Download PDF
CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2020; 80(05): 499-507
DOI: 10.1055/a-1091-8630
GebFra Science
Review/Übersicht
Georg Thieme Verlag KG Stuttgart · New York

HELLP Syndrome or Acute Fatty Liver of Pregnancy: A Differential Diagnostic Challenge

Common Features and Differences Article in several languages: English | deutsch
Werner Rath
1   Medizinische Fakultät, Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
Panagiotis Tsikouras
2   Democritus University of Thrace, Department of Obstetrics and Gynecology, Alexandroupolis, Greece
,
Patrick Stelzl
3   Frauenklinik, Universitätsklinikum Erlangen, Erlangen, Germany
› Author Affiliations
Further Information

Publication History

received 06 November 2019
revised 15 December 2019

accepted 08 January 2020

Publication Date:
18 May 2020 (online)

Also available at
   Permissions and Reprints

Abstract

HELLP syndrome and the less common acute fatty liver of pregnancy (AFL) are unpredictable, life-threatening complications of pregnancy. The similarities in their clinical and laboratory presentations are often challenging for the obstetrician when making a differential diagnosis. Both diseases are characterised by microvesicular steatosis of varying degrees of severity. A specific risk profile does not exist for either of the entities. Genetic defects in mitochondrial fatty acid oxidation and multiple pregnancy are considered to be common predisposing factors. The diagnosis of AFL is based on a combination of clinical symptoms and laboratory findings. The Swansea criteria have been proposed as a diagnostic tool for orientation. HELLP syndrome is a laboratory diagnosis based on the triad of haemolysis, elevated aminotransferase levels and a platelet count < 100 G/l. Generalised malaise, nausea, vomiting and abdominal pain are common symptoms of both diseases, making early diagnosis difficult. Clinical differences include a lack of polydipsia/polyuria in HELLP syndrome, while jaundice is more common and more pronounced in AFL, there is a lower incidence of hypertension and proteinuria, and patients with AFL may develop encephalopathy with rapid progression to acute liver failure. In contrast, neurological symptoms such as severe headache and visual disturbances are more prominent in patients with HELLP syndrome. In terms of laboratory findings, AFL can be differentiated from HELLP syndrome by the presence of leucocytosis, hypoglycaemia, more pronounced hyperbilirubinemia, an initial lack of haemolysis and thrombocytopenia < 100 G/l, as well as lower antithrombin levels < 65% and prolonged prothrombin times. While HELLP syndrome has a fluctuating clinical course with rapid exacerbation within hours or transient remissions, AFL rapidly progresses to acute liver failure if the infant is not delivered immediately. The only causal treatment for both diseases is immediate delivery. Expectant management between 24 + 0 and 33 + 6 weeks of gestation is recommended for HELLP syndrome, but only in cases where the mother can be stabilised and there is no evidence of foetal compromise. The maternal mortality rate for HELLP syndrome in developed countries is approximately 1%, while the rate for AFL is 1.8 – 18%. Perinatal mortality rates are 7 – 20% and 15 – 20%, respectively. While data on the long-term impact of AFL on the health of mother and child is still insufficient, HELLP syndrome is associated with an increased risk of developing cardiovascular, metabolic and neurological diseases in later life.

Key words

HELLP syndrome - acute fatty liver of pregnancy - Swansea criteria - differential diagnosis - treatment and prognosis
 

  • References/Literatur

  • 1 Bicocca MJ, Sparling JD, Chauhan SP. Intrahepatic cholestasis of pregnancy: Review of six national and regional guidelines. Eur J Obstet Gynecol Reprod Biol 2018; 231: 180-187
    CrossrefPubMedGoogle Scholar
  • 2 Haram K, Svendson E, Abilgaard U. The HELLP syndrome: clinical issues and management: a review. BMC Pregnancy Childbirth 2009; 9: 8
    CrossrefPubMedGoogle Scholar
  • 3 Italian Association for the Study of the Liver (AISF). AISF Position Paper on liver disease and pregnancy. Dig Liver Dis 2016; 48: 120-137
    CrossrefPubMedGoogle Scholar
  • 4 Brown MA, Magee LA, Kenny LC. et al. Hypertensive Disorders of Pregnancy: ISSHP Classification, diagnosis, and management recommendations for international practice. Hypertension 2018; 72: 24-43
    CrossrefPubMedGoogle Scholar
  • 5 Rath W, Faridi A, Dudenhausen JW. HELLP syndrome. J Perinat Med 2000; 28: 249-260
    PubMedGoogle Scholar
  • 6 AWMF-Leitlinie 015/018, 2019. Hypertensive Schwangerschaftserkrankungen: Diagnostik und Therapie. Online: http://www.dggg.de last access: 03.11.2019
    PubMedGoogle Scholar
  • 7 Minakami H, Morikawa M, Yamada T. et al. Differentiation of acute fatty liver of pregnancy from syndrome of hemolysis, elevated liver enzymes and low platelet counts. J Obstet Gynaecol Res 2014; 40: 641-649
    CrossrefPubMedGoogle Scholar
  • 8 Ko H, Yoshida EM. Acute fatty liver of pregnancy. Can J Gastroenterol 2006; 20: 25-30
    CrossrefPubMedGoogle Scholar
  • 9 Bacq Y, Assor P, Gendrot C. et al. Recurrent acute fatty liver of pregnancy. Gastroenterol Clin Biol 2007; 31: 1135-1138
    CrossrefPubMedGoogle Scholar
  • 10 Knight M, Nelson-Piercy C, Kurinczuk JJ. et al. A prospective national study of acute fatty liver of pregnancy in UK. Gut 2008; 57: 951-956
    CrossrefPubMedGoogle Scholar
  • 11 Audibert F, Friedman SA, Frangieh AY. et al. Clinical utility of strict diagnostic criteria for the HELLP syndrome. Am J Obstet Gynecol 1996; 175: 460-468
    CrossrefPubMedGoogle Scholar
  • 12 Chen G, Huang K, Ji B. et al. Acute fatty liver of pregnancy in a Chinese tertiary care center: a retrospective study. Arch Gynecol Obstet 2019; 300: 897-901 doi:10.1007/s00404-019-05259-w
    CrossrefPubMedGoogle Scholar
  • 13 Nelson DB, Yost NP, Cunningham FG. Acute fatty liver of pregnancy: clinical outcomes and expected duration of recovery. Am J Obstet Gynecol 2013; 209: 456.e1-456.e7
    CrossrefPubMedGoogle Scholar
  • 14 Allen AM, Kim WR, Larson JJ. et al. The epidemiology of liver diseases unique to pregnancy in a US community: a population-based study. Clin Gastroenterol Hepatol 2016; 14: 287-294
    CrossrefPubMedGoogle Scholar
  • 15 Liu J, Ghaziani TT, Wolf JL. Acute fatty liver disease of pregnancy: Updates in pathogenesis, diagnosis, and management. Am J Gastroenterol 2017; 112: 838-846
    CrossrefPubMedGoogle Scholar
  • 16 Sims HF, Brackett JC, Powell CK. et al. The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy. Proc Natl Acad Sci U S A 1995; 92: 841-845
    CrossrefPubMedGoogle Scholar
  • 17 Browning MF, Levy HL, Wilkins-Haug LE. et al. Fetal fatty acid oxidation defects and maternal liver disease in pregnancy. Obstet Gynecol 2006; 107: 115-120
    CrossrefPubMedGoogle Scholar
  • 18 den Boer ME, Wanders RJ, Morris AA. et al. Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency: clinical presentation and follow-up of 50 patients. Pediatrics 2002; 109: 99-104
    CrossrefPubMedGoogle Scholar
  • 19 Jebbink J, Wolters A, Fernando F. et al. Molecular genetics of preeclampsia and HELLP syndrome – a review. Biochim Biophys Acta 2012; 1822: 1960-1969
    PubMedGoogle Scholar
  • 20 Sibai BM, Ramadan MK, Usta I. et al. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol 1993; 169: 1000-1006
    CrossrefPubMedGoogle Scholar
  • 21 Chʼng CL, Morgan M, Hainsworth I. et al. Prospective study of liver dysfunction in pregnancy in Southwest Wales. Gut 2002; 51: 876-880
    CrossrefPubMedGoogle Scholar
  • 22 Goel A, Ramakrishna B, Zachariah U. et al. How accurate are the Swansea criteria to diagnose acute fatty liver of pregnancy in predicting hepatic microvesicular steatosis?. Gut 2011; 60: 138-139
    CrossrefPubMedGoogle Scholar
  • 23 Sibai BM. HELLP syndrome. 2019 Online: http://www.uptodate.com last access: 03.11.2019
    PubMedGoogle Scholar
  • 24 Rahman TM, Philips M, Wendson J. et al. Rare fetal complications of acute fatty liver of pregnancy. Crit Care 2000; 3 (Suppl. 01) 186
    PubMedGoogle Scholar
  • 25 Minuk GY, Lui RC, Kelly JK. Rupture of the liver associated with acute fatty liver of pregnancy. Am J Gastroenterol 1987; 82: 457-460
    PubMedGoogle Scholar
  • 26 Sang C, Wang S, Zhang Z. et al. Characteristics and outcome of severe preeclampsia/eclampsia concurrent with or complicated by acute pancreatitis: a report of five cases and literature review. J Matern Fetal Neonatal Med 2019; 32: 633-640
    CrossrefPubMedGoogle Scholar
  • 27 Rath W. Das HELLP-Syndrom: eine interdisziplinäre Herausforderung. Dtsch Ärztebl 1998; 95: 2997-3002
    PubMedGoogle Scholar
  • 28 Garcia-Romero CS, Guzman C, Cervantes A. et al. Liver disease in pregnancy: medical aspects and their implications for mother and child. Ann Hepatol 2019; 18: 553-562
    CrossrefPubMedGoogle Scholar
  • 29 Westbrook RH, Dusheiko G, Williamson C. Pregnancy and liver disease. J Hepatol 2016; 64: 933-945
    CrossrefPubMedGoogle Scholar
  • 30 Minakami H, Takahashi T, Tamada T. Should routine liver biopsy be done for the definite diagnosis of acute fatty liver of pregnancy?. Am J Obstet Gynecol 1991; 164: 1690-1691
    PubMedGoogle Scholar
  • 31 Minakami H, Oka N, Sato T. et al. Preeclampsia: a microvesicular fat disease of the liver?. Am J Obstet Gynecol 1998; 159: 1043-1047
    PubMedGoogle Scholar
  • 32 Rolfes DB, Ishak KG. Acute fatty liver of pregnancy: a clinicopathologic study of 35 cases. Hepatology 1985; 5: 1149-1158
    CrossrefPubMedGoogle Scholar
  • 33 Dani R, Mendes GS, Medeiros J. et al. Study of the liver changes occurring in preeclampsia and their possible pathogenetic connection with acute fatty liver of pregnancy. Am J Gastroenterol 1996; 91: 292-294
    PubMedGoogle Scholar
  • 34 Visser W, Wallenburg HC. Temporising management of severe preeclampsia with and without the HELLP syndrome. BJOG 1995; 102: 111-117
    CrossrefPubMedGoogle Scholar
  • 35 Mikolasevic I, Filipec-Kanizaj T, Jakopcic I. et al. Liver disease during pregnancy: a challenging clinical issue. Med Sci Monit 2018; 24: 4080-4090
    CrossrefPubMedGoogle Scholar
  • 36 Thomas T, Jophy R, Mhaskar A. et al. Are we increasing serious maternal morbidity by postponing termination of pregnancy in severe pre-eclampsia/eclampsia?. J Obstet Gynaecol 2005; 25: 347-351
    CrossrefPubMedGoogle Scholar
  • 37 Meng J, Wang S, Gu Y. et al. Prenatal predictors in postpartum recovery for acute fatty liver of pregnancy: experiences at a tertiary referral center. Arch Gynecol Obstet 2016; 293: 1185-1191
    CrossrefPubMedGoogle Scholar
  • 38 Martin JN, Blake PG, Perry KG. et al. The natural history of HELLP syndrome: patterns of disease progression and regression. Am J Obstet Gynecol 1991; 164: 1500-1509
    CrossrefPubMedGoogle Scholar
  • 39 Tran TT, Ahn J, Reau NS. ACG Clinical Guideline: Liver Disease and Pregnancy. Am J Gastroenterol 2016; 111: 176-194
    CrossrefPubMedGoogle Scholar
  • 40 Erkurt M, Berber I, Berktas HB. et al. A life-saving therapy in Class 1 HELLP syndrome: Therapeutic plasma exchange. Transfus Apher Sci 2015; 52: 194-198
    CrossrefPubMedGoogle Scholar
  • 41 Levin G, Kalish Y, Attari R. et al. Plasmapheresis–A lifesaving treatment for life threatening HELLP syndrome. Eur J Obstet Gynecol Reprod Biol 2019; 235: 125-126
    CrossrefPubMedGoogle Scholar
  • 42 Rebahi H, Still ME, El Adib AR. A successful use of therapeutic plasma exchange in a fulminant form of acute fatty liver of pregnancy. J Gynaecol Obstet Hum Reprod 2019; 48: 133-137
    PubMedGoogle Scholar
  • 43 Wang HY, Jiang Q, Shi H. et al. Effect of caesarean section on maternal and foetal outcomes in acute fatty liver of pregnancy: a systematic review and meta-analysis. Sci Rep 2016; 6: 28826
    CrossrefPubMedGoogle Scholar
  • 44 Reck T, Bussenius-Kammerer M, Ott R. et al. Surgical treatment of HELLP syndrome – associated liver rupture – an update. Eur J Obstet Gynecol Reprod Biol 2001; 99: 57-65
    CrossrefPubMedGoogle Scholar
  • 45 Hay JE. Liver disease in pregnancy. Hepatology 2008; 47: 1067-1076
    CrossrefPubMedGoogle Scholar
  • 46 Wallace K, Harris S, Addison A. et al. HELLP syndrome: Pathophysiology and current therapies. Curr Pharm Biotechnol 2018; 19: 816-826
    CrossrefPubMedGoogle Scholar
  • 47 van Oostwaard MF, Langenveld J, Schuit E. et al. Recurrence of hypertensive disorders of pregnancy: an individual patient data metaanalysis. Am J Obstet Gynecol 2015; 212: 624.e1-624.e17
    CrossrefPubMedGoogle Scholar
  • 48 Leeners B, Neumaier-Wagner P, Kuse S. et al. Recurrence risks of hypertensive diseases in pregnancy after HELLP syndrome. J Perinat Med 2011; 39: 673-678
    PubMedGoogle Scholar
  • 49 Ahmed KT, Almashhrawi AA, Rahman RN. et al. Liver diseases in pregnancy: diseases unique to pregnancy. World J Gastroenterol 2013; 19: 7639-7646
    CrossrefPubMedGoogle Scholar
  • 50 Xiong HF, Liu JY, Guo JM. et al. Acute fatty liver of pregnancy: over six months follow-up study of twenty-five patients. World J Gastroenterol 2015; 21: 1927-1931
    CrossrefPubMedGoogle Scholar
  • 51 Amaral LM, Cunningham MW, Cornelius DC. et al. Preeclampsia: long-term consequences for vascular health. Vasc Health Risk Manag 2015; 11: 403-415
    PubMedGoogle Scholar
  • 52 Chen CW, Jaffe IZ, Karumanchi SA. Preeclampsia and cardiovascular disease. Cardiovasc Res 2014; 101: 579-586
    CrossrefPubMedGoogle Scholar
  • 53 Davidson KM, Simpson LL, Knox TA. et al. Acute fatty liver of pregnancy in triplet gestation. Obstet Gynecol 1998; 91: 806-808
    PubMedGoogle Scholar
  • 54 Shekhawat P, Bennett MJ, Sadovsky Y. et al. Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases. Am J Physiol Endocrinol Metab 2003; 284: E1098-E1105
    CrossrefPubMedGoogle Scholar
  • 55 Haram K, Mortensen JH, Mastrolia SA. et al. Disseminated intravascular coagulation in the HELLP syndrome: how much do we really know?. J Matern Fetal Neonatal Med 2017; 30: 779-788
    CrossrefPubMedGoogle Scholar
  • 56 Rajasri AG, Srestha R, Mitchell J. Acute fatty liver of pregnancy (AFLP) – an overview. J Obstet Gynaecol 2007; 27: 237-240
    CrossrefPubMedGoogle Scholar