Acute fatty liver of pregnancy:Over six months follow-up study of twenty-five patients

AIM:To evaluate the prognosis of patients with acute fatty liver of pregnancy(AFLP)6 mo or longer after discharge.METHODS:The records of pregnant patients diagnosed with AFLP at Beijing Ditan Hospital over a 16-year period were reviewed in November 2012.Patients weremonitored using abdominal ultrasound,liver and kidney functions,and routine blood examination.RESULTS:A total of 42 patients were diagnosed with AFLP during the study period,and 25 were followed.The mean follow-up duration was 54.5 mo(range:6.5-181 mo).All patients were in good physical condition,but one patient had gestational diabetes.The renal and liver functions normalized in all patients after recovery,including in those with pre-existing liver or kidney failure.The ultrasound findings were normal in12 patients,an increasingly coarsened echo-pattern and increased echogenicity of the liver in 10 patients,and mild to moderate fatty liver infiltration in 3 patients.Cirrhosis or liver nodules were not observed in any patient.CONCLUSION:Acute liver failure and acute renal failure in AFLP patients is reversible.Patients do not require any specific long-term follow-up after recovery from AFLP if their liver function tests have normalized and they remain well.

Effects of plasma exchange combined with continuous renal replacement therapy on acute fatty liver of pregnancy

BACKGROUND: Acute fatty liver of pregnancy (AFLP) in the third trimester or early postpartum period can lead to fatal liver damage. Its traditional therapy is not very effective in facilitating hepatic recovery. The safety and effect of plasma exchange (PE)in combination with continuous renal replacement therapy(CRRT) (PE+CRRT) for AFLP still needs evaluation.METHODS: Five AFLP patients with hepatic encephalopathy and renal failure were subjected to PE+CRRT in our department from 2007 to 2012. Their symptoms, physical signs and results were observed, and all relevant laboratory tests were compared before and after PE+CRRT.RESULTS: All the 5 patients were well tolerated to the therapy. Four of them responded to the treatment and showed improvement in clinical symptoms/signs and laboratory results and they were cured and discharged home after the treatment One patient succeeded in bridging to transplantation for slowing down hepatic failure and its complications process after2 treatment sessions. Intensive care unit stay and hospital stay were 9.4 (range 5-18) and 25.0 days (range 11-42), respectively.CONCLUSION: PE+CRRT is safe and effective and should be used immediately at the onset of hepatic encephalopathy and/or renal failure in patients with AFLP.

Chronic pancreatitis:a sequela of acute fatty liver of pregnancy

BACKGROUND: Chronic pancreatitis following acute fatty liver of pregnancy is rarely reported.METHODS: We treated a 34-year-old woman who developed acute fatty liver of pregnancy (AFLP) after delivery by caesarean section at 32 weeks of gestation. AFLP was complicated by acute pancreatitis and multiple organ failure. The management of the disease was primarily supportive. She recovered from acute fulminant liver failure and multi-organ failure, apart from the development of symptomatic chronic pancreatitis thereafter. RESULTS: Investigations failed to identify any other causes of chronic pancreatitis. The patient responded very well to pancreatic enzyme supplement for the treatment of steatorrhoea.CONCLUSION: To our knowledge, this is the first report of chronic pancreatitis as a consequence of multi-organ dysfunction caused by AFLP.

Acute fatty liver of pregnancy:An update on pathogenesis and clinical implications

Acute fatty liver of pregnancy (AFLP) is a serious maternal illness occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. Till recently, it has been considered a mysterious illness. In this editorial, we review the recent advances in understanding the pathogenesis of AFLP and discuss the studies documenting a fetal-maternal interaction with a causative association between carrying a fetus with a defect in mitochondrial fatty acid oxidation and development of AFLP. Further, we discuss the impact of these recent advances on the offspring born to women who develop AFLP, such that screening for a genetic defect can be life saving to the newborn and would allow genetic counseling in subsequent pregnancies. The molecular basis and underlying mechanism for this unique fetal-maternal interaction causing maternal liver disease is discussed.

Acute fatty liver of pregnancy associated with severe acute pancreatitis:A case report

Acute fatty liver of pregnancy is a rare disease that affects women in the third trimester of pregnancy. Although infrequent, the disease can cause maternal mortality. The diagnosis is not always clear until the pregnancy is terminated, and significant complications, such as acute pancreatitis, can occur. Pancreatic involvement typically only occurs in severe cases after the development of hepatic and renal impairment. To date, little knowledge is available regarding how the disease causes pancreatitis. Treatment involves supportive measures and pregnancy interruption. In this report, we describe a case of a previously healthy 26-year-old woman at a gestational age of 27 wk and 6 d who was admitted with severe abdominal pain and vomiting. This case illustrates the clinical and laboratory overlap between acute fatty liver of pregnancy and pancreatitis, highlighting the difficulties in differentiating each disease. Furthermore, the hypothesis for this overlapping is presented, and the therapeutic options are discussed.

Case Report: Acute Fatty Liver of Pregnancy

Acute fatty liver of pregnancy (AFLP) is a rare disease in Vietnam. Diagnosis by recorded literature is often difficult to distinguish from viral hepatitis, paraplegia, or bile duct disease, so AFLP diagnosis is often delayed. The prevalence of hepatitis B in Vietnam in pregnant women is estimated at 10% REF _Ref494526757 \r \h [1], preeclampsia is estimated at 0.2% REF _Ref494526760 \r \h [2]. A case pregnant woman has 35.5-week gestational age with AFLP, who was safely delivered both mother and infant at Hung Vuong hospital, Vietnam. A careful history and physical examination, in conjunction with compatible laboratory and ultrasound imaging results, are often sufficient to make the diagnosis, and liver biopsy is rarely indicated. Intensive adjuvant therapy and rapid birth control are essential for maternal and fetal outcomes.

Case Report-Early Detection of Acute Fatty Liver of Pregnancy in Urgent Care Department with Nonspecific Symptoms

Acute fatty liver of pregnancy is a rare but serious disorder affecting pregnancy. The rarity of this situation along with nonspecific symptoms makes it difficult to diagnose and thus causes catastrophic events. Biochemical parameters are required to diagnose this condition and differentiate it from other life threatening causes of pregnancy like HELLP syndrome and Preeclampsia. To avoid complications it is imperative to diagnose this condition at the earliest by doing blood test investigation and symptomatic management and delivery. We present a case in our hospital which came to urgent care with nonspecific symptoms and was diagnosed on blood tests and managed promptly and thus averted a catastrophic event.

Advances in understanding and treating liver diseases during pregnancy:A review

Liver disease in pregnancy is rare but pregnancyrelated liver diseases may cause threat to fetal and maternal survival.It includes pre-eclampsia;eclampsia;haemolysis,elevated liver enzymes,and low platelets syndrome;acute fatty liver of pregnancy;hyperemesis gravidarum;and intrahepatic cholestasis of pregnancy.Recent basic researches have shown the various etiologies involved in this disease entity.With these advances,rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival.The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention.Therefore,correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis.Therefore,here we review and summarized recent advances in understanding the etiologies,clinical courses and management of liver disease in pregnancy.This information will contribute to physicians for diagnosis of disease and optimum management of patients.

Liver diseases in pregnancy: Diseases unique to pregnancy

Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver.Liver disease can cause significant morbidity and mortality in both pregnant women and their infants.This review summarizes liver diseases that are unique to pregnancy.We discuss clinical conditions that are seen only in pregnant women and involve the liver;from Hyperemesis Gravidarum that happens in 1out of 200 pregnancies and Intrahepatic Cholestasis of Pregnancy(0.5%-1.5%prevalence),to the more frequent condition of preeclampsia(10%prevalence)and its severe form;hemolysis,elevated liver enzymes,and a low platelet count syndrome(12%of pregnancies with preeclampsia),to the rare entity of Acute Fatty Liver of Pregnancy(incidence of 1 per 7270 to 13000deliveries).Although pathogeneses behind the development of these aliments are not fully understood,theories have been proposed.Some propose the special physiological changes that accompany pregnancy as a precipitant.Others suggest a constellation of factors including both the mother and her fetus that come together to trigger those unique conditions.Reaching a timely and accurate diagnosis of such conditions can be challenging.The timing of the condition in relation toward which trimester it starts at is a key.Accurate diagnosis can be made using specific clinical findings and blood tests.Some entities have well-defined criteria that help not only in making the diagnosis,but also in classifying the disease according to its severity.Management of these conditions range from simple medical remedies to measures such as immediate termination of the pregnancy.In specific conditions,it is prudent to have expert obstetric and medical specialists teaming up to help improve the outcomes.

Liver diseases in pregnancy: Liver transplantation in pregnancy

Pregnancy in patients with advanced liver disease is uncommon as most women with decompensated cirrhosis are infertile and have high rate of anovulation.However,if gestation ensued;it is very challenging and carries high risks for both the mother and the baby such as higher rates of spontaneous abortion,prematurity,pulmonary hypertension,splenic artery aneurysm rupture,postpartum hemorrhage,and a potential for life-threatening variceal hemorrhage and hepatic decompensation.In contrary,with orthotopic liver transplantation,menstruation resumes and most women of childbearing age are able to conceive,give birth and lead a better quality of life.Women with orthotopic liver transplantation seeking pregnancy should be managed carefully by a team consultation with transplant hepatologist,maternal-fetal medicine specialist and other specialists.Pregnant liver transplant recipients need to stay on immunosuppression medication to prevent allograft rejection.Furthermore,these medications need to be monitored carefully and continued throughout pregnancy to avoid potential adverse effects to mother and baby.Thus delaying pregnancy 1 to 2 years after transplantation minimizes fetal exposure to high doses of immunosuppressants.Pregnant female liver transplant patients have a high rate of cesarean delivery likely due to the high rate of prematurity in this population.Recent reports suggest that with close monitoring and multidisciplinary team approach,most female liver transplant recipient of childbearing age will lead a successful pregnancy.

基于CiteSpace和VOSviewer的AFLP相关研究可视化分析

目的采用文献可视化网络知识图谱的方式探究妊娠期急性脂肪肝相关性研究的热点和发展趋势,旨在对该领域的进一步研究提供新的线索和思路。方法以Web of Science核心合集数据库(Woscc)和中国知网(China National Knowledge Infrastructure,CNKI)来源检索2004—2023年文献,Woscc英文数据库检索主题为TS=“acute fatty liver of pregnancy”OR TS=“liver disease during pregnancy”AND“Abnormal fatty acid oxidation”OR TS=“liver disease during pregnancy”AND“Abnormal oxidation of short chain fatty acids”OR TS=“liver disease during pregnancy”AND“Abnormal oxidation of short chain fatty acids”OR TS=“liver disease during pregnancy”AND“Abnormal oxidation of medium-chain fatty acids”OR TS=“liver disease during pregnancy”AND“Abnormal oxidation of long chain fatty acids”,CNKI中文数据库检索主题为:“妊娠期急性脂肪肝”,检索日期:2024年1月23日。运用CiteSpaceⅤ6.1.R6和VOSviewer 1.6.18软件进行作者、机构、国家及关键词分析。结果CNKI中文数据库获得有效文献499篇,Woscc外文数据库获得348篇,美国在该领域研究处于主导地位且影响力最大,国内发文机构中山大学附属第三医院产科位居首位,国外是贝拿勒斯印度教大学,国内发文作者最多的是:唐卉,国外是Hisanori Minakmi和Mamoru Morikawa。CNKI中文数据库关键词聚类和突现显示包括:“发病机制”、“预测模型”,Woscc外文数据库关键词聚类和突现显示“死亡(death)”“肝脏病变(liver disease)”“产妇死亡率(materal mortality)”为该领域的最新研究前沿。期刊双图叠加可视化图谱显示AFLP的研究已经向转化医学方向进展。结论本研究运用文献可视化分析揭示妊娠期急性脂肪肝的研究现状和最新前沿,其结果可能促进研究者对该领域的研究热点和趋势进行更深的挖掘。

Progress in the treatment of acute fatty liver of pregnancy and management of perioperative anesthesia review

Acute fatty liver of pregnancy is a rare and critical disease in obstetrics,mainly characterized by liver failure,severe coagulopathy and other clinical manifestations,with rapid progression and high mortality.This article discusses the epidemic characteristics,pathogenesis,clinical manifestations,laboratory examination,clinical diagnosis and treatment of acute fatty liver during pregnancy.This paper summarizes the related contents of perioperative anesthesia in anesthesia methods,drug selection,coagulation regulation,organ protection and postpartum disease outcome.

Acute Fatty Liver of Pregnancy： A Retrospective Analysis o 56 Cases

Background： Acute fatty liver of pregnancy （AFLP） is a rare but life-threatening complication occurring in the third trimester. It is often fatal to both mother and fetus. The complicated clinical manifestations as well as an insufficient understanding of the disease make the precise diagnosis and effective treatment of AF LP challenging. A full understanding of the risk factors, clinical features, and test findings of AFLP is critical for its timely diagnosis and treatment. Methods： We performed a retrospective study of 56 patients with AFLP between June 2008 and July 2013. We analyzed the clinical features, laboratory results, perioperative management, and patient outcomes. Results： The initial symptoms varied considerably, with nausea and vomiting （13/56, 23%） being the most common. Liver-function indexes were remarkable, including elevated levels of serum alanine aminotransferase （262.16 ± 281.71 U/L）, aspartate aminotransferase （260.98 ± 237.91 U/L）, lactic dehydrogenase （1011.76 ± 530.34 U/L）, and direct bilirubin （85.59 ± 90.02 μmol/L）. Coagulation disorders were indicated by abnormal levels offibrinogen （245.95 ± 186.11 mg/dL）, D-dimer （2.46 ±4.01 mg/L）, and fibrin degradation products （43.62 ±48.71 mg/L）. The main maternal complications were hypoproteinemia （75%）, coagulopathy （54%）, and acute renal failure （39%）. Multivariate logistic regression analysis identified prothrombin time （PT; odds ratio [OR] = 1.558, 95% confidence interval [CI] =1.248-1.946, P= 0.016） and international normalized ratio （INR; OR = 40.034, 95% CI= 2.517-636.693, P = 0.009） as risk factors. The perinatal infant death rate was related to gestational age at delivery （OR = 1.298, 95% CI- 1.040-1.618, P = 0.021）, direct bilirubin （OR = 1.05, 95% CI = 1.008 1.094, P = 0.020）, and fibrin degradation products （OR - 0.973, 95% CI = 0.950 0.996, P= 0.021）. Conclusions： Nausea and vomiting may be the most common symptoms of AFLP. Indexes of liver dysfunction and coagulation disorders should also be considered. PT and INR are risk factors for fatal complications in patients with AFLP, and perinatal mortality is linked to the level of fibrin degradation products. Timely delivery is crucial to controlling the development of AFLR

Acute fatty liver of pregnancy: diagnosis and management of 8 cases

Objective To investigate the early recognition and management of acute fatty liver of pregnancy (AFLP) to improve maternal and fetal survival. Methods Eight cases of AFLP seen in our hospital during the past three years were studied retrospectively. Symptoms, laboratory findings, timing of liver biopsy, and maternal and fetus outcome were assessed. Results The mean gestational age at onset was 34 ± 2 weeks. All cases were primigravida. In the early stages, all patients presented malaise, nausea, vomiting and epigastric distress followed by jaundice in the third trimester of pregnancy. Laboratory findings:all had raised transaminases and serum bilirubin (32 .5 - 510. 8 umol/L), hypoalbuminemia (22 .4 -30.0 g/L ), hypofibrinogenemia (< 180 mg/dl ),prolonged prothrombin time and prolonged partial thromboplastin time. Maternal complication included hepatic encephalopathy (6 cases ), ascites (6 ),hypoglycemia (5), hematemesis (2), and postpartum hemorrhage (5) and preeclampsia (4). Emergency cesarean section was performed in 3 cases. One mother died of fulminant hepatic failure and the others survived. There was no fetus death. Liver biopsy was done on the 5th to 15th postpartum day in 8 cases. Conclusion With increasing awareness, especially in the early recognition of milder cases, and prompt progressive management including early termination of pregnancy by cesarean section and large dose infusion of fresh frozen plasma and albumin alternately, the prognosis of AFLP can be improved.

CSOG MFM Committee Guideline:Clinical Management Guidelines for Acute Fatty Liver of Pregnancy in China(2021)

Acute fatty liver of pregnancy(AFLP)is a rare but critical obstetric-specific disease with a high fatality rate,posing a serious threat to the safety of mothers and infants.These guidelines were specially formulated to standardize AFLP clinical pathways and to improve maternal and infant outcomes.Based on a two-round questionnaire survey,the guideline development team identified the following nine clinical issues that clinicians were most concerned about,and developed recommendations for each of them:prenatal outpatient screening for AFLP,diagnosis,preoperative risk assessment,delivery modes and timing,anesthesia methods,perinatal complications,selecting AFLP patients for artificial liver treatment,prognostic assessment,and monitoring during treatment.The guidelines cover the key issues related to AFLP diagnosis and treatment that concern clinicians.

妊娠期急性脂肪肝患者预后并发症发生影响因素及预测

目的:探究妊娠期急性脂肪肝(AFLP)患者预后并发症发生影响因素。方法:回顾性收集2020年1月-2023年10月本院收治的153例AFLP患者临床资料,收集患者基本信息、血液学指标及急性生理和慢性健康评估系统(APACHEⅡ)评分,剖宫产术后随访6个月,采用比例风险模型分析AFLP患者预后发生并发症影响因素;绘制受试者工作特征(ROC)曲线,评价影响因素预测AFLP患者预后发生并发症性能。结果:AFLP患者剖宫产术后发生并发症23.5%(36/153);多因素回归分析,发病至就诊时间、总胆红素、凝血酶原时间和APAC均是AFLP患者预后发生并发症的独立影响因素;ROC曲线分析,发病至就诊时间(AUC=0.712)、总胆红素(AUC=0.741)、凝血酶原时间(AUC=0.734)、APACHEⅡ评分(AUC=0.758)及4项联合(AUC=0.906)预测AFLP患者预后发生并发症均有一定效能。结论:发病至就诊时间长、总胆红素水平高、凝血酶原时间大与APACHEⅡ评分高均为AFLP患者预后发生并发症的独立影响因素,4种因素预测AFLP患者预后发生并发症有一定价值。

PE联合DPMAS治疗对AFLP患者凝血功能的影响

目的探讨小剂量血浆置换(plasma exchange,PE)联合双重血浆分子吸附(dual plasma molecular adsorption system,DPMAS)在妊娠期急性脂肪肝(acute fatty liver of pregnancy,AFLP)中应用对患者凝血功能的影响。方法选取我院2016年1月—2018年8月因AFLP需住院治疗患者46例作为研究对象。按照随机数字表法,将其分成观察组和对照组,每组各23例。观察组予以小剂量PE联合DPMAS治疗,对照组仅予以PE治疗。比较两组患者治疗前后凝血酶原时间(PT)、凝血酶原活动度(PA)、纤维蛋白原(FIB)、活化部分凝血时间(APPT)和血小板(PLT)水平。结果治疗后,两组患者凝血功能均明显改善,与治疗前相比,差异具有统计学意义(P <0.05);虽观察组PT、APPT低于对照组,PA、FIB、PLT水平高于对照组,但组间比较,差异无统计学意义(P> 0.05)。结论小剂量PE联合DPMAS在AFLP中应用临床效果较好,有效改善患者凝血功能。

22例妊娠期急性脂肪肝临床特征分析

目的分析妊娠期急性脂肪肝(AFLP)的临床特征。方法选取2010年1月至2020年9月滨州市人民医院收治的22例AFLP患者,分析AFLP的临床特征。结果22例患者中,16例发生消化道症状,且均有不同程度的黄疸,14例纤维蛋白原<1.5 g/L,7例白蛋白<20 g/L,3例发生肝性脑病,6例并发肾衰竭,5例并发多器官功能障碍综合征,2例胎死宫内。结论对AFLP患者及时终止妊娠,积极预防弥散性血管内凝血,补充凝血物质,根据病情及时给予输血及血制品输注、血液置换及血液净化等对症治疗,有利于改善AFLP患者及胎儿的预后。

妊娠期急性脂肪肝患者住院时间影响因素分析及预测模型建立

目的探讨影响妊娠期急性脂肪肝(acute fatty liver of pregnancy,AFLP)患者住院时间相关因素并建立预测模型。方法回顾性分析本院2008年1月—2023月1月共49例AFLP病例资料,根据患者住院时间中位数分组:A组(n=21例),B组(n=28例)。分析2组术前一般实验室资料、临床特征和产后不良后果。采用多因素二元Logistic回归分析影响AFLP住院时间的独立影响因素,建立住院时间预测模型。结果B组与A组比较,住院天数(d)(15.5 vs 8)、术前黄疸[n(%)][16(57.1%)vs 3(14.3%)]、TT(s)(24.2 vs 21.3)、PT(s)(16.8 vs 15.3)、APTT(s)(52.3 vs 40.7)、TBIL(μmol/L)(77.2 vs 45.2)、IBIL(μmol/L)(21.2 vs 10)、Cre(μmol/L)(171.97±53.34 vs 131.81±45.06)、TT延长[n(%)][24(85.7%)vs 11(52.4%)]、APTT延长[n(%)][27(96.4%)vs 7(33.3%)]、IBIL升高[n(%)][19(67.9%)vs 4(19%)]、Cre浓度升高[n(%)][21(75%)vs 8(38%)],产后血浆置换次数[n(%)][23(82.1%)vs 5(23.8%)]和妊娠后合并感染现象[n(%)][21(75%)vs 4(19%)],显著高于A组。B组与A组比较,术前Plt(×10~9/L)(128 vs 221)与Fib含量(g/L)(0.9 vs 1.6),明显低于A组。单因素Logistic回归分析发现术前黄疸、妊娠后合并感染、产后需血浆置换次数、术前TT延长、术前APTT延长、Cre浓度升高是AFLP住院时间的影响因素。根据AIC(赤池信息量准则)指标最小值结果,逐步法多因素Logistic二元回归显示:产后血浆置换需≥4次、黄疸、术前APTT延长三者是AFLP患者住院时间的独立危险因素并将三者纳入建立逻辑回归预测模型。逻辑回归预测模型经正则化技术评估解决过拟合问题,并通过自助法技术为每个模型获取了估计效应大小的置信区间。结论术前黄疸、术前APTT延长(APTT>43 s)和产后血浆置换次数是AFLP患者住院时间延长的独立危险因素,并成功建立预测效能高的AFLP住院时间逻辑回归预测模型。

血浆置换联合血浆灌流治疗重症妊娠急性脂肪肝的临床效果

目的:观察重症妊娠急性脂肪肝应用血浆置换联合血浆灌流治疗的临床效果。方法:选取2021年8月—2022年12月临沂市中心医院收治的60例重症妊娠急性脂肪肝患者作为研究对象,随机分为观察组与对照组,各30例。对照组应用血浆灌流治疗,观察组应用血浆置换联合血浆灌流治疗。比较两组治疗效果。结果:治疗前,两组血浆凝血酶原时间(PT)、纤维蛋白原(FIB)水平比较,差异无统计学意义(P>0.05);治疗后,两组PT短于治疗前,且观察组短于对照组,两组FIB水平高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05)。治疗前,两组丙氨酸氨基转移酶(ALT)、血清肌酐(Scr)、血尿素氮(BUN)、总胆红素(TBiL)水平比较,差异无统计学意义(P>0.05);治疗后,两组ALT、Scr、BUN、TBiL水平低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。治疗前,两组血小板计数、白细胞计数比较,差异无统计学意义(P>0.05);治疗后,两组血小板计数低于治疗前,且观察组低于对照组,两组白细胞计数高于治疗前,且观察组高于对照组,差异均有统计学意义(P<0.05)。结论:血浆置换联合血浆灌流治疗重症妊娠急性脂肪肝的效果显著,能改善患者肝肾功能、凝血功能、血常规指标。