Cirrhosis of the liver complicating pregnancy

Ctrrftosis of the. Hver

cemplicatin~

pregnancy

A presentation of 2 cases and a review of the literature

CARL R. SLAUGHTER, M.D. K E R }..1 I 1' :E. K R..A I'J 'f Z,

~..1.

D.

Kansas City, Kansas

T H E occurrence of pregnancy in a patient with cirrhosis of the liver is an uncommon finding. This may be caused by the age at which cirrhosis occurs, or the fact that amenorrhea and irregular menstrual periods arc common in the cirrhotic patient. 1 Only 2!i women with cirrhosis who have been delivered have heen reported in the litcrature.'· 1 '' These women have been delivered of a total of 29 infants (Table I). Five have undergone a shunting procedure for portal hypertension prior to delivery. 1 ·11 1 '"· • t:l.. '' In one case, the shunting pro1 cedure was nerfonnerl C!urimr nreP"nanr.v l---;- " 12 ln addition to these cases, Nabriski refers to one nf Bromberg's patients in 1947, and GoldenH refers to 38 instances in the eighteenth and nineteenth centuries in which pregnancy was complicated by ascites. LTndoubtedly. Bromberg's patient and some of those with ascites must have had cirrhosis, but details are not available. The Maternity Mortality Conference of Ohio reported on a 40-year-old white primigravida with cirrhosis who was to be delivered, but died of hemorrhage at 7 month's gcstation.H1 Fish 17 reported on a patimt with portal hypertension, hut tlw liver profile and biopsy were normal. In 1892. Milrov 1' \vas the first to describe ;t congenital familial Pderna. now known as Milrov·s diseast'. Some autf1ors 1 '' ha\'c classi~

Frmn thr

---

---

/.'nii,l
Medical Cni/n.

---cJ

of

fied cases of familial edema, in which the edema was not present at birth, as Milroy's disease. Most authors, 20 however, believe that Milroy's disease should be reserved for cases of congenital familial edctna. In this paper 2 patients are presented who had cirrhosis, 1 had Milroy's disease. Both patients became pregnant and were delivered of viable infants. The first patient was delivered twice and the second, once. Both had shunting procedures; the first was done after the delivery and the second before delivery.

-,,::~----

Case reports

Case 1. The patient, an 18-year-old gravida 0, para 0, white woman, was seen for the first time on Oct. 28, 1950, with the complaint of jaundice, fever, and abdominal pain. Her past history was significant in that in 1944, at the age of 12, she developed jaundice. The gall bladder was "drained" at that time. One year later she had a cholecystectomy. She had had intermittent fever and jaundice since. 1\-1enarche

occurred at the age of 15, with periods varying from 28 to 90 days in interval. Three to 5 pads per day were required. Upon admission, the spleen was palpable at 1 fingerbrcadths, and the liver at 3 fingNhreadths below thP- costal margin. An esophagogram revealed no varicosities. A liver biopsy i Fig. l) showt:d periportal fibrosis. The diagnosis was cholangiolar cirrhosis. The patient became pregnan! in November, l'J.'JO, and during the pregnancy severe prf'eclampsia developed. On Aug. 18, 1051, after

Ka.n1as

1060

Volume 86 Number 8

Cirrhosis of liver 1061

a 25 hour and 56 minute labor, she was de-

livered, by low forceps of a 3,000 gram viable male who died shortly after birth. The cause of death given after autopsy was intracranial hemorrhage secondary to laceration of the tentorium cerebelli. The patient became febrile, and 10 clays post partum 2,000 c.c. of fluid was removed by paracentesis. The woman again became pregnant in July, 1953, and again had pre-eclampsia. At 37 weeks' gestation, she was delivered, by elective cesarean section of a 2,885 gram viable male infant. The infant was noted to be a poor feeder, but otherwise did well. The spleen showed progressive enlargement, and, on July 26, 1954, a splenectomy and splenorenal shunt were performed. Prior to operation, a percutaneous portogram revealed an enlarged splenic vein (Fig. 2). She '<\as last seen on April 17, 1956, at which time the liver was palpable at 1 fingerbreadth below the costal margin. Although she was still having episodes of intermittent jaundice, thPy were less frrquent. Significant laboratory work is found in Table IT. Case 2. A 22-year-old gravida 0, para 0, white woman was admitted to the hospital for the first time on Jan. 30, 1959. A review of her past history revealed a painful swelling of the right Jpg since birth and a painful swelling of the left leg of 6 month-s' duration. At 12 years of age, a diagnosis of rheumatic fever was made, but prophylactic antibiotics were not administered. There was no past history of jaundice, vomiting, or excessive alcoholic intake. Her family history was &ignificant in that a brother also had painful swelling of the legs since birth. Menarche took place at the age of 12, with a norrLal 5 day flow every 28 days, which required 3 to 5 pads per day. The spleen was 3 em. below the costal margin, and the liver was barely palpable. She had 2+ pretibial edema. Protein electrophoresis revealed an albumin of 44 per rent, alpha 1 globulins of 4 per cent, alpha 2 globulins of 6 per cent, beta globulins of 12 per cent, and an f'levated gamma globulin of 34 pPr rent. A liver biopsy showed focal periportal fibrosis. An esophagoscopy showed enlarged veins at the cardia, but no definite varicosities. She was readmitted on Aug. 10, 1959, after an episode of syncope and hematemesis. A repeat protein electrophoresis revealed a low albumin of

Hg. 1. Liver biopsy of patient in Case 1 showing bile duct proliferation and fibrosis. ( ':90 magnification.)

Fig. 2. Percutaneous portogram showing enlarged splenic and portal vein of the patient in Case l.

\ugu:~t

1062 Slaughter and Krantz

l 5. l 9td

,\m. J, Obst. & Gynn .

27 per cent and an elevated gamma globulin of 38 per cent. Hepatic vein catheterization via the right arm indicated portal hypertension, and a splenectomy with a splenoretzius shunt was performed. The liver at the time of the shunt was noted to be nodular and fibrotic. Blood am-

monias ranged from 160 gamma per cent nn the day of admission to 80 gamma pt•r n·ut immediately prior to disc-harge. The patient became pregnant in March, 1961, with an expected date of confinement of Jan. 2, 1962. During the course of the pregnancy,

Table I. Reported cases of cirrhosis of the liver complicating pregnancy Case

No.

Author

Date

Age

(From Burslem)

1923

25

Multipara

Autopsy

1927

38

2

Clinical

3

(From Burslem) Kraul1 Hesseltine2

1930

42

4

Tenney and King3

1934

20

()

Laparotomy

5 6

} .. shton 4 (From Burslem) Lascano and Peyreyra 7 Go!den 6

Parity

Diagnosis

Scaglioner

2

Laparotomy

1934

25

1936

37

0 9

Autopsy

1949

25

2

Clinical

Javert and Morrison" Javert and Morrison" ]avert and Morrison" Burs! em, et a!. 7 Burslem, et a!. 7 Burslem, et a!. r Mack et aJ.s

1951 1951 1951 1952 1952 1952 1953

30

2

24 25 28

0 1

Clinical Biopsy Biopsy Biopsy

1953 1954

27

Multipara

18

Mack et al. 8 Slater9 Bearn et aJ.l Abrams10 Abrams10 Adno and Hughesll, 14

19 20a

7 8

9 10 11

12a 12b 13

14 15 16 17a 17b

i\.utopsy

?

()

Laparotomy Biopsy Biopsy Biopsy Biopsy Biopsy

29 29

0 0 ()

1957

27 28 24

Nabriskil2

1958

34

Multipara

Biopsy

Nabriski12

1958

27

( 2 abortions)

Biopsy Biopsy

1955 1956

1956

1 2

20b

Nabriski 12

1958

28

0 ( 2 abortions) 1

21

Labby13

1960

21

0

Laparotomy

22

Moore Moore Moore Moore

Hughes14 Hughes14 Hughes14 HughesH

1960 1960 1960 1960

38

0

23 24a 24b

29

1

33

0

35

1

Biopsy Biopsy Laparotomy Laparotomy

25

O'Leary and Bepko15

1962

33

5

Biopsy,

26a

Present study

1962

19

0

Biopsy

26b

Present study Present study

1962 1962

21

1

23

0

Biopsy Biopsy

27

and and and and

laparotOrrly

Cirrhosis of liver 1063

Volume 86

:-lumber 8

time of the operation. The patient did well following the delivery and was last seen 8 wet'ks postpartum. The infant was discharged after a 13 day hospital stay, was doing well at 4 weeks. and showed no evidence of edema.

she required hospitalization at 4 weeks, 23 weeks, and 30 weeks' gestation because of nausea, vomiting, and nonverified hematemesis. A viable 2,205 gram female infant was delivered, bY elective cesarean section, at 3912 weeks' gestation. A tubal sterilization was performed at the

~~~-,---~---;--~~-~--,-----~---~~~~-~-,~~~

Sex

Weight (grams)

Type of delivery

Alive at 6 months

Lived

Alive at 2 years

Lived

2.850

36 weeks, spontaneous Tem1 cesarean section Low forceps Spontaneous

Died at 6 months Died 19 days post partum

Lived Stillborn

Died post splenectomy Died of hematemesis

:~,240

Spontaneous

Alive at 6 months

Lived

Ascites. abnormal function test

Lived Lived Died at Alive at Alive at Alive at Alive at

Lived Lived Lived Lived Lived Lived Lived

?

? F

? 3,033 3,543 3,486 ~~.381

2,550

3,181 :1.402

Spontaneous Spontaneous Spontaneous 32 weeks, cesarean section 16 weeks hysterotomy Low forceps Vaginal Low forceps Spontaneous Forceps

Premature 32 weeks, cesarean section Cesarean section

Lived Alive at Alive at Alive at Alive at Alive

delivery 6 months 16 months 1 month 1 year 1 year

2 years 1 year

3 months

Same patient

Portacaval shunt Same patient, portacaval shunt Splenorenal shunt prior to pregnancy, previous cesarean section Cesarean section, done for vaginal bleeding

Lived

Lived

Same patient, cesarean section for prolapsed cord

39 weeks, cesarean

Alive at 5 months

Lived

Splenorenal shunt

Alive Alive Alive Alive

M

:!,466

M

2,325

Mid forceps

Alive at 1 month

M

3,000

Low forceps

Alive at 4Y2 years

M F

2,885 2,205

Cesarean section 39Y2 weeks, cesarean section

Alive at 2 years Alive at 8 weeks

:3,289

Hepatosplenomegaly

Lived

section Spontaneous Low forceps Low forceps Low forceps

3,459 Term

Died Lived Lived Lived Lived Lived

Maternal death due to hematemesis Large nodular liver, big spleen

Alive at 6 weeks but worse Alive at 11 months

:!,700

:l, 181

F M M

Comment

Lived

~:,550

F F F F

Infant

Died 14 hrs. post partum Alive at 6 months

~:,200

M M M M

Mother

8 months, spontaneous Vaginal

~.,400

F

-~-----~-~

Follow-up

at at at at

3 2 3 6

years years years months

Lived

Alive at 3 years Alive at 2 years Alive at 3 years Died of congenital anomalies Alive at 1 month Died at delivery •Lived Lived

Scanty menstrual periods Same patient, esophageal varices Portacaval shunt during pregnancy Same patient, splenorenal shunt 3 months after delivery Splenorenal shunt

1064

\u~ust

Slaughter and Krantz

:\m.

Pertinent laboratorv work can he found m Table III. Comment

There appears to be no increase in infant mortality m patients with cirrhosis if the

J.

1:-1. 14tj)

Oh,t. &

<~ym·c.

usual complications of labor are avoided. Of the 27 mothers with cirrhosis, 4 died and another was progressively becoming worse at the time of publication. 4 • 5 • 7 • 12 Only 1 patient died intra partum. Another died in the immediate postpartum period. 5 • 7

Table II. Pertinent laboratory results of Case 1 Date

Total protein

Albumin

Globulin

Bromsulphalein

Thymol turbidity

10-28-50 11-1-50

6.5

3.50

3.00

10

6

8-17-51

5.48

2.17

3.11

II

9-7-51 9-21-51

5.25 8.30

3.00 4.10

2.25 4.20

I 0-30-53 3-26-54

7.00 6.90

4.70 4.25

2.30 2.65

Cephalin flocculation

Alkaline phosphatase

16 Last menstrual period 11-?-50, 10.9

2 13 6.5 9

Delivery 12.3 13.5

]~

3+

Last menstrual period 7-17-53, 3+ 9.8 ~egative 5.6 Cesarean

4-3-54 5-21-54 7-21-54

8-3-54 1-10-.55 4-3-56 4-17-56

7.68 6.90

4.19 4.14

3.49 2.76

6.65

3.96

2.69

7.80 8.45

5.07 5.65

2.73 2.80

12 14

J+

9.0 7.0

3+

Splenectomy splenorenal 20.6 2+

8 9

:.!+

15.6 17.3

Thymol turbidity

Cephalinflocculation

Alkalin phosphatase

Table III. Pertinent laboratory results of Case 2 Date 1-14-59 1-30-59 8-10-59 8-24-59

Total protein

Albumin

Globulin

5.40

2.48

2.92

Bromsulphalein

12 22 15

3+

~.6

+~

3.1

5.935.98

2.37 2.45

3.56 3.53

9-8-59 [ 2-1-59 1-28-60 2-22-61

6.56 6.71

2.48 4.16

4.08 2.55

9 4

Splenecto.rny splenoret::izo I+ 5.9 ~+ 1.8

4-18-61 9-12-61 10-31-61 12-27-61

5.77 5.26 4.73 4.63

2.94 2.57 2.14 1.71

2.83 2.69 2.59 2.92

2

Last menstrual period 3-26-61, ]~ :J.3

1-1-62

4.17

1.32

2.85

10

16 20

2.8

1 3

]+ ~+

:2+

2

Negative

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Cesarean 4.9

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Cirrhosis of liver 1065

Volume 86 Number 8

vaginally; the type of delivery of the other was unknown. Eight of the infants were premature; the maturity of 9 others was not known. Three of the premature infants were delivered by cesarean section. Our second patient continued to show a

In the group of 27 patients, there were 11 spontaneous deliveries, 9 forceps deliveries, 7 cesarean sections, and 1 hysterotomy. In 4 instances the type of delivery \\ as unknown. Of the 2 subjects who died during and soon after delivery, 1 was delivered 7

Bilirul1in Total

Cholesterol

Hemoglobin

92

9

"'"'

11')

100

66

1(\.,

48 65

85

Esters

2.00

296 300

141 50

estimated date of confinement 8-i-51 o; on 11.0 v.uv 320

I

100 100

Total

2.75

I

Fasting blood sugar

Direct

Proth.rombin tzme

.LV./

Platelets

126,000

I')C:.(\

nnn

~uv,vvv

.8-18-51

9.5 3.2

6.5 1.6

210 410

• estimated date of confinement 4-22-54 0.8 300 1.7 4.1 2.3 292 section 4-2-54 3.3 3.6 1.85

1.9 1.3 0.9

shunt 7-26 54 1.0 1.1 1.2 2.7

0.6 0.7 0.7 1.5

322 260

65 172

231 55

Direct

(10)

fl<'l

0.2

0.1

V,J

fl'l V,,J

shunt 8-26-59 0.5 0.5

v . .::;

82

86

88

Prot~rombin time

U'1'

0:1

64

65

65

£'A

!04

Fasting I blood sugar

nn

10<'1

n 1 Vd

135

69

'"0

1')0

"1'1

0.3 0.1

158 216

66 57

estimated dat~• of confinement 1-2-62 0.4 0.1 164 0.3 0.1 178

0.2

87

202 159

Biliru'IJin Total

55

82

300 270 230

9.1 8.8

f,J

65 72

0.1

87

68 65 57

10.1 11.8

131,000

12.0 10.9 10.0

98,000 70,000

11.5 13.4

1,060,000 348,000

13.9

314,000

Hemoglobin

Platelets

1L7

120,000

8.7 10.3

80,000 97,000

13.0 12.6

87,000 251,000

14.1 11.0 10.2 11.9

293,000

section 12-29-61

252

73

11.0

1066 Slaughter and Krantz

decreasing serum protein during pregnancy. This decrease was mainly manifested by a low serum albumin. It appeared to be greater than the physiological hypoalbuminemia of normal pregnancy. 21 • ~ 2 • 23 Although elevated globulin has been reported in patients with a normal pregnancy as well as in those with cirrhosis, our subjects failed to show a significant increase during the course of their disease. 1 ' 12 ' 21 • 24 Although the total globulins were not significantly increased in our patients, the gamma globulin fraction of our second patient, as shown by electrophoretic pattern, was elevated. This is consistent with the findings of most other investigators. 1 • n, 24 • 25 • 26 • 27 Interestingly enough, hypergammaglobulinemia has been shown to be present in the cord blood of infants delivered to cirrhotic mothers. This increase apparently diminishes over a period of time. 9 The increased maternal gamma globulin level is stated to be the result of increased liver destruction, followed by increased antiliver antibodies which are reflected in higher gamma globulin levels. 25 • 26 Perhaps the antibodies cross the placental barrier, and the increase in the fetal gamma globulin reflects their presence.

\ug1nt I\ l'lld \m. J. Ohst. & Gynec

Conclusions 1. Two cases of pregnancy complicated by cirrhosis have been presented. One of the patients also had Milroy's disease. They represent the twenty-sixth and twentyseventh cases, and the thirtieth, thirty-first, and thirty-second documented deliveries in which pregnancy was complicated by cirrhosis. 2. A splenectomy and a shunting procedure were performed on both subjects. Surgery was performed prior to the pregnancy of one, and after the last delivery of the other. 3. A brief outline of the previously rc~ ported cases has been presented. 4. The danger of delivering a premature infant to a cirrhotic mother appears to be real; but there seems to be no increase in perinatal mortality over that which would be expected under similar circumstances in a normal patient. 5. There are too few cases to adequately determine the effect of pregnancy on a cirrhotic patient, but there appears to be an increased moroidity associated with the combination.

REFERENCES

1. Bearn, A. G., Kunkel, H. G., and Slater, R. J.: Am. J. Med. 21: 3, 1956. 2. Hesseltine, H. C.: AM. J. 0BsT. & GvNEc.

3. L

5. 6. 7.

8.

9. 10. 11. 12.

65: 859, 1953. Tenney, B., Jr., and King, R. B.: New England J Med. 208: 1157, 1933. Ashton, D. L.: AM. J. 0BST. & GvNEC. 28: 280, 1934. Javert, C., and Morrison, R. C.: Texas State J. Med. 47: 137, 1951. Golden, A.: AM. J. 0BST. & GYNEC. 57: 385, 1949. Burslem, R. W., Gardikas, C., and Israels, M. C. G.: J. Obst. & Gynaec. Brit. Emp. 59: 777, 1952. Mack, H. C., et al.: Obst. & Gynec. 1: 204, 1953. Slater, R. J: PediatriCs 13: 308, 1954. Abrams, F. R.: Obst. & Gynec. 10: 451, 1957. Adno, J.: South African M. J 31: 1189, 1957. Nabriski, S., Zelof, D., Fleishman, P., and

13. 14.

15. 16.

17. 18. 19. :!0.

21. 22.

23.

Lewitw, Z.: J. Obst. & Gynaec. Brit. Emp. 65: 462, 1958. Labby, D~ H.: GP 22: 114, 1960. Moore, R. M., and Hughes, P. K.: Obst. & Gynec. 15: 753, 1960. O'Leary, J. A., and Bepko, F. J.: Obst. & Gynec. 20: 243, 1962. ClinicopathologiCal Conference: Ohio State M. J. 54: 919, 1958. Fish, G., and Mills, W.: Illinois M. J. 119: 20, 196L Milroy, W. F.: New York M. J. 56: 505, 1892. Hope, W. B., and French, H.: Quart. J. Med. 1: 312, 1907. Allen, E. V., and Ghormley, R. K.: Ann. Int. Med. 9: 516, 1935. Coryell, M. N., et al.: J. Clin. Invest. 29: 1559, 1950. Day, E. M., and Hellestrand, A. L.: M. J. Australia 2: 325, 1947. Guttmacher, A. F., and Rovinsky, J. J.: Medical, Surgical, and Gynecological Com-

Volume 86 Number 8

plications of Pregnancy, Baltimore, 1960, Williams & Wilkins Company. 24. Ha:rrison, T. R.: Principles of Internal Medicine, New York, 1950, The Blakiston Com-

pany. 25. Eaton, M. D., Murphy, W. D., and Hanford, V. L.: }. Exper. Med. 79: 539, 1944. 26. Zimmerman, H. J., Heller, P., and Hill, R. P.: New England J. Med. 244: 245, 1951.

Cirrhosis of liver 1067

27. London, I. M.: In Youmans, ]. B., editor: Symposium on Nutrition of Robert Gould Research Foundation Inc., Plasma protein, Springfield, Ill., 1950, Charles C Thomas, Publisher. 39th and Rainbow Kansas City 12, Kansa>

Erratum In the article, "Vaginal cytology in postradiational cancer of the cervix uteri," by Howard L. Walker, M.D., in the May 1, 1963, issue of the JouRNAL, page 137, Figs. 1 and 2 were transposed. Fig. 2 should have been Fig. 1 and vice versa.