligible subjects were included and divided into three groups: TAF group, TDF group and ETV group. Clinical and laboratory test results were collected and the survival status, virus suppression status and liver and renal function improvement were observed during follow‐up. No drug‐related adverse events were observed within a 48‐week observation period. At week 48, the survival rates of the three groups were 56.5%, 78.3% and 59.5% (p = 0.262). HBV DNA undetectable rates were similar (80.0% vs.75.0% vs.84.6%, respectively, p = 0.863). Liver function improved in all the three groups over time. Compared with the other two groups, patients in the TAF group had a greater decrease in serum creatinine (CR) and an increase in estimated glomerular filtration rate (eGFR), especially at week 12. At week 48, the median changes of CR were −0.7 (IQR −3.0, 13.0) vs. 15.0 (IQR −3.0, 21.0) vs. 5.0 (IQR −9.0, 14.0), respectively (p = 0.334), while the median changes of eGFR were −2.12 (IQR −13.87, 1.44) vs. −10.43 (IQR −20.21, 3.18) vs. −5.31 (IQR −14.72, 5.44) ml/min/1.73 m2, respectively (p = 0.592). In this real‐world clinical study, TAF is as effective as TDF and ETV, and may be more beneficial in protecting renal function in the early stages of antiviral therapy. [ABSTRACT FROM AUTHOR]

Background and Aims: Serum immunoglobulins are frequently increased in patients with chronic liver disease, but little is known about the role of serum immunoglobulins and their correlations with interleukin-27 (IL-27) in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). This study was aimed at determining the role of serum immunoglobulin (IgG, IgA, and IgM) levels and their associations with IL-27 in noncirrhotic patients with HBV-ACLF.Methods: Samples were assessed from thirty patients with HBV-ACLF, twenty-four chronic hepatitis B (CHB) subjects, and eighteen normal controls. Disease severity of HBV-ACLF was evaluated. Serum IL-27 levels were examined by enzyme-linked immunosorbent assay. Immunoglobulin levels were assessed using immunoturbidimetric assay. Correlations between immunoglobulin levels and IL-27 were analyzed. Receiver operating characteristic (ROC) curves were used to predict the 3-month mortality.Results: 25 (83.3%) HBV-ACLF patients had elevated serum IgG levels (>1 ULN), 14 (46.7%) patients had elevated IgA, and 15 (50%) had raised IgM. IgG, IgA, and IgM levels were higher in HBV-ACLF patients than in CHB patients and normal controls. Moreover, IgG, IgA, and IgM levels were positively correlated with Tbil levels but negatively correlated with prothrombin time activity (PTA) levels. Additionally, IgG levels were significantly increased in nonsurviving patients than in surviving HBV-ACLF patients (P = 0.007) and positively correlated with MELD score (r = 0.401, P = 0.028). Also, IgG levels were positively correlated with IL-27 levels in HBV-ACLF patients (r = 0.398, P = 0.029). Furthermore, ROC curve showed that IgG levels could predict the 3-month mortality in HBV-ACLF patients (the area under the ROC curve: 0.752, P = 0.005).Conclusions: Our findings demonstrated that serum immunoglobulins were preferentially elevated in HBV-ACLF patients. IgG levels were positively correlated with IL-27 and may predict prognosis in HBV-ACLF patients. [ABSTRACT FROM AUTHOR]

Background: IL-17-producing CD8+ T (Tc17) cells promote inflammation and have been identified in chronic hepatitis. However, the role of Tc17 cells in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) remains unclear.Methods: The frequency of Tc17 cells in blood samples from 66 patients with HBV-ACLF was determined by flow cytometry. The levels of Tc17 cell-related cytokines were measured by FlowCytomix assays. The prognostic prediction accuracy was evaluated by the receiver operating characteristic (ROC) curve analysis. Survival was analyzed using Kaplan-Meier curves. Mortality predictors were determined by the Cox regression analysis.Results: The frequency of Tc17 cells was markedly higher in patients with HBV-ACLF than in those with chronic hepatitis B and normal control subjects. Increased frequencies of Tc17 cells may indicate liver injury and were positively correlated with disease severity. The Tc17 cell frequency was significantly higher in non-surviving patients with HBV-ACLF than in surviving patients. The ROC curve analysis showed that Tc17 cell frequency accurately predicted 90-day survival in patients with HBV-ACLF, with an accuracy equivalent to those of the Model for End-Stage Liver Disease (MELD), MELD-Na, and Chronic Liver Failure Consortium ACLF scores. Kaplan-Meier analysis showed an association between the increase in circulating Tc17 cells and poor overall survival in patients with HBV-ACLF. Moreover, the multivariate Cox regression analysis showed that Tc17 cell frequency was an independent predictor of overall survival in patients with HBV-ACLF.Conclusion: Tc17 cells may play a proinflammatory role in HBV-ACLF pathogenesis. Furthermore, the increased frequency of circulating Tc17 cells could be an independent prognostic biomarker in patients with HBV-ACLF. [ABSTRACT FROM AUTHOR]

The complement is thought to be involved in the pathogenesis of multiple liver disorders. However, its role in patients with HBV related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Serum levels of the third and fourth complement components (C3, C4) and complement function (CH50) were examined in this prospective, observational study. Associations between their expression and disease activity were analyzed. Survival was analyzed by Kaplan-Meier curves. Predictors of clinical outcome were determined by Cox regression analysis. C3, C4, and CH50 levels were significantly lower in HBV-ACLF patients compared to controls. C3, C4, and CH50 levels were negatively correlated with Tbil levels but positively associated with PTA levels. C3 levels were negatively associated with MELD-Na. C3 levels were significantly lower in HBV-ACLF patients who died compared to patients who survived. In a median hospital stay of 39 days, mortality occurred in 41 patients with a progressive increase based on C3 grade (P=0.008). The actuarial probability of developing mortality was significantly higher in patients with low C3 grade compared to those with high C3 grade (P<0.001). Multivariate Cox regression analysis showed that C3 levels were an independent predictor of mortality. Complement played a pathogenic role in HBV-ACLF patients and C3 was an independent predictor of mortality. [ABSTRACT FROM AUTHOR]

Background: Many studies on T helper (Th)1, Th2, T regulatory and Th17 cells have been carried out in acute-on-chronic liver failure (ACLF). However, CD8 T cell, as a main participant in immune-mediated injuries and defense against microorganisms, has seldom been studied in ACLF. Aims: The purpose of this study was to investigate the CD8 T cell function, and the outcomes of patients with severe hepatitis [SH; serum bilirubin (SB) ≥10 mg/dl and prothrombin activity (PTA) <60 %]. Methods: Thirty-six patients with chronic HBV-associated SH were included. Twenty normal chronic hepatitis B (CHB) patients (2 < SB < 10 (mg/dl) and PTA ≥ 60 %) and 28 healthy volunteers were enrolled as control groups. Results: Twenty-six patients with SH were diagnosed with ACLF (SB ≥ 10 mg/dl and PTA ≤ 40 %). The non-recovered ACLFs (NR-ACLF) had higher HBV DNA loads than recovered ACLFs (R-ACLF) (6.03 ± 1.79 vs. 4.36 ± 1.61 (log, IU/L)). The NR-ACLFs had the highest neutrophil:lymphocyte ratios (5.10 ± 2.37) (all P < 0.001; a = 0.05). The CHBs had higher perforin and T (CD45RACD62LCCR7) proportions [31.28 ± 19.51, 5.32 ± 3.57 (%)] compared to R-ACLFs (11.75 ± 15.35, 0.78 ± 0.76 (%); P = 0.004, 0.001, respectively), or NR-ACLFs (11.61 ± 5.79, 1.14 ± 0.67 (%); P = 0.006, 0.003). The non-ACLF SHs had higher CD38 proportions than R-ACLFs or NR-ACLFs (25.46 ± 8.02 vs. 16.24 ± 7.77 or 16.81 ± 6.30 (%), P = 0.039, 0.023). Conclusions: High neutrophil:lymphocyte ratios and a decrease in activated CD8 T cells may be related to poor outcomes in patients with SH. [ABSTRACT FROM AUTHOR]