HBV-associated Acute-on-chronic Liver Failure Research Articles

Prevalence and Severity of HBV-Associated Acute-on-Chronic Liver Failure Due to Irregular Medication of Nucleos(t)ide Analogs

Abstract Hepatitis B virus (HBV) represents the commonest etiologic agent of acute-on-chronic liver failure (ACLF) in most Asian countries. Nucleos(t)ide analogs (NAs) are effective in the treatment of chronic HBV infections, but may also exacerbate the disease and stimulate its development into HBV-associated ACLF if not used appropriately. The current study aimed to assess the prevalence and severity of HBV-associated ACLF as a result from irregular medication of NAs (IMNA). A total of 1134 individuals with HBV-associated ACLF in nine hospitals in Heilongjiang Province were enrolled in this study between 2005 and 2015. Among these, 777 chronic hepatitis B (CHB) and 357 HBV-associated liver cirrhosis cases were classified based on various predisposing factors, including IMNA, HBV reactivation (HBVR), infections, treatment drugs, alcohol use and others (hepatitis C virus, hepatitis E virus, gastrointestinal bleeding and unknown reasons). The percentage and improvement rate were examined. Among individuals with HBV-associated ACLF and CHB, IMNA was found in 9.01%, HBVR in 46.20%, infections in 9.52%, treatment drugs in 14.67%, alcohol in 11.71%, and others in 24.58% as predisposing factors. Improvement rates in cases with IMNA, HBVR, infections, treatment drugs, alcohol and others were 41.43%, 58.50%, 58.11%, 56.14%, 53.85%, and 65.97%, respectively. Multivariable analysis showed that IMNA, others, infections, hepatic encephalopathy and hepatorenal syndrome were associated with prognosis. Only IMNA independently predicted HBV-associated ACLF prognosis. Overall, our study demonstrated that the percentage of IMNA-induced HBV-associated ACLF was 12.61%, and worse disease conditions resulted from IMNA compared with other factors. Thus, the suitability of treatment with NAs should be thoroughly evaluated.

Low hemoglobin levels are associated with direct antiglobulin test positivity in patients with acute-on-chronic liver failure

BackgroundMultiple factors contribute to anemia in patients with Hepatitis B virus (HBV)related acute-on-chronic liver failure (ACLF); however, the mechanism is unclear. The purpose of this study was to evaluate the clinical significance of the direct antiglobulin test (DAT) in patients with HBV related ACLF. MethodsDAT was used to detect immunoglobulins and/or complement proteins on the surface of erythrocytes. ResultsWe recruited 78 HBV-associated ACLF patients, 30 chronic hepatitis B(CHB)patients and 40 healthy people between October 2015 and May 2016. In HBV related ACLF patients, the hemoglobin concentration, number of erythrocytes, and hematocrit value were significantly lower, while the erythrocyte distribution width was significantly higher, compared to patients with CHB and healthy controls (HCs) (P < 0.001). The rates of DAT positivity in HBV related ACLF patients, CHB patients, and HCs were 62.8 %, 13.3 %, and 0%, respectively. DAT-positive ACLF patients exhibited lower Hb levels, older average age, as well as higher total bilirubin, alanine aminotransferase, and complement component 3 levels compared to DAT-negative patients. ConclusionsHBV related ACLF patients showed significant alterations in erythrocyte parameters, possibly reflecting disease development and severity. The high presence of erythrocyte autoantibodies suggested that immunologic clearance of erythrocytes contributed to multifactorial anemia in HBV related ACLF patients.

IFI16 is involved in HBV-associated acute-on-chronic liver failure inflammation

BackgroundHepatitis B virus (HBV) is a hepatotropic DNA virus, and its DNA may be a potent inflammatory molecule. Interferon-inducible protein 16 (IFI16), a newly discovered DNA sensor, plays an important role in the process of inflammation in viral infections. Our study sought to identify a correlation between IFI16 expression and inflammation in patients with chronic hepatitis B (CHB) and HBV-associated acute-on-chronic liver failure (HBV-ACLF).MethodsWe performed flow cytometry to measure IFI16 levels in peripheral blood mononuclear cells (PBMC) and used immunohistochemistry and western blotting to measure IFI16 protein levels in liver tissues. The cellular source of IFI16 was detected using double immunofluorescence. All datum were analyzed using SPSS 13.0 and GraphPad Prism 6.ResultsThe number of IFI16+ cells was significantly associated with the degree of inflammation. In detail, the number of IFI16+ cells was higher in livers but lower in PBMCs in HBV-ACLF patients than those in CHB patients and healthy controls. There was no significant difference between CHB patients and healthy controls in numbers of IFI6+ cells in livers and PBMCs. There was no significant relationship between IFI16 expression levels and HBV parameters. Furthermore, IFI16 was expressed in the nucleus of Kupffer cells (KCs), endothelial cells, natural killer cells, dendritic cells, and hepatic stellate cells in healthy donors and CHB patients, but only in the cytoplasm of KCs in the livers of HBV-ACLF patients.ConclusionsIFI16 was closely related to the degree of inflammation in CHB and HBV-ACLF patients and may serve as a vital contributor to the pathogeneses of liver damage in HBV-ACLF.

Serum levels of miRNA in patients with hepatitis B virus-associated acute-on-chronic liver failure

BackgroundHepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum miRNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF. MethodsSerum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to 30 chronic asymptomatic HBV carriers as controls. The miRNAs expressions were measured by real-time quantitative PCR (q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed miRNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model. ResultsReal-time q-PCR indicated that serum miR-146a-5p, miR-122-3p and miR-328-3p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and miR-122-3p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+ − 1.72 × INR − 4.963 × gastrointestinal bleeding (Yes = 0; No = 1)−0.278 × (miR-122-3p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve (AUROC) was 0.847. ConclusionsExpression levels of these miRNAs (miR-146a-5p, miR-122-3p and miR-328-3p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.

Serum osteopontin is a predictor of prognosis for HBV-associated acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome with a high rate of short-term mortality, and clinically it is important to identify patients at high risk of mortality. The present study evaluated the value of osteopontin (OPN) in the prediction of 90-day mortality in patients with ACLF. A total of 54 patients with HBV-associated ACLF were enrolled, and serum OPN levels were determined in a prospective, observational study design. Survival analysis was performed using Kaplan-Meier curves, and multivariate Cox proportional hazards regression was used to analyze independent risk factors of mortality. Serum OPN was significantly higher in HBV-ACLF patients compared with patients with chronic hepatitis B and healthy controls (both P<0.01), and furthermore, was higher in those patients who succumbed to HBV-ACLF compared with surviving patients (P<0.05). OPN level positively correlated with total bilirubin (r=0.554, P<0.001), Model for End-Stage Liver Disease (MELD) score (r=0.234, P=0.038), MELD-Na score (r=0.379, P=0.005) and monocyte count (r=0.282, P=0.039), and OPN was an independent risk factor for 90-day mortality in ACLF (P=0.021, odds ratio=1.104, 95% confidence interval: 1.003-1.116). Furthermore, ACLF patients were stratified into three groups according to serum OPN levels (low mortality risk: <6,135 ng/ml; intermediate risk: 6,135-9,043 ng/ml; and high risk: >9,043 ng/ml), for which the 90-day mortality rates were 27.78 (5/18), 52.94 (9/17) and 73.68% (14/19), respectively, and those in the high risk had a poorer prognosis compared with the low risk group (P=0.009). In conclusion, serum OPN may be an independent risk factor associated with HBV-ACLF prognosis.

Gamma-glutamyl transpeptidase-to-platelet ratio predicts the prognosis in HBV-associated acute-on-chronic liver failure

BackgroundThe gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a new noninvasive marker for assessing liver fibrosis. We aimed to evaluate the performance of GPR for prediction of 90-day mortality in patients with acute-on-chronic liver failure (ACLF). MethodsA total of 355 patients with HBV-associated ACLF were enrolled from two clinical centers and divided into training group (n=210) and validation group (n=145). Potential risk factors for 90-day mortality were analyzed. ResultsAge, MELD score and GPR were independent risk factors associated with ACLF prognosis. A new scoring system (MELD-GPR) was developed. MELD-GPR=9.211−0.029×age−0.290×MELD−0.460×GPR. For ACLF patients with liver cirrhosis, the area under the receiver operating characteristic curve (AUROC) of MELD-GPR was 0.788, which was significantly higher than that of MELD and MELD-Na (0.706 and 0.666, respectively). Patients were stratified into three groups according to MELD-GPR scores (high risk: <−0.19, intermediate risk: −0.19–0.95, and low risk: >0.95), and the high-risk group (MELD-GPR<−0.19) had a poor prognosis (P<0.01). For ACLF patients without liver cirrhosis, MELD-GPR<0.95 predicted a poor prognosis. ConclusionsIncorporating GPR into MELD may provide more accurate survival prediction in patients with HBV-ACLF.

The Comparative Efficacy and Safety of Entecavir and Lamivudine in Patients with HBV-Associated Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis.

Background. Currently, both of entecavir and lamivudine are effective for patients with HBV-associated acute-on-chronic liver failure (ACLF). However, there is no consensus on the efficacy of entecavir versus lamivudine for patients with HBV-associated ACLF. The aim of the study was to compare the efficacy and safety of entecavir with that of lamivudine for HBV-associated ACLF patients. Methods. Publications on entecavir versus lamivudine in HBV-associated ACLF patients were comprehensively identified. Odds ratio and mean difference were used to measure the effect. Results. Ten studies, totaling 1254 patients, were eligible. No significant differences between the two drugs presented in the 1-, 2-, 3-, or 6-month survival rates. However, after 12 months of treatment, patients prescribed entecavir had a statistically higher survival rate (p = 0.008) and lower total bilirubin (p < 0.0001) and alanine aminotransferase (p = 0.04) levels compared to patients prescribed lamivudine. More patients achieved HBV negative levels when taking entecavir as measured at 1-, 3-, and 12-month time points and had a lower rate of HBV recurrence. Conclusion. While entecavir and lamivudine are both relatively safe and well tolerated, entecavir was more efficacious in terms of survival rate and clinical improvement in long-term treatment. Further prospective randomized controlled trials are needed to validate these results.

Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation

Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence. A prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses. SMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p<0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN. SMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease.

Artificial liver support system improves short- and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure: a single-center experience.

For patients with acute-on-chronic liver failure (ACLF), artificial liver support system (ALSS) may help prolong lifespan and function as a bridge to liver transplantation (LT), but data on its long-term benefit are lacking. We conducted this prospective, controlled study to determine the efficacy of ALSS and the predictors of mortality in patients with hepatitis B virus (HBV)-associated ACLF.From January 2003 to December 2007, a total of 234 patients with HBV-associated ACLF not eligible for LT were enrolled in our study. They were allocated to receive either plasma exchange centered ALSS plus standard medical therapy (SMT) (ALSS group, n = 104) or SMT alone (control group, n = 130). All the patients were followed-up for at least 5 years, or until death.At 90 days, the survival rate of ALSS group was higher than that of the control group (62/104 [60%] vs 61/130 [47%], respectively; P < 0.05). Median survival was 879 days in the ALSS group (43% survival at 5 years) and 649 days in the control group (31% survival at 5 years, log-rank P < 0.05). ALSS was found to be associated with favorable outcome of these patients by both univariate and multivariate analysis. Multivariate Cox regression analysis also revealed that lower serum sodium levels, higher grades of encephalopathy, presence of cirrhosis, hepatorenal syndrome, and higher model for end-stage liver disease scores were independent predictors for both 90-day and 5-year mortality due to ACLF.Our findings suggest that ALSS is safe and may improve the short- and long-term prognosis of patients with HBV-associated ACLF.

Imbalance of interleukin‐17‐producing CD4 T cells/regulatory T cells axis occurs in remission stage of patients with hepatitis B virus‐related acute‐on‐chronic liver failure

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. 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. 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. 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.

Enhanced Peripheral γδT Cells Cytotoxicity Potential in Patients with HBV-Associated Acute-On-Chronic Liver Failure Might Contribute to the Disease Progression

The current study explored the characteristics of γδ T cells in the blood of HBV-associated acute-on-chronic liver failure (HBV-ACLF) patients and examined the relationship between γδ T cells and the clinical parameters. Blood samples were obtained from 26 patients with HBV-ACLF, 40 patients with chronic hepatitis B virus (HBV) infection (CHBV), and 25 healthy controls (HC). The frequencies of γδ T cells, subtype Vδ1T or Vδ2T, and CD45RO(+)γδ T cells were determined using flow cytometry. Intracellular cytokine staining analysis was used to evaluate the proportion of the IFN-γ-, TNF-α-, or IL-17-producing γδ T cells, and CD107a- or granzyme B-positive γδ T cells. We found that the proportion of γδ T cells in blood samples from HBV-ACLF patients was much lower than in samples from CHBV patients or healthy controls. After stimulation with PMA and ionomycin, γδ T cells from HBV-ACLF patients produced the greatest amount of TNF-α or IL-17 among the three groups. Granzyme B- or CD107a-positive γδ T cells were significantly more frequent than in CHBV or control samples. There was a negative correlation between the percent of TNF-α(+)γδ T cells and ALT or AST levels, and between the percent of CD107a(+)γδ T cells and TBiL or DBiL levels. These results suggest that γδ T cells might participate in liver injury in HBV-ACLF patients by producing increased amounts of inflammatory cytokines and/or cytotoxicity ability. These findings provide novel information regarding the pathogenesis of HBV-ACLF.

Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy

Acute-on-chronic liver failure (ACLF) is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells (mDCs) and the efficacy of methylprednisolone (MP) treatment for hepatitis B virus (HBV)-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at 10-day intervals; 26 patients received conservative medical (CM) management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.

Prevalence and clinical significance of Cryptosporidium infection in patients with hepatitis B virus-associated acute-on-chronic liver failure

Patients with acute-on-chronic liver failure (ACLF) are often highly susceptible to microbial infection due to a depressed immune system. This study was carried out to investigate the prevalence and clinical significance of Cryptosporidium infection in patients with hepatitis B virus (HBV)-associated ACLF in Hunan Province, China. Fecal samples from 218 patients with HBV-associated ACLF, 122 patients with chronic hepatitis B (CHB), and 140 children with diarrhea were collected; Cryptosporidium infection was detected by auramine-phenol staining, modified acid-fast staining, and the polymerase chain reaction. The clinical characteristics of this parasitic infection in Cryptosporidium-positive ACLF patients were further evaluated. The prevalence of Cryptosporidium infection in the HBV-associated ACLF patients was 6.0% (13/218), which was markedly higher than that found in CHB patients (0.8%, 1/122) and in children with diarrhea (1.4%, 2/140). Although watery diarrhea was not seen in the 13 Cryptosporidium-positive ACLF patients, eight (61.5%) of them had diarrhea. Moreover, our investigation showed that Cryptosporidium infection was not associated with the severity of the disease in ACLF patients. The prevalence of Cryptosporidium infection is high among patients with HBV-associated ACLF and might be a significant cause of diarrhea in this population.

The Ratio of Th-17 to Treg Cells is Associated with Survival of Patients with Acute-on-Chronic Hepatitis B Liver Failure

Both T-helper 17 cells (Th-17) and CD4(+)CD25(+) regulatory T cells (Tregs) play important roles in the pathogenesis of hepatitis B virus (HBV) infection. Recent studies have suggested that Th-17 and Treg cells are increased in patients with chronic hepatitis B (CHB). This study further characterizes Th-17 and Treg cells in the blood of HBV-associated acute-on-chronic liver failure (ACLF) patients, and aids our understanding of how the two subsets of CD4(+) T cells affect each other and contribute to survival. Blood samples were obtained from 30 patients with HBV-associated ACLF, 30 patients with CHB, and 30 normal controls (NC). The frequencies of Th-17 and Treg cells were determined by intracellular cytokine staining analysis. To observe the suppressive function of Tregs, purified CD4(+)CD25(+) Tregs from peripheral blood mononuclear cells (PBMCs) were co-cultured with CD4(+)CD25(-) T cells for 48 h, and then IFN-γ and IL-17A from the supernatants were measured by ELISA. We found that both Th-17 and FoxP3(+) Treg cells were increased in ACLF patients. IL-17A secretion by CD4(+) T cells was not regulated by Treg cells, even though Tregs exhibited significant inhibition of IFN-γ production. Most importantly, the ratio of Th-17 to Treg cells was associated inversely with the survival of ACLF patients. These findings provide new information regarding the pathogenesis of HBV-associated ACLF, and the ratio of Th-17 to Tregs may represent a potential prognostic marker for the disease.

Submassive pulmonary embolism in a middle-age man with trivial avulsion fracture

Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence.A prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15–90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses.SMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p <0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN.SMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease.

Imbalanced Intrahepatic Cytokine Expression of Interferon-γ, Tumor Necrosis Factor-α, and Interleukin-10 in Patients With Acute-on-Chronic Liver Failure Associated With Hepatitis B Virus Infection

This study attempts to determine expressions of intrahepatic proinflammatory and anti-inflammatory cytokines and their secreting immunocytes to evaluate their roles in the pathogenesis of acute-on-chronic liver failure (ACLF) in chronically hepatitis B virus (HBV)-infected patients. ACLF generally affects patients with established, compensated chronic liver diseases who develop an acute deterioration in liver function. In China, HBV-associated ACLF patients account for more than 80% of ACLF patients owing to a high prevalence of chronic HBV infection. Clinical observation showed that the deterioration of this disease may correlate with host immune responses, but related underlying mechanism remains largely unknown. In situ expressions of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and their secreting CD4, CD8 T cells, and Kupffer cells (KCs) were analyzed in the livers of patients with ACLF, chronic hepatitis B (CHB), and normal controls (NC) using immunohistochemistry. Intrahepatic proinflammatory IFN-gamma and TNF-alpha expressions were markedly up-regulated in ACLF compared with CHB and NC. However, similar anti-inflammatory IL-10 expressions were observed in ACLF and CHB. IFN-gamma overexpression correlated significantly with increased CD4 and CD8 T-cell accumulation. TNF-alpha up-regulation also correlated significantly with increased KCs. The imbalanced expression of proinflammatory and anti-inflammatory cytokines and increased accumulation of CD4, CD8 T cells, and KCs may contribute to immunopathogenesis in HBV-infected ACLF.