A novel gut microbiome-immune axis influencing pathology in HCMV infected infants with neonatal cholestasis.

The interplay of active HCMV infection with gut dysbiosis in the immunopathology of cholestasis in neonates and infants remains unexplored. In this study, we evaluated gut microbiome profiles and immune dysfunction in a cohort of HCMV infected cholestatic infants (IgM positive, N = 21; IgM negative, N = 25) compared to healthy infants, N = 10. HCMV infected IgM positive individuals exhibited increased clinical severity in terms of liver dysfunction, altered CD4+: CD8+ ratio, and elevated Granzyme B levels in cellular immune subsets. Gut microbiome analysis revealed distinct and differential diversity and composition within infected groups aligned with clinical severity reflected through the increased abundance of Gammaproteobacteria, reduced Bifidobacteria, and a unique signature mapping to the HCMV infected IgM negative group. Correlation analyses revealed associations between Bifidobacterium breve, Gammaproteobacteria, Firmicutes, Clostridia, Finegoldia magna, Veillonella dispar, and Granzyme B expressing immune cell subsets. Our study describes a novel gut microbiome-immune axis that may influence disease severity in cholestatic infants with active HCMV infection.

Correlation of endoscopic findings with Doppler ultrasound in portal hypertension in children.

AIM OF THE STUDY: To determine the correlation of the endoscopic findings with portal Doppler and ultrasound (USG) in children with suspected portal hypertension (PHT). MATERIAL AND METHODS: Eighty children with extrahepatic portal vein obstruction (EHPVO) and chronic liver disease (CLD) were included in this retrospective study conducted over a period of 1 year. All patients underwent upper gastrointestinal (GI) endoscopy and Doppler. RESULTS: The etiology was EHPVO in 30 (37.5%) patients, biliary atresia in 12 (15%), Budd-Chiari syndrome in 11 (13.7%), Wilson's disease in 10 (12.5%), idiopathic CLD in 8 (10%), autoimmune hepatitis in 4 (5%), glycogen storage disease (GSD) in 3 (3.8%), non-alcoholic liver disease (NAFLD) in 1 (1.3%) and systemic lupus erythematosus (SLE) in 1 (1.3%) patient. Fifty-three (66.25%) patients had esophageal varices on endoscopy, of whom 3 (3.8%) had associated gastric varices. Portal hypertensive gastropathy (PHG) was present in 30 (37.5%) patients, of whom 10 (12.5%) had severe PHG. Forty-one (51.3%) patients had PHT on Doppler (κ correlation 0.43). Kappa correlation was 0.43 in patients with biliary atresia, 0.31 in Budd-Chiari syndrome, 0.23 in idiopathic CLD, 0.21 in CLD, and 0.05 in Wilson's disease. All (100%) EHPVO patients and 39 (78%) CLD patients had PHT on USG. Endoscopic findings of PHT were seen in 24 (80%) EHPVO patients and 29 (58%) CLD patients. All patients with EHPVO had cavernous transformation of the portal vein on Doppler. For patients with CLD, the common Doppler findings were collaterals seen in 35 patients and reversal of flow in 12 patients. CONCLUSIONS: Doppler ultrasound followed by endoscopy should be used to diagnose PHT in children. In children with biliary atresia, Doppler ultrasound may miss changes of PHT.

Multi-Drug Resistant and Extensively-Drug Resistant Tuberculosis.

India is one of the high burden countries for tuberculosis (TB) including multi-drug resistant TB (MDR-TB) and extensively-drug resistant (XDR) TB. Drug-resistant (DR) TB has threatened the TB care and is a major health problem in many countries; treatment of DR TB has been difficult requiring use of reserve or second-line drugs, cost factors, has extensive side-effect profile and long duration of treatment. Treatment in MDR-TB are increasingly becoming individualised mainly due to preference for oral over injectable, results of drug susceptibility testing (DST), population resistance levels, history of previous TB treatment, drug tolerability and drug-to-drug interactions. Bedaquilline (BDQ) and delaminid (DLM) are new drugs available for treatment of these patients. World Health Organization (WHO) recommends use of BDQ in more than 15 y (>15 kg) patients only. Under Revised National Tuberculosis Control Programme (RNTCP) the use of this drug is recommended for patients older than 18 y only. Under RNTCP, the use of DLM is approved in children 6 y and above. Pediatric MDR/XDR TB treatment outcome with newer anti-TB drugs and regimen is lacking. Children when treated with individualized regimens have improved survival.

Hepatic interferon γ and tumor necrosis factor a expression in infants with neonatal cholestasis and cytomegalovirus infection.

AIM OF THE STUDY: To determine the hepatic interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) levels in infants with neonatal cholestasis (NC) and associated cytomegalovirus (CMV) infection. MATERIAL AND METHODS: This study was conducted in 21 infants with NC over a period of 6 months from June 2017 to December 2017 to determine the hepatic IFN-γ and TNF-α levels in infants with NC and associated CMV infection. RESULTS: IFN-γ levels were positive in 16 (80%), low positive in 3 (16%) and negative in 1 (5%) patients. High positive and positive TNF-α levels were seen in 9 (56.3%) patients with positive liver CMV PCR and low positive levels were seen in 7 (43.7%) patients with positive liver CMV PCR (odds ratio [OR] = 2.6). Positive IFN-γ was present in 13 (81.3%) patients with positive liver CMV PCR and low positive or negative IFN-γ was seen in 3 (18.7%) patients with positive liver CMV PCR (OR = 2.2). Six (60%) patients with positive or high positive TNF-α levels in liver tissue had biliary atresia (BA) whereas 7 (77.7%) with low positive TNF-α levels had non-BA neonatal hepatitis (OR = 5.25). Six (37.5%) patients with positive IFN-γ had BA whereas 2 (50%) patients with low positive or negative IFN-γ had BA (OR = 0.6). CONCLUSIONS: There is high prevalence of CMV in liver tissues in patients with NC and elevated TNF-α and IFN-γ levels are seen in these patients. Elevated TNF-α is also seen in patients with BA. The association of elevated TNF-α, BA and CMV infection needs to be evaluated further.