848 Part XII HEPATOBILIARY TRACT AND PANCREAS

8. Szmuness W, Stevens CE, Zang EA, et al: A controlled 11. Beasley RP, Hwang L-Y, Stevens CE, etal: Efficacy of he pat i• clinical trial of the efficacy of the hepatitis B vaccine (Hep• tis B immune globulin for prevention of perinatal transmis• tavax B): a final report. Hepatology 1:377-385, 1981 sion of the hepatitis B virus carrier state: Final report of a 9. Maupas P, Chiron JE, Barin F, et al: Efficacy of hepatitis B randomized double-blind, placebo-controlled trial. Hepato• vaccine in prevention of early HBsAg carrier state in chil• logy 3:135-141, 1983 dren. Controlled trials in an endemic area (Senegal). Lancet 12. Tada H, Yanagida M, Michina J, et al: Combined passive and 1:289-292, 1981 active immunization for preventing perinatal transmission 10. Barin F, Goudeau A, Denis F, et al: Immune responses in of hepatitis B virus carrier state. Pediatrics 70:613-619, 1983 neonates to hepatitis B vaccines. Lancet 1:252-253, 1982

129. PREGNANCY AND CHRONIC LIVER DISEASE

William M. Lee

INTRODUCTION contraceptives, with maximal levels reached in the third trimester. One study suggests an increased incidence of Pregnancy in patients with chronic liver disease is infre• fetal wastage in such patients.2 Jaundice may lessen in quent because cirrhosis primarily affects postmenopausal patients with Rotor's syndrome during pregnancy. The women and because younger women with liver disease rare patient with familial benign recurrent intrahepatic frequently are amenorrheic and presumably anovulatory cholestasis may sustain an exacerbation of disease charac• as well. Nevertheless, pregnancy may occur in all stages terized by intense pruritus and jaundice during pregnan• of chronic liver disease, and a careful assessment of the cy or with oral contraceptive therapy. This would be diffi• risk to mother and fetus is necessary in each case. A favor• cult to distinguish from intrahepatic cholestasis of able outcome for the pregnancy is frequently possible but pregnancy except by the history of the patient or other is dependent on the type and severity of the underlying family members having previous attacks of pruritus and condition. Generally, pregnancy does not worsen the jaundice lasting weeks or months and occuring while nei• concomitant liver disease except in certain cholestatic dis• ther pregnant nor receiving contraceptive medication. eases such as primary biliary cirrhosis. In these patients, improvement in the cholestasis can be expected to occur following delivery. Liver blood flow is thought to be un• BILIARY TRACT DISEASE altered in pregnancy, although significant increases in blood volume, fluid retention, and intraabdominal pres• Cholesterol gallstones are more common in women sure characterize the third trimester. The presence of than men in all populations, and one explanation for this esophageal varices has been noted by one author to occur may involve the effects of pregnancy. Pregnancy and oral in normal pregnancy,l and portal pressures during labor contraceptives are considered risk factors for cholelithia• are markedly increased. Despite these theoretical haz• sis, although a strong correlation with multiparity per se ards, earlier recommendations of termination of preg• is not evident. Gallbladder volume is increased twofold in nancy and of sterilization of young women with chronic pregnancy, and contraction following a meal is sluggish liver disease have given way to a more conservative and so that incomplete emptying occurs. 3 This has been sug• expectant approach judged on a case-by-case basis. Al• gested as the reason for the increased frequency of cho• though the natural history of the chronic liver disease lesterol cholelithiasis in previously pregnant women; may not be altered by the pregnancy, it should be borne however, hormonal factors may also be at play. Despite in mind that many such mothers will not live to see their these facts, no increased incidence of cholecystitis or cho• children grow up, and this may merit consideration when langitis is apparent in pregnancy. In one large series, only making recommendations to these patients. 27 of 456 patients with jaundice during pregnancy were found to have biliary obstruction by stones as the cause of their disease. 4 In any case, the diagnosis and manage• THE HYPERBILIRUBINEMIAS ment of biliary tract disease occurring during pregnancy are those accorded the nonpregnant patient. Urgent sur• Congenital hyperbilirubinemias such as Gilbert's gery may be required on occasion for cholangitis or acute syndrome (asymptomatic unconjugated hyperbilirubi• cholecystitis but diagnostic studies requiring standard nemia) usually do not significantly alter the outcome of X-ray techniques are to be avoided where possible. pregnancy for mother or fetus. Pregnancy has been said to improve the mild increase in unconjugated bilirubin seen in patients with Gilbert's syndrome, although this INFECTIOUS DISEASES has not been thoroughly studied. In Dubin-Johnson syn• drome, a further increase in conjugated bilirubin has In general, treatment of suspected chronic liver in• been noted in association with pregnancy and with oral fections such as tuberculosis or other granulomatous dis- N. Gleicher (ed.), Principles of Medical Therapy in Pregnancy © Plenum Publishing Corporation 1985 Chapter 129 CHRONIC LIVER DISEASE 849 eases is not altered by pregnancy, and a liver biopsy may housewives and children are also exposed, usually by certainly be performed during pregnancy if indicated. contact with contaminated water. Cases occurring in Several infections have received particular attention, in• pregnant women have been reported and appear to result cluding amebiasis and herpesvirus infection, because the in increased fetal wastage. Too few cases have been re• course of the disease appears to be more severe in the corded to know whether increased maternal mortality pregnant patient. occurs. Differential diagnosis includes staphylococcal septicemia (which has also been associated with cho• lestatic jaundice), meningitis, viral hepatitis, and Amebiasis acetaminophen overdose. The diagnosis is made by a va• Chronic infection with Entamoeba histolytica fre• riety of serologic tests involving agglutination of live lep• quently causes diarrhea, but even asymptomatic infec• tospires by patient serum. Acute and convalescent sam• tion may become more active during pregnancy because ples are needed. Jaundice appears to be caused by both of altered immunity, humoral factors, or direct pressure intrahepatic cholestasis and hemolysis as well as by on the liver by the gravid uterus. Experimental evidence failure to excrete conjugated bilirubin via the kidneys if suggests that progesterone may promote amebic growth. renal failure is present. Although tetracycline has been Additionally, immunoglobulin levels that are diminished used, penicillin G intramuscularly is the drug of choice during pregnancy may be responsible for an altered im• for the pregnant patient in view of the suggested associa• mune response leading to abscess enlargement. Rupture tion of tetracycline with acute fatty liver of pregnancy. of amebic liver abscesses does occur in pregnancy, usu• ally near term or in the puerperium, and seems to occur more often than in males and nonpregnant females, al• though this has been debated.s THE HEPATIC PORPHVRIAS The clinical presentation begins with the syndrome of "prerupture" characterized by a period of local per• Acute intermittent porphyria (AlP) is characterized itoneal irritation in the right upper quadrant followed by by periodic attacks of abdominal pain, vomiting, sei• frank spillage of abscess contents into the peritoneal cav• zures, and personality change. The diagnosis is fre• ity. Liver scan, serum immune hemagglutination assay, quently missed in the initial medical contact. Drugs in• and aspiration of the cavity under ultrasound guidance cluding barbiturates and estrogens have been implicated may establish the diagnosis in the prerupture period; in initiation of the attacks, and hypertension is a frequent however, frank peritonitis demands surgical exploration concomitant finding. Thus, it is not surprising that this and drainage as well as antibiotic therapy, usually with form of porphyria may go unrecognized or be mistaken metronidazole plus a second broad-spectrum agent. for toxemia in the pregnant patient. The diagnosis of AlP Prognosis for the mother is generally good with prompt is made by use of the Watson-Schwartz test, which iden• diagnosis, but some instances of stillbirth or spontaneous tifies the presence of porphobilinogen in the urine. abortion have occurred. 6 Treatment of the unruptured Whether AlP attacks are precipitated more fre• amebic abscess is with metronidazole. quently by pregnancy is debatable. Likewise, the in• creased maternal mortality suggested by early studies has recently been questioned. In one recent study, only 32% Herpesvirus Infection of patients with AlP had attacks during pregnancy. Fetal Fulminant hepatitis caused by Herpesvirus hominis is a wastage was 16%, which approximates that for the nor• mal population, and no maternal deaths were recorded. 7 rare occurrence in the healthy adult and usually occurs in The disease does not remit with delivery and, if undiag• the setting of severe immune deficiency resulting from high-dose immunosuppressive therapy or leukemia. nosed, may lead to continued symptoms and further use of barbiturates and other sedatives, leading to further Several instances of fulminant herpesvirus infection have occurred in pregnant women, suggesting a role for al• acute attacks. It is noteworthy that use of sedatives dur• tered immune defenses during pregnancy in this disease ing pregnancy may be responsible for the increased fre• as well. The initial presentation is that of a sore throat, lip quency of attacks in such patients. Treatment is mainly ulceration, and signs of systemic toxicity. Cowdry type A symptomatic after removal of any offending agents. Pa• intranuclear inclusions can be seen on liver biopsy or at tients with the rarer hereditary coproporphyria have autopsy. Consideration of liver biopsy and appropriate been found to experience a similar frequency (16%) of culture should be made in patients who develop a hepati• attacks during pregnancy, a figure that is probably not tic picture with antecedent sore throat or lip lesions in increased from that expected for the disease in the non• view of the generally fatal outcome and the possibility pregnant woman. that cytosine arabinoside may be effective once a specific diagnosis is made. WILSON'S DISEASE Leptospirosis Much has been written concerning Wilson's disease Leptospirosis or Weil's disease is characterized by and pregnancy since patients frequently manifest this the sudden onset of nausea, vomiting, fever, and jaun• disease in the reproductive years. 8 (See Chapter 29.) The dice. Hemorrhagic manifestations occur in many organs. disease is characterized by two defects relating to copper Renal failure and cardiac and central nervous system in• metabolism: (1) diminished levels of ceruloplasmin, a volvement also may be present. Although cases were ini• plasma copper transport protein, and (2) abnormal se• tially seen primarily in miners and sewer and abattoir questration of copper in the liver as a result of ineffective workers, exposure to leptospires is now ubiquitous, and biliary copper excretion. Characteristically, the disease is 850 Part XII HEPATOBILIARY TRACT AND PANCREAS initially recognized when signs of acute or chronic hepati• in most instances. Although viruses such as those caus• tis or cirrhosis appear in adolescence or young adults. ing hepatitis B and non-A, non-B hepatitis (see Chapter Mental deterioration and dystonic movements secondary 128) may trigger the initial damage to the liver, the devel• to damage to the basal ganglia herald disease progression opment of a state of chronic liver damage is thought to as copper begins to accumulate secondarily in the brain as involve altered recognition of self-antigens or "autoim• well as the liver. Kayser-Fleischer corneal rings are evi• munity." Such patients have been noted to have autoan• dent in those with significant CNS copper accumulation tibodies such as those directed against smooth muscle but are not evident in many with advanced liver disease. and frequently display extrahepatic manifestations such The liver may not be enlarged; but the spleen is usually as rash, arthritis, colitis, amenorrhea, and Cushingoid quite prominent, and ascites and variceal hemorrhage are body habitus. Since the term chronic hepatitis is applied common complications. The use of penicillamine, which to a wide variety of conditions, it is helpful to classify such increases urinary copper excretion, has significantly al• patients on the basis of severity and presumed etiology, tered the outcome for Wilson's disease patients, and the the group as a whole being referred to as chronic active neurologic manifestations are reversible for the most liver disease (CALD). part. The cirrhosis does not progress further, and im• provement in portal pressures may occur with decreasing Chronic Persistent Hepatitis inflammation once treatment is undertaken. Ceruloplasmin levels increase in pregnancy and with Chronic persistent hepatitis (CPH) is a term that oral contraceptives in Wilson's disease patients as well as characterizes a milder form of chronic liver injury, detect• in normal women. Patients not on therapy with pen• able as slight elevations in transaminase levels in serum icillamine have been said to show improvement in symp• and a characteristic biopsy picture. Such patients have a toms during pregnancy, presumably because the fetus favorable prognosis for remission of their hepatitis, al• removes significant quantities of maternal copper. though it may take months or years. Corticosteroid thera• Since penicillamine therapy is lifesaving and is gen• py is seldom used. As might be expected, pregnancy is erally well tolerated by Wilson's disease patients, it well tolerated by such patients, and no increase in fetal or seems logical to continue such therapy during pregnan• maternal morbidity or mortality or disease activity should cy. However, many drugs are contraindicated for use be seen.!l Exacerbation of disease during pregnancy, during pregnancy, and penicillamine came under suspi• should it occur, might call the diagnosis into question. cion following the birth of an abnormal infant to a moth• er with cystinuria who had been on penicillamine thera• Chronic Active Hepatitis py. The baby was found to have a "connective-tissue defect." Since penicillamine is believed to alter collagen Chronic active hepatitis (CAH) is more common and formation, the drug was implicated. Two series that, more severe than CPH. Since its initial description in the when combined, total 28 mothers and 44 pregnancies 1950s, more subtle forms occurring in the absence of auto• failed to demonstrate any increased maternal or fetal antibodies have become evident, and an association with morbidity or mortality related to penicillamine thera• hepatitis B and with non-A, non-B hepatitis has been py.9,10 In all, two children were born prematurely, and made. The latter represents, in most instances, posttran• one apparently normal child died secondary to pre• fusion hepatitis, which appears in a chronic low-grade maturity. One mother died at 7 months post-partum as a form leading to cirrhosis and in which markers for hepati• result of progression of her liver disease. tis B and for hepatitis A are notably absent. As with hepa• Recommendations based on these observations titis B, sporadic cases may occur, and a carrier state is would include therapeutic abortion for the mother with thought to be present, but no serum markers for this severe liver disease or documented variceal hemor• infection have been consistently detected. However, rhage. Penicillamine should be continued in the usual both of these conditions are unusual in pregnancy since dose throughout the pregnancy unless cesarean section patients with hepatitis B tend to be males, and those with is contemplated, in which case the dose is reduced to non-A, non-B hepatitis are frequently older and have 0.25 g in the third trimester so as not to hinder postoper• usually received transfusions for major surgery. This is ative wound healing. No clear risk to the fetus can be an important consideration since in contrast to "autoim• attributed to penicillamine at the present time, and pre• mune" CAH, these forms are not generally considered to vention of relapse in this condition is a reasonable goal. be as amenable to treatment with corticosteroid therapy Maternal mortality in treated or untreated Wilson's dis• as is the autoimmune type. ease appears to be a function of the severity of the Most typically, the young nonpregnant female pa• hepatic injury, which may not at all times be fully appre• tient with autoimmune CAH presents with several weeks ciated. Nevertheless, pregnancy is well tolerated by the of fatigue, anorexia, and mild jaundice. Amenorrhea may well-treated and compensated patient and should be ante cede all other symptoms and suggests chronicity. viewed optimistically in light of the nearly normal life• This is often confirmed by the finding of established cir• span for most treated patients. rhosis in addition to portal tract inflammation in the initial liver biopsy. Most disease manifestations will re• spond promptly to prednisone in doses of from 20 to 60 CHRONIC HEPATITIS mg/day, although the cirrhotic features do not improve. Azathioprine is often added in a dose of 50-100 mg/day Young women make up the largest single group of since it appears to be steroid sparing though ineffective patients with chronic hepatitis and nonalcoholic cir• by itself. With remission, normal menstrual cycles and rhosis. The pathogenesis of the liver damage is unknown improved fertility return. Despite treatment, cirrhosis Chapter 129 CHRONIC LIVER DISEASE 851 often progresses, although complete remiSSIOns are ters in lieu of portacaval anastomotic surgery; however, sometimes seen in early cases without established fibro• reports of its use in pregnant patients have not appeared sis, and prednisone may at times be discontinued with• thus far, and its place in the therapy of variceal bleeding is out subsequent relapse. still unclear. Since conception is unlikely in patients with severe Ascites does not occur with greater frequency in CAH, most pregnant patients with CAH have milder dis• pregnancy despite the tendency to increased fluid ac• ease. Pregnancy does not appear to result in worsening of cumulation. Development of abdominal fluid is probably the hepatitis, nor does it significantly improve it. Mater• limited by the already increased intraabdominal pres• nal mortality is increased in patients with chronic active sure, at least during the latter stages of pregnancy. Di• hepatitis when cirrhosis is present but not above that uretics may be used, the most satisfactory of which is expected for the disease in the nonpregnant woman. generally spironolactone. Hepatic encephalopathy is Spontaneous abortion rates (less than 20 weeks) approxi• usually engendered in the cirrhotic not by worsening mate those of the normal population; however, increased liver function but by injudicious use of sedatives or by fetal wastage and prematurity occur as with other forms gastrointestinal hemorrhage, infection, constipation, or of cirrhosis. 12, 13 Based on these considerations, the use of diuretic therapy, all of which are amenable to manage• prednisone should be dictated by the need to control the ment. Lactulose or neomycin may be used to diminish liver disease and should remain otherwise unaltered gut absorption of nitrogenous components, but attention throughout the pregnancy. Generally, doses of 15-20 mg to the cause of the decompensation is equally important. daily can be tolerated during pregnancy without any dif• ficulty. Although some evidence of teratogenicity has been noted with azathioprine in experimental animals, EXTRAHEPATIC PORTAL VEIN OBSTRUCTION none has been reported in man. Nevertheless, its use in pregnancy is discouraged since the disease is generally This uncommon condition may be caused by mild, and increased doses of corticosteroid may be sub• omphalitis and umbilical vein thrombosis leading to por• stituted if necessary for the limited duration of the tal vein thrombosis in the neonatal period.14 Intermittent pregnancy. variceal hemorrhage, usually beginning in the second As with Wilson's disease, termination of pregnancy decade of life, may continue over many years with rela• is seldom indicated. The one exception is for cases with tively good preservation of liver function. Although the evidence of severe hepatic decompensation (encepha• cause of the portal vein occlusion may be apparent in lopathy, ascites, variceal hemorrhage, jaundice), but those with known umbilical vein infections or abdominal such patients, as noted above, are infrequently pregnant. Portacaval shunts have been performed in such patients trauma, the majority of cases of extrahepatic portal vein obstruction (EHPVO) are idiopathic. Portal vein block successfully. The prognosis for a full life is probably may also occur in the setting of advanced cirrhosis of any somewhat less than for the treated patient with Wilson's disease, although very variable in this condition. cause, and the prognosis for such patients is poor. Other causes of extrahepatic portal vein occlusion include schistomiasis, which produces a portal fibrosis, and "pre• hepatic" portal hypertension with splenomegaly and CIRRHOSIS variceal bleeding. Except for the cirrhotic patient, those with EHPVO typically have nearly normal liver function Most series describing the outcome of pregnancy in tests and tolerate surgery quite well. These patients are cirrhosis include all forms of cirrhosis together without regard to the probable causes. Patients with Laennec's good candidates for portacaval anastomoses except that technical difficulties will be encountered in finding a suit• cirrhosis are likely to fare worse than those with inactive able vessel if the main portal channels are thrombosed. cryptogenic cirrhosis or primary biliary cirrhosis, but ac• curate figures are not available. Maternal health will be Fertility of patients with EHPVO is near normal un• generally well preserved through most pregnancies if the less cirrhosis is present, and the number of expected cirrhosis is reasonably compensated. However, in• spontaneous abortions and stillbirths approaches that for creased fetal mortality (as high as 30-40%) characterizes the general population. Variceal hemorrhage is the com• all forms of cirrhosis. mon complication of this condition but does not appear The most dreaded complication in all cirrhotic pa• with particularly increased frequency during pregnancy. tients is variceal hemorrhage. This is not thought to occur Management is similar to that for such patients in the with increased frequency in pregnancy, although this nonpregnant state. would intuitively seem likely. The current therapy for acute variceal hemorrhage includes stabilization with blood and blood products, early endoscopy, and intra• HEPATIC VEIN THROMBOSIS (BUDD-CHIARI venous pitressin therapy. The latter might be prohibited SYNDROME) because of the possibility of inducing labor, but the alter• native, Blakemore-Sengstaken balloon tamponade, is Acute hepatic vein thrombosis is characterized by also dangerous in view of its frequent association with right upper quadrant pain from acute hepatic enlarge• aspiration and poor results in inexperienced hands. ment and rapid onset of ascites in previously healthy in• When these measures are needed to stem the massive dividuals. A strong association has been established be• hemorrhage typical of such patients, one or the other tween hepatic vein thrombosis and oral contraceptive must be used. Esophageal injection sclerotherapy via a medication, and a weaker one between this condition and flexible endoscope is currently being used in many cen- pregnancy. When the Budd-Chiari syndrome occurs, it 852 Part XII HEPATOBILIARY TRACT AND PANCREAS

is usually in the immediate postpartum period. 15.16 The without careful histologic study. This is of particular im• diagnosis is established by liver biopsy and by hepatic portance in view of the radically different prognoses of venous angiographic studies demonstrating the occlu• these conditions. Chemotherapy in HCC has not proved sion. Treatment with anticoagulation, diuretics, ascites particularly helpful and should in any case be avoided in reinfusion, or portacaval shunts is only occasionally suc• pregnancy. Occasionally, resection of a hepatic lobe will cessful. be curative for a localized HCC. Careful diagnostic distinctions need to be made, par• ticularly in patients with heap tic neoplasms, since the prognosis is so different for each of these. HEPATIC TUMORS

Focal Nodular Hyperplasia and liver Cell Adenoma REFERENCES Two benign lesions in the liver have been associated with oral contraceptive medication and have been re• 1. Palmer ED: Clinical Gastroenterology. New York, Hoeber, ported to occur in pregnancy: liver cell adenoma (LCA) 1963, p 514 and focal nodular hyperplasia (FNH). Although there has 2. Friedlander P, Osler M: Icterus and pregnancy. Am] Obstet been some confusion surrounding the differences be• GynecoI97:894-900, 1967 tween these tumors, they are morphologically distinct 3. Everson GI, McKinley C, Lawson M, et al: Gallbladder function in the human female: Effect of the ovulatory cycle, and carry different prognoses. 17 Both tumors are almost pregnancy, and contraceptive steroids. Gastroenterology exclusively seen in women, but liver cell adenoma is a 82:711-719, 1982 true neoplasm and is strongly associated with oral con• 4. Haemmerli UP: Jaundice in pregnancy with special refer• traceptives. Although focal nodular hyperplasia is a hy• ence on recurrent jaundice during pregnancy and its differ• pervascular lesion and adenomas are only poorly vas• ential diagnosis. Acta Med Scand [Suppl] 444:1-111, 1966 cularized, it is the adenomas that are associated with 5. Cowan DB, Houlton MC: Rupture of an amoebic liver ab• intraperitoneal hemorrhage, which occurs in approx• scess in pregnancy. A case report. S Afr Med J 53:460-461, imately 25% of reported cases. Liver function tests for 1978 both are typically normal. Like hepatocellular carcinoma, 6. Wagner VP, Smale LE, Lischke ]H: Amebic abscess of the both FNH and LCA may be multifocal. Their angiogra• liver and spleen in pregnancy and the puerperium. Obstet GynecoI43:191-195, 1974 phic appearances are different, reflecting their distinct 7. Brodie MJ, Beattie AD, Moore MR, et al: Pregnancy and vascular patterns. Neither appears to have significant hereditary hepatic porphyria, in Doass M (ed): Porphyrins in malignant potential, and there is no association with pre• Human Diseases. Basel, S Karger, 1976, p 251 existing liver disease as there is with hepatocellular 8. Toaff R, Toaff ME, Peyser MR, et al: Hepatolenticular degen• carcinoma. eration (Wilson's disease) and pregnancy. Obstet Gynecol Several reports have indicated that adenomas can Surv 32:497-507, 1977 cause high maternal and fetal mortality secondary to 9. Scheinberg IH, Sternleib I: Pregnancy in penicillamine-treat• acute rupture. Whether bleeding and rupture are more ed patients with Wilson's disease. N Engl J Med 293:1300- frequent in pregnancy is unclear, and it is equally not 1302,1975 10. Walshe ]M: Pregnancy in Wilson's disease. Q J Med 181:73- known whether the increased estrogen levels of pregnan• 83, 1977 cy might stimulate growth of previously established 11. Infeld DS, Borkowf HI, Varma RR: Chronic-persistent hepa• tumors. titis and pregnancy. Gastroenterology 77:524-527, 1979 12. Borhanmanesh F, Haghighi P: Pregnancy in patients with Hepatocellular Carcinoma cirrhosis of the liver. Obstet Gynecol 36:315-324, 1970 13. Cheng Y-S: Pregnancy in liver cirrhosis and/ or portal hyper• Primary hepatocellular carcinoma (HCC) is distinctly tension. Am J Obstet GynecoI128:812-817, 1977 unusual in young women without antecedent liver cir• 14. Maddrey WC, BaSil Mallik KC, Iber FL, et al: Extra-hepatic rhosis. Rare instances of HCC in association with oral obstruction of the portal venous system. Surg Gynecol contraceptive medication have been reported. It is of note Obstet 127:989-998, 1968 that human chorionic goadotropin is occasionally synthe• 15. Khuroo MS, Datta DV: Budd-Chiari syndrome following sized by primary hepatocellular carcinomas. Serum a• pregnancy. Report of 16 cases with roentgenologic, hemo• fetoprotein levels are a useful tumor marker in the normal dynamic and histologic studies of the hepatic outflow tract. or cirrhotic patient with HCC. These levels are also ele• Am J Med 68:113-121, 1980 16. Tiliacos M, Tsantoulas D, Tsoulias A, et al: The Budd-Chiari vated in normal pregnancy and are particularly high with syndrome in pregnancy. Postgrad Med J 54:686-691, 1978 twinning or with fetal demise but are of still greater mag• 17. Knowles DM, Casarella WI, Johnson PM, et al: The clinical, nitude in HCC than in any of the above conditions of radiologic and pathologic characterization of benign hepatic pregnancy. Intraperitoneal hemorrhage also occurs with neoplasms. Alleged associations with oral contraceptives. HCC, and it may be difficult to distinguish LCA and HCC Medicine (Baltimore) 57:223-237, 1978