the age - standardized incidence is approximately 1 per 100,000 women in the united states and few cases have been reported since 1957.2- 
 4 hcc is aggressive during pregnancy and has a poor prognosis with an overall one - year survival of 23% , which could be explained by two main etiologies : estrogen elevation which accelerates the evolution of hcc and immune suppression during pregnancy . we present a case of hcc in a 41-year - old pregnant patient who referred to our academic hospital with abdominal pain , icter , laboratory features of microangiopathic hemolytic anemia and low alpha fetoprotein ( afp ) . a 41-year - old pregnant woman referred to our hospital in the 22nd week of gestational age with right upper abdominal pain and jaundice . she had mild abdominal pain six weeks before presentation which was aggravated one week before admission . four days before admission , she had icter , tea colored urine and edema in her lower extremities . she had nausea and vomiting but no headache , blurred vision or bleeding was mentioned . a past history was remarkable for two abortions and one live birth prior to this pregnancy . she took only ferrous sulfate and aspirin in this pregnancy and no other drugs , herbal medicines or oral contraceptives ( ocps ) . there was no history of blood transfusion , hepatitis or exposure to aflatoxin in her past history however her father died from hcc due to hepatitis b virus ( hbv ) . laboratory investigations showed features of microangiopathic hemolytic anemia that included schistocytes , elevated prothrombin time and erythrocyte sedimentation rate ( esr ) , and negative viral markers(negative hbsag and hbcab ) . differential diagnoses of hellp syndrome , thrombotic thrombocytopenic purpura ( ttp ) or acute fatty liver of pregnancy ( aflp ) were made for further evaluation and management . her blood pressure was 110/70 mmhg with a pulse rate of 110 beats / min , respiratory rate about 18/min and oral temperature of 37c . her abdomen was tender , particularly in the right upper quadrant , but without rebound and guarding . lower extremities had 3 + pitting edema and there were ecchymotic lesions at previous injection sites . blood electrolytes were normal but there was direct hyperbilirubinemia and liver enzymes showed a cholestatic pattern . peripheral blood smear showed features of microangiopathic hemolytic anemia that included target cells , tear drop and nucleated rbcs , and numerous schistocytes . urine analysis was positive for microscopic hematuria and proteinuria.a 24-hour urine collection showed 226 milligrams of protein . viral markers of hbv and hcv , autoantibodies and adisintegrin - like and metalloproteinase with thrombospondin type 1 motif ( adamts)-13 antigen and antibody ( markers for thrombotic thrombocytopenic pupura = ttp ) were all negative . afp level was 90.7 and cancer antigen 125 ( ca125 ) titer was > 1000 . transabdominalsonography showed a normal fetus with a gestational age of about 23 weeks and normal amniotic fluid in the breech position . no lesion was noted in the portal vein , which had a diameter of 10 mm . a possible diagnosis of hellp was made and supportive care for correction of coagulation disorder with fresh frozen plasma ( ffp ) and corticosteroids were administrated . because of deterioration in her mental state in conjunction with an increased bilirubin level and international normalized ratio ( inr ) , the pregnancy was terminated . vaginal delivery was not possible because of the patient s decreased mental state so a cesarean section was performed . the fetus was delivered and transferred to nicu but expired because of immaturity . at laparotomy , approximately one liter of ascitic fluid was noted in the abdomen and the liver had multiple malignant appearing mass lesions , which were biopsied with wedge resection . surgical specimen of the liver showed pleomorphic appearances that confirmed hepatocellular carcinoma ( hcc ) ( arrows ) . after delivery the patient experienced progressive loss of conscious along with multi - organ failure and unfortunately died after a few days . hcc during pregnancy is very rare and only 48 cases have been reported since roddie s first report in 1957 until 2010 according to a pubmed literature review . the incidence of hcc in pregnant women is about 1 per 100,000 , of which most reside in africa and asia . according to the literature , the mean age of pregnant women with hcc was 28.94.4 years after 1995 . these women had fewer pregnancies , fewer signs and symptoms , and higher survival rates compared to women diagnosed before 1995 who were older ( 31.47.2 years ) , diagnosed late in pregnancy and many of whom received no curative treatment . choi et al . have shown that in the african or asian race , particularly among the chinese , hbv and ocps are the main etiologies for hcc during pregnancy . our case had negative hbsag , hbcab , and hcv ab levels and had no past history of ocp consumption . our case was 41 years old and diagnosis was made in during the fourth pregnancy . the risk of hcc increases with parity4 as shown in the present case but is very low in those who are hbsag non - carriers , with an incidence of 0.55 per 100,000 in women reported by fwuet al . hcc is rare during pregnancy because of the lower incidence of hcc in women during the reproductive years and infertility that is due to cirrhosis . pregnancy may have an adverse effect on the progression of hcc because of the effects of estrogen viral hepatitis carcinogenesis , however some authors disagree . late menopause , early menarche , ocps and multiparity have been reported as risk factors for hcc , again suggestive of the negative impact of pregnancy on hcc . estrogen can increase hepatocyte mitosis , hypervascularity , free radicals , reactivate hbv and decrease humoral immunity.11 , 
 12 
 
 hcc is asymptomatic in its early stages during pregnancy but right upper quadrant pain or the presence of a mass , weight loss and hepatomegaly have been the most frequent presentations , however our case presented with nausea and vomiting and abnormal liver enzymes which have been rare in reported cases ( each , 6.4% in the literature ) . our patient had hemolytic microangiopathic anemia , which was not found in previous cases and had no history of weight loss . in addition , a family history of hcc was only found in 8% of cases3 , which again was present in our case . 
 
 in our case , the afp level was about 90ng / ml and unusual for hcc . maternal afp levels are used to screen for down syndrome or neural tube defects and it has been suggested that elevated afp in a pregnant patient with a normal fetus is indicative of maternal disease , particularly hcc . however afp screening for hcc lacks sensitivity because it depends on maternal weight , age , diabetes and ethnicity . previous studies have shown that 10% of pregnant women can have hcc with normal afp levels and 55.3% have afp levels less than 400 ng / ml , thus afp alone has a high positive predictive value . ca 125 , which is primarily used for ovarian cancer could be rarely elevated in hcc ; elevations more than 1000ng / dl as seen in our patient have been previously reported . other laboratory abnormalities that include hyperbilirubinemia , prolonged of prothrombin time and hypoalbuminemia , which were present in this case have been reported in less than 10% of previous studies . 
 
 our patient also had multiple lesions and her barcelona clinic liver cancer staging system ( blcl staging ) was stage 4 . choi et al . reported 33.3% of their patients had multiple lesions and 21.7% were blcl stage 4 . liver resection is the best management if possible but in cases such as ours termination of pregnancy as soon as possible is recommended.1 
 , 
 3 improvement in the surgery methods would result in a three - year survival rate of 62.5% and the potential for uneventful pregnancy in such cases . hcc during pregnancy has a poor outcome and 20% of patients have distant metastasis at presentation according to previous reports , however fibrolamellar hcc has a better prognosis . delivery was by cesarean section in 44.82% and live births were present in only 58.7% cases . unfortunately our patient and her fetus both died soon after diagnosis and cesarean section . 
 
 as conclusion , those with a family history of cancer should be more closely worked up , even if they present with unusual manifestations .