Functionally aberrant dendritic cell subsets and expression of DC-SIGN differentiate acute from chronic HBV infection.

BACKGROUND: Dendritic cells (DCs) promote pathogen recognition, uptake and presentation of antigen through DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and toll-like receptors (TLRs). AIMS AND OBJECTIVES: We aimed to study temporal changes in DCs, TLRs and DC-SIGN during acute viral hepatitis B (AVHB) infection and compare them to chronic (CHB) and to investigate the earliest time point of activated pathogen recognition receptors in hepatitis B viral infection. METHODS: We measured the frequencies of circulating myeloid (mDC) and plasmacytoid (pDC) dendritic cells and IFN-α production along with the expression of DC-SIGN and Toll Like Receptors (TLR's) in HBV patients at different time points. Also investigated in healthy volunteers, the dynamic changes in TLRs expression after receiving hepatitis B vaccine. RESULTS: On follow-up of AVHB patients, we found the mDC population was significantly higher at week 4 and 6 (p < 0.02, 0.01), whereas the pDC population was unchanged at week 6 compared with week 0. Whereas frequencies of mDCs and pDCs were found to be elevated in AVHB and CHB patients than HC (p < 0.00 and 0.01, respectively) but was comparable among AVHB vs CHB. The DCs in CHB patients were functionally impaired with significantly low IFN-α production and low DCSIGN expression (p < 0.04 and 0.00, respectively). Even after stimulation by TLR agonists, no change was found in IFN-α production in CHB patients. MyD88 and IL-6, IFN-α mRNA levels were also found down-regulated. Interestingly, on follow-up after HBV vaccine, TLRs expression was found high at day 3 after vaccination. DISCUSSION: The initial events of immune activation might be responsible for modulating immune response. These novel observations would pave the way for the development of antiviral strategies for chronic HBV infection.

Addition of probiotics to norfloxacin does not improve efficacy in the prevention of spontaneous bacterial peritonitis: a double-blind placebo-controlled randomized-controlled trial.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) may occur despite antibiotic prophylaxis. We investigated whether the addition of probiotics to norfloxacin enhances its efficacy in the prevention of SBP. METHODS: A double-blind, randomized-controlled trial was conducted among consecutive cirrhotic patients who had either recovered from SBP (secondary prophylaxis) or who were at a high risk for the development of SBP (low ascitic fluid protein or serum bilirubin ≥ 2.5 mg/dl; primary prophylaxis). Norfloxacin 400 mg/day with probiotics capsules (Enterococcus faecalis JPC 30 million, Clostridium butyricum 2 million, Bacillus mesentericus JPC 1 million, Bacillus coagulans 50 million spores) at a dose of two capsules three times daily (group 1) or norfloxacin with a placebo (group 2) was given and the occurrence of SBP within a period of 6 months (primary endpoint) or side-effects of therapy and mortality (secondary endpoints) were recorded. RESULTS: From April 2005 through August 2007, 110 patients were randomized to group 1 (n=55) or group 2 (n=55) and 45 (82%) and 43 (78%) of them completed the trial, respectively. The baseline characteristics were comparable. On intention-to-treat analysis, the cumulative probability of treatment failures was similar in both the groups [19/55 (34%) in group 1 vs. 20/55 (36%) in group 2, P=0.840]. The cumulative probability of mortality was also similar [13/45 (29%) in group 1 vs. 14/43 (32%) in group 2, P=0.834]. The frequency of side-effects was also comparable. In subgroup analyses, the frequencies of SBP and deaths were similar in the two groups in the subgroups of primary and secondary prophylaxes. The presence of encephalopathy and serum bilirubin of greater than 3.65 mg/dl were found to predict mortality independently. CONCLUSION: The addition of probiotics to norfloxacin does not improve its efficacy in primary or secondary prophylaxis of SBP or in reducing the mortality in cirrhotic patients with ascites.

Prevalence, risk factors and virological profile of chronic hepatitis B virus infection in pregnant women in India.

A large program was conducted by the Government of India to study the prevalence and profile of chronic hepatitis B virus (HBV) infection and its risk factors in pregnant women attending a tertiary care hospital in India. From September 2004 to December 2008 consecutive pregnant women attending the antenatal clinic were screened and those found positive for HBsAg were enrolled. Healthy non-pregnant women of child-bearing age, who presented for blood donation during the same period, served as controls. Women with symptoms of liver disease or those aware of their HBsAg status were excluded. Of the 20,104 pregnant women screened, 224 (1.1%) and of the 658 controls, 8 (1.2%) were HBsAg positive (P = ns). Previous blood transfusions and surgery were significant risk factors for infection with HBV. Of the women who were HBsAg positive, the ALT levels were normal in 54% of the women and HBV DNA levels were above 2,000 IU/ml in 71% of women. The median HBV DNA levels were higher in women who were HBeAg positive compared to the HBeAg negative group. The most common HBV genotype was D (84%) followed by A + D and A (8% each). In conclusion, the prevalence of HBsAg positivity among asymptomatic pregnant women in North India is 1.1% with 71% having high HBV DNA levels. These women may have a high risk of transmitting infection to their newborns.

Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT.

BACKGROUND & AIMS: There is a paucity of data on hepatitis B virus (HBV) DNA levels and histologic lesions in patients with chronic HBV (CHBV) infection and persistently normal alanine aminotransferase (ALT) levels (PNALT). We studied the ALT, HBV DNA levels, and spectrum of histologic lesions in such patients. METHODS: One thousand three hundred eighty-seven incidentally detected asymptomatic hepatitis B surface antigen (HBsAg)-positive patients with >/=1-year follow-up and either PNALT (n = 189; hepatitis B e antigen [HBeAg(+)], 73; HBeAg(-), 116) or persistently or intermittently elevated ALT (PIEALT; n = 1198; HBeAg(+), 530; HBeAg(-), 668) were included. RESULTS: In the PIEALT and PNALT patients, baseline DNA >/=5-log copies/mL was seen in 73.8% and 60.3% in HBeAg(+) (P = .018) and 76% and 35.3% in HBeAg(-) (P < .001) patients and histologic fibrosis stage >/=2 in 65.5% and 40.2% in HBeAg(+) (P < .001) and 63.9% and 13.8% in HBeAg(-) (P < .001) patients, respectively. Approximately 21% of HBeAg(-) patients with PNALT and HBV DNA <5-log copies/mL had histologically active liver disease (histologic activity index >/=3 and/or fibrosis stage >/=2). CONCLUSIONS: A fair proportion of patients with CHBV infection with PNALT have HBV DNA >/=5-log copies/mL and significant histologic fibrosis. Use of ALT and HBV DNA levels without resorting to liver biopsy to define "inactive carrier state" in HBeAg(-) PNALT patients may miss histologically significant disease in a proportion of patients.