Drug-Induced Liver Injury in Pregnancy: The U.S. Drug-Induced Liver Injury Network Experience.

There are limited data on the causative agents and characteristics of drug-induced liver injury in pregnant individuals. Data from patients with drug-induced liver injury enrolled in the ongoing multicenter Drug-Induced Liver Injury Network between 2004 and 2022 and occurring during pregnancy or 6 months postpartum were reviewed and compared with cases of drug-induced liver injury in nonpregnant women of childbearing age. Among 325 individuals of childbearing age in the Drug-Induced Liver Injury Network, 16 cases of drug-induced liver injury (5%) occurred during pregnancy or postpartum. Compared with drug-induced liver injury in nonpregnant women, pregnancy-related drug-induced liver injury was more severe (P<.05). One elective termination and three miscarriages were documented; there were no maternal deaths. We recommend that isoniazid for latent tuberculosis be deferred to the postpartum period whenever feasible and that ß-blockers or calcium channel blockers rather than methyldopa be used for hypertension management during pregnancy.

Addressing hepatitis delta in primary care practices in the US: a narrative review.

OBJECTIVE: Infection with the hepatitis delta virus (HDV), a unique RNA virus that requires hepatitis B virus (HBV) antigens for its assembly, replication, and transmission, causes severe viral hepatitis. Compared to HBV monoinfection, HDV infection increases the risk of severe liver disease, necessity for liver transplant, and mortality. Global HDV prevalence estimates vary from 5% to 15% among persons with HBV, but screening guidelines for HDV are inconsistent; some recommend risk-based screening, while others recommend universal screening for all people with HBV. Among primary care providers (PCPs) in the US, there is a lack of awareness and/or insufficient adherence to current recommendations for the screening of HDV infection and management of chronic HDV. METHODS: Publications were obtained by conducting literature searches between July and August 2022 using the PubMed database and by manual searches of the retrieved literature for additional references. Information was synthesized to highlight HDV screening and management strategies for PCPs. Best practices for PCPs based on current guidelines and comanagement strategies for patients with HBV and HDV infection were summarized. RESULTS: We recommend universal screening for HDV in patients positive for hepatitis B surface antigen. Confirmed HDV infection should prompt evaluation by a liver specialist, if available, with whom the PCP can comanage the patient. PCPs should counsel patients on the expected course of the disease, lifestyle factors that may influence liver health, need for consistent disease monitoring and follow-up, and risk of disease transmission. Screening is suggested for sexual partners, household contacts, and family members, with HBV immunization recommended for those found to be susceptible. There are currently no US Food and Drug Administration-approved therapies for HDV infection; thus, management is limited to treatments for chronic HBV infection plus long-term monitoring of liver health. CONCLUSIONS: PCPs can be a valuable point of care for patients to access HDV/HBV screening, HBV immunization, and education, and can comanage patients with HBV and/or HDV infection.

Hepatitis delta virus (HDV) infection only occurs in the presence of hepatitis B virus (HBV) infection. People with an HDV infection are at higher risk for severe liver disease, liver transplant, and death compared to those who only have an HBV infection. The estimated global prevalence of HDV infection ranges from 5% to 15% among people living with HBV. These measurements vary due to different study methods, inconsistent HDV screening guidelines, and patient risk factors for infection.In the US, primary care providers (PCPs) play an important role in improving community access to HDV information and testing. However, poor funding and inadequate resources have created a lack of awareness and insufficient adherence by PCPs to current recommendations for screening and management of HDV infection. This narrative review aims to fill this gap by providing an overview of HDV infection, patient risk factors, and practice guidelines for PCPs.The recommendations for PCPs in this review include providing universal screening for HDV to people with an HBV infection, especially those at high risk. PCPs can educate and comanage patients with liver specialists. Topics to discuss with patients include expected disease outcomes, lifestyle factors that may influence liver health, and the need for consistent follow-up appointments. Patient risk of disease transmission can also be discussed to identify sexual partners, household contacts, and family members who will need screening and HBV vaccination. While there are no FDA-approved therapies for treating HDV infection, we provide an overview of available and emerging HDV treatments.

Maternal neighbourhood-level social determinants of health and their association with paediatric hepatitis C screening among children exposed to hepatitis C in pregnancy.

BACKGROUND: Current guidelines recommend HCV screening by 18 months of age for those exposed to HCV in utero; yet, screening occurs in the minority of children. OBJECTIVES: To evaluate the association between maternal neighbourhood-level social determinants of health (SDOH) and paediatric HCV screening in the general population in a publicly funded healthcare system in Canada. METHODS: Retrospective cohort study using administrative healthcare data held at ICES. Children born to individuals positive for HCV RNA in pregnancy from 2000 to 2016 were identified and followed for 2 years. Major SDOH were identified, and the primary outcome was HCV screening in exposed children (HCV antibody and/or RNA). Associations between SDOH and HCV screening were determined using multivariate Poisson regression models adjusting for confounding. RESULTS: A total of 1780 children born to persons with +HCV RNA were identified, and 29% (n = 516) were screened for HCV by age two. Most mothers resided in the lowest income quintile (42%), and most vulnerable quintiles for material deprivation (41%), housing instability (38%) and ethnic diversity (26%) with 11% living in rural locations. After adjustment for confounding, maternal rural residence (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.62, 1.07) and living in the highest dependency quintile (RR 0.83, 95% CI 0.65, 1.07) were the SDOH most associated with paediatric HCV screening. Younger maternal age (RR 0.98 per 1-year increase, 95% CI 0.97, 0.99), HIV co-infection (RR 1.69, 95% CI 1.16, 2.48) and GI specialist involvement (RR 1.18, 95% CI 1.00, 1.39) were associated with higher probabilities of screening. CONCLUSIONS: Among children exposed to HCV during pregnancy, rural residences and living in highly dependent neighbourhoods showed a potential association with a lower probability of HCV screening by the age of 2. Future work evaluating barriers to paediatric HCV screening among rural residing and dependent residents is needed to enhance the screening.

Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF).

BACKGROUND: Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH. METHODS: We included derivation (n = 790) and validation (n = 565) cohorts from international tertiary centers. Patients underwent laboratory assessment and liver biopsy for metabolic dysfunction-associated steatotic liver disease. Based on 12 lipids, body mass index, aspartate aminotransferase, and alanine aminotransferase, the MASEF score was developed to identify at-risk MASH and compared to the FibroScan-AST (FAST) score. We further compared the performance of a FIB-4 + MASEF algorithm to that of FIB-4 + liver stiffness measurements (LSM) by vibration-controlled transient elastography (VCTE). RESULTS: The diagnostic performance of the MASEF score showed an area under the receiver-operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of 0.76 (95% CI 0.72-0.79), 0.69, 0.74, 0.53, and 0.85 in the derivation cohort, and 0.79 (95% CI 0.75-0.83), 0.78, 0.65, 0.48, and 0.88 in the validation cohort, while FibroScan-AST performance in the validation cohort was 0.74 (95% CI 0.68-0.79; p = 0.064), 0.58, 0.79, 0.67, and 0.73, respectively. FIB-4+MASEF showed similar overall performance compared with FIB-4 + LSM by VCTE ( p = 0.69) to identify at-risk MASH. CONCLUSION: MASEF is a promising diagnostic tool for the assessment of at-risk MASH. It could be used alternatively to LSM by VCTE in the algorithm that is currently recommended by several guidance publications.

Maternal-to-Child Transmission of Hepatitis B Virus and Hepatitis Delta Virus.

Maternal-to-child transmission of hepatitis B virus (HBV) and hepatitis delta virus (HDV) can lead to the risk of progressive liver disease in infants, but fortunately effective interventions exist to decrease transmission. Counseling on the risk of maternal-to-child transmission, care pathways to decrease transmission, and the implications of HBV and HDV on pregnancy outcomes are the key components of caring for pregnant people living with HBV and HDV.

Intermittent fasting improves hepatic end points in nonalcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Despite NAFLD being the most prevalent liver disease globally, currently there are no FDA-approved treatments, and weight loss through caloric restriction and enhanced physical activity is the recommended treatment strategy. Intermittent fasting (IF) has been proposed as an alternative strategy with additional cardiometabolic benefits. In this systematic review and meta-analysis, we evaluated the anthropometric, biochemical, and hepatic impacts of IF in patients with NAFLD. METHODS: MEDLINE, EMBASE, Cochrane Central, and conference abstracts were searched for IF interventions in adults with NAFLD until April 2, 2023. Meta-analysis with a random effects model was used to compare pre-intervention and post-intervention changes in anthropometric, biochemical, and hepatic end points in the IF intervention group with the control group. Publication bias was assessed using Egger's test. RESULTS: Fourteen studies were included in the systematic review and ten in the meta-analysis (n = 840 participants, 44.64% male). Studies varied in modalities for NAFLD diagnosis, duration of IF (4-52 weeks), and type of IF (5:2 diet, modern alternate-day fasting, time-restricted eating, or religious fasting). Body weight, body mass index, and waist to hip ratio all significantly improved following fasting intervention (p< 0.05). Adults with NAFLD showed an improvement in serum alanine transaminase, aspartate aminotransferase, hepatic steatosis (controlled attenuation parameter measured by vibration-controlled transient elastography), and hepatic stiffness (measured by vibration-controlled transient elastography) after fasting intervention (p < 0.05). CONCLUSIONS: There is limited, but moderate- to high-quality evidence to suggest that IF can improve hepatic end points and promote weight loss in adults with NAFLD. Larger randomized controlled studies with extended duration are needed to further validate our findings.

Evaluation of 2-year outcomes in infants born to mothers with and without NAFLD in pregnancy.

Nonalcoholic fatty liver disease (NAFLD) affects an estimated 17% of pregnant patients in the USA. However, there are limited data on the impact of maternal NAFLD on pediatric outcomes. We prospectively evaluated outcomes in infants born to mothers with and without NAFLD in pregnancy over their first 2 years of life. Maternal subjects were identified through an ongoing prospective study in which pregnant individuals were screened for NAFLD. Pediatric outcomes of infants born to these mothers-including adverse neonatal outcomes and weight and weight-for-length percentile at 6, 12, 18, and 24 months-were prospectively evaluated. Multivariate logistic regression was performed to evaluate the association of maternal NAFLD with pediatric outcomes, as well as to adjust for potentially confounding maternal characteristics. Six hundred thirty-eight infants were included in our cohort. The primary outcomes assessed were weight and growth throughout the first 2 years of life. Maternal NAFLD was also not associated with increased infant birth weight or weight-for-gestational-age percentile or weight or weight-for-length percentile over the first 2 years of life. Maternal NAFLD was significantly associated with very premature delivery before 32 weeks, even after adjustment for confounding maternal characteristics (aOR = 2.83, p = 0.05). Maternal NAFLD was also significantly associated with neonatal jaundice, including after adjusting for maternal race (aOR = 1.67, p = 0.03). However, maternal NAFLD was not significantly associated with any other adverse neonatal outcomes.    Conclusion: Maternal NAFLD may be independently associated with very premature birth and neonatal jaundice but was not associated with other adverse neonatal outcomes. Maternal NAFLD was also not associated with any differences in infant growth over the first 2 years of life. What is Known: • Maternal NAFLD in pregnancy may be associated with adverse pregnancy and neonatal outcomes, but the findings are inconsistent across the literature. What is New: • Maternal NAFLD is not associated with any differences in weight at birth or growth over the first 2 years of life. • Maternal NAFLD is associated with very premature delivery and neonatal jaundice, but is not associated with other adverse neonatal outcomes.

Transient elastography and controlled attenuation parameter to evaluate hepatic steatosis and liver stiffness in postpartum patients.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) affects 30% of adults in the United States. Transient elastography (TE) (Fibroscan, Echosens, Paris, France) with controlled attenuation parameter (CAP) is a noninvasive way to evaluate liver steatosis and liver stiffness. The primary objective of this study was to assess prevalence of elevated liver stiffness and steatosis immediately postpartum. Furthermore, we sought to evaluate whether there were differences in rates of metabolic disorders of pregnancy (gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia) and pre-pregnancy conditions (type 2 diabetes mellitus (DM), chronic hypertension, and obesity) in those with elevated postpartum liver steatosis/liver stiffness. METHODS: IRB approved prospective cross-sectional study in which TE and liver function tests were performed 1-2 days postpartum. CAP ≥300 dB/m was classified as significant steatosis. Increased liver stiffness was defined as ≥7 kPa. Prevalence was determined by proportion of individuals undergoing TE/CAP who met criteria. Chi-square analysis was used to compare differences between groups. RESULTS: Eighty-nine patients were included: 20 (22%) had GDM, 13 (15%) had gestational hypertension, and 15 (17%) had preeclampsia. Women with kPa ≥7 were more likely to have ALT ≥25, type 2 diabetes, and preeclampsia (p < .05). Pre-gravid BMI, BMI at delivery, and GDM were not associated with increased kPa. Pregravid BMI ≥25 and chronic hypertension were associated with CAP ≥ 300 dB/m (p < .05). GDM, preeclampsia, and gestational hypertension were not associated with CAP ≥300 dB/m. CONCLUSIONS: Patients with preeclampsia, type 2 diabetes, and elevated ALT were more likely to have elevated postpartum liver stiffness. Pregravid BMI ≥25 and ≥30 were associated with increased liver steatosis, although did not impact liver stiffness. GDM was not associated with increased liver stiffness or steatosis. Consideration should be made for screening pregnant patients with preeclampsia, type 2 DM and overweight or obese BMI for liver disease in the postpartum period with potential for lifestyle intervention.

Assisted Reproductive Technology Treatment Outcomes in Women With Liver Disease.

INTRODUCTION: There is a need for evidence-based counseling for women with chronic liver disease (LD) who may experience impaired fertility. Currently, the literature on assisted reproductive technology (ART) treatment in women with LD has been limited to a single European case series. We evaluated ART treatment outcomes in patients with LD and compared with controls. METHODS: The retrospective study evaluated women with and without LD who had normal ovarian reserve and underwent ART treatment in a high-volume fertility practice from 2002 to 2021. RESULTS: We identified 295 women with LD (mean age 37.8 ± 5.2 years) who underwent 1,033 ART treatment cycles; of these women, 115 underwent 186 in vitro fertilization (IVF) cycles. Six women (2.0%) had cirrhosis, 8 (2.7%) were postliver transplantation, and 281 (95.3%) had chronic LD, with viral hepatitis (B and C) being the most prevalent. In the subgroup who underwent IVF and embryo biopsy, the median fibrosis-4 score was 0.81 (0.58-1.03), and there were no statistically significant differences in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome in patients with LD compared with controls. In those who subsequently underwent a single thawed euploid embryo transfer to achieve pregnancy, there were no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live birth in patients with LD compared with controls. DISCUSSION: To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with LD. Our study demonstrates that patients with LD have similar ART treatment outcomes compared with those without LD.

Modeling-Based Response-Guided Hepatitis C Treatment During Pregnancy and Postpartum.

Treating hepatitis C virus (HCV) in pregnancy would address HCV during prenatal care and potentially reduce the risk of vertical transmission. Response-guided therapy could provide a means to individualize and the reduce duration of HCV treatment during pregnancy. Data from a 27-year-old woman indicated that, pretreatment, HCV was stable and that it dropped in a biphasic manner during sofosbuvir/velpatasvir therapy, reaching target not detected at time of delivery-16 days post-initiation of therapy. Mathematical modeling of measured HCV at days 0, 7, and 14 predicted that cure could have been achieved after 7 weeks of sofosbuvir/velpatasvir, reducing the duration of therapy by 5 weeks.

Delta hepatitis epidemiology and the global burden of disease.

Delta Hepatitis is considered the most severe form of hepatitis, with varied prevalence, genotype distribution and risk factors worldwide. Current knowledge of global epidemiology is limited due to variable screening practices for HDV. Here, we summarize what is currently known about the prevalence of testing and prevalence of HDV positivity globally.

Evaluation of Liver Disease in Pregnancy.

Liver disease in pregnancy often requires diagnostic and therapeutic considerations that are unique to pregnancy. Liver disease in pregnancy is commonly thought of as either liver disease unique to pregnancy, chronic liver disease, or liver disease coincidental to pregnancy. This review summarizes the approach to evaluation of liver disease in pregnancy.

Hepatitis Delta: Current Knowledge and Future Directions.

Hepatitis delta virus (HDV) infection is caused by a unique circular RNA virus that relies on both the hepatitis B virus (HBV) antigen and human host polymerases for its transmission and replication. HDV infection can be acquired simultaneously with HBV as a coinfection or as a superinfection in patients already chronically infected with HBV. Chronic HDV is the most severe and progressive form of viral hepatitis-induced liver disease, accounting for significant morbidity and mortality worldwide. Despite the severity of disease and poor clinical outcomes, there are few therapeutic options for the treatment of HDV infection. This article discusses the epidemiology of HDV globally and in the United States, the diagnosis and clinical course of HDV infection, and the current and future therapeutic options for the management of HDV infection.

Prevalence of elevated alanine aminotransferase (ALT) in pregnancy: A cross-sectional labor and delivery-based assessment.

Since liver tests are not routinely checked in pregnancy, the prevalence of abnormal liver tests and liver-related abnormalities in pregnancy in a US-based population is not known. We sought to determine the prevalence of abnormal alanine aminotransferase (ALT) among pregnant Individuals who present to labor and delivery for evaluation and to evaluate prevalence of underlying diagnosed liver conditions. Prospective study evaluating liver tests in consecutive samples obtained on the labor and delivery unit. Patient characteristics were compared between those with and without abnormal ALT and those with and without abnormal ALT without a liver-related diagnosis made in clinical practice, using t tests for continuous measures and χ2 or Fisher's exact tests as appropriate for categorical measures. Logistic regression was utilized to identify factors associated with abnormal ALT in this subcohort to determine predictors of abnormal ALT in those without a known liver-related diagnosis. We collected 1024 laboratory specimens from 996 patients. Of these patients, 131 of 996 (13.2%) had elevated ALT ≥25 IU/L; 20 (2%) had ALT ≥50, 6 (0.6%) had ALT ≥125 and 3 (0.3%) had ALT ≥250. 61/131 (46.6%) of patients with ALT ≥25 IU/L had not had LTs checked during routine pregnancy care. 20 (15%) of individuals with abnormal LT had preeclampsia; 5 (4%) had cholestasis of pregnancy; 1 (0.8%) had hepatitis C; there were no other chronic liver diseases diagnosed. There were no significant demographic or clinical differences between those with and without ALT ≥25, whether liver disease diagnosis was made or not. We identified an over 10% prevalence of abnormal LTs in consecutive pregnant individuals who presented to L&D, most of whom did not have a liver-related condition diagnosed in clinical practice. Among those with liver-related diagnoses, PE and ICP were the most common among individuals with ALT≥25 IU/mL, with chronic liver disease rarely diagnosed. Further evaluation of the role of ALT testing as part of routine prenatal care is needed, particularly in establishing a baseline prevalence of liver test abnormalities in pregnancy and independent association with pregnancy outcomes.