Liver disorders during pregnancy and their management
Arun Kumar Mitra, MBBS, DGO, MO, FICOG, FRCOG PhD (London)Former Professor and Head, Department of Obstetrics and Gynecology, Medical College. Calcutta.
Pralhad S. Patki* , M.D., Head -Medical Services and Clinical Trials
S.K. Mitra, M.D., Executive Director R&D Center, The Himalaya Drug Company, Bangalore, India.
Liver disorders during pregnancy and their management
Autoimmune Hepatitis (AIH)
Autoimmune hepatitis is a progressive liver disease that predominantly affects women of all ages. Women with AIH can become pregnant and carry successful pregnancies to term with the expectation of delivering a normal baby. However the disease activity is unpredictable in pregnancy. Attenuation of disease activity and spontaneous remissions have been reported due to the immune tolerance induced by the pregnancy. Flares of the disease have also been described in 11% of cases during pregnancy and up to 50% in the postpartum period. Maternal deaths due to liver decompensation, variceal bleeding and porto-pulmonary hypertension have been reported especially when treatment is withdrawn. Preterm delivery and fetal loss occur in 24%.19
A few cases of pregnancy have been described in women with primary biliary cirrhosis (PBC). This is partly due to the later age at presentation of the disease. Although reports suggest an increased risk for premature delivery, still births and liver failure, there are no good data on the outcome of pregnancy in women with PBC. When pregnancy occurs, PBC may induce a new onset pruritus. Diagnosis and management are similar to the non pregnant state. There is no indication for termination of pregnancy in these patients.
Gallstone Disease in Pregnancy:
The risk for sludge and gallstone formation doubles by the end of gestation in comparison with the first trimester (10% versus 5% respectively), and it is further increased with parity. Gallstones are found in 6.5% to 8.4% of nulliparous women, and in 18.4% to 19.3% of women with two or more pregnancies. Most sludge and a third of gallstones disappear spontaneously after pregnancy without resulting in symptoms. Acute cholecystitis and gallstone pancreatitis rarely occur during pregnancy (<1/8000) but they require immediate attention. Medical intervention is often effective.20
Liver disease in pregnancy may manifest as a benign entity that resolves with delivery of the fetus without any consequences, or a more serious disease that could adversely affect the overall well being of both mother and baby potentially resulting in liver failure and death. Although there are no available clinical markers by which to predict with certainty how and when such situations may be encountered, prior history of liver disease, knowledge of the patient’s risk factors for liver disease and the gestational age of the pregnancy are the best guides to a differential diagnosis.
Drug induced hepatitis
While pregnancy is not reported to increase the susceptibility to drug induced liver disease, drug hepato-toxicity should always be considered in pregnant women taking prescription or non prescription medications.
Pregnant women can react to drug causing jaundice in an exaggerated way as manifested with the use of tetracycline, anaesthetic agents, sulfonamides etc. Antitubercular drugs are also known to induce drug related hepatitis. Therefore selection of drug therapy in pregnancy needs to be carefully made.
Management
Liver disease makes a normal pregnancy a high-risk pregnancy. Extreme vigilance is needed to detect early signs and symptoms of liver dysfunction and to distinguish these from the anticipated benign hepatic changes of pregnancy. Prompt management can save the life of the mother and the baby. Management of liver disease in pregnancy requires a concerted effort between the primary care physician, liver specialist, and obstetrician.
Acute liver failure (ALF) in pregnancy is a common challenging clinical problem both in terms of correct diagnosis and management. Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute viral hepatitis is unaffected by pregnancy, except in patients with hepatitis E (HEV), particularly from endemic countries like India, where ALF carries a high mortality. In both HEV infection and herpes simplex infections, maternal and fetal mortality rates are significantly increased. ALF specific to pregnancy including pre-eclampsia, associated with hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, acute fatty liver of pregnancy, and hepatic infarction result in increased maternal and fetal mortality if not recognized and acted on early. Early recognition of possible causes and prompt treatment are crucial for successful outcome of ALF in pregnancy. Treatment involves prompt delivery, whereupon the liver disease quickly reverses.
Indigenous drugs
Our team has studied the efficacy and safety of Liv.52 in the management of liver disorders in pregnancy. Our study which was conducted way back in 1974-75 consisted of 84 cases of liver disorder in pregnancy and we were interested to know the efficacy and safety of Liv.52 in the treatment of jaundice in pregnancy. This study, we believe is first of its kind at least in those days because it involved management of pregnant women with jaundice.21
In this study population of 84 patients, there were 9 pregnant women who were down with severe viral hepatitis. 21 of eighty four patients had undergone liver biopsy, of course after their written informed consent. Histopathological examinations of these patients of viral hepatitis had indicated extensive periportal round cell infiltration, fibrosis and scaring. All these patients recovered completely after 6 weeks of treatment except one patient (19 years, second trimester of pregnancy). This patient had also undergone liver biopsy and the histopathology revealed severe round cell infiltration, fibrosis and nodule, all suggestive of cirrhosis. The typing of viral hepatitis of this patient was not conducted since the facility in those days’ was not available. This patient initially showed clinical improvement but died after 6 weeks of treatment. Along with Liv.52 she was also receiving Vit. K and B. Complex vitamins. The cause of death in this unfortunate patient was severe acute viral hepatitis with cirrhosis of liver. The cause of death in this patient appears to be due to extentivity of liver pathology and cannot be attributed to any medication. Further, Liv.52 did not produce any adverse effects in any of the 84 patients who underwent Liv.52 drug therapy. Drug therapy with Liv.52 brought down the earlier reported mortality from 26.7% to 1.1% in patients of jaundice with pregnancy. However, a larger trial will be needed to confirm these findings. Liv.52 is a well studied herbal formulation in various diseases.22,23 It could be a very handy medication in management of Liver diseases in pregnancy.
Liver holds a very important position in the metabolic system of the body. Its active participation in metabolism of carbohydrates, proteins and fats including detoxification of noxious substances gives it a unique position in controlling the metabolic pathways of the body. In spite of tremendous strides in modern medicines, few drugs are known to protect the liver from damage. Liv 52 showed a great promise in this situation as a safet and effective medication.22,23 Further work in this direction will be highly beneficial.
References:
1. Asimuakopoulos, G. Pregnancy and liver disease. Rev Med Chir Soc Med Nat Iasi.2006; 110(2): 326-333.
2. Silvia Sookoian. Liver diseases during pregnancy: Acute viral hepatitis. Annals of Hepatol.
2006; 5: 231-236.
3. Lee, W.M. Pregnancy in patients with chronic liver disease. Gastroenterol Clin North Am.
1992; 21: 889-903.
4. Riely, C.A. Hepatic diseases in pregnancy. Am J Med 1994; 17: 18s-22s.
5. Mishra, L., Seeff, L.B. Viral hepatitis A through E, complicating pregnancy. Gastroenterol Clin North Am. 1992; 21: 873-887.
6. Adams, R.H., Combes, R. Viral hepatitis during pregnancy. JAMA 1965; 192: 195-198.
7. Cahill, K.M. Hepatitis in pregnancy. Surg. Gynecol Obst. 1962; 114: 545-552.
8. Kamat, S.K. Prognosis of infection hepatitis in pregnant women. In: Hepatitis. Vakil, B.J., Shah S.G. (Eds.). Adoni Publishers, Bombay, 1975: pp. 50-53.
9. Sanyal, M., Roy Choudhary, N.N. Jaundice complicating pregnancy. J Obs Gynecol India. 1975; 5: 580-587.
10. Beniwal, M., Kumar, A., Kar, P. Prevalence and severely of acute viral hepatitis and fulminant hepatitis during pregnancy. Ind J Med Microbiol. 2003; 21: 184-185.
11. Dahiya Mona, Kumar Ashok, Kar, P, Gupta, R.K. Kumar Ajay. Acute viral hepatitis in third trimester of pregnancy. Ind J Gastroenterol. 2005; 24: 128-129.
12. Jayanthi, V., Udayakumar, N. Acute liver failure in pregnancy: An overview. Minerva Gastroenterol Dietol. 2008; 54(1): 75-84.
13. Fleming, J.W., Zein, N.N. The liver in pregnancy: Disease vs benign changes. Cleveland Clinic J Med. 2005; 72: 713-721.
14. Acharya, S.K., Panda, S.K., Saxena, A. Acute viral hepatitis in India: A percpective from the East. J Gastroenterol Hepatol. 2000; 15: 9-20.
15. Hieber, J.P., Dalton, D. Hepatitis and pregnancy. J Pediatrics. 1997; 91:545-549.
16. Ohto, H., Terzawa, S. Transmission of Hepatitis C from mother to infant. N Engl J Med.
1994; 330: 744- 750.
Autoimmune hepatitis is a progressive liver disease that predominantly affects women of all ages. Women with AIH can become pregnant and carry successful pregnancies to term with the expectation of delivering a normal baby. However the disease activity is unpredictable in pregnancy. Attenuation of disease activity and spontaneous remissions have been reported due to the immune tolerance induced by the pregnancy. Flares of the disease have also been described in 11% of cases during pregnancy and up to 50% in the postpartum period. Maternal deaths due to liver decompensation, variceal bleeding and porto-pulmonary hypertension have been reported especially when treatment is withdrawn. Preterm delivery and fetal loss occur in 24%.19
A few cases of pregnancy have been described in women with primary biliary cirrhosis (PBC). This is partly due to the later age at presentation of the disease. Although reports suggest an increased risk for premature delivery, still births and liver failure, there are no good data on the outcome of pregnancy in women with PBC. When pregnancy occurs, PBC may induce a new onset pruritus. Diagnosis and management are similar to the non pregnant state. There is no indication for termination of pregnancy in these patients.
Gallstone Disease in Pregnancy:
The risk for sludge and gallstone formation doubles by the end of gestation in comparison with the first trimester (10% versus 5% respectively), and it is further increased with parity. Gallstones are found in 6.5% to 8.4% of nulliparous women, and in 18.4% to 19.3% of women with two or more pregnancies. Most sludge and a third of gallstones disappear spontaneously after pregnancy without resulting in symptoms. Acute cholecystitis and gallstone pancreatitis rarely occur during pregnancy (<1/8000) but they require immediate attention. Medical intervention is often effective.20
Liver disease in pregnancy may manifest as a benign entity that resolves with delivery of the fetus without any consequences, or a more serious disease that could adversely affect the overall well being of both mother and baby potentially resulting in liver failure and death. Although there are no available clinical markers by which to predict with certainty how and when such situations may be encountered, prior history of liver disease, knowledge of the patient’s risk factors for liver disease and the gestational age of the pregnancy are the best guides to a differential diagnosis.
While pregnancy is not reported to increase the susceptibility to drug induced liver disease, drug hepato-toxicity should always be considered in pregnant women taking prescription or non prescription medications.
Pregnant women can react to drug causing jaundice in an exaggerated way as manifested with the use of tetracycline, anaesthetic agents, sulfonamides etc. Antitubercular drugs are also known to induce drug related hepatitis. Therefore selection of drug therapy in pregnancy needs to be carefully made.
Management
Liver disease makes a normal pregnancy a high-risk pregnancy. Extreme vigilance is needed to detect early signs and symptoms of liver dysfunction and to distinguish these from the anticipated benign hepatic changes of pregnancy. Prompt management can save the life of the mother and the baby. Management of liver disease in pregnancy requires a concerted effort between the primary care physician, liver specialist, and obstetrician.
Acute liver failure (ALF) in pregnancy is a common challenging clinical problem both in terms of correct diagnosis and management. Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute viral hepatitis is unaffected by pregnancy, except in patients with hepatitis E (HEV), particularly from endemic countries like India, where ALF carries a high mortality. In both HEV infection and herpes simplex infections, maternal and fetal mortality rates are significantly increased. ALF specific to pregnancy including pre-eclampsia, associated with hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, acute fatty liver of pregnancy, and hepatic infarction result in increased maternal and fetal mortality if not recognized and acted on early. Early recognition of possible causes and prompt treatment are crucial for successful outcome of ALF in pregnancy. Treatment involves prompt delivery, whereupon the liver disease quickly reverses.
Indigenous drugs
Our team has studied the efficacy and safety of Liv.52 in the management of liver disorders in pregnancy. Our study which was conducted way back in 1974-75 consisted of 84 cases of liver disorder in pregnancy and we were interested to know the efficacy and safety of Liv.52 in the treatment of jaundice in pregnancy. This study, we believe is first of its kind at least in those days because it involved management of pregnant women with jaundice.21
In this study population of 84 patients, there were 9 pregnant women who were down with severe viral hepatitis. 21 of eighty four patients had undergone liver biopsy, of course after their written informed consent. Histopathological examinations of these patients of viral hepatitis had indicated extensive periportal round cell infiltration, fibrosis and scaring. All these patients recovered completely after 6 weeks of treatment except one patient (19 years, second trimester of pregnancy). This patient had also undergone liver biopsy and the histopathology revealed severe round cell infiltration, fibrosis and nodule, all suggestive of cirrhosis. The typing of viral hepatitis of this patient was not conducted since the facility in those days’ was not available. This patient initially showed clinical improvement but died after 6 weeks of treatment. Along with Liv.52 she was also receiving Vit. K and B. Complex vitamins. The cause of death in this unfortunate patient was severe acute viral hepatitis with cirrhosis of liver. The cause of death in this patient appears to be due to extentivity of liver pathology and cannot be attributed to any medication. Further, Liv.52 did not produce any adverse effects in any of the 84 patients who underwent Liv.52 drug therapy. Drug therapy with Liv.52 brought down the earlier reported mortality from 26.7% to 1.1% in patients of jaundice with pregnancy. However, a larger trial will be needed to confirm these findings. Liv.52 is a well studied herbal formulation in various diseases.22,23 It could be a very handy medication in management of Liver diseases in pregnancy.
Liver holds a very important position in the metabolic system of the body. Its active participation in metabolism of carbohydrates, proteins and fats including detoxification of noxious substances gives it a unique position in controlling the metabolic pathways of the body. In spite of tremendous strides in modern medicines, few drugs are known to protect the liver from damage. Liv 52 showed a great promise in this situation as a safet and effective medication.22,23 Further work in this direction will be highly beneficial.
1. Asimuakopoulos, G. Pregnancy and liver disease. Rev Med Chir Soc Med Nat Iasi.2006; 110(2): 326-333.
2. Silvia Sookoian. Liver diseases during pregnancy: Acute viral hepatitis. Annals of Hepatol.
2006; 5: 231-236.
3. Lee, W.M. Pregnancy in patients with chronic liver disease. Gastroenterol Clin North Am.
1992; 21: 889-903.
4. Riely, C.A. Hepatic diseases in pregnancy. Am J Med 1994; 17: 18s-22s.
5. Mishra, L., Seeff, L.B. Viral hepatitis A through E, complicating pregnancy. Gastroenterol Clin North Am. 1992; 21: 873-887.
6. Adams, R.H., Combes, R. Viral hepatitis during pregnancy. JAMA 1965; 192: 195-198.
7. Cahill, K.M. Hepatitis in pregnancy. Surg. Gynecol Obst. 1962; 114: 545-552.
8. Kamat, S.K. Prognosis of infection hepatitis in pregnant women. In: Hepatitis. Vakil, B.J., Shah S.G. (Eds.). Adoni Publishers, Bombay, 1975: pp. 50-53.
9. Sanyal, M., Roy Choudhary, N.N. Jaundice complicating pregnancy. J Obs Gynecol India. 1975; 5: 580-587.
10. Beniwal, M., Kumar, A., Kar, P. Prevalence and severely of acute viral hepatitis and fulminant hepatitis during pregnancy. Ind J Med Microbiol. 2003; 21: 184-185.
11. Dahiya Mona, Kumar Ashok, Kar, P, Gupta, R.K. Kumar Ajay. Acute viral hepatitis in third trimester of pregnancy. Ind J Gastroenterol. 2005; 24: 128-129.
12. Jayanthi, V., Udayakumar, N. Acute liver failure in pregnancy: An overview. Minerva Gastroenterol Dietol. 2008; 54(1): 75-84.
13. Fleming, J.W., Zein, N.N. The liver in pregnancy: Disease vs benign changes. Cleveland Clinic J Med. 2005; 72: 713-721.
14. Acharya, S.K., Panda, S.K., Saxena, A. Acute viral hepatitis in India: A percpective from the East. J Gastroenterol Hepatol. 2000; 15: 9-20.
15. Hieber, J.P., Dalton, D. Hepatitis and pregnancy. J Pediatrics. 1997; 91:545-549.
16. Ohto, H., Terzawa, S. Transmission of Hepatitis C from mother to infant. N Engl J Med.
1994; 330: 744- 750.
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