Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure.

AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19(th) Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multi-organ failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8(th) week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8(th) week of follow-up was significantly lower than that during the peak TBIL (2.89% ± 0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8(th) week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis.

The balance between intrahepatic IL-17(+) T cells and Foxp3(+) regulatory T cells plays an important role in HBV-related end-stage liver disease.

BACKGROUND: IL-17(+) T helper cells and Foxp3(+) regulatory T cells are CD4(+) T helper cells with reciprocally regulated differentiation and function. Their frequency and function vary in patients with chronic hepatitis B. In this study, we investigated the balance between IL-17(+) T cells and Foxp3(+) regulatory T cells and illustrated their function in the aggravation of chronic hepatitis B (CHB). RESULTS: Twenty-six patients with chronic HBV -related liver failure (CLF), thirty-one patients with acute on chronic HBV-related liver failure (ACLF) and twelve normal controls were enrolled in our study. The expressions of IL-17, Foxp3, CD4, CD8 and perforin in liver tissue were measured by immunochemistry for the evaluation of liver-infiltrating lymphocytes. The frequency of liver IL-17(+) T cells on liver inflammatory cells and their proportion in the total CD4(+) T cell population increased markedly in the ACLF group, while the frquency of Foxp3+ T cells and their proportion in the total CD4(+) T cell population did not show a significant difference in the two HBV infection groups. In addition, the ACLF group showed a dramatically higher IL-17(+) /Foxp3(+) ratio than the CLF group. CD4(+) T cells increased significantly in the liver of patients with ACLF, compared with those in the liver of patients with CLF. CONCLUSIONS: Our findings suggest that intrahepatic IL-17(+) T cells play an important role in the development of chronic HBV and that the imbalance between IL-17(+) and Foxp3(+) T cells in the liver may lead to progression of the disease but the mechanism should be further explored.

Diagnosis and management of interstitial pneumonitis associated with interferon therapy for chronic hepatitis C.

Interstitial pneumonitis (IP) is an uncommon pulmonary complication associated with interferon (IFN) therapy for chronic hepatitis C virus (HCV) infection. Pneumonitis can occur at any stage of HCV treatment, ranging from 2 to 48 wk, usually in the first 12 wk. Its most common symptoms are dyspnoea, dry cough, fever, fatigue, arthralgia or myalgia, and anorexia, which are reversible in most cases after cessation of IFN therapy with a mean subsequent recovery time of 7.5 wk. Bronchoalveolar lavage in combination with chest high resolution computed tomography has a high diagnostic value. Prompt discontinuation of medication is the cornerstone, and corticosteroid therapy may not be essential for patients with mild-moderate pulmonary functional impairment. The severity of pulmonary injury is associated with the rapid development of IP. We suggest that methylprednisolone pulse therapy followed by low dose prednisolone for a short term is necessary to minimize the risk of fatal pulmonary damage if signs of significant pulmonary toxicity occur in earlier stage. Clinicians should be aware of the potential pulmonary complication related to the drug, so that an early and opportune diagnosis can be made.

[Clinical features of interstitial pneumonitis due to interferon alpha therapy for chronic hepatitis C].

OBJECTIVE: To analyze the clinical features of interstitial pneumonitis (IP) associated with interferon therapy for chronic hepatitis C. METHODS: We report the first case of IP in China resulting from pegylated interferon alpha-2a in combination with ribavirin for treatment of hepatitis C viral infection. A statistical analysis of the related literatures documenting such IP cases was performed using SPSS 11.5 software. RESULTS: Of the 22 patients reported to develop IP after interferon therapy alone or in combination with ribavirin, 83%, 72% and 56% of the patients had the symptoms of dyspnoea, dry cough and fever, respectively. Twenty of these cases presented with restrictive pulmonary functional impairment and/or hypoxemia, and diffuse infiltration on chest radiography and/or CT. Complications were documented in 71% of the cases within 12 weeks of the treatment. The majority (85%) of the patients had favorable prognoses with an average recovery time of 7.5 weeks. Compared with the patients with mild and moderate pulmonary function impairment, 8 patients with severe pulmonary functional impairment had early onset of IP during the interferon therapy (6.6 vs 14.1 weeks, P<0.05), and a higher rate of corticosteroid treatment (75% vs 54%, P>0.05). CONCLUSION: IP is a rare pulmonary complication associated with IFN therapy, and patients with chronic hepatitis C should be followed up closely in the first 12 weeks of interferon therapy. Prompt discontinuation of medication is mandatory in the presence of IP, and corticosteroid therapy may not be essential for patients with mild or moderate pulmonary functional impairment under close monitoring. The severity of pulmonary damage is associated with the time of complication occurrence, and corticosteroids are required when obvious pulmonary toxicity occurs in early stage of the treatment (within 6 weeks) to reduce the pulmonary damage.