European Journal of Cardiovascular Medicine

Biochemical hepatic dysfunction in pregnancy, whilst relatively rare, has potentially serious consequences for maternal and fetal health. Liver disease in pregnancy encompasses a spectrum of diseases encountered during gestation and the postpartum period that result in abnormal liver parenchymal and hepatobiliary dysfunction or both. It occurs in 3% to 10% of all pregnancies. [1] The cause of liver disease in pregnancy can be difficult to diagnose. Making the correct diagnosis is of paramount importance, as failure to do so can result in morbidity or mortality for not only the mother, but also for her fetus. Pregnancy causes very few alterations in the results of standard liver tests. The aminotransferases (AST and ALT), glutamyl transpeptidase (GGTP), total bilirubin, and serum bile acid level remain within the normal range. Alkaline phosphatase rises modestly in the third trimester. The albumin level is lower than in non-pregnant women, and the [2] cholesterol level higher. Thus, elevations in aminotransferases or GGTP signify pathology, and should prompt a search for disease. Liver involvement in pregnancy is of three types, namely,

1. liver diseases peculiar to pregnancy like fatty liver of pregnancy, cholestatic jaundice of pregnancy, PIH, HELLP
2. liver diseases coincidental to pregnancy like hepatitis A,

Hepatitis E 

3. pregnancy in patients with pre-existing liver disease like chronic type B hepatitis, cirrhosis of liver

Causes of biochemical hepatic dysfunction in pregnancy include:

Acute & chronic viral hepatitis:

This is the most common cause of biochemical hepatic dysfunction in pregnancy with infections due to hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E viruses. the incidence of hepatitis in pregnancy varies greatly around the world; in developed countries the incidence varies around 0.1% whilst in developing countries it can range from 3-20% or higher. [3,4] -the course of most viral hepatitis infections is unaltered by pregnancy- exception is hepatitis E, where pregnant women who contract the disease exhibit fatality rates of 10-20%

• Hepatitis A:

The disease is passed almost exclusively to the mother by fecal-oral route. It is rarely transmitted to the fetus.

• Hepatitis B:

This is the most common cause of acute viral hepatitis in pregnancy and can occur in acute, subclinical or chronic form. The presence HBeAg is associated with a very high risk of neonatal infection.

• Hepatitis C:

              -Diagnosis is by presence of serum Anti-HCV. mostly causes chronic hepatitis

• Hepatitis D:

This develops as a co-infection with hepatitis B when present it increase, the incidence of acute hepatic failure.

• Hepatitis E:

This is rare in developed world but, in developing countries, it is responsible for a high level of fulminant hepatic failure and mortality in pregnant women.

Epidemology

This may affect as many as 6% of pregnant women but biochemical hepatic dysfunction occurs only in about 1 in 20 of these women. Pregnancy alters bile composition and gall bladder emptying slows in the second trimester, increasing the risk of gallstones.

• Chronic liver disease:
  • Chronic liver disease in pregnancy is associated with an increased

risk of fetal loss:

• In patients with primary biliary cirrhosis, cholestasis may worsen during pregnancy with PBC. [5, 6]

• Autoimmune hepatitis:
  • This can present with an acute attack.
  • Serum bilirubin increase depends on:
    1. Type of disease
    2. Presence of anti-nuclear, small muscle, liver-kidney microsomal antibodies or antibodies to soluble liver Ag/liver-pancreas

Abs. [7, 8]

-There is generally a favorable prognosis for both mother and baby.

• PIH & HELLP SYNDROME-

Complete: elevated AST (>70 IU/L), low platelet counts (<100,000/μL), hemolysis (suggestive peripheral smear with increased reticulocytes). Partial: elevated AST (>40 IU/L), low platelet count (<150,000/μL), absence or presence of hemolysis.[9]

• Acute fatty liver of pregnancy-

Six or more of the following features in the absence of another explanation: vomiting, abdominal pain, polydipsia or polyuria, encephalopathy, leukocytosis, elevated bilirubin, elevated transaminases, elevated ammonia, hypoglycemia, renal impairment, coagulopathy, elevatedurate, ascites or bright liver on ultrasound, and microvesicularsteatosis on liver biopsy. [10, 11, 12]

• Intrahepatic cholestasis of pregnancy (ICP)

Pruritus without any local or other systemic cause, with elevated transaminases, which disappeared soon after delivery. Intrahepatic cholestasis can lead to chronic placental insufficiency, resulting in fetal complications that include anoxia, prematurity, perinatal death, fetal distress, and stillbirth. Various studies have been done to evaluate the maternal and foetal outcome in different conditions causing jaundice in pregnancy. [13, 14, 15,16]

Design:

This study was a Prospective Observational Study, which was conducted in Tertiary Care Hospital during the period of December 2015 to December 2017 was informed and written consent was well sought from all subject’s close relative before the initiation of study.

Participants:

A total of 100 pregnant patients were studied. Among which 50 Patients with biochemical hepatic dysfunction and 50 Patients without biochemical hepatic dysfunction. Inclusion criteria comprise, all pregnant women between 18 yrs to 50 yrs with biochemical hepatic dysfunction (Serum Bilirubin, SGOT, SGPT, Serum Alkaline Phosphatase, Urine bilirubin), and all pregnant women with normal biochemical hepatic function. Whereas in exclusion criteria, those were not willing to give consent and not willing for follow up.

Interventions:

Patients were selected from Tertiary Care Hospital wards. Patients were selected on the basis of biochemical hepatic dysfunction either single or combined. Patients without biochemical hepatic dysfunction were also be selected an informed consent was taken from every selected case. History was obtained in detail and thorough clinical examination was done. Obstetric examination findings were collected from obstetrician. Investigations were carried out after consideration of clinical presentations so as to arrive at diagnosis, etiology, complications in patients with biochemical hepatic dysfunction in pregnancy. Each patient was followed up to 42 days of PNC and final outcome was noted in the form of complication/recovery/death.

Data analysis:

Complete History, Clinical Examination, Diagnostic Evaluation. Statistical Analysis between clinical profile and its outcome. Quantitative data were analyzed by Paired t-test or Unpaired t-test. Qualitative data were analyzed by Chi-Square test.

Table 1: Residence & Maternal outcome in pts with hepatic dysfunction

Chi square value is 4.082 with p value 0.044 (<0.05) which is statistically significant.

Out of 35(70%) pts of hepatic dysfunction from rural area 8(22.86%) pts was died and 27 (77.14%) survived, there were no death of pts from urban area.

Table 2: ANC visits

Out of 100 pts 52 pts were booked, but among 50 pts with hepatic dysfunction only 20(40%) pts was booked compared to 32 (64%) pts without hepatic dysfunction.

P value equals 0.0272 (<0.05) is considered to be statistically significant.

Figure 3

Table 3: ANC visits & Maternal outcome in pts with hepatic dysfunction

Chi square value is 6.897 with p value 0.008(<0.05) which is statistically significant.

Table 4:  Mode of delivery

Out of 100 pts 58 pts were delivered by normal vaginal delivery and 42 pts required caesarean delivery. Rate of LSCS was 64% in pts with hepatic dysfunction compared to 20% in pts without hepatic dysfunction.

P value is less than 0.0001 (<0.05) is considered to be extremely statistically significant.

Figure 5

Table 5: maternal complication and its outcome

Maternal death rate in pts with hepatic dysfunction pregnancy was HELLP syndrome i.e. 8% f/b 6% with pregnancy induced hypertension.

Chi square value is 115.472, p value is 0.02 (<0.05) which is statistically Significant.

Table 6: Biochemical and other parameters

P value is 0.0001 which is <0.05 which is statistically extremely significant.

Hepatic dysfunction is very important cause of mortality and morbidity in pregnancy. This study was undertaken to study maternal and fetal outcome, etiology and complication in pts with hepatic dysfunction.

 In our study maximum cases were from rural areas i.e. 70% pts with hepatic dysfunction & 64% pts without hepatic dysfunction were from rural areas. With P value equals 0.6709(>0.05) is considered to be not statistically significant.  Maternal mortality is significantly high in pts from rural areas with p value 0.044 (<0.05) which is statistically significant. 

In our study it is observed that hepatic dysfunction in pregnancy is slightly higher in illiterate pts i.e. 60% than literate pts (56%) this is may be due to fact that literate pts have more ANC visits than illiterate. maternal mortality was highest in pts who were illiterate with p value 0.087 (>0.05) which is statistically not significant.

Significant difference was found that 60% pts with hepatic dysfunction were unbooked compared to only 36 % of pts without hepatic dysfunction P value equals 0.0272 (<0.05) is considered to be statistically significant. Almost all maternal mortality was occurred in unbooked pts, p value 0.008(<0.05) which is statistically significant.

In our study it is found that hepatic dysfunction is more common in multigravida pts ie 60% than primigravida (40%), P value equals 0.4216 (>0.05) is considered to be not statistically significant with p value 0.29(>0.05) which is statistically not significant ant. Maternal mortality was more common in multigravida pts than primigravida. 

Out of 50 pts with hepatic dysfunction 32 (64%) pts was delivered by LSCS. P value is less than 0.0001 (<0.05) is considered to be extremely statistically significant. Similar results were found in study done by C L Chang et al were 46 % pts required LSCS because of detoriating liver function and out of 50 pts without hepatic dysfunction only 10 (20%) pts required LSCS.

In our study maximum case were from age group 25-35 i.e. 60% followed by 30% from 18-25 yrs similar results were found in study done by Divykala K et al [17] who recorded that maximum pts with hepatic dysfunction were from age group 25-35 i.e. 75.68% . maternal mortality was more common in pts with age group 36-35 yrs. Chi square value is 2.42 with p value 0.18(>0.05) which is statistically not significant.

Pregnancy induced hypertension remains the most common cause of hepatic dysfunction in 42 % of pts followed by cholestatic jaundice in 30% pts in our study. Similar results were found in study done by C L Chang et al [18] who Recorded preeclampsia was the commonest underlying etiology for hepatic dysfunction in pregnancy i.e. 48 %   f/b cholestatic jaundice 18%, in both studies incidence of AFLP is 4%.

A prospective study done by Umang R et al [19] at KEM hospital Mumbai found that PIH is the most common cause of hepatic dysfunction in 33.64% pts 

Similar results were also found in study done by Amrita T et al [20] at BRD medical college who recoreded thst among pregnancy specific liver diseases hypertensive disorders was the commonest abnormality (66.35%).

Dattatray et al [21] did a prospective study in western India who also noted pregnancy specific causes of liver dysfunction is the major cause of hepatic dysfunction on pregnancy found in 39% pts, in his study viral hepatitis was the most common cause found in 36.1% pts followed by pregnancy induced hypertension in 30.5% pts followed by intrahepatic cholestasis of pregnancy 11.1% pts.

Most common clinical finding was jaundice and nausea/vomiting found in 92% of pts with hepatic dysfunction, the most common cause of jaundice was PIH including HELLP i.e. 29 (58%), similar results were found in study done by Divyakala K et al [17] who recorded that jaundice is the most common clinical finding and PIH including HELLP was the most common etiology i.e. in 64.86% pts. Pruritus was the most common and most characteristic clinical finding found in almost all pts with ICP.

Out of 50 pts with hepatic dysfunction, Bilirubin elevated in 92% of pts with mean 8.06 mg/dl and standard deviation 5.16 in pts with hepatic dysfunction group. The P value is less than 0.0001 (<0.05) this difference is considered to be extremely statistically significant. Study done by Divyakala K et al [17] at Belgum Karnataka recorded similar results with mean peak sr. bilirubin of 10 mg/dl. Maternal mortality was high with bilirubin level above 6 mg /dl. 

AST and ALT elevated in 60 % pts with mean 184 & 172 with SD 220 & 211 respectively in pts with hepatic dysfunction group, The P value is less than 0.0001 (<0.05) this difference is considered to be extremely statistically significant, for both. Bile acids were raised in 30% pts with mean 26.6 & SD of 5.1 

Other laboratory findings among 50 pts with abnormal LFT were as follows 

Thrombocytopenia were found in 28% with mean 1.97 lacs/cumm & SD 0.87.

Sr. creatinine were increased in 20% pt with hepatic dysfunction group with mean 1.78 & SD 1.66 

Mean peak lipase level in pts with hepatic dysfunction group was 475 with SD of 19.76

In present study liver diseases were most frequent in 3rd trimester i.e. 60% of pts these results are comparable with study done by Dattatray et al [21]     rd in his study he also noted that liver disease was most frequent in 3 trimesters i.e. 69.9%.

In our study timing of PIH in 47.61% pts presented in 2nd trimester and 52.38% in 3rd trimester whereas HELLP syndrome presented in 3rd trimester in 87.15 % pts also ICP were more commonly presented in 3rd trimester in 73.33% pts.

These results are comparable with study done by Reema S et al [22] who recorded that HELLP syndrome found in 3rd trimester in 100% pts and pts (92.5%) with ICP presented in 3rd trimester.

In present study maternal mortality was recorded in 16% cases in pts with hepatic dysfunction group. Similar results were recorded in studies done by Umang R et al [19] in which maternal mortality were 19.7% and by Amrita et al a study done at BRD medical college found that maternal mortality were 13.02%.

Most common Causes of Maternal mortality in our study was PIH (24 %) and also in study done by Dattatray et al [21] PIH was the most common of cause of maternal mortality in 32% pts. 

Perinatal mortality in present study was 24% in pts with hepatic dysfunction group compared to 10% in pts without hepatic dysfunction. While perinatal mortality in Studies done by Umang R et al [19] & Amrita et al [20] was 35.4% & 29.17% respectively & 38.7 % in study done by Dattatray et al [21]

Child Pugh score in our study found that in pts with hepatic dysfunction, it was category B in 64 % pts and category C in 34 % pts indicating poor prognosis, out of 17 pts with CPS category C, 8 pts died indicating 47% mortality, while 12 babies died indicating 70 % mortality While in pts without hepatic dysfunction group CPS category was A in 100% pts. 

APGAR score for babies born to mothers with hepatic dysfunction was average 7.2 at 1 minute and 8.1 at five minute, in contrast with pts without hepatic dysfunction it was 7.7 at one minute and 8.8 at five minute ( p<0.007 and p<0.002, respectively). There was no significant difference between APGAR score according to specific maternal diagnosis. Similar results were found in study done by C L Chang et al [18] in southwest Wales who recorded that APGAR score in babies born to abnormal liver tests was 8.1 at one minute and 9.3 at five minute, in contrast with 8.4 and 9.6 respectively, for a control group.

Acknowledgment

Nil

Author contributions

Conceptualization: all authors. Data collection: all authors. Data analysis: all authors. First draft of the manuscript: all authors. Approved this manuscript for submission: all authors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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