Risk of stillbirth in United States patients with diagnosed intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with a 4- to 10-fold increase in the risk of stillbirth in the absence of intervention, leading to recommendations for antenatal assessment, ursodiol use, and often preterm or early term delivery. OBJECTIVE: This study aimed to determine whether current management strategies for intrahepatic cholestasis of pregnancy mitigate the elevated risk of stillbirth at a population level. STUDY DESIGN: This was a retrospective cohort study using the 2015-2020 National Readmissions Database, an administrative database developed by the United States Agency for Healthcare Research and Quality. Our study identified delivery hospitalizations, gestational age at delivery, occurrence of intrahepatic cholestasis of pregnancy and stillbirth, and comorbid conditions using the International Classification of Diseases diagnosis and procedure codes. Moreover, this study compared the timing of delivery and stillbirth rates of pregnant patients with intrahepatic cholestasis of pregnancy vs those without intrahepatic cholestasis of pregnancy at the time of delivery hospitalization. RESULTS: This study identified a cohort of 9,987,705 delivery hospitalizations in the National Readmissions Database, corresponding to a weighted national estimate of 18,609,207 births. Of these births, 152,040 (0.8%) were noted to have an intrahepatic cholestasis of pregnancy diagnosis. Patients with an intrahepatic cholestasis of pregnancy diagnosis were older, with small differences in comorbidities, such as a higher rate of gestational diabetes mellitus, than patients without an intrahepatic cholestasis of pregnancy diagnosis at delivery hospitalization. The overall rates of stillbirth were lower among those with intrahepatic cholestasis of pregnancy than among those without intrahepatic cholestasis of pregnancy (252 vs 386 per 100,000 deliveries; risk difference, 133 fewer per 100,000 deliveries; 95% confidence interval, 98-170), a finding that persisted after adjustment for insurance status, socioeconomic factors, and comorbid conditions (risk difference, 160 fewer stillbirths per 100,000 deliveries; 95% confidence interval, 127-194). Furthermore, although patients with intrahepatic cholestasis of pregnancy were more likely to deliver before term than those without intrahepatic cholestasis of pregnancy (30.1% vs 9.3%; P<.001), increased rates of stillbirth were not noted at any point after stratification of the cohort by gestational age at delivery. CONCLUSION: Patients with intrahepatic cholestasis of pregnancy diagnosis codes delivered earlier than those without intrahepatic cholestasis of pregnancy diagnosis codes, but the percentage of births affected by stillbirth was lower, even when stratifying for gestational age at birth. These results may provide reassurance to patients receiving an intrahepatic cholestasis of pregnancy diagnosis that current management does mitigate stillbirth risk in intrahepatic cholestasis of 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.

Identification and Management of Abdominal Wall Varices in Pregnancy.

BACKGROUND: Portal hypertension in pregnancy is associated with elevated risk of variceal hemorrhage. Ectopic varices, those located outside the esophagus or stomach, are rare but have a high risk of associated maternal morbidity or mortality. CASE: A 31-year-old woman, gravida 2 para 0010, with cirrhosis and portal hypertension was found to have abdominal wall ectopic varices on third-trimester obstetric ultrasonography. Computed tomography angiography confirmed these findings. Given concern for catastrophic hemorrhage during delivery, she underwent transjugular intrahepatic portosystemic shunt placement at 35 weeks of gestation, with reduction in the pressure gradient within the portosystemic circulation. She subsequently underwent an uncomplicated cesarean delivery. CONCLUSION: Identification of ectopic varices on obstetric ultrasonography may allow for treatment before delivery, decreasing the risk of serious maternal morbidity or mortality.

Amiodarone-Induced Liver Injury and Cirrhosis.

We present a case report of an 80-year-old woman with volume overload thought initially to be secondary to heart failure, but determined to be amiodarone-induced acute and chronic liver injury leading to submassive necrosis and bridging fibrosis consistent with early cirrhosis. Her histopathology was uniquely absent of steatosis and phospholipidosis, which are commonly seen in AIC.

Liver disease in menopause.

There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure.

Liver disease in pregnancy.

Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

Disparities in liver transplantation before and after introduction of the MELD score.

CONTEXT: In February 2002, the allocation system for liver transplantation became based on the Model for End-Stage Liver Disease (MELD) score. Before MELD, black patients were more likely to die or become too sick to undergo liver transplantation compared with white patients. Little information exists regarding sex and access to liver transplantation. OBJECTIVE: To determine the association between race, sex, and liver transplantation following introduction of the MELD system. DESIGN, SETTING, AND PATIENTS: A retrospective cohort of black and white patients (> or = 18 years) registered on the United Network for Organ Sharing liver transplantation waiting list between January 1, 1996, and December 31, 2000 (pre-MELD cohort, n = 21 895) and between February 28, 2002, and March 31, 2006 (post-MELD cohort, n = 23 793). MAIN OUTCOME MEASURES: Association between race, sex, and receipt of a liver transplant. Separate multivariable analyses evaluated cohorts within each period to identify predictors of time to death and the odds of dying or receiving liver transplantation within 3 years of listing. Patients with hepatocellular carcinoma were analyzed separately. RESULTS: Black patients were younger (mean [SD], 49.2 [10.7] vs 52.4 [9.2] years; P < .001) and sicker (MELD score at listing: median [interquartile range], 16 [12-22] vs 14 [11-19]; P < .001) than white patients on the waiting list for both periods. In the pre-MELD cohort, black patients were more likely to die or become too sick for liver transplantation than white patients (27.0% vs 21.7%) within 3 years of registering on the waiting list (odds ratio [OR], 1.51; 95% confidence interval (CI), 1.15-1.98; P = .003). In the post-MELD cohort, black race was no longer associated with increased likelihood of death or becoming too sick for liver transplantation (26.5% vs 22.0%, respectively; OR, 0.96; 95% CI, 0.74-1.26; P = .76). Black patients were also less likely to receive a liver transplant than white patients within 3 years of registering on the waiting list pre-MELD (61.6% vs 66.9%; OR, 0.75; 95% CI, 0.59-0.97; P = .03), whereas post-MELD, race was no longer significantly associated with receipt of a liver transplant (47.5% vs 45.5%, respectively; OR, 1.04; 95% CI, 0.84-1.28; P = .75). Women were more likely than men to die or become too sick for liver transplantation post-MELD (23.7% vs 21.4%; OR, 1.30; 95% CI, 1.08-1.47; P = .003) vs pre-MELD (22.4% vs 21.9%; OR, 1.08; 95% CI, 0.91-1.26; P = .37). Similarly, women were less likely than men to receive a liver transplant within 3 years both pre-MELD (64.8% vs 67.6%; OR, 0.80; 95% CI, 0.70-0.92; P = .002) and post-MELD (39.9% vs 48.7%; OR, 0.70; 95% CI, 0.62-0.79; P < .001). CONCLUSION: Following introduction of the MELD score to the liver transplantation allocation system, race was no longer associated with receipt of a liver transplant or death on the waiting list, but disparities based on sex remain.

Frequency and predictors of de novo hepatocellular carcinoma in patients awaiting orthotopic liver transplantation during the model for end-stage liver disease era.

In the current system of allocation, patients awaiting orthotopic liver transplantation (OLT) remain at risk of developing de novo hepatocellular carcinoma (HCC) and removal from the waiting list. Using the United Network for Organ Sharing database, we calculated the rate and identified predictors of de novo HCC in patients listed for OLT between February 2002 and December 2004. Among 8566 patients, 1167 (13.6%) developed de novo HCC. Predictors of increased odds of de novo HCC were older age, male gender, Asian race, other race, hepatitis C, and hepatitis B. A sensitivity analysis of 2067 patients waiting at least 6 months found that 16.2% developed de novo HCC. Older age [odds ratio (OR) 1.05; 95% confidence interval (CI) 1.03, 1.07], male gender (OR 2.01; 95% CI 1.49, 2.71), Asian race (OR 2.39; 95% CI 1.20, 4.76), other race (OR 1.94; 95% CI 1.40, 2.68), hepatitis C (OR 2.36; 95% CI 1.76, 3.16), and hepatitis B (OR 1.96; 95% CI 1.19, 3.23) remained predictors of increased odds of de novo HCC, and alcoholic liver disease (OR 1.40; 95% CI 1.06, 1.86) emerged as a predictor of increased odds of de novo HCC. A significant proportion of patients listed for OLT develop de novo HCC. Identifying predictors of HCC in these patients may facilitate timely HCC screening and diagnosis.

Compliance with referral for hepatitis C evaluation among veterans.

GOALS: The goals of this study were to quantify the rate and to identify predictors of compliance with outpatient hepatitis C evaluation. BACKGROUND: Challenges in hepatitis C management include patient compliance with multiple clinic visits, laboratory tests, and radiologic studies throughout the management of hepatitis C. However, the success of hepatitis C management begins with the patient's compliance with referral for hepatitis C evaluation. STUDY: The administrative databases and medical records of patients who were newly referred to the Durham Veterans Affairs Medical Center for hepatitis C evaluation between 2002 and 2004 were reviewed. RESULTS: A total of 376 veterans were identified as being newly referred to the Durham Veterans Affairs Medical Center gastroenterology and liver clinics for hepatitis C evaluation. The mean age of referred patients was 51.2+/-6.1 years, and 94.7% were men. The majority of patients (87%) were compliant with referral for hepatitis C evaluation. In multivariable logistic regression adjusting for age, race, marital status, history of psychiatric disease, history of substance abuse, origin of referral, and wait time, keeping other outpatient appointments was a significant predictor of compliance with referral for hepatitis C evaluation (odds ratio 6.00; 95% confidence interval 1.52, 23.67). CONCLUSIONS: Veterans have a high rate of compliance with referral for hepatitis C evaluation, and their compliance is likely reflective of their motivation to maintain general health care. Future studies assessing other factors, such as patient educational level and socioeconomic status, may help to elucidate more fully the factors impacting compliance with hepatitis C management.