2. Acute Fatty Liver With Pregnancy Dr. Mohammed Abdalla Egypt, Domiat General Hospital

3. Historical points (AFLP) was first identified by Sheehan in 1940 The name AFLP has replaced earlier terminologies, “acute yellow atrophy of pregnancy” and “acute obstetric fatty metamorphosis of liver”

4. Incidence and Characteristics once in every 7,000 to 11,000 deliveries

5. Acute fatty liver of pregnancy most frequently complicates the third trimester and is commonly associated (or complicated ) with preeclampsia (50 to 100 percent). Riely CA. Hepatic disease in pregnancy. Am J Med 1994;96(1A):18S-22S. 3. Samuels P, Cohen AW. Pregnancies complicated by liver disease and liver dysfunction. Obstet Gynecol Clin North Am 1992;19:745-63 Incidence and Characteristics

6. Incidence : 1/7000 -11,000 Age, (mean, range) 26 (16-39) Primiparous (%): 67 Male baby (%) :60 Onset week of pregnancy :33% (28-38) Mortality (%): ( Maternal )18% - ( Fetal) 47% Incidence and Characteristics

7. Liver Function Tests liver function tests” describes a panel of laboratory tests profiling discrete aspects of liver function No single liver function test is available to quantify liver disease

8. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) evaluate Liver cell injury or necrosis Liver Function Tests Marked ALT elevation (viral hepatitis) Moderate ALT elevation (drug-induced hepatotoxicity, hyperemesis gravidarum, cholelithiasis, HELLP.AFLP.)

9. evaluate liver synthetic function (are depressed in cirrhosis or severe acute liver disease) Liver Function Tests  albumin level  prothrombin time

10.  alkaline phosphatase,  bilirubin,  gamma glutamyl transpeptidase Liver function tests In normal pregnancies, alkaline phosphatase levels may be elevated three- to fourfold, secondary to placental alkaline phosphatase levels evaluate Cholestasis and biliary obstruction

11. Pathogenesis The etiology is not known precisely.

12. A genetic component has been suggested Recent research suggests that AFLP is associated with a Glu474Gln mutation in the long-chain 3-hydroxy acyl-coenzyme A dehydrogenase (LCHAD), a fatty acid β oxidation enzyme. Matern D, Hart P, Murtha AP, Vockley J, Gregersen N, Millington DS, et al. Acute fatty liver of pregnancy associated with short-chain acyl- coenzyme A dehydrogenase deficiency. J Pediatr 2001;138:585-8. [76]. Brackett JC, Sims HF, Rinaldo P, et al. Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency. J Clin Invest 1995;95:2076-82. Pathogenesis

13. CLINICAL PRESENTATION Vomiting 80 Abdominal pain 52 Jaundice 93 Encephalopathy 87 Polydipsia 80 Pruritus 60 Ascitis 47 Symptoms/ Signs %

14. with or without polyuria, frequently is an early symptom in AFLP. Bourl iere M, Berman J, Ducrotte S, et al: Polyuro- polydipsie et steatose hepatique aigue gravidique. Discussion a propos d'un cas. J Gynecol Obstet Biol Reprod 18:79, 1989 Cammu H, Velkeniers B, Charels K, et al: Idiopathic acute fatty liver of pregnancy associated with transient diabetes insipidus polydipsia,

15. The patient may drink 2 or 3 liters of liquids overnight. it often exceeds the magnitude of vomiting. It has been interpreted as a transient diabetes insipidus. polydipsia,

16. After hours or a few days, some patients become lethargic and may decline into hepatic coma, or milder degrees of mental impairment. Lethargy and encephalopathy

17. ascitis Usually transient and rarely prominent.

18. After delivery, most patients improve slowly, and a full clinical and laboratory recovery may take from 1 to 4 weeks. But marked deterioration after delivery has been observed

19. LABORATORY FEATURES Liver test abnormalities  conjugated hyperbilirubinemia (usually between 5 and 15 mg/dL)  increased alkaline phosphatase (normal <170)  and modest increases in serum aminotransferases normal <50 (usually<1000 IU/L)  Leukocytosis occurs commonly  thrombocytopenia  decreased clotting factors  Hypoglycemia and renal dysfunction

20. Histopathology fatty metamorphosis by liver biopsy: Sherlock S. Acute fatty liver of pregnancy and the microvesicular fat diseases. Gut 1983;24:265-9.  The hepatic architecture is intact and the lobules are swollen with compressed sinusoids  Centrilobular microvesicular fatty infiltration of hepatocytes  ballooning of hepatocytes

21. In contrast with viral hepatitis and other common causes of fulminant hepatic failure, necrosis of hepatocytes is always minor. Vigil-De Gracia P, Lavergne JA. Acute fatty liver of pregnancy. Int J Gynaecol Obstet 2001;72:193-5. Histopathology

22. Complications  cerebral edema,  renal failure (60%),  hypoglycemia (53%),  infections (45%)  gastrointestinal hemorrhage (33%),  coagulopathy (30%),  fetal death  severe postpartum hemorrhage

23. The upper gastrointestinal hemorrhage may be caused by Mallory-Weiss syndrome, acute gastric or duodenal lesions (e.g., gastritis, duodenitis, peptic ulcers), or it can be a manifestation of a coagulopathy. Cano RI, Delman MR, Pitchumoni CS, et al: Acute fatty liver of pregnancy. Complication by disseminated intravascular coagulation Killam AP, Dillard SH, Patton RC, et al: Pregnancy-induced hypertension complicated by acute liver disease and disseminated intravascular coagulation. Am J Obstet Gynecol 123:823, 1975

24. renal involvement is less severe than with toxemia (a mild proteinuria,mild edema and a mild increase in blood urea nitrogen and creatinine).

25. When renal failure is aggravated, it usually is impossible to distinguish from toxemia.

26. A severe hypoglycemia often appears at any stage of the disease, or even during clinical recovery.

27. Ascites, detected clinically or by ultrasound, is transient and rarely prominent.

28. Maternal mortality (18%) usually is attributed to one of its complications (gastrointestinal hemorrhage, bleeding disorder, renal failure, acute pancreatitis) but not to liver failure alone.

29. It often is impossible to immediately perform a liver biopsy in pregnant patients with severe coagulation abnormalities. next

30. Therefore, in many cases, it is necessary to rely on the clinical and laboratory data and, in the physician's and obstetrician's experience, next

31. the emergency therapeutic decisions usually are made without waiting for a histologically proven diagnosis.

32. Liver biopsy is not indicated for diagnosis Riely CA, Latham PS, Romero R, Duffy TP. Acute fatty liver of pregnancy. A reassessment based on observations in nine patients. Ann Intern Med 1987;106:703-6.

33. Ultrasound is most important in the exclusion of biliary tract disorders, but its value and the value of CT and MR imaging, has been considered limited and not helpful for the diagnosis and management of patients with AFLP. Castro MA, Ouzounian JG, Colletti PM, et al: Radiologic studies in acute fatty liver of pregnancy. A review of the literature and 19 new cases. J Reprod Med 41:839, 1996

34. The mild jaundice. and modest increase in serum aminotransferases are important signs the diagnosis of. fulminant hepatitis (viral or toxic).

35. the mild increase in blood pressure, hyperuricemia, and the intense thirst are in fulminant hepatitis. and they favor the diagnosis of acute fatty liver of pregnancy.

36. No specific treatment

37. All patients should be hospitalized as soon as the diagnosis of AFLP is suspected

38. Moderate or severely affected patients (encephalopathic, deeply jaundiced, with a prothrombin time less than 40% of the control), or with any extrahepatic complications, should be attended in intensive care units.

39. it seems convenient to maintain glucose infusions. Because of the risk of a sudden hypoglycemia until a full metabolic recovery is obtained.

40. Two laboratory tests: prothrombin time and blood glucose, should be repeated at least daily, Prothrombin time helps to assess the prognosis of liver failure, and blood glucose detects a severe hypoglycemia.

41. Pregnancy termination ( yes OR no ) ( yes OR no ) next

42. importance of interrupting pregnancy may seem questionable, next

43. As it noticed in some patients that the disease does not immediately improve after delivery next

44. But also that no patient has yet been reported with a recovery before delivery. next

45. Vanjak D, Moreau R, Roche-Sicot J, et al: Intrahepatic cholestasis of pregnancy and acute fatty liver of pregnancy. An unusual but favorable association? Gastroenterology 100: 1123, 1991 Riely CA: Liver diseases of pregnancy. In Kaplowitz N (ed): Liver and biliary diseases, ed 2. Baltimore, Williams & Wilkins, 1996, p 483 Reyes H, Sandoval L, Wainstein A, et al: Acute fatty liver of pregnancy: A clinical study of 12 episodes in 11 patients. Gut 35:101, 1994 Hou SH, Levin S, Ahola S, et al: Acute fatty liver of pregnancy. Survival with early cesarean section. Dig Dis Sci 29:449,1984

46. AFLP should be suspected when persistent vomiting, malaise, encephalopathy or jaundice appear in the final weeks of pregnancy or in the early puerperium.

47. Diagnosis is mainly based on clinical and laboratory grounds. Liver biopsy is usually confirmatory,if done.. the emergency therapeutic decisions usually are made without waiting for a histologically proven diagnosis.

48. AFLP is a medical and obstetric emergency because of the metabolic alterations and complications and because of the impending need to interrupt pregnancy.

49. close surveillance of future pregnancies in patients affected previously by this disease is recommended.

50. an impaired fatty acid metabolism during childhood. may affect babies born of pregnancies with AFLP.

51. Thank You Dr. Mohammed Abdalla EGYPT, Domiat general hospital