Acute fatty liver of pregnancy (AFLP) is an idiopathic disorder with an unknown cause occurring in late pregnancy. The treatment in these patients is often immediate termination of pregnancy, and plasmapheresis provides an effective treatment option. In this paper, we introduce three pregnant women treated with plasmapheresis. The first case was a 22-year-old primigravida woman treated with 22 sessions of plasmapheresis due to AFLP, hepatic and renal failure, coagulopathy, and ventilator-dependent respiratory failure. The second case was a 23-year-old woman in her second pregnancy treated with 4 plasmapheresis sessions due to AFLP, hepatic and renal failure, coagulopathy, and hypoglycemia. The third patient was a 23-year-old primigravida woman treated with 3 plasmapheresis sessions due to AFLP, renal failure, and coagulopathy. Plasmapheresis can be a life-saving treatment in patients with AFLP and is strongly recommended for patients with severity of their disease accompanied by other organ disorders. In addition, shortening the time interval between the termination of pregnancy and initializing plasmapheresis improves the outcome and reduces the duration of hospital stay and sessions of plasmapheresis.
Acute fatty liver of pregnancy (AFLP) was first described in 1940 [
AFLP is associated with high maternal and fetal mortality rates which are reported as 7–85% in different studies. In cases of acute fatty liver of pregnancy, the classic treatment after pregnancy termination includes protective procedures like the modification of anemia and hypoglycemia, electrolyte regulation, acidosis correction, fat-soluble vitamins replacement, and correction and replacement of coagulation factors, but sometimes there is a need for the liver transplant. Even with these procedures, improvement needs long duration which may take several days to weeks [
Plasmapheresis is one of the newly introduced treatments which can be very effective [
A 22-year-old woman, G1 P1, at 37 weeks gestational referred with nausea, abdominal pain, and vaginal bleeding. After evaluating and performing laboratory tests (Table
Laboratory data of the first patient.
Admission day | 1 | 2 | 8 | 9 | 15 | 22 | 27 | 29 | 43 |
Plasmapheresis session | — | — | 1 | 2 | 8 | 15 | 20 | 22 | — |
PT (sec) | 22 | 21 | 22.9 | 18 | 13.3 | 12 | 14.2 | 13.3 | 12 |
INR | 2.3 | 2.2 | 3 | 2.2 | 1.2 | 1 | 1.3 | 1.2 | 1 |
PTT (sec) | 55 | 50 | 43 | 45 | 32 | 26 | 27 | 25 | 23 |
WBC (×103/mm3) | 27 | 32.1 | 30.2 | 26.4 | 15.8 | 14.5 | 13.2 | 14 | 15.7 |
Hemoglobin (g/dL) | 9.1 | 9.3 | 6 | 9.4 | 8.8 | 10.8 | 12.3 | 12 | 11.5 |
Platelet (×103/mm3) | 61 | 43 | 39 | 54 | 43 | 91 | 133 | 220 | 348 |
Glucose (mg/dL) | 110 | 87 | 90 | 156 | 189 | 200 | 167 | 250 | 160 |
Total bilirubin (mg/dL) | 9 | 10 | 8.5 | 9.5 | 5.4 | 2.8 | 2 | 1.3 | 1.2 |
Direct bilirubin (mg/dL) | 6.8 | 6.8 | 5.9 | 7.2 | 3.2 | 1.6 | 1.2 | 0.6 | 0.5 |
LD (U/L) | 952 | 1050 | 1120 | 870 | 546 | 711 | 458 | 420 | 325 |
AST (U/L) | 178 | 150 | 71 | 60 | 55 | 65 | 40 | 30 | 32 |
ALT (U/L) | 186 | 130 | 42 | 50 | 24 | 35 | 28 | 29 | 27 |
Creatinin (mg/dL) | 1.2 | 3.1 | 3.1 | 0.8 | 0.7 | 0.8 | 0.9 | 0.7 | 0.6 |
Ascites | + | + | + | + | − | − | − | − | − |
PT: prothrombin time.
INR: international normalized ratio.
PTT: partial thromboplastin time.
WBC: white blood cell.
LD: lactate dehydrogenase.
AST: aspartate aminotransferase.
ALT: alanine aminotransferase.
The patient was a 32-year-old woman, G2 P1, at 34 weeks gestation, applied to the emergency department with complaints of abdominal pain and nausea. At initial evaluation and laboratory tests (Table
Laboratory data of the second patient.
Admission day | 1 | 2 | 3 | 7 | 8 | 10 | 11 |
Plasmapheresis session | — | — | — | 1 | 2 | 3 | 4 |
PT (sec) | 20 | 18.7 | 19 | 16.7 | 15.5 | 14.2 | 13 |
INR | 2.7 | 2.1 | 2.6 | 2 | 1.8 | 1.4 | 1.2 |
PTT (sec) | 60 | 39 | 38 | 39 | 30 | 38 | 30 |
WBC (×103/mm3) | 16000 | — | — | — | — | — | — |
Hemoglobin (g/dL) | 10.2 | 9.2 | 9.8 | 9.5 | 8.5 | 9 | 9.5 |
Platelet (×103/mm3) | 153000 | 81000 | 77000 | 63000 | 94000 | 132000 | 190000 |
Glucose (mg/dL) | 80 | 50 | 44 | 60 | 114 | 120 | 122 |
Total bilirubin (mg/dL) | 9.8 | 11.2 | 16.3 | 16.9 | 15.9 | 11.8 | 7.3 |
Direct bilirubin (mg/dL) | 4.8 | 4.4 | 4.4 | 6 | 5.6 | 3.1 | 1.9 |
LD (U/L) | 671 | 654 | 602 | 558 | 426 | 520 | 420 |
AST (U/L) | 191 | 124 | 142 | 136 | 38 | 47 | 30 |
ALT (U/L) | 217 | 169 | 136 | 126 | 83 | 42 | 20 |
Creatinin (mg/dL) | 1.7 | 2.1 | 2.6 | 2.2 | 1.6 | 1.4 | 0.9 |
Ascites | + | + | + | + | + | − | − |
A 23-year-old woman, G1 P1, at 36 weeks gestation referred to the emergency department due to abdominal pain and nausea. Laboratory tests (Table
Laboratory data of the third patient.
Admission day | 1 | 2 | 4 | 7 | 8 |
Plasmapheresis session | 1 | 2 | 3 | — | — |
PT (sec) | 18 | 17.1 | 13 | 12 | 12 |
INR | 1.9 | 1.8 | 1.2 | 1 | 1 |
PTT (sec) | 50 | 41 | 30 | 32 | 28 |
WBC (×103/mm3) | 16000 | 17000 | 14000 | 12000 | 12500 |
Hemoglobin (g/dL) | 9.2 | 8.2 | 9.9 | 10 | 10.5 |
Platelet (×103/mm3) | 60000 | 80000 | 120000 | 130000 | 194000 |
Glucose (mg/dL) | 80 | 120 | 160 | 150 | 114 |
Total bilirubin (mg/dL) | 3.6 | 1.7 | 1 | 1 | 1 |
Direct bilirubin (mg/dL) | 2 | 0.5 | 0.3 | 0.4 | 0.4 |
LD (U/L) | 813 | 728 | 506 | 490 | 281 |
AST (U/L) | 370 | 124 | 32 | 25 | 19 |
ALT (U/L) | 596 | 331 | 53 | 31 | 10 |
Creatinin (mg/dL) | 1.9 | 1.5 | 1.3 | 1.2 | 0.9 |
Ascites | + | + | + | − | − |
The exact cause of AFLP and its pathogenesis is unknown yet but there is a well-established association between AFLP and inherited defects in beta-oxidation of fatty acids. This connection is empirically supported by similar clinical and histological findings in patients with AFLP and those with Jamaican vomiting sickness, a liver disease caused by a toxin in unripe ackee fruit that disables intramitochondrial beta-oxidation of fatty acids. AFLP may develop regardless of maternal genotype if the fetus is deficient in LCHAD and carries at least one allele for the G1528C mutation [
These changes result in diffuse infiltration of fat in hepatic cells, hepatocyte swelling, slight necrosis, and inflammation of hepatic cells. The lobar structure of the liver is somewhat intact, but it can be associated with varying degrees of hepatic failure and the failure of other organs such as the brain, renal, and pancreas [
To confirm the diagnosis (based on Swansea’s criteria), the patient must have at least 6 of the following symptoms: nausea, abdominal pain, polydipsia/polyuria, encephalopathy, hypoglycemia, hyperuricemia, leukocytosis, ascites, increased hepatic aminotransferase and bilirubin, ammonia increase, renal failure, coagulopathy (increased prothrombin time) and microvesicular steatosis in liver biopsy, metabolic acidosis, and pancreatitis [
The initial treatment after diagnosis is pregnancy termination. However, it has been reported that after the termination of pregnancy, the severity of icter increased [
Plasmapheresis can replace a patient’s plasma by a donor plasma and remove lots of harmful substances in the bloodstream. It also replaces the coagulating factors, albumin and biologically active substances that normally have to be carried out by the liver cells. Consequently, it can be considered equivalent to an artificial liver, and, in addition, in this method, high amounts of FFP can be injected to patients without concern of increased volume [
This therapy had been used in myasthenia gravis, lupus syndrome (antiphospholipid), severe preeclampsia (HELLP syndrome), and thrombotic thrombocytopenic purpura [
Comparison of similar studies.
Variables | Author | ||||
---|---|---|---|---|---|
Tang | Jin | Chu | Martin | Current study | |
Publication year | 2012 | 2012 | 2012 | 2008 | 2012 |
| |||||
Number of cases | 28 cases in two groups | 39 | 11 | 6 | 3 |
| |||||
Patient characteristics | 13 treatment with plasmapheresis |
19 renal failure |
All cases had liver and renal failure and coagulopathy |
4 encephalopathy |
First patient: hepatic and renal failure, encephalopathy, ventilator dependency and DIC |
| |||||
Time of plasmapheresis initiation after pregnancy termination | 6 hours later | 1–5 days later | 0–3 days later | 2 days later | First patient: 8 days |
| |||||
Number of plasmapheresis sessions | 1–3 | 1–4 | 2–8 | 2–4 | First patient: 22 |
| |||||
Results | Obvious reduction in liver function recovery time, hospital stay and ICU admission duration with plasmapheresis |
37 treatment |
10 treatments |
Complete recovery in all patients |
Plasmapheresis in theory can lead to the removal of ammonia, endotoxins, bilirubin, and inflammatory cytokines from the circulation that must be performed by liver cells. Also, injection of large volumes of FFP in this method can help to improve the DIC and removing renin angiotensin and other vasoactive factors may improve renal function [
There are few studies about this therapeutic method in AFLP patients (Table
In another article in 2012 by Chu et al., 11 AFLP patients were plasmapheresed and 10 patients were treated [
They found that plasmapheresis improved the amount of Creatinine, BUN, total bilirubin, AST, and ALT, and this difference was statistically significant (
In another important study in this issue, Tang et al. compared two groups of AFLP patients. They treated 13 patients with plasmapheresis and 15 patients with injected cultured liver cells assigned in case and control groups. They stated that treatment with plasmapheresis increased the speed of liver function improvement and reduced the length of ICU and hospital stay, but the rate of morbidity and mortality was equal in both groups [
The important finding of this paper was obtaining promising results for early initiation of plasmapheresis within 6 hours after delivery. According to the above research and reports of the patients in our study, it seems that performing immediate plasmapheresis in patients suffering from AFLP, especially in the severe form, can be an effective and lifesaving therapeutic method and should be considered by the physicians. In addition, shortening the time interval between the termination of pregnancy and initializing plasmapheresis improves the outcome and reduces duration of hospital stay and sessions of plasmapheresis.
The authors would like to thank Mrs. Fatemeh Hosseinzadeh (Clinical Research Development Center) for translating the paper.