Liver Disease In Pregnancy Research Articles

Fulminant hepatic failure in pregnancy: challenges, management strategies, prognosis and outcomes

Fulminant hepatic failure is defined as a sudden, severe impairment of hepatic function leading to an encephalopathy, which occurs within eight weeks of appearance of first symptoms in the absence of pre-existing liver disease. The spectrum of liver disease in pregnancy may range from mild asymptomatic transaminitis to fatal and irreversible deterioration in liver function leading to significant morbidity and even mortality. Hepatic dysfunction in pregnancy may be categorized into Pre-eclampsia-associated liver diseases such as pre-eclampsia/eclampsia, the HELLP syndrome and Acute fatty liver of pregnancy (AFLP), and other causes of hepatic dysfunction namely Hyperemesis gravidarum (HG) and Intrahepatic cholestasis of pregnancy (IHCP). For this review, a search was conducted for published articles, case reports and clinical trials in MEDLINE/Pubmed from 1970 to 2020 with the keyword’s fulminant hepatic failure, acute liver failure in pregnancy, pre-eclampsia, HELLP and AFLP. We concluded that fulminant hepatic failure is one of the most dreaded complications in pregnancy in obstetrical units worldwide. Mandatory screening for etiology, early diagnosis and initiation of supportive management as soon as possible are absolutely essential to ensure better maternal and fetal outcomes. Effective communication with the obstetrician regarding timely delivery/termination of pregnancy ensures a favourable prognosis in the majority of cases. Liver transplant is a definitive life-saving option for cases of severe fulminant hepatic failure in pregnancy, and management has to be suited to each patient individually, keeping in mind the well-being of both the mother, and the child.

Liver diseases in pregnancy and outcomes: A retrospective study from Saudi Arabia.

Liver diseases unique to pregnancy are common causes of both maternal and fetal mortality and morbidity. We retrospectively studied liver diseases unique to pregnancy, including hyperemesis gravidarum (HG); intrahepatic cholestasis of pregnancy; eclampsia; preeclampsia; hemolysis, elevated liver enzymes, and a low platelets (HELLP) syndrome; and acute fatty liver of pregnancy. We collected data including maternal age, gestational weeks at presentation and at delivery, mode of delivery, number of parity, and laboratory markers at 0, 1 week, and within 24 hours after delivery; from 112 patients (mean age, 29.8 years) from April 2015 - March 2017. SPSS 22 was used for statistical analysis. We The commonest liver disease in pregnancy was pre-eclampsia followed by HG. HG patients were younger compared with those with eclampsia and preeclampsia (P=0.025). Gestational week at presentation and the week of delivery were significantly greater for preeclampsia/eclampsia and HELLP patients compared to HG. Primigravida represented 42.9% of our patients. Fetal complications were reported in 29 (26%) of cases. Of those, 17 had fetal or neonatal death. Fourteen mothers (12.5%) had ICU admission. Pregnancy related liver diseases are important causes for fetal mortality and morbidity. Maternal age and gestational weeks are important predictors of fetal and maternal outcomes.

A rare presentation of acute fatty liver disease in pregnancy in the background of T-cell non-Hodgkin lymphoma

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Relevance of reproductive health to comprehensive hepatology care

In the USA, chronic liver disease is the sixth most common cause of mortality in young women aged 20–44 years.1 Moreover, non-alcoholic fatty liver disease, which is now the leading cause of chronic liver disease in the USA, has seen the most marked rise in incidence in young adults compared with other age groups.2 These epidemiological trends are consistent with pregnancy data showing a near tripling of the prevalence of non-alcoholic fatty liver disease in pregnancy over the past decade, and an increase in alcohol-related liver disease in women of reproductive age.

The problem of uncertain adherence to study interventions: what can we conclude?

Intrahepatic cholestasis of pregnancy (ICP), the most common liver disease in pregnancy, is characterised by elevated bile acid concentrations and maternal pruritus, and has been associated with increased rates of stillbirth, preterm birth, and neonatal unit admission. Fetal complications have been associated with rising serum bile acids (Glantz et al, Hepatology 2004;40:467- 474) and, according to a recent individual patient data meta-analysis (Ovadia et al, The Lancet 2019;393:899-909), the risk of stillbirth increased in women with serum bile acid concentrations of 100 μmol/l or more.

The Diagnosis and Management of Acute Fatty Liver of Pregnancy

Acute fatty liver of pregnancy (AFLP) is a rare catastrophic illness constituting an obstetric emergency in third trimester of pregnancy and may have complications for both mother and fetus, including death. Yet it is still unclear, the pathogenesis of AFLP has been identified related to defects in fatty acid metabolism during pregnancy, especially in the setting of fetal genetic defects in fatty oxidation. Establishing the diagnosis of AFLP is challenging, further it may overlap with other liver diseases of pregnancy, such as preeclampsia and hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome. The management of AFLP is a multidisciplinary progress providing the prompt intervention more than the termination of the pregnancy. The awareness of AFLP is highly needed to provide early diagnosis and management so that it can reduce the morbidity and mortality.

Liver disease in pregnancy.

Development of liver diseases during pregnancy is not uncommon. They are caused by either a disorder that is unique to pregnancy or an acute or chronic liver disease that already exists or coincidentally develops as a comorbidity of pregnancy. Liver diseases unique to pregnancy include hyperemesis gravidarum; hypertensive disorders of pregnancy, such as pre-eclampsia/eclampsia; hemolysis, elevated liver enzymes, and low platelet count syndrome; intrahepatic cholestasis of pregnancy; and acute fatty liver of pregnancy. Chronic liver diseases that affect pregnancy, or are affected by pregnancy, mainly include autoimmune liver diseases and non-alcoholic fatty liver disease. Prompt diagnosis and management of liver diseases in pregnancy, while very challenging, is extremely important, as they might cause adverse maternal and fetal outcomes. Therefore, a multidisciplinary, collaborative approach involving both hepatologists and obstetricians is required. In this review article, the up-to-date epidemiology, etiology, clinical features, and outcomes of liver diseases in pregnancy are discussed, to promote a deeper understanding among physicians, and subsequently improved outcomes.

Non-alcoholic fatty liver disease in pregnancy is associated with adverse maternal and perinatal outcomes

The prevalence of non-alcoholic fatty liver disease (NAFLD) is rising in young adults, with potential implications for reproductive-aged women. Whether NAFLD during pregnancy confers more serious risks for maternal or perinatal health is unclear. Using weighted discharge data from the US national inpatient sample, we evaluated temporal trends of NAFLD in pregnancies after 20 weeks gestation, and compared outcomes to pregnancies with other chronic liver diseases (CLDs) or no CLD. Study outcomes included preterm birth, postpartum hemorrhage, hypertensive complications (pre-eclampsia, eclampsia, and/or hemolysis, elevated liver enzymes, and low platelets syndrome), and maternal or fetal death. NAFLD prevalence was estimated by calendar year and temporal trends tested by linear regression. Outcomes were analyzed by logistic regression adjusted for age, race, multiple gestation, and pre-pregnancy diabetes, obesity, dyslipidemia and hypertension. Among 18,574,225 pregnancies, 5,640 had NAFLD and115,210 had other, non-NAFLD CLD. Pregnancies with NAFLD nearly tripled from 10.5/100,000 pregnancies in 2007 to 28.9/100,000 in 2015 (p <0.001). Compared to the other groups, patients with NAFLD during pregnancy more frequently experienced gestational diabetes (7-8% vs. 23%), hypertensive complications (4% vs. 16%), postpartum hemorrhage (3-5% vs. 6%), and preterm birth (5-7% vs. 9%), all pvalues ≤0.01. On adjusted analysis, compared to no CLD, NAFLD was associated with hypertensive complications, preterm birth, postpartum hemorrhage and possibly maternal (but not fetal) death. The prevalence of NAFLD in pregnancy has nearly tripled in the last decade and is independently associated with hypertensive complications, postpartum hemorrhage and preterm birth. NAFLD should be considered a high-risk obstetric condition, with clinical implications for pre-conception counseling and pregnancy care. The prevalence of non-alcoholic fatty liver disease (NAFLD) in pregnancy has almost tripled over the past 10 years. Having NAFLD during pregnancy increases risks for both the mother and the baby, including hypertensive complications of pregnancy, bleeding after delivery, and preterm birth. Thus, pre-conception counseling is warranted with consideration of high-risk obstetric management among women with NAFLD in pregnancy.

Contributors: Liver Disease in Pregnancy

Contributors: Liver Disease in Pregnancy

Chronic Liver Disease in the Obstetric Patient.

Chronic liver disease in pregnancy is rare. Historically, many chronic liver diseases were considered contraindications to pregnancy; however, with current monitoring and treatment strategies, pregnancy may be considered in many cases. Preconception and initial antepartum consultation should focus on disease activity, medication safety, risks of pregnancy, as well as the need for additional monitoring during pregnancy. In most cases, a multidisciplinary approach is necessary to ensure optimal maternal and fetal outcomes. Despite improving outcomes, pregnancy in women with the chronic liver disease remains high risk.

Foreword: Liver Disease in Pregnancy.

Foreword: Liver Disease in Pregnancy.

Liver Disease in Pregnancy: What's New.

Liver disease in pregnancy may present as a disorder that is unique to pregnancy or as an acute or chronic liver disease occurring coincidentally in pregnancy. Hepatic diseases that are unique to pregnancy include hyperemesis gravidarum; preeclampsia/eclampsia; the syndrome of hemolysis, elevated liver enzymes, and low platelets; intrahepatic cholestasis of pregnancy; and acute fatty liver of pregnancy. Acute and chronic forms of primary hepatic disorders that are seen in pregnancy include viral hepatitis, autoimmune hepatitis, nonalcoholic fatty liver disease, and cirrhosis. Because of the need to consider both maternal and fetal health, there are special considerations for the implementation of diagnostic strategies and pharmacologic therapies for liver disease that occurs in pregnancy. An understanding of the pathogenesis and expression of liver diseases in pregnancy has been evolving, and various diagnostic and prognostic tools have been studied in order to determine noninvasive approaches to identifying and staging of such diseases. Investigations have also been underway to evaluate the safety and utility of existing and new therapeutic agents that previously were thought to not be compatible with pregnancy. This review will explore updates in the epidemiology, diagnosis, and management of various liver diseases seen in pregnancy.

Laboratory evaluation of deranged liver chemistries in pregnancy

Liver chemistries (LCs) serve as important noninvasive methods of assessing liver function, hepatocellular injury and cholestasis. In pregnant women, alterations in some LCs occur as a result of the normal physiologic changes of pregnancy. Despite this, majority of LCs including platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, gamma-glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH), remain within normal limits throughout the course of pregnancy. On the contrary, levels of alpha fetoprotein (AFP) and alkaline phosphatase are expected to rise. Similarly, the coagulation system undergoes significant changes, increasing production of clotting factors and reducing native anticoagulants, all which act to induce a prothrombotic state in preparation for the blood loss associated with delivery. It is, therefore, important to distinguish between laboratory changes associated with normal physiological changes and liver diseases in pregnancy. Abnormal LCs occur at an overall rate of 3–5% in pregnant women. Detection of these abnormalities in LC’s may indicate an underlying liver disease or disease process affecting the liver, which can have negative health implications for both the mother and unborn fetus. A classic approach to liver disease in pregnancy includes liver diseases that are unique to pregnant women, pre-existing liver diseases, and those emerging coincidentally during pregnancy. A variety of changes in LC’s are observed in liver disease in pregnancy, each with a unique pattern of derangements. This review summarizes the differential diagnosis and approach consideration for presentation of deranged LCs in pregnant women, while giving special emphasis to laboratory investigations.

2393 A Unique Case of Liver Disease in Pregnancy

INTRODUCTION: Pregnancy-related liver disease is seen in up to 3% of all pregnancies. Pregnancy-related etiologies include hyperemesis gravidarum, pre-eclampsia, HELLP, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy (AFLP). Given the significant morbidity and mortality associated with these conditions, there is a need for early recognition. Here we present a unique case of pregnancy-related liver disease in an asymptomatic patient. Despite a thorough evaluation for liver and non-liver related causes, her lack of symptomatology and associated laboratory findings made establishing a definitive diagnosis difficult. CASE DESCRIPTION/METHODS: 30 year-old woman G1P0 at 29 weeks gestation with dichorionic triamniotic triplets presented with generalized weakness. Her past medical and surgical histories were otherwise non-contributory and her only medication included prenatal vitamins. The physical exam was unremarkable except for a gravid uterus. Throughout her hospital course, she remained normotensive. Admission labs were significant for an abnormal liver profile: AST 200 U/L, ALT 349 U/L, ALP 121 U/L, and total bilirubin 0.5 mg/dL, compared to a previous normal baseline. Complete blood count and renal function were normal. Abdominal ultrasound (US) showed increased liver echogenicity consistent with fatty liver disease. Additional work-up revealed a normal coagulation profile, fibrinogen, lactate dehydrogenase, and haptoglobin. Urinalysis was negative for proteinuria. Serologies for viral and autoimmune hepatitis were negative. Total bile acids were mildly elevated at 9.3 umol/L (normal &lt; 6.8umol/L) and 24-hour urinary copper was normal. Though she remained asymptomatic, liver enzymes continued to uptrend. On day 16 she underwent urgent C-section due to rising liver enzymes and evidence of fetal distress. Liver enzymes continued to rise until POD1 before rapidly declining. DISCUSSION: This was a unique case of pregnancy-related liver disease of unknown etiology, but most consistent with an early manifestation of AFLP. We suspected AFLP based on the steatosis noted on US, however, since we could not check her children for LCHAD deficiency a definitive diagnosis could not be made. Surveillance US showing resolution of steatosis would have helped confirm the diagnosis however the patient was lost to follow up. This was an interesting presentation of AFLP as most cases are discovered in women presenting with acute liver failure; this case was unique in that it was discovered unexpectedly.

Intrahepatic Cholestasis of Pregnancy: Spontaneous vs in vitro Fertilization.

Aim:Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnancy. Although it was shown that multiple pregnancy and hormone therapies increase the risk of ICP, there is limited information that compared spontaneous fertilization and in vitro fertilization (IVF) from the aspect of developing ICP. In our study, we investigated the potential relationship between ICP and IVF/ spontaneous pregnancy.Materials and methods:We reviewed the records (between June 2007 and December 2014) of pregnancies with ICP who were referred to gastroenterology clinics in three different hospitals. Fifty-nine pregnancies (43 spontaneous fertilization, 16 IVF) with ICP were analyzed from the aspect of age, fertilization type, multiple/singleton pregnancy, delivery week, and biochemical results.Results:We found that serum bile acid levels were higher in the IVF group than the spontaneous fertilization group (32.8 ± 20 vs 19.6 ± 19 μmol/L; p < 0.05). There was a significant inverse correlation between serum bile acid levels and gestational age (r = -0.42, p < 0.01) in the whole group. There was no difference between IVF and spontaneous fertilization groups in term of age, onset time of symptoms, serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin levels, prothrombin time (PT), international normalized ratio (INR), and platelet count.Conclusion:Our results suggest that the serum bile acid levels are higher in IVF than in spontaneous pregnancies with ICP, but its clinical implications are not clear. Further prospective studies with large number of ICP cases are needed to clarify the effect of IVF on ICP.How to cite this article: Bolukbas FF, Bolukbas C, Balaban HY, Aygun C, Ignak S, Ergul E, Yazicioglu M, Ersahin SS. Intrahepatic Cholestasis of Pregnancy: Spontaneous vs in vitro Fertilization. Euroasian J Hepato-Gastroenterol 2017;7(2):126-129.

Acute Fatty Liver Disease of Pregnancy: A Review

Acute fatty liver disease of pregnancy (AFLP) is an uncommon but serious obstetrical emergency, usually occurring during the third trimester. The

Essential phospholipids use in the treatment of drug-induced liver injury in pregnant women

The aim of the study was evaluation the efficiency of essential phospholipids for the treatment of drug-induced liver disease in pregnant women. In the research group included 67 pregnant women with clinical and biochemical manifestations of drug-induced cytolytic syndrome, 58 pregnant women (the main group) were treated with hepatoprotectors, 9 women (the control group) the treatment of essential phospholipids wasn’t carried out. Patients of both groups were eliminated hormonal drugs and other drugs or their dosage is reduced as much as possible. Drug liver disease in pregnancy is manifested by increased transaminase, in some cases accompanied by increased level of gamma glutamyl transpeptidase, liver glutamate dehydrogenase. Against the background of the treatment in both groups decrease in transaminases have been reported. But the rate of decline of aminotransferases was differed, so in the main group decrease of ALT and AST was occurred faster than in the control group.

LABORATORY DIAGNOSIS OF DRUG-INDUCED LIVER DAMAGE IN PREGNANCY

The publication provides the latest data on the problem of drug liver disease, particularly during pregnancy. Classification of liver diseases, selected risk factors, mechanisms of drug liver damage and laboratory tests are described. Physiological changes in liver function during pregnancy that must be considered in the diagnosis of drug liver disease in pregnancy are outlined.

A Case of Idiopathic Acute Hepatitis with Complications in Mid-Trimester Pregnancy

Although liver diseases in pregnancy are rare, they can seriously affect mother and fetus. Although any type of liver disease can develop during pregnancy, it is difficult to identify features of liver disease in pregnant women because of physiological changes. Physiologic changes of pregnancy can be confounding with the symptoms of liver diseases. It can not only complicate mother’s life but also burden life of fetus to growth restriction. We describe an uncommon case of acute hepatitis with disseminated intravascular coagulation and clinical chorioamnionitis coincidentally in mid-trimester pregnancy. She experienced the development of acute hepatitis of unknown causes. She presented with fever, maternal tachycardia, and fetal tachycardia. We decided termination of pregnancy because of 16 weeks’ gestation. After termination, she was managed about acute hepatitis. So we report our case with a brief reviews of the literature. Key words: Hepatitis; Mid-trimester pregnancy; Chorioamnionitis

Obstetric Outcome in Women with Chronic Liver Disease.

This study determines the prevalence, causes and outcome of pregnancy in women with chronic liver diseases in a tertiary level teaching institute in Southern India. Retrospective analysis of case records was carried out between December 2010 and May 2015 in the departments of Obstetrics and Gynecology and Gastroenterology including pregnant women diagnosed to have chronic liver diseases prenatally or during pregnancy. The frequency of chronic liver disease in pregnancy was 50 among 10,823 deliveries (0.4%). Twenty-six women with chronic liver disease had 50 pregnancies during the study period. Fifty percent of the women had cirrhosis. Maternal complications occurred in 22% of the study group. Variceal hemorrhage occurred in 4%, and hepatic decompensation occurred in 16%. There were two maternal deaths (4%). Obstetric complication such as preeclampsia, postpartum hemorrhage and puerperal infection occurred in 18, 14 and 18%, respectively. Abortion occurred in 34%, 55% in cirrhotic and 4.8% in non-cirrhotic. Live birth rate of 76% was significantly higher (p<0.014) in the non-cirrhotic group compared to cirrhotic group. Pregnancies in chronic liver disease are associated with high rate of abortions. Live birth rates are better and complications such as variceal bleeding or decompensation of liver disease are less common than previously reported.