Akute Schwangerschaftsfettleber – Fallserie einer seltenen Schwangerschaftskomplikation

Zusammenfassung

Die akute Schwangerschaftsfettleber (acute fatty liver in pregnancy, AFLP) ist mit einer Prävalenz von 0,01–0,03% eine seltene, potentiell lebensbedrohliche Komplikation in der Schwangerschaft. Durch die meist unspezifischen Symptome lässt sie sich schwer von anderen, teils häufigeren, Schwangerschaftserkrankungen wie HELLP Syndrom, aHUS und TTP abgrenzen. Ihre Seltenheit führt dazu, dass sie durch in der Geburtshilfe tätige Personen als Differentialdiagnose oft nicht in Erwägung gezogen wird. Dabei ist gerade die frühzeitige Diagnosestellung und schnellstmögliche Entbindung als einzige kausale Therapie entscheidend zur Verhinderung schwerwiegender Komplikationen und mütterlicher Todesfälle. In nachfolgender Arbeit wird anhand von Fallbeschreibungen dreier Uniklinika die Pathophysiologie, Bedeutung, Diagnose und Therapie der akuten Schwangerschaftsfettleber für die klinische Routine hervorgehoben und auf mögliche Befunde, welche in der Diagnosefindung zielführend sind, hingewiesen. Hierbei spielt auch der angiogene Präeklampsie-Marker sFlt-1 eine Rolle und bietet neue Betrachtungsweisen pathophsiologischer Ansätze.

Abstract

With a prevalence of 0,01-0,03%, acute fatty liver in pregnancy (AFLP) is a rare and dangerous complication of pregnancy and is difficult to distinguish from other, sometimes more common, pregnancy diseases such as HELLP syndrome, aHUS and TTP because of its mostly non-specific symptoms. Due to its rarity, AFLP is often not obvious to the obstetrician as a possible differential diagnosis. Yet early diagnosis and the fastest possible delivery is the only causal therapy and is important for the mortality rate. In the present manuscript, the pathophysiology, diagnosis and therapy of acute fatty liver in pregnancy are highlighted for the clinical routine based on case descriptions from three university hospitals, and reference is made to possible findings that are helpful in establishing the diagnosis. The angiogenic preeclampsia marker sFlt-1 plays a role and provides new opportunities to consider pathophysiological approaches.

Schlüsselwörter

Akute Schwangerschaftsfettleber (AFLP) - Schwangerschaftsspezifische Lebererkrankungen - Swansea-Kriterien - Unspezifisches Krankheitsgefühl in der Schwangerschaft

Key words

acute fatty liver of pregnancy (AFLP) - pregnancy-specific liver diseases - Swansea criteria - nonspecific feeling of illness in pregnancy

• Literatur

• 1 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 e281-282
• 2 Naoum EE, Leffert LR, Chitilian HV. et al. Acute Fatty Liver of Pregnancy: Pathophysiology, Anesthetic Implications, and Obstetrical Management. Anesthesiology 2019; 130: 446-461
• 3 Rath W, Tsikouras P, Stelzl P. HELLP Syndrome or Acute Fatty Liver of Pregnancy: A Differential Diagnostic Challenge: Common Features and Differences. Geburtshilfe Frauenheilkd 2020; 80: 499-507
• 4 Janati-Idrissi Y, Slama L, Taheri H. et al. Recurrent acute fatty liver of pregnancy: About a case and a review of the literature. Gynecol Obstet Fertil Senol 2022; 50: 620-623
• 5 Tyni T, Ekholm E, Pihko H. Pregnancy complications are frequent in long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. Am J Obstet Gynecol 1998; 178: 603-608
• 6 Ibdah JA. Acute fatty liver of pregnancy: an update on pathogenesis and clinical implications. World J Gastroenterol 2006; 12: 7397-7404
• 7 Shekhawat PS, Matern D, Strauss AW. Fetal fatty acid oxidation disorders, their effect on maternal health and neonatal outcome: impact of expanded newborn screening on their diagnosis and management. Pediatr Res 2005; 57: 78R-86R
• 8 Hay JE. Liver disease in pregnancy. Hepatology 2008; 47: 1067-1076
• 9 Steingrub JS. Pregnancy-associated severe liver dysfunction. Crit Care Clin 2004; 20: 763-776
• 10 Natarajan SK, Thangaraj KR, Eapen CE. et al. Liver injury in acute fatty liver of pregnancy: possible link to placental mitochondrial dysfunction and oxidative stress. Hepatology 2010; 51: 191-200
• 11 Prasun P, LoPiccolo MK, Ginevic I. Long-Chain Hydroxyacyl-CoA Dehydrogenase Deficiency/Trifunctional Protein Deficiency. In: Adam MP, Everman DB, Mirzaa GM et al., Hrsg. GeneReviews((R)). Seattle (WA). 1993
• 12 Monga M, Katz AR. Acute fatty liver in the second trimester of pregnancy. Prim Care Update Ob Gyns 1998; 5: 191
• 13 Panther E, Blum HE. Liver diseases in pregnancy. Dtsch Med Wochenschr 2008; 133: 2283-2287
• 14 Dashe JS, Ramin SM, Cunningham FG. The long-term consequences of thrombotic microangiopathy (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) in pregnancy. Obstet Gynecol 1998; 91: 662-668
• 15 Ch'ng CL, Morgan M, Hainsworth I. et al. Prospective study of liver dysfunction in pregnancy in Southwest Wales. Gut 2002; 51: 876-880
• 16 Trottmann F, Raio L, Amylidi-Mohr S. et al. Soluble fms-like tyrosine kinase 1 (sFlt-1): A novel biochemical marker for acute fatty liver of pregnancy. Acta Obstet Gynecol Scand 2021; 100: 1876-1884
• 17 Stepan H, Hund M, Andraczek T. Combining Biomarkers to Predict Pregnancy Complications and Redefine Preeclampsia: The Angiogenic-Placental Syndrome. Hypertension 2020; 75: 918-926
• 18 Nelson DB, Yost NP, Cunningham FG. Acute fatty liver of pregnancy: clinical outcomes and expected duration of recovery. Am J Obstet Gynecol 2013; 209: e451-e457
• 19 Westbrook RH, Yeoman AD, Joshi D. et al. Outcomes of severe pregnancy-related liver disease: refining the role of transplantation. Am J Transplant 2010; 10: 2520-2526
• 20 Pecks U, Mand N, Kolben T. et al. SARS-CoV-2 Infection During Pregnancy – An Analysis of Clinical Data From Germany and Austria From the CRONOS Registry. Dtsch Arztebl Int 2022; 10.3238/arztebl.m2022.0266
• 21 Kleinwechter H, Groten T, Schafer-Graf U. et al. COVID-19 and pregnancy. Gynakologe 2021; 54: 357-365
• 22 García-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
• 23 Bergmann F. RW. The differential diagnosis of thrombocytopenia in pregnancy–an interdisciplinary challenge. Dtsch Arztebl Int 2015; 112: 795-802
• 24 Rath W. Das HELLP-Syndrom – eine interdisziplinäre Herausforderung. Dtsch Arztebl International. 1998; 95 A-2997
• 25 Abou-Dakn M. Microangiopathy during pregnancy: HELLP/aHUS/TTP taking COVID-19 in pregnancy into account. 2022
• 26 Mjahed K, Charra B, Hamoudi D. et al. Acute fatty liver of pregnancy. Arch Gynecol Obstet 2006; 274: 349-353
• 27 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
• 28 Pecks U, Rath W, Kleine-Eggebrecht N. et al. Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies. Geburtshilfe Frauenheilkd 2016; 76: 799-808
• 29 Contini C, Winkler BS, Maass N. et al. Concomitant intrauterine growth restriction alters the lipoprotein profile in preeclampsia. Pregnancy Hypertens 2019; 15: 154-160
• 30 Contini C, Jansen M, Konig B. et al. Lipoprotein turnover and possible remnant accumulation in preeclampsia: insights from the Freiburg Preeclampsia H.E.L.P.-apheresis study. Lipids Health Dis 2018; 17: 49
• 31 Wetzka B, Hoffmann MM, Friedrich I. et al. Transient remnant removal disease in acute fatty liver of pregnancy. Hypertens Pregnancy 2004; 23: 143-153