Success of antiviral therapy in chronic hepatitis C infection relates to functional status of myeloid dendritic cells.

Chronic hepatitis C infection poses a major global health predicament and appears to be potent threat to mankind. The treatment in wide use is interferon/ribavirin combination therapy which is generally effective in about 60-70 per cent of patients carrying genotype 3 and causes significant morbidity. The response to therapy is largely guided by limited number of factors such as genotype of virus, rapid virological response, ethnicity, pre-therapy viral load, etc. While involvement of host genetic factors has been a major focus of research in playing an important role in the outcome of disease, the role of immune system cannot be marginalized. Poor cellular trafficking and suboptimal T cell responses in liver, the hall marks of chronic hepatitis C virus infection, might be attributed to defective antigen presentation. Various immunological factors, both innate and adaptive, play role in the pathogenesis of the disease and become dysfunctional in active disease. Recent reports suggest the major impact of functional and numerical status of dendritic cells in deciding the fate of antiviral therapy. In this review we take a look at the involvement of dendritic cells in playing an important role in the response to therapy.

Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study.

Background: Hepatocellular carcinoma (HCC) is notorious for poor prognosis with limited therapeutic options. A better understanding of the role of regulatory T-cells (Tregs) in HCC is important for design of immunotherapy based clinical protocol. The objective of the present study was to evaluate the presence of Tregs in tumor microenvironment in patients with HCC compared to chronic hepatitis (CH). Materials and Methods: The frequency of CD4 + CD25 + Treg cells was evaluated from peripheral blood (PB) of 28 patients of HCC and 30 controls including CH cases and healthy donors using flowcytometry. Intratumoral Treg were also analyzed in tissue samples from 17 HCC cases and 15 CH cases. In addition the expression of FOXP3 and CTLA-4 was also studied by RT-PCR. Results: Frequency of CD4 + CD25 + cells in the PBMCs of HCC cases was significantly higher than in HC (10.8 ± 7.64 vs 3.05 ± 1.30, P < 0.005) and CH patients (2.88 ± 1.92, P < 0.005). Also Treg population was significantly higher in HCC tumor microenvironment compared to CH biopsies (15.8 ± 5.32 vs 5.51 ± 3.40, P < 0.05). Expression of FOXP3 and CTLA-4 was also significantly higher in HCC patients ( P < 0.05) compared to CH group. Conclusions: We provide evidence of an increased population of Treg not only in the PB but also in tumor microenvironment of HCC patients, suggesting association of enhanced Treg activity with poor immune responses to tumor antigens. These findings may in future play a significant role in designing immunotherapeutic approaches in HCC.

Human papillomavirus and skin tags: is there any association?

BACKGROUND: Low-risk human papillomavirus (HPV) infections are related to the genesis of various benign lesions. In an isolated report available, HPVs have been implicated in the causation of skin tags too. AIMS: The present study was designed to detect the existence of low-risk HPV types 6 and 11 in cutaneous soft fibromas (skin tag) in north Indians. METHODS: A total of 37 cases of skin tags from various sites were analyzed. Highly sensitive and comprehensive polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays were done for the detection of low-risk HPV types 6 and 11. RESULTS: The results revealed the presence of HPV DNA 6/11 in 48.6% of the skin tags examined by PCR-RFLP. CONCLUSION: This result corroborates the hypothesis that HPV plays a part in the etiology of benign lesions like cutaneous soft fibromas. The identification of HPV 6/11 in these lesions, which are benign proliferations of the skin, further expands the spectrum of HPV-linked lesions.

Comparative analysis of HBV and HCV infection in hepatocellular carcinoma and chronic liver disease--an autopsy based study.

Hepatocellular carcinoma (HCC) is one of the common malignancies worldwide including Asian countries. Chronic viral hepatitis is implicated as an important etiological factor in carcinogenesis of liver. AIM: To study incidence of hepatitis B (HBV) and C (HCV) viruses in HCC and to compare the incidences with that of chronic liver disease. MATERIALS AND METHOD: 40 cases each of HCC (group I) and chronic liver disease including cirrhotic liver (group II) who died of the liver disease. All cases were stained with HBsAg and HBcAb for HBV and RT-PCR for HCV RNA. Different groups were compared using student's t-paired and chi-square tests. RESULTS: Group I--HCC was seen in 37 cirrhotics and 3 non-cirrhotic cases. HBsAg was positive in 32 cases (80%), HBcAb in 22 cases (55%) and HCV in 23 cases (57.5%) (p<0.05). Dysplastic nodule (DN) was seen in 25 cases, HBsAg and HBcAg positivity were seen in 18 and 15 cases respectively. Group II--32 cases were cirrhotic and 8 were non-cirrhotics. HBsAg was positive in 28 (70%), HBcAb in 12 (30%) and HCV in 18 (45%) cases. DN was seen 24 cases, HBsAg and HBcAg postiviy were seen in 16 and 7 cases respectively. HBV and HCV co-infection was seen in 20 and 15 cases, and HCV with HBcAb positivity was seen in 13 and 9 cases in groups I and II respectively. Number of cells in each case showing positivity for HBcAb was also significantly higher in group I (p<0.01). Age and sex distribution did not show any distinctive differences between the two groups. CONCLUSION: the study highlights a high incidence ofHBVand HCV infection in cases of chronic liver disease and HCC. HBcAb positive state appears to be an independent risk factor for HCC.

Poor responses to recombinant HBV vaccination in patients with HIV infection.

The study was conducted with an aim to assess the efficacy of recombinant HBV vaccination in untreated HBV seronegative HIV/AIDS subjects as compared to normal controls. The second objective was to identify differences in CD4 and CD8 T cell numbers/kinetics/functions and levels of TH2 cytokines (IL4 and IL10) in different groups during the three-dose vaccination regimen. 40 HIV/AIDS patients were subdivided into groups 1A where patients had a high CD4 (> 200/mm3) count and IB where patients had a low CD4 (< 200/mm3) count. Twenty normal healthy control subjects were also recruited in the study (group II). Patients received 40 micro and controls received 20 micro of recombinant HBV vaccine in each dose. All subjects received 3 doses of the vaccine. Detection of CD4 and CD8 cells was done by flowcytometry. TH2 type of cytokines IL4 and IL10 were estimated in the culture supernatant of PHA stimulated leukocyte rich plasma by sandwich ELISA. Anti-HBs levels were estimated in the serum by ELISA. Anti-HBs response was severely compromised in patients as compared to controls. Groups II, 1A and 1B showed titers of 16906 +/- 21303, 8834 +/- 14136 and 462 +/- 814 m/U/m/ respectively. Both CD4 and CD8 cells increased significantly after vaccination in all the groups irrespective of the disease status. On the other hand, IL4/IL10 responses to PHA stimulation in the HIV-positive groups were much lower than in controls (P< 0.1). Despite a double dose of vaccine in patients, the antibody response was significantly lower which correlated with a lower CD4 count. Cytokines IL4 and IL10 which regulate antibody response, were also lower in-patients and this together with a low CD4 count possibly accounted for the low anti-HBs levels. All patients with high CD4 lymphocyte count were responders while only 47% of patients with low CD4 lymphocyte count responded to immunization. Patients with a CD4 count of less than 50 failed to respond. Thus early immunization is advocated in all HIV patients at a stage when they are still capable of mounting an adequate immune response.