Hepatitis B virus (HBV)-specific T-cell responses to recombinant HBV core protein in patients with normal liver function and co-infected with chronic HBV and human immunodeficiency virus 1 (HIV-1).

BACKGROUND: Little is known about HBV-specific T-cell responses in chronic Hepatitis B patients (HBV) that are co-infected with Human immunodeficiency virus type 1 (HIV-1), especially those with normal alanine aminotransferase (ALT) levels. METHODS: Twenty-five patients with chronic HBV (11 hepatitis B e antigen [HBeAg]-positive, 14 HBeAg-negative) were enrolled in a cross-sectional study. A longitudinal study as also conducted in which follow-up was done at 3, 12, and 24 months, after acute HIV-1 infection, in 11 individuals who also had chronic HBV. Peripheral blood mononuclear cells were stimulated with recombinant HBV surface protein (S protein), core protein (C protein) or gag peptide. IFN-γ-secreting T cells were identified by ELISPOT assay. RESULTS: In the cross-sectional study, co-infected chronic HBV patients had lower C protein-specific T-cell responses compared with mono-infected individuals, though the difference was not significant. In co-infected, chronic HBV patients, the magnitude of C protein-specific T-cell responses was significantly greater in HBeAg-positive subjects compared to HBeAg-negative subjects (p = 0.011). C protein-specific T-cell responses were positively correlated with HBV viral load (rs = 0.40, p = 0.046). However, gag-specific T-cell responses were negatively correlated with HIV viral load (rs = -0.44, p = 0.026) and positively correlated with CD4+ count (rs = 0.46, p = 0.021). The results were different in mono-infected individuals. PBMCs from co-infected HBeAg-positive patients secreted more specific-IFN-γ in cultured supernatants compared with PBMCs from co-infected HBeAg-negative patients (p = 0.019). In the longitudinal study, S protein- and C protein-specific T-cell responses were decreased as the length of follow-up increased (p = 0.034, for S protein; p = 0.105, for C protein). Additionally, the S protein- and C protein-specific T-cell responses were significantly higher in HBeAg-positive patients than in HBeAg-negative patients at 3 and 12 months after HIV-1 infection (all p < 0.05), but not at 24 months. A positive correlation (trend) was found between C protein-specific T-cell responses and HBV viral load at 3 and 12 months after HIV-1 infection. CONCLUSIONS: HBV-specific T-cell responses to recombinant HBV core protein were reduced in chronic HBV patients co-infected with HIV-1. The reduced C protein-specific T cell responses were positively correlated with HBV viral load in co-infected, chronic HBV patients.

Bioactivity of CD34+ cells in patients with acute-on-chronic liver failure.

Liver failure is a life-threatened serious disease with many complications and high mortality rate. Stem cells have been applied to replacement therapy, gene therapy and tissue engineering for its capacity of self-renewal and multi-lineage differentiation. To investigate the bioactivity of the peripheral blood hematopoietic stem cells (PBHSC) in patients with acute-on-chronic liver failure, we isolated CD34+ cells from peripheral blood of patients with acute-on-chronic liver failure and healthy controls. After cultured it in serum-free medium (SFEM), we studied the bioactivity of CD34+ cells by observing the morphology, recording growth curve, detecting cell cycle and cell apoptosis. CD34+ cells and culture solution were collected at the time points of 3, 5, 7, 10, 12 and 14 days, and the levels of hepatocyte growth factor (HGF), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in culture solution were detected by ELISA. Also, the expressions of pyruvate kinase muscle isoenzyme 2 (PKM2), integrin-ß1 and liver-type pyruvate kinase (LPK) were detected by RT-PCR and immunofluorescence. Our results showed the bioactivity of CD34+ cells from patients with acute-on-chronic liver failure was identified to be similar with that from healthy controls. HGF, MMP-9, TNF-α and IL-6 were found in cell culture medium. RT-PCR and immunofluorescence results indicated that PKM2, Integrin-ß1 expressed on CD34+ cells from patients with acute-on-chronic liver failure. In conclusion, bioactivity of CD34+ cells of patients with acute-on-chronic liver failure was demonstrated to be normal, which could secrete HGF, MMP-9, TNF-α and IL-6, promote the growth of hepatocytes, and differentiate along a direction to hepatocyte lineage.

Efficacy and tolerability of low-dose interferon-α in hemodialysis patients with chronic hepatitis C virus infection.

AIM: To evaluate the efficacy and tolerability of low-dose standard or pegylated interferon (PEG-IFN) in hepatitis C virus (HCV)-positive hemodialysis patients. METHODS: In total, 19 patients were enrolled in this study, of which 12 received PEG-IFNα-2a 67.5 µg 1 time/wk (Group 1) and 7 received standard interferon α-2b subcutaneously 1.5 × 106 U 3 times/wk (Group 2). The treatment durations were 48 wk for patients infected with HCV genotype 1 and 24 wk for patients infected with HCV genotype 2/3. All patients were prospectively followed after the completion of therapy. The efficacy and tolerability of the treatment were evaluated based on the sustained virological response (SVR) and treatment-related drop-out rate. RESULTS: In Group 1, 11 of the 12 patients completed the treatment. Early virological response (EVR) and sustained virological response (SVR) rates were 83.3% and 91.7%, respectively. One patient withdrew from treatment due to an adverse event (leukopenia). The drop-out rate was 8.3% in this group. In Group 2, 5 of the 7 patients completed the treatment with an EVR and SVR of 85.7% and 71.4%, respectively. Two patients withdrew due to treatment-related adverse events (nausea and depression). In this group, the drop-out rate was 28.6%. In total, 16 of the patients attained EVR, and 15 of them completed the treatment. The SVR rate for the patients who attained EVR was 93.7%. Anemia was the most frequent side effect and was observed in 10/19 patients (55.5%), but could be effectively managed with erythropoietin. CONCLUSION: Low-dose interferon monotherapy, either with PEG-IFNα-2a or standard interferon α-2b, is an effective treatment option for hemodialysis patients with chronic hepatitis C.

[Research of hepatic pathology and clinical characteristics of patients chronic infected with hepatitis B virus in immune tolerant stage].

OBJECTIVE: To investigate the characteristics of the hepatic pathological and clinical features of patients with hepatitis B virus (HBV) in immune tolerant stage and find the better measure of diagnosing patients chronic infected by HBV in immune tolerant phase. METHODS: 135 patients with HBV chronic infection and persistently normal serum alanine aminotransferase (ALT) levels were involved in this study, whose serum HBeAg and HBV DNA were positive. Statistical analysis included the ages, sex, serum levels of HBVDNA, ALT and histological grade. The grades of inflammation and fibrosis were obtained through hepatic biopsy performed on all the patients. RESULTS: Mean age in those patients was 22.61 +/- 8.95 years old. All those patients were divided into two groups according to histological grade: low- histological grade group, G < or = 1 and S < or = 1; and high-histological grade group, G > or = 2, S > or = to 2. Levels of histological grade were low in most of patients (99/135). Patients of low-histological grade had no difference in age, sex and family history of HBsAg carriers. Compared with low-normal ALT (ALT less than 30U/L), those with high-normal ALT (ALT > or = 30U/L) had a greater frequencies of high-histological grade. Compared with high HBVDNA (HBVDNA > or = 10(7) copies/ml), those with low HBVDNA (HBVDNA less than 10(7) copies/ml) had a greater frequencies of high-histological grade. CONCLUSION: Levels of histological grade were low in most of patients with HBV chronic infection, serum HBeAg and HBVDNA positive, persistently normal serum ALT levels, but some of them were high-histological grade. It showed those patients were not all in immune tolerant stage of chronic HBV infection. Examination of ALT and HBVDNA are helpful to evaluate hepatic pathological damage for them.

[Features of onset of chronic severe hepatitis in 520 cases].

OBJECTIVE: To discuss features of onset of chronic severe viral hepatitis (CSH). METHODS: The patterns of onset of 520 cases of CSH were analyzed by SPASS and STATA software. RESULTS: 1. Within less than 10 days, less than 2 weeks, 2 to 4 weeks, 4 weeks to 6 months, 10.4%, 18.1%, 17.1% and 64.8% of 520 cases deteriorated into severe hepatitis respectively. 2. There were no definite predisposing factors in more than 40% cases. There were 1 to 3 or more predisposing factors in more than 30% cases. The incidence of concurrent infection was the highest (P<0.01). 3. The pathogenic basis in more than 50% cases was cirrhosis. 4. Hepatic encephalopathy did not occur in more than 50% of the cases. Ascites occurred in more than 75% of cases. Hepatic encephalopathy first occurred in less than 5% cases and ascites in more than 10% of cases. 5. The latest time for occurrence of hepatic encephalopathy was later than the time of deteriorating into severe hepatitis. CONCLUSIONS: 1. Gradual deterioration into CSH was found in all the 520 cases. 2. The predisposing factors, pathogenic bases, incidence and occurring time of hepatic encephalopathy, firstly occurring complication and so on in CSH are not the same as those in acute and subacute severe hepatitis. Therefore, CSH should be independently named and the study of CSH should be strengthened.

[Single factor study of prognosis from 520 cases with chronic severe hepatitis].

OBJECTIVE: To further understand chronic severe hepatitis (CSH) and to improve the level of diagnosis and treatment and to explore the methods to reduce the fatality rate of CSH through analysing the factors related to prognosis of CSH. METHODS: The factors related to prognosis from 520 cases with CSH were analyzed by SPASS and STATA software. RESULTS: 1. The fatality rate in cases with age > or = 40 years was higher than that in cases with age <40 years (P<0.001), there was no significant difference (P>0.05) in sex and pathogenic basis of CSH; 2. The fatality rate rose in cases with WBC > or = 10.0 x 10(9) per liter or platelet <100 x 10(9) per liter; 3. The fatality rate increased gradually with the ratio of aspartic aminotransferase to alanine aminotransferase (AST/ALT) and serum total bilirubin (TBil), appearance of deviation of TBil and ALT, decrease in prothrombin activity (PTA), total cholesterol (TC), cholinesterase and albumin (Alb) (P<0.001). 4. The fatality rate increased with appearance of complications such as ascites, electrolyte disturbance, spontaneous peritonitis and so on (P<0.001). CONCLUSIONS: The important factors related to prognosis were age, > or = 40 years, WBC 10.0 x 10(9) per liter or platelet <100 x 10(9) per liter; the ratio of AST/ALT, TBil, Tc, cholinesterase, Alb and complication, to monitor dynamically laboratory indexes such as TBil, PTA, Tc, cholinesterase and so on and to prevent and cure various complications are important measures to reduce the fatality rate of CSH.

[Treatment of severe viral hepatitis with artificial liver support system].

BACKGROUND: To investigate the method and therapeutic efficacy of artificial liver support system (ALSS) in treatment of severe viral hepatitis. METHODS: A total of 83 patients including 66 with severe viral hepatitis were treated with ALSS using Baxter-550 artificial kidney and Biologic-DT system. RESULTS: The levels of mean bilirubin, ALT, AST, BUN, Cr and endotoxin was significantly decreased after the treatment. Of the 66 patients?with severe viral hepatitis, 31(47.0%) had improvement in symptoms and 35 (53.0%) died or left hospital. In the control group,50(27.6%) out of the 181 had improvement in symptoms and 131(72.4%) died or left hospital. CONCLUSIONS: ALSS could exert certain therapeutic effects on severe viral hepatitis.

[Detection of coagulation factor V in patients with severe hepatitis and its clinical significance].

BACKGROUND: To investigate the prognostic significance and role of coagulation factor V (CFV) levels in clinical diagnostic criteria for severe hepatitis. METHODS: The CFV level and prothrombin activity (PTA) were tested by turbidimetry for 129 times in 58 patients with severe hepatitis. Comparative studies and clinical significance of CFV and PTA were analyzed by SPSS and SDAS softwares. RESULTS: 1. The levels of CFV and PTA were 15.3%+/-9.7% and 23.5%+/-10.0%, respectively, at the onset of severe hepatitis. 2. The mortality of severe hepatitis gradually increased with the gradual decrease of CFV or PTA during the most severe stage of the illness (P=0.000). 3. The levels of CFV and PTA decreased continually and rapidly in patients who died but gradually increased in survivors. The decrease or increase of PTA preceded that of CFV on the exacerbation or convalescent stage. 4. Hepatic encephalopathy occurred in 14 cases (24.14%). In 10 cases, it occurred in the terminal stage of the illness, far later than the time of the decrease of CFV. 5. The level of CFV was closely related to PTA (the correlation coefficient was 0.812), the level of CFV was almost consistent with that of PTA. CONCLUSION: 1. The level of CFV is an important prognostic indicator in severe hepatitis and is more specific than PTA. 2. Simultaneous determination of CFV and PTA may be helpful in earlier and more accurate diagnosis of severe hepatitis. 3. Possible use of CFV as one of the criteria for liver transplantation in patients with severe hepatitis should be studied.