Gut microbiota dysbiosis associated with plasma levels of Interferon‐γ and viral load in patients with acute hepatitis E infection

Genotype 3 (GT3) is responsible for most European autochthonous hepatitis E virus (HEV) infections. This study analyzed circulating genotypes and GT3 subtypes in the Lazio region, Italy, between 2011 and 2019, as well as their pathogenic characteristics. Of the 64 evaluable HEV GT3 patient-derived sequences, identified subtypes included GT3f (n = 36), GT3e (n = 15), GT3c (n = 9), GT3a (n = 1) and three unsubtyped GT3 sequences. GT3c strains were similar to Dutch sequences (96.8–98.1% identity), GT3e strains showed high similarity (96.8%) with a United Kingdom sequence, while the most related sequences to GT3f Italian strains were isolated in France, Belgium and Japan. One sequence was closely related to another Italian strain isolated in raw sewage in 2016. The liver functioning test median values for 56 evaluable GT3 patients were: alanine aminotransferase (ALT), 461 (range 52–4835 U/L); aspartate aminotransferase (AST), 659 (range 64–6588 U/L); and total bilirubin, 3.49 (range 0.4–33 mg/dL). The median HEV RNA viral load for 26 evaluable GT3 patients was 42,240 IU/mL (range 5680–895,490 IU/mL). Of the 37 GT3 patients with available clinical information, no correlation was observed between HEV clinical manifestations and GT3 subtype. HEV symptoms were comparable among GT3c/e/f patients across most analyzed categories except for epigastric pain, which occurred more frequently in patients with HEV GT3e (75%) than in patients with GT3c (50%) or GT3f (19%) (p = 0.01). Additionally, patients with HEV GT3c exhibited significantly higher median international normalized ratio (INR) than patients with GT3e and GT3f (p = 0.033). The severity of GT3 acute hepatitis E was not linked to HEV RNA viral load or to the GT3 subtype.

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Association of poor virus specific immunoglobulin G antibody responses with higher viral load is seen in Bangladeshi pregnant women having acute Hepatitis E Genotype 1 infection

10.1101/2020.06.12.148528 ◽

2020 ◽

Author(s):

Rosy Sultana ◽

Md Tarikul Islam ◽

Golam Sarower Bhuyan ◽

Farjana Akther Noor ◽

Suprovath Kumar Sarker ◽

...

Keyword(s):

Viral Load ◽

Acute Hepatitis ◽

Pregnant Women ◽

South Asian ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Genotype 1 ◽

Asian Countries ◽

Igg Antibody ◽

Acute Hepatitis E

AbstractAlthough Hepatitis E viral illness is usually self-limiting, higher rates of morbidity and mortality are frequently observed during pregnancy in South Asian countries including Bangladesh. Of the four common variants, hepatitis E virus genotype 1 is mainly prevalent in South Asian countries. Pregnant women usually suffer from a state of immunosuppression. It is yet to be known whether virus specific immunoglobulin G (IgG) immune responses have any association with the vulnerability of pregnant women to acute hepatitis with E virus. The study aimed to compare the viral load and IgG responses of hepatitis E-infected pregnant women with that of non-pregnant women with same infection. Real Time –quantitative reverse transcription Polymerase Chain Reaction and Sanger sequencing were performed to determine the viral load and genotype, respectively, whereas Enzyme Linked Immunosorbent Assay method was used to determine hepatitis E virus specific serum IgG antibody index along with IgG avidity index. Although significant negative correlations were observed between log viral copy number and log IgG antibody index in the late acute phases of jaundice for both pregnant (r= −0.7971, p=0.0002) and non-pregnant women (r= −0.9117, p=0.0002), serum log viral copy number of pregnant women was significantly higher than that of the non-pregnant counterpart (p=0.0196) in the late acute stage of jaundice. In addition, log hepatitis E virus IgG antibody index of pregnant women was significantly lower than the non-pregnant women in the late phase of jaundice induced by hepatitis E virus (p=0.0303). Moreover, pregnant women with acute hepatitis E had higher cross-reactive IgG than in the non-pregnant women (p=0.0017). All the patients got infected with hepatitis E virus were in Genotype 1 variety. The study demonstrates that virus-specific poor IgG responses might be responsible for vulnerability of pregnant women to acute hepatitis with hepatitis E virus.Author SummaryAcute hepatitis caused by hepatitis E virus (HEV) Genotype 1 is a public health problem in Asian countries and especially it poses a potential health threat to pregnant women causing 19% to 25% mortality, particularly in South Asian countries including Bangladesh. The study aimed to explore whether HEV IgG immune responses were compromised during pregnancy, which might contribute to higher viral load and disease severity. Accordingly, pregnant and non-pregnant women with acute hepatitis (clinically presented with nausea, loss of appetite and /or jaundice) were enrolled from different tertiary care hospitals in Dhaka city. All these patients were screened and hepatitis E were differentiated from other hepatitis (caused by A, B, C) using Enzyme Linked Immunosorbent Assay (ELISA) methods. HEV IgG antibody/avidity indices and viral loads were measured using ELISA and real time quantitative polymerase chain reaction (RT-qPCR), respectively. The study showed that pregnant women with acute hepatitis E had lower IgG indices with higher viral load than their non-pregnant counterpart. Overall, the study revealed that virus-specific poor IgG responses might render pregnant women vulnerable to acute hepatitis E of varying degree of severity which might be associated with higher viral load.

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Th1/Th2 Cells and Associated Cytokines in Acute Hepatitis E and Related Acute Liver Failure

Journal of Immunology Research ◽

10.1155/2020/6027361 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Jian Wu ◽

Yurong Guo ◽

Xuan Lu ◽

Fen Huang ◽

Feifei Lv ◽

...

Keyword(s):

Viral Load ◽

Liver Failure ◽

Acute Liver Failure ◽

Acute Hepatitis ◽

Hepatitis E ◽

Th2 Cells ◽

Upward Trend ◽

Significant Difference ◽

Acute Hepatitis E ◽

Ifn Γ

Background and Aims. The involvement of cellular immunity in the development of hepatitis E virus (HEV) infection is rare. We aimed to study the roles of viral load and Th cell responses in acute hepatitis E (AHE) and HEV-related acute liver failure (HEV-ALF). Methods. We evaluated viral load and Th1/Th2 cytokine levels in 34 patients with HEV infection, including 17 each with AHE or HEV-ALF. Seventeen healthy controls (HCs) were also included who were negative for anti-HEV IgM and IgG. Results. There was no significant difference in viral load and HEV RNA in the AHE and HEV-ALF groups (both P > 0.05 ). The Th lymphocyte levels (CD3+, CD4+) in the AHE and HEV-ALF groups were significantly higher than those in the HC group (both P < 0.05 ), but there was no significant difference between the AHE and HEV-ALF groups ( P > 0.05 ). Both IFN-γ and IL-10 showed gradual upward trend from the HC group to the AHE (both P < 0.01 ), but IFN-γ showed a sharp downward trend from the AHE group to the HEV-ALF group ( P < 0.01 ) and IL-4 showed gradual upward trend from the AHE group to the HEV-ALF group ( P < 0.01 ).There was no significant difference in Th1 and Th2 cytokines between the HEV RNA(+) group and HEV RNA(-) group (all P > 0.05 ). Th2 bias was observed from the AHE ( ratio = 58.65 ) to HEV-ALF ( ratio = 1.20 ) groups. The level of IFN-γ was associated with the outcome of HEV-ALF patients. Conclusions. HEV viral load was not associated with aggravation of AHE, and the HEV-ALF patients showed significant Th2 bias, which may be involved in the aggravation of AHE.

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IgG antibody response demonstrates inverse correlation with viral load in Bangladeshi women with acute hepatitis E virus genotype 1 infection

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2020.12.081 ◽

2021 ◽

Vol 104 ◽

pp. 482-490

Author(s):

Rosy Sultana ◽

Md Tarikul Islam ◽

Golam Sarower Bhuyan ◽

Suprovath Kumar Sarker ◽

Farjana Akther Noor ◽

...

Keyword(s):

Viral Load ◽

Antibody Response ◽

Acute Hepatitis ◽

Hepatitis E Virus ◽

Inverse Correlation ◽

Hepatitis E ◽

Genotype 1 ◽

Virus Genotype ◽

Igg Antibody ◽

Acute Hepatitis E

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Lower Levels of Transaminases but Higher Levels of Serum Creatinine in Patients with Acute Hepatitis E in Comparison to Patients with Hepatitis A

Pathogens ◽

10.3390/pathogens10010060 ◽

2021 ◽

Vol 10 (1) ◽

pp. 60

Author(s):

Thomas Theo Brehm ◽

Omid Mazaheri ◽

Thomas Horvatits ◽

Marc Lütgehetmann ◽

Julian Schulze zur Wiesch ◽

...

Keyword(s):

Serum Creatinine ◽

Acute Hepatitis ◽

Hepatitis A ◽

Medical Center ◽

Hepatitis E ◽

Distribution Width ◽

Lymphocyte Ratio ◽

Median Serum ◽

Acute Hepatitis E ◽

Hematological Manifestations

In patients with hepatitis E virus (HEV) infections, extrahepatic, particularly renal and hematological manifestations, are increasingly reported in the medical literature but have never been studied compared to a control cohort. We retrospectively analyzed medical records of consecutive patients that were diagnosed with acute hepatitis E (AHE) (n = 69) or acute hepatitis A (AHA) (n = 46) at the University Medical Center Hamburg Eppendorf from January 2009 to August 2019 for demographical, clinical, and laboratory information. Patients with AHE had significantly lower median levels of ALAT (798 U/L) and total bilirubin (1.8 mg/dL) compared to patients with AHA (2326 U/L; p < 0.001 and 5.2 mg/dL; p < 0.001), suggesting a generally less severe hepatitis. In contrast, patients with AHE had significantly higher median serum creatinine levels (0.9 mg/dL vs. 0.8 mg/dL; p = 0.002) and lower median estimated glomerular filtration rate (eGFR) (91 mL/min/1.73 m2 vs. 109 mL/min/1.73 m2; p < 0.001) than patients with AHA. Leucocyte, neutrophil and lymphocyte count, hemoglobin, platelets, red cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR), and RDW to lymphocyte ratio (RLR) did not differ between patients with AHE and those with AHA. Our observations indicate that renal but not hematological interference presents an underrecognized extrahepatic feature of AHE, while inflammation of the liver seems to be more severe in AHA.

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