Jayanta Borkakoti

Does high viral load of hepatitis E virus influence the severity and prognosis of acute liver failure during pregnancy

The incidence and mortality in pregnant women with acute liver failure caused by hepatitis E virus (HEV) is high. Data on the viral load of HEV during pregnancy are limited. The study was designed to determine the viral load of HEV and its association with the disease severity in patients with acute liver failure. A total of HEV related 163 patients with acute liver failure which included 105 pregnant, 46 non‐pregnant women and girls and 12 men and 730 patients with acute viral hepatitis which comprised of 220 pregnant women; 282 non‐pregnant women and girls and 228 men were included. Viral load was measured by real‐time PCR. Comparison was made between the pregnant and non‐pregnant women. HEV RNA was detectable in 265 patients (142 pregnant; 75 non‐pregnant and 48 men) and 104 patients with acute liver failure (64 pregnant, 34 non‐pregnant and 6 men). The viral load of HEV in pregnant women with acute liver failure and acute viral hepatitis was significantly higher 129,984.0 ± 103,104.17 and 768.92 ± 1,105.40 copies/ml, respectively compared to the non‐pregnant women which was 189.2 ± 225 and 12.73 ± 7.8 copies/ml (P < 0.0001). The viral load of HEV was also significantly higher in the pregnant patients with acute liver failure compared to the pregnant women with acute viral hepatitis and also men (P < 0.0001). High viral load of HEV during pregnancy could be one of the factors responsible for the severity of the infection during pregnancy. J. Med. Virol. 85:620–626, 2013.

Report of a novel C1483W mutation in the hepatitis E virus polymerase in patients with acute liver failure.

Here, we report the molecular alterations in the HEV genome from patients with acute liver failure (ALF) and acute viral hepatitis (AVH) from North India, including pregnant women and its association with the poor outcome of the disease. We partially sequenced the RNA Dependent RNA polymerase (RdRp) region of the ORF 1 protein in the HEV genome from representative samples from patients with ALF and AVH and identified two novel mutations Cysteine 1483 Tryptophan and Asparagine 1530 Threonine in 100% (25/25) of the patients with ALF compared to none (0/30) of the patients with AVH (P<0.0001). Disease severity parameters along with viral load corresponding to the samples with C1483W and N1530T mutations were significantly higher compared to those lacking the mutation showing significant association with the outcome in ALF patients. The nucleotide substitutions in the RdRp region may play a crucial role in enhancing HEV replication thus leading to disease severity.

Role of HEV antigen detection in HEV‐related acute viral hepatitis and acute liver failure

Detection of HEV antigen presents as an interesting low cost, novel, and rapid diagnostic technique to ascertain HEV viremia where facilities for reverse transcriptase polymerase chain reaction (RT PCR) are sparse. This study was undertaken to assess the relative efficacy of HEV antigen detection by ELISA with currently available diagnostic tests in patients of HEV‐related acute viral hepatitis (AVH) and acute liver failure (ALF). This study included 36 ALF and 64 AVH cases. HEV RNA and HEV viral load were determined by RT PCR and real time PCR, respectively. Evidence of recent HEV infection was detected in 45/64 AVH cases and 22/36 ALF cases. IgM anti‐HEV antibody, HEV RNA, and HEV antigen were positive in 34/45 (75.56%), 26/45 (57.77%), and 21/45 (46.66%), in the AVH group, and 16/22 (72.72%), 14/22 (63.63%), 12/22 (54.54%) in ALF group, respectively. The concordance between HEV RNA and HEV antigen was 75.56% (P < 0.01) with κ‐coefficient of 0.516 and 75.27% (P = 0.07) with κ‐coefficient of 0.441 (P = 0.07) in the AVH and ALF patients, respectively, indicating moderate concordance. It was established that HEV antigen detection can be used as a valuable marker of active viremia and a cheaper surrogate to HEV RT PCR, particularly in window period, pregnant and immunocompromised patients, however, it did not correlate with severity of disease or influence the final outcome of illness in any of the study groups. J. Med. Virol 88:2179–2185, 2016.

Novel molecular alterations in the ORF 2 capsid gene of hepatitis E virus in patients with acute liver failure in North India

Hepatitis E virus (HEV) is evolving as a major global threat to public health, including in developed countries. We partially sequenced the ORF 2 capsid protein genes of HEV genomes from patients with acute liver failure, including pregnant women in the northern part of India. Five unique synonymous substitutions and one non-synonymous substitution, along with a novel mutation, P259S, in the capsid gene, were identified that might be associated with the poor outcome in the patients. Phylogenetic analysis revealed that the isolates belonged to genotype 1 with subtype 1a. The significance of these findings for disease pathogenicity needs to be investigated further.