Association between MFN2 gene polymorphisms and the risk and prognosis of acute liver failure: a case-control study in a Chinese population

This study aimed to determine the role of mitofusin 2 (MFN2) gene polymorphisms in the risk and prognosis of acute liver failure (ALF). A total of 298 blood samples were collected from 138 ALF patients (case group) and 160 healthy participants (control group). Coagulation function, glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), total bilirubin (TB), blood ammonia and lactic acid (LA) were measured. The predictive evaluation of MFN2 gene polymorphisms in the risk and prognosis of ALF patients was estimated using Kaplan-Meier survival analysis, haplotype analysis, binary logistic regression analysis and Cox regression analysis. Higher levels of GPT, GOT, TB, blood ammonia and LA were observed in ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 than in those with the CC genotype of these two SNPs. The GTACAGC and GTGTGGC haplotypes were a protective factor and a risk factor for ALF, respectively. Blood ammonia and LA levels were independent risk factors and the CC genotype of rs873457 and the CC genotype of rs4846085 were protective factors for ALF. ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 had a lower survival rate than those with other genotypes of these two SNPs. The rs4846085 and rs873457 polymorphisms were both independent factors affecting the prognosis of ALF patients. MFN2 gene polymorphisms (rs873457, rs2336384, rs1474868, rs4846085 and rs2236055) may be associated with ALF and the rs873457 and rs4846085 polymorphisms are correlated with the risk and prognosis of ALF.

Differential gene expression profiles in acute hepatic failure model in mice infected with MHV-3 virus intervened by anti-hepatic failure compound / 华中科技大学学报（医学）（英德文版）

Differential gene expression profiles in Balb/cJ mouse model of acute hepatic failure infected with MHV-3 virus intervened by anti-hepatic failure compound (AHFC) and the changes of cytokines regulated by genes were investigated. The Balb/cj mice were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was established. The survival rate in the two groups was observed. It was found that the survival rate in the AHFC-intervened group and control group was 90% and 50% respectively 48 h after intraperitoneal injection of MHV-3 (P<0.05). Before and after the experiment, the cytokines in peripheral blood of the survival mice were determined, and RNA was extracted from survival mouse liver tissue for the analysis of the differential gene expression by a 36 kb mouse oligonucleotide DNA array. In all the genes of microarray there were 332 genes expressed differently in the two groups, in which 234 genes were up-regulated and 78 genes down-regulated. Through clustering analysis, the differential expression of immune related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fgl2, IL-8, IL-6, IFN-gamma, TNF-alpha etc. might be related with the curative effectiveness of AHFC. It was suggested that AHFC can balance the immune state of mouse model of acute hepatic failure infected with MHV-3 virus mainly through regulating the expression of immune related genes, decrease the immune damage and inhibit liver cell apoptosis of mouse acute hepatic failure model obviously so as to increase the survival rate of mouse models of acute hepatic failure.

Caracterización molecular del virus de hepatitis E en tres casos de falla hepática fulminante en niños de Argentina / Molecular characterization of hepatitis E virus in three acute liver failure cases in children in Argentina

Las cepas de virus de hepatitis E (HEV) encontradas en casos esporádicos humanos y en cerdos en Argentina corresponden al genotipo 3. Se han descripto variantes de este genotipo asociadas a fallas hepáticas fulminantes (FHF) en adultos de Japón e Inglaterra. En Argentina el 30% de las FHF en adultos y en niños es de etiología desconocida. Para estudiar si el HEV podría ser el agente etiológico asociado a FHF en niños se analizaron el suero y/o la materia fecal de 35 niños (edad media 6 años, 20 mujeres, 15 varones) durante 2003 y 2004. El HEV RNA fue detectado por RT-nested PCR con cebadores dirigidos a las regiones ORF 1 y ORF 2. El HEV RNA pudo detectarse en 3 casos. Dos eran varones de 12 años residentes en la provincia de Buenos Aires y el tercero, una niña de 3 años de la provincia de Corrientes. El análisis de las secuencias muestra que las 3 variantes son distintas, pero pertenecen todas al genotipo 3 y están muy relacionadas a las cepas encontradas previamente en casos esporádicos en humanos y en cerdos de Argentina. Estos datos sugieren una posible relación entre FHF y HEV en niños de Argentina e indican la necesidad de considerar la infección con HEV en el diagnóstico diferencial de las FHF. Se necesitan más estudios que demuestren el verdadero impacto de esta infección y el beneficio potencial de na vacuna para HEV, actualmente en fase III.

Strains of hepatitis E virus (HEV) isolated from Argentinian patients with sporadic hepatitis, as well as from swine from Argentina, belong to genotype 3. HEV genotype 3 variants have been described associated with acute liver failure (ALF) in adults from Japan and the United Kingdom. In Argentina, 30% of ALF in adults and children are of unknown aetiology. To study if HEV could be an aetiological agent associated with ALF in children, serum and/or fecal samples from 35 children (mean age: 6 years, 20 female, 15 male) were analyzed during 2003 and 2004. HEV RNA was detected by RT-nested PCR with primers designed within ORF 1 and ORF 2 regions. HEV RNA could be detected in three cases. Two were 12-year-old boys from Buenos Aires province and the third was a 3- year-old girl from Corrientes province. Sequence analysis indicates that the three isolates are distinct from each other but all belong to genotype 3, exhibiting a close relationship with swine and human strains from sporadic cases of HEV, previously reported in Argentina. This data suggests a potential link between ALF and HEV in children in Argentina and indicates the need for the determination of HEV status in the differential diagnosis in ALF. Further studies would aid in determining the true impact of this infection in Argentina and the potential benefits of a vaccine against HEV, presently in phase III trials.