Case 2 -
Resolving Acute Fatty Liver of Pregnancy Complicated by HELLP Syndrome
Charles R. Lassman
UCLA Center for Health Sciences
Los Angeles, California
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The patient is a 22 year old woman, G3P1, S/P C-section for full-term pregnancy, transferred to UCLA
Medical center with deep jaundice and acute liver failure. There was no prior history of liver
disease. She was approximately 38 weeks gravid when she noted ankle swelling and elevated blood pressure
was detected. There was no pruritus and no alteration in mental status. She presented to a local
Medical Center (1 week prior to transfer) with an approximately 1-week history of increasing jaundice.
Upon admission, she was noted to be deeply jaundiced and anemic. The fetus was bradycardic. A STAT
C-section was performed, and the baby was reported to be doing well
Following delivery, she developed hypotension and was transferred to the ICU for close monitoring.
There, she was given PRBC's and FFP for anemia and coagulopathy. She remained afebrile. On
post-operative day #1, she was noted to be somewhat lethargic. Her serum bilirubin continued to rise,
though her transaminases remained low. She developed progressive thrombocytopenia to 43,000. She was
started on IV antibiotics. Over the subsequent days, her coagulopathy progressed with increasing jaundice requiring supportive transfusions. Her renal function progressively worsened. She
also developed increasing abdominal distention and discomfort. Paracentesis revealed bloody fluid
without obvious infection. In view of her worsening clinical picture, she was transferred for a higher level of care. The clinical
differential diagnosis included acute fatty liver of pregnancy and HELLP syndrome. Over the ensuing
week, the coagulopathy worsened, renal function deteriorated, encephalopathy developed and the bilirubin
continued to rise. The AST and ALT remained mildly elevated. The patient underwent orthotopic liver
transplantation approximately 2 weeks following her initial presentation. A summary of lab values is
| ||OLT-14 days ||OLT-7days ||OLT - 1day|
|AST ||51 ||81 ||87|
|ALT ||38 ||32 ||41|
|Total bili ||20.7 ||34.3 ||41.5|
|Alk phos ||333 ||252 ||173|
|HCT ||30.5 || || |
|PLTS ||75 || || |
|WBC ||11.7 ||30.6 || |
Major causes of hepatic dysfunction in late pregnancy
Acute fatty liver of pregnancy is the most serious of the pregnancy related liver diseases.
Without treatment the maternal and fetal mortality rate was as high as 80%
increasing recognition, earlier diagnosis and recognition of more mild forms of the disease, the
mortality rate for both mother and fetus has decreased to 5-50%, with one study reporting no deaths in 28
patients . Prompt termination of pregnancy and improvements in supportive care for acute liver
failure are thought to contribute to the improved outlook
- Acute fatty liver of pregnancy
- Toxemia of pregnancy
- HELLP syndrome
- Acute viral hepatitis
The most common clinical presentation is a prodromal illness characterized by pruritus severe vomiting
and jaundice in the final 10 to 4 weeks of pregnancy in a primigravid female. Acute liver failure ensues
with modest elevations of transaminases, bilirubin and doubling of prothrombin time. Many patients will
have hypertension and proteinuria. Jaundice may develop following delivery .
Grossly the liver is yellow, and usually small. Microscopically hepatocytes are swollen and the
cytoplasm is transformed by tiny fat vacuoles
. The vesicles of microvesicular steatosis may be
too small to appreciate on routine stains; in this case, fat stains or electron microscopy may be
necessary . Microvesicular steatosis is most prominent in zone 3, usually involves zones 2 and 3, an
is not infrequently panacinar. While hepatocellular necrosis is not generally prominent,
hepatocellular loss can be demonstrated on the reticulin stain, and indirectly by Kupffer cell
hypertrophy and reduced organ weight. Other less specific features include canalicular and
hepatocellular cholestasis, and mild mixed portal infiltrates with lymphocytes, eosinophils and plasma
cells. Serial biopsies in patients who have survived have demonstrated rapid resolution of
microvesicular steatosis within days of delivery with zone 3 hepatocytes being the last to resolve .
Toxemia of pregnancy includes preeclampsia and eclampsia and is characterized by hypertension,
proteinuria and edema (preeclampsia) and when more severe includes disseminated intravascular coagulation
. Fewer than 50% of patients will have clinical evidence of liver disease, and many of
these patients will have normal biopsies. When jaundice occurs in toxemia it is usually not due to liver
involvement but instead is due to hemolysis. The most characteristic findings are those of DIC with
deposition of fibrin in sinusoids, and focal hepatocellular necrosis of varying degrees, often but not
Portal areas will have minimal infiltrates and arterioles (and larger arteries)
may have evidence of DIC with swollen endothelial cells and mural insudates.
HELLP syndrome or Hemolysis, Elevated
Liver tests, and Low Platelets is seen in a small percentage of patients with preeclampsia/eclampsia. It
may occur a few days following delivery. There is not complete agreement as to whether HELLP is a mild
form of DIC or a subtype of toxemia. The histology is variable ranging from normal, to mild portal and
lobular hepatitis to focal necrosis. Hepatic infarction has been reported
Gross and microscopic description
The liver weighed 1400 grams, was tan/brown without obvious hemorrhage, was vaguely micronodular on
sectioning and dark green upon fixation. Microscopic sections show mild perturbation of lobular
architecture by marked periportal regeneration. Portal areas are expanded and contain mild predominantly
lymphocytic infiltrates. There is an extensive ductal reaction at the interface with numerous
metaplastic appearing ductal structures with gaping lumens containing bile. Zone 1 hepatocytes
demonstrate marked regenerative activity with minimal macro and microvesicular steatosis. Zone 2 and 3
hepatocytes demonstrate moderate macrovesicular steatosis occasional cells with microvesicular droplets,
occasional ballooning, rare necrosis and marked cholestasis with canalicular dilation and rosette
formation. There is patchy zone three hepatocellular drop out, hemorrhage and there is extensive Kupffer
The distinction between AFLP and toxemia is complicated by overlapping clinical findings, and the
evolution or resolution of histologic findings. Because a significant proportion of patients with AFLP
develop toxemia and DIC, histologic findings suggestive of toxemia and DIC do not exclude a diagnosis of
AFLP. As biopsy studies have demonstrated rapid resolution of microvesicular steatosis after
parturition, the absence of diffuse microvesicular steatosis does not rule out AFLP. In Rolfes and
Ishak's 1985 report of 35 cases of AFLP, three types of steatosis were reported: ballooning cells with
droplets too small to be appreciated by light microscopy; microvesicles and macrovesicles. Ballooning in
this context is thought to represent the earliest manifestation of microvesicular steatosis, and
macrovesicular steatosis is thought to result form coalescence of microvesicles over time.
This patient presented with hypertension and peripheral edema and following delivery developed
hemolysis with low platelets consistent with HELLP syndrome and possibly toxemia. Histology demonstrated
minimal microvesicular steatosis and moderate macrovesicular steatosis, mostly in acinar zone 3. Zone
three necrosis/dropout was accompanied by portal tract changes often seen in ischemia. Periportal
fibrin was not appreciated, nor was there extensive periportal hemorrhage. The findings of zone three
dropout and of periportal ductal reaction argue for an element of ischemia most likely secondary to DIC.
Some investigators believe that fatty liver of pregnancy may be part of the spectrum toxemic disease.
In one series , microvesicular steatosis was found in 41 of 41 biopsies performed in preeclamptic
patients. Furthermore, periportal sinusoidal fibrin has been reported in AFLP
. This finding
should not however be surprising as a significant number of patients with AFLP develop toxemia.
Resolving acute fatty liver of pregnancy complicated by HELLP syndrome.
- Arias F, Manchilla-Jimenez R. Hepatic fibrinogen deposits in preeclampsia. Immunofluorescent evidence. N Engl J Med, 1976; 295-578-582.
- Barron WM. The syndrome of pre-eclampsia. Gastroenterol Clin North Am, 1992; 21:851-872.
- Barton JR, Sibai BM. Care of the pregnancy complicated by HELLP syndrome. Gastroenterol Clin North Am, 1992; 21:937-950.
- Burroughs AK, Seong NH, Dojcinov DM et al. Idiopathic acute fatty liver of pregnancy in twelve patients. Q J Med, 1982; 204-481-497.
- Burt AD, Portmann BC, MacSween RNM. Liver pathology associated with diseases and other organs or systems. in Liver Pathology, 4th Edition, 2002; 16:827-883.
- Castro MA, Fasset JM, Reynolds RB, Shaw KJ, Goodwin TM. Reversible peripartum liver failure: a new perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy based on 28 consecutive cases. Am J Obstet Gynecol, 1999; 181:389-396.
- Knox TA, Olans LB. Liver disease in pregnancy. N Engl J Med, 1996; 22:569-576.
- Monga M, Katz AR. Acute fatty liver in the second trimester. Obstet Gynecol, 1999; 93:811-813.
- Minakama H, Oka, N, Sako T, Tamada T, Yasuda T, Hirota N, Preeclampsia: A microvesicular fat disease of the Liver? Am J Obstet Gynecol Jun;40(6):754-60.
- Pockros PJ, Peters RL, Reynolds TB. Idiopathic fatty liver of pregnancy: findings in ten cases. Medicine, 1984; 63:1-11.
- Rolfes DB, and Ishak KG. Acute Fatty Liver of Pregnancy: A clinicopathologic study of 35 cases. Hepatology, 1985; 5:1149-1158.
- Rolfes DB, Ishak KG. Liver disease in pregnancy. Histopathology, 1986 10:555-570.
- Sheehan HL. The pathology of hyperemesis and vomiting of late pregnancy. J Obstet Gynacecol, 1940; 46:658-699.
- Sibai BM, Taslimi MM, El-Nazer A et al. Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia-eclampsia. Am J Obstet Gynecol, 1986; 155:501-509.
- Stone JH. HELLP syndrome: Hemolysis, elevated liver enzymes, and low platelets. JAMA, 1998; 280:559-562.