Impact Of New Diagnostic Strategies And Related Genetic Tests On Acute Fatty Liver Of Pregnancy And Corresponding Diagonistic Values And Comments

[Objective]1.We take the Swansea Criteria as the standard to diagnose Acute Fatty Liver of Pregnancy（AFLP）.Restropective analysis has been carried out on the cases to put forward new diagnostic strategies and explore the value of these strategies.2.Through carrying out genetic tests on 9 genes of 27 diagnosed AFLP patients,their spouses,the parents of their spouses,the newborns during the disease,and the newborns of a second pregnancy without AFLP,we have discussed diagnostic meaning of related genetic tests on AFLP.[Method]New diagnostic strategies: Disease records of 73 AFLP patients who were admitted into our hospital and Shenzhen No.3 People’s Hospital during the period from 2003 to Januray,2017.The diagnosis standards were based on liver biopsy,or the criteria established by Swansea University in England.The patients were in this way included into the case group.In the meantime,patients at similar age and of similar gestational weeks were chosen as the control group.The patients in the control group had symptoms in upper gastrointestinal tracts and abnormal liver function.The new diagnostic strategies（attack in late trimester of pregnancy,with symptoms in upper gastrointestinal tracts,accompanied by abnormal liver function,abnormal kidney function,and coagulation disorders;the clinical manifestation of the aforementioned symptoms caused by other reasons should be excluded）and Swansea criteria have been applied respectively to diagnosis and statistical analysis.Genetic test: 27 samples have been collected based on 9 families with AFLP for genetic tests.Chips were used to caputure the images of high-throughput sequencing（the second generation gene sequencing）.Combined with the first generation gene sequencing method,the verification process has been completed.The tests were performed on the coding area of the target genes and the DNA of surrounding splicing area through 5ml venous blood of the patient and her spouse,and 2ml venous or umbilical cord blood of the newborn.Analysis has been made afterwards.[Results]1.The range of onset is 35.6±2.81 pregnancy weeks.89.71%（n=61）of the patients have upper digestive tract symptoms and 67.65% of them get nausea and vomit,66.18% get atony and inappetence,100%（n=68）get abnormal liver function,86.76%（n=59）get abnormal kidney function and 91.18%（n=62）get coagulation disorders.2.The diagnositc sensitivity of the new strategy Se=92.62%,Sp=95.24%;PV+=96.92%;α=4.76;β=7.35%;PV-=88.89%.T LR+=19.46,and LR-is 0.08.Kappa value validity evaluation has been carried out.The Kappa value is 0.88.The consistency check shows statistical significance（P=0.000）.It is considered that the two methods to diagnose AFLP have consistency.3.Among the 9 patients of AFLP,2 have abnormal genetic test results,accounting for22.22%.4.Patient A has hyterozytotic mutations with c.365C>T on CPT2 genes.Such mutations have unclear clinical meanings.The husband of the patient has no genetic mutation.The boy infant of the patient during AFLP died so there is no genetic test for it.For the next pregnancy,the baby boy also has hyterozytotic mutations with c.365C>T,but the girl fetus has no genetic mutations.Patient B has no genetic mutation,and her second husband has hyterozytotic mutations with c.439G>A on ACADVL genes.During the period of the disease,the boy fetus has no genetic mutations.5.Patient C has AFLP for the previous pregnancy and has two hyterozytotic mutations（c.2228₂229 ins AACA and c.652G>C）.On the HADHA gene of the patient’s spouse,there exists hyterozytotic mutations（c.1720₁721 del CT and c.415A>G）.Her father in law has a heterozygotic mutation,c.415A>G,and her mother in law,c.1720₁721 del CT.Because she got AFLP,her male fetus died in last pregnancy.After that,she delivered an infant girl,and a mutation of c.415A>G was found in the HADHA gene of the baby.[Conclusion]1.The gestational week of AFLP is mostly the 36 th week.Most patients have symptoms of upper gastrointestinal tracts,like nausea,vomitting,lack of strength and poor appetite.AFLP is a disease affecting multiple organs.There exist abnormal liver function,abnormal kidney function and different degrees of coagulation disorder.2.The new diagnostic strategy put forward by this research（attack in late trimester of pregnancy;show symptoms of upper gastrointestinal symptom,accompanied by abnormal liver function,abnormal kidney function,and coagulation disorder;the clinical manifestation of the aforementioned symptoms caused by other reasons should be excluded）is consistent with the Swansea criteria in terms of AFLP diagnosis.That is to say,the new diagnostic strategy is effective,reliable and feasible in AFLP diagnosis.Besides,the new diagnostic strategy is concise,easy to master and beneficial for early-stage diagnosis.3.AFLP is caused by multiple factors.Related genetic deficiency is just one of the factors.4.CPT2,ACADVL,HADHA genetic deficiency may be related to the attack of AFLP.