© Springer International Publishing AG 2017
Bijan Eghtesad and John Fung (eds.)Surgical Procedures on the Cirrhotic Patient10.1007/978-3-319-52396-5_1818. Gynecological Procedures and Pregnancy in Women with Liver Cirrhosis
(1)
Section of Maternal-Fetal Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA
(2)
Section of Gynecologic Oncology, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA
(3)
Cleveland Clinic Lerner College of Medicine and Chair Obstetrics, Gynecology and Women’s Health Institute, 9500 Euclid Avenue – A81, Cleveland, OH, USA
Keywords
Menstrual disordersTumor marker- CA-125Pre-conception evaluationPostpartum hemorrhagePerinatal mortalityPre-eclampsiaIntroduction
Women with liver cirrhosis are more likely to have menstrual problems and vaginal bleeding than healthy women. This is likely related to altered homeostasis, clotting factor deficiency, and high concentration of estrogen [1, 2]. The incidence of hysterectomy has been reported to be higher in women with liver cirrhosis due to higher rate of vaginal bleeding [3]. Postoperative mortality and morbidity are significantly higher in women with liver cirrhosis. The overall risk of postoperative complications and/or mortality is related to several factors including severity of liver disease quantified by Model of End-stage Liver Disease (MELD score), comorbid conditions, age, ASA class, type of surgery, and surgical expertise [4]. Cardiac surgery has the highest risk, while extra-thoracic/extra-abdominal procedures have the lowest risk [5]. The mortality for abdominal surgery fluctuates between 11 and 76% [5]. In one report in women with liver cirrhosis undergoing hysterectomy, the risk of death within 30 days after discharge was 11-fold higher compared to women with no liver cirrhosis [6].
Menstrual Abnormalities and Liver Cirrhosis
Heavy menstrual bleeding and amenorrhea are common in women with chronic liver disease and liver cirrhosis. High estrogen concentration associated with chronic liver disease often results in unopposed stimulation and proliferation of the endometrial linings which consequently lead to heavy menstrual or anovulatory cycle. In a study of postmenopausal women with chronic liver disease, free estrogen concentrations and free estrogen to androgen ratio were found to be higher than in age-matched controls [3]. In women undergoing liver transplant for liver disease, 28% had irregular and unpredictable bleeding and 30% had amenorrhea [7]. After transplant, 26% had irregular bleeding and 26% had amenorrhea. A total of 95% of women under the age of 46 had return of menstrual bleeding within the first year after transplantation. Liver function did not correlate with menstrual pattern [7]. After liver transplant, the majority of the patients are expected to resume their sexual activity and can get pregnant [7]. The average time for recovery of menstrual function is about 3 months [8]. In one report and among the 24 patients under 45 year old, six women conceived seven pregnancies [7].
Tumor Markers in Liver Cirrhosis
CA-125 level is a marker often used in patients with adnexal masses or suspected ovarian/tubal or primary peritoneal malignancies. CA-125 is often elevated in patients with liver cirrhosis especially in those with ascites. The average CA-125 levels in patients with liver cirrhosis with ascites is about 275–321 U/ml vs. 13–72 U/ml in those with no ascites [9, 10]. The average CA-125 level in patients with liver cirrhosis and ascites is not different from those with malignant ascites. The level does correlate with presence and amount of ascites and degree of liver insufficiency but not to the etiology of ascites or liver cirrhosis [9–11]. Therefore, it is important to take this into consideration in evaluating ascites and adnexal masses among patients with liver cirrhosis and elevated CA-125 to avoid unnecessary surgery especially given the high rate of postoperative morbidity and mortality.
Risk Factors and Timing of Surgery
Abdominal surgery is associated with significant morbidity and mortality risks in patients with liver cirrhosis. The perioperative morality from nonhepatic abdominal surgery range from 16 to 75%. Reported risk factors include low hemoglobin, low albumin levels, being on dialysis, high ASA class, respiratory failure, gastrointestinal (GI) bleeding, active infection, and emergency surgery. In one study of 772 patients with liver cirrhosis undergoing major surgery, patients with liver cirrhosis were at increased risk of mortality up to 90 days after surgery. In multivariate analysis, Model of End-Stage Liver Disease (MELD) score, ASA class, and age were the only risk factors that predicted mortality within 30 days, 90 days, 1 year, and long term regardless of type of surgery [4].
MELD score is a continuous score based on only laboratory data, which include serum bilirubin, serum creatinine and International Normalized Ratio (INR) levels. It has been created and validated to predict short-term outcome in patients with liver disease. Child–Turcotte–Pugh score is based on both objective laboratory data and assessment of ascites and encephalopathy. Compared to MELD’s score, Child’s score places patients in categories and it is not a continuous score. The two scoring system has been shown to predict perioperative outcome including morbidity and mortality. The 30-day mortality range from 5.7% in patients with MELD score of <8 and can be as high as >50% in those with MELD score of >20 [4]. In patients undergoing elective colorectal surgery, the 30-day mortality, major complications, and respiratory complications were significantly correlated with MELD score. The 30-day mortality was 0.69% for patients with MELD score of 6, 1.6% for those with score of 7–11, 4.5% for those with score of 11–15, and 5% for those with score of >15 [12]. In general surgery literature, for every 1-point increase greater than the mean MELD score, there was a 7.8–11.6% increase in any postoperative complication [13]. In the study of 30-day postoperative outcome after hysterectomy in patients with liver cirrhosis, Nielsen et al. reported 30-day mortality of 7.6% in patients with liver cirrhosis compared to 0.6% in patients without liver cirrhosis [6]. Postoperative mortality after major abdominal surgery in patients with MELD score of 9 or more has been reported to be 29% in one report while the mortality in patients with Child’s score of A, B, and C are 10%, 30–31%, and 76–82%, respectively [14]. Teh et al. in the study of operative mortality following surgery reported that patients with a MELD score of 7 or less had a mortality rate of 5.7%; patients with a MELD score of 8–11 had a mortality rate of 10.3%; and patients with a MELD score of 12–15 had a mortality rate of 25.4% [4]. In this study, age and ASA class were also a predictor of mortality beside MELD score. ASA class of IV was equivalent to MELD score of 5.5 and ASA class of V was associated with 100% mortality. Age greater 70 years was equivalent to MELD score of 3 [4].
Preoperative Work Up and Operative Planning
Preoperative management of patients with liver cirrhosis relies on optimal medical management of expected conditions associated with liver cirrhosis including management of ascites, coagulopathy, prevention of encephalopathy and treatment of postoperative complications like acaluculus acute cholecystitis [15]. Patients with liver cirrhosis tend to have reduced hepatic blood flow related to decreased portal blood flow. Further, anesthetic agents can lead to decrease in hepatic blood flow by 40–50%. Therefore, agents that have less effect on hepatic arterial blood flow are preferred [14, 16].
Risk factors for acute intraoperative hypoxemia include ascites, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension.
Patients with ascites or hepatic hydrothorax should be managed and optimized before surgery. On the other hand, elective major surgery should be avoided if possible and replaced with alternative nonsurgical options for patients with hepatopulmonary syndrome or portopulmonary hypertension [14, 17].
Patients with liver cirrhosis might need larger doses of muscle relaxant due to the increased volume of distribution in these patients. Sedative, narcotics, and intravenous induction agents are safe in patients with compensated liver disease but should be used with caution in patients with hepatic dysfunction as they may lead to hepatic encephalopathy and prolonged time of depressed consciousness [14].
Patients with known liver disease need extensive preoperative work up and should be optimized for an elective surgery. Minimally invasive surgery using either robotic or traditional laparoscopic platforms has been found to be associated with faster recovery time, favorable perioperative outcome, and shorter hospital stay compared to open laparotomy [18–21]. Therefore, all efforts should be directed to utilize the minimally invasive approach in those patients. Further, these surgeries need to be done by an expert surgeon and in a tertiary center with expertise in taking care of those patients.
Contraindications to elective surgery in patients with liver disease include acute liver or renal failures, acute viral hepatitis, alcoholic hepatitis, cardiomyopathy, severe coagulopathy, and hypoxemia [14].
Postoperative Management
After surgery, patients with liver cirrhosis should be monitored for signs of hepatic decompensation like coagulopathy, renal dysfunction, and encephalopathy. Prothrombin time and serum bilirubin levels can be helpful. Renal function and serum glucose level should be monitored too. Maintenance of intravascular volume is very important to avoid risk of underperfusion or fluid overload [14].
Alternative Nonsurgical Options for Abnormal Uterine Bleeding
Given the significant morbidity and mortality associated with surgery in patients with liver cirrhosis, it is important to consider other conservative nonsurgical options. These options include oral combined contraceptive pills, antifibrinolytic agents like tranexamic acid, and progesterone therapy. Progesterone can be oral, injectable, or intrauterine. Minor procedures might be considered for acute bleeding like dilation/curettage or endometrial ablation.
Pregnancy and Cirrhosis
Pregnancy in women with liver cirrhosis is an uncommon clinical situation estimated to occur in 1 in 5,950 pregnancies [22]. The rarity of this occurrence can be attributed to the decreased fertility associated with cirrhosis as well as the low incidence of cirrhosis in women in their reproductive years. Cirrhosis is typically associated with anovulation and amenorrhea secondary to the metabolic and hormonal derangements associated with chronic liver disease. In addition, it is estimated that only 45 cases of cirrhosis occur in every 100,000 women of reproductive age [23]. However, with advances in treatment of liver disease and the increased incidence of conditions leading to cirrhosis, more women with cirrhotic liver disease are becoming pregnant [24].
The existing literature on cirrhosis and pregnancy outcomes consists mainly of small case series, case reports and retrospective reviews [22, 25–30]. Many of these are from decades ago and thus do not reflect important advances in medical care such as routine administration of antenatal steroids prior to preterm delivery and neonatal intensive care. More recent literature suggests decreased maternal mortality and pregnancy complications compared to reports from prior decades. This likely reflects advances in treatment of liver disease and its complications as well as contemporary standards in maternal and neonatal care [24, 31, 32]. Maternal and neonatal morbidity and mortality, however, are still significantly higher than the general population. Therefore, comprehensive, multidisciplinary prenatal care with specialists in maternal–fetal medicine, gastroenterology, anesthesiology, surgery, and neonatology in a tertiary care center is critical for successful outcomes in these pregnancies.
Preconception Evaluation
Although the majority of pregnancies are unplanned, preconception evaluation and counseling with individualized evaluation of risk can be extremely valuable in women with cirrhosis who may be considering pregnancy. Furthermore, the decreased fertility associated with cirrhosis may lead women to seek assisted reproductive technologies posing a complex clinical situation requiring expert consultation. As with pregnancy in the setting of any preexisting medical condition, risks can be considered in two major categories: (1) what is the effect of the disease and its treatment on the pregnancy and fetus and (2) how will the pregnancy affect the natural course of the disease. Many diseases impact maternal physiology in ways that can adversely affect placental and fetal development. In addition, medications used to treat conditions must be evaluated for teratogenicity and other effects on the fetus. Dosage adjustments secondary to the increased volume of distribution during pregnancy must also be considered. Pregnancy itself can also impact the natural course of a disease secondary to the increased physiologic demands and hormonal changes. In the event of an unplanned pregnancy, termination of pregnancy may be a consideration depending on the severity of maternal disease and risk for major morbidity and mortality.
Although pregnancy outcomes with cirrhosis are typically related to the severity of disease and not necessarily the etiology, it is still important to consider the pregnancy implications of the etiology of the cirrhosis. Infectious causes such as viral hepatitis may be transmittable to the fetus and therefore necessary precautions and interventions should be considered. Genetic causes such as hemochromatosis and alpha-1 antitrypsin deficiency also pose a risk of transmission and genetic counseling and prenatal diagnosis should be offered. Fetal alcohol syndrome should be discussed in cases of alcohol related liver injury if alcohol is still being used. Fetal-alcohol syndrome, characterized by fetal growth restriction, dysmorphic facial features, and cognitive and behavioral impairments, is common when alcohol use does not cease during pregnancy [33]. Many etiologies of cirrhosis such as autoimmune hepatitis (AIH) will typically require medical treatment throughout pregnancy typically with prednisone and azathioprine [34].
The Model for End-Stage Liver Disease (MELD) score was initially developed to predict mortality after transjugular intrahepatic portosystemic shunt (TIPS) insertion but is now widely used in clinical practice to predict prognosis in patients with cirrhosis and to prioritize for liver transplantation. The MELD score has been evaluated as a tool for prediction of maternal and neonatal outcomes in pregnancies complicated by cirrhosis. In 62 pregnancies occurring in 29 women with cirrhosis, higher MELD scores at the time of conception were associated with preterm delivery (<37 weeks), Neonatal Intensive Care Unit (NICU) admission, and significant maternal complications including variceal bleeding and hepatic decompensation. In this cohort, the median MELD score at conception was 7 and a 58% live birth rate was reported of which 64% were premature births. The rate of serious maternal morbidity was 10%. A MELD score of 10 or above prior to conception had an 83% sensitivity and specificity for predicting a major maternal complication while a MELD score of 6 or less was not associated with significant morbidity. Based on these results the MELD score can useful in preconception counseling [35].
Preconception evaluation allows the opportunity for evaluation of the severity of disease, review and tailoring of maternal medication regimens and discussion of the risks and benefits of these medications during pregnancy and breastfeeding. It also allows for the identification of women at high risk for significant maternal complications in whom pregnancy may be contraindicated. A frank discussion of neonatal outcomes and prematurity should similarly be included.
Pregnancy Complications
Maternal mortality has been reported to range from 10 to 18% in older studies however more recent reports suggest a significantly lower rate of approximately 1.6% and decompensation rates of 10% [31]. Variceal bleeding, hepatic decompensation, splenic artery aneurysm rupture, and postpartum hemorrhage are among the major maternal complications associated with cirrhosis. Fetal/neonatal complications include spontaneous abortion, stillbirth, and preterm delivery with its associated neonatal morbidity and mortality.
Esophageal Varices
Bleeding from esophageal varices is the most common cause of death during pregnancy in the setting of cirrhotic liver disease [22]. Esophageal variceal bleeding has been reported in 18–32% of pregnant women with cirrhosis, 50% of those with cirrhosis and known portal hypertension, and up to 78% with known esophageal varices [36, 37]. The physiologic changes of pregnancy such as increased plasma volume and the compression of the inferior vena cava by the gravid uterus worsen portal hypertension and esophageal varices [23]. Bleeding is most likely to occur in the second and third trimesters when these changes are the greatest.
In the 1980s, endoscopic sclerotherapy was generally accepted as the first-line treatment procedure for bleeding esophageal varices and most reports of variceal bleeding during pregnancy were treated this way [38–41]. There are no studies regarding the safety of the conventionally used sclerosing agents on the fetus and the potential for adverse effects remains unknown. Vasoactive drugs used to achieve hemostasis such as vasopressin are contraindicated during pregnancy as they decrease placental perfusion and may lead to an increased risk of placental abruption [37].
Currently, endoscopic band ligation is the preferred method of treatment and for acute hemorrhage from esophageal varices in both pregnant and nonpregnant patients. Band ligation appears to have a greater efficacy and fewer complications compared to sclerotherapy [23, 31, 42–44]. In addition, band ligation avoids any potential fetal risk from chemical instillation of sclerosing agents. In 1998, Starkel et al. reported the first case of successful band ligation in a pregnant patient with acute bleeding from esophageal varices in a pregnant patient [42]. Transjugular intrahepatic portosystemic shunt or TIPS procedure has been successfully reported during pregnancy complicated by refractory variceal hemorrhage [45, 46].
Ideally screening endoscopy should be performed prior to pregnancy for evaluation and treatment for esophageal varices. If identified prior to conception, prophylactic endoscopic band ligation or initiation of beta-blocker treatment is thought to decrease risk of variceal bleeding during pregnancy [31]. Beta-blockers reduce pulse pressure in the varices and are widely used in the nonpregnant population for primary prophylaxis. Beta-blockers are used extensively in pregnancy to treat various conditions including hypertension, arrhythmias, and migraines. Their use has not been linked to an increase in fetal malformations and they are generally considered to be safe in pregnancy. Some studies have reported an increase in fetal growth restriction and neonatal hypoglycemia and monitoring for these conditions is suggested [47].
Related posts:
Hernia Repair in Cirrhotic Patients: Type, Timing, and Procedure of Choice
Head and Neck Issues in Cirrhotic Patients
Ophthalmic Surgery in Cirrhosis
Oral Surgery on the Patient with Cirrhosis
Pathophysiology of Cirrhosis and Portal Hypertension
Non-transplant Management of Portal Hypertension in Children
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