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.

Best Practices for Hepatitis C Linkage to Care in Pregnant and Postpartum Women: Perspectives from the TiP-HepC Community of Practice.

There is an increasing burden of hepatitis C virus (HCV) among persons of reproductive age, including pregnant and breastfeeding women, in many regions worldwide. Routine health services during pregnancy present a critical window of opportunity to diagnose and link women with HCV infection for care and treatment to decrease HCV-related morbidity and early mortality. Effective treatment of HCV infection in women diagnosed during pregnancy also prevents HCV-related adverse events in pregnancy and HCV vertical transmission in future pregnancies. However, linkage to care and treatment for women diagnosed in pregnancy remains insufficient. Currently, there are no best practice recommendations from professional societies to ensure appropriate peripartum linkage to HCV care and treatment. We convened a virtual Community of Practice (CoP) to understand key challenges to the HCV care cascade for women diagnosed with HCV in pregnancy, highlight published models of integrated HCV services for pregnant and postpartum women, and preview upcoming research and programmatic initiatives to improve linkage to HCV care for this population. Four-hundred seventy-three participants from 43 countries participated in the CoP, including a diverse range of practitioners from public health, primary care, and clinical specialties. The CoP included panel sessions with representatives from major professional societies in obstetrics/gynecology, maternal fetal medicine, addiction medicine, hepatology, and infectious diseases. From this CoP, we provide a series of best practices to improve linkage to HCV treatment for pregnant and postpartum women, including specific interventions to enhance co-location of services, treatment by non-specialist providers, active engagement and patient navigation, and decreasing time to HCV treatment initiation. The CoP aims to further support antenatal providers in improving linkage to care by producing and disseminating detailed operational guidance and recommendations and supporting operational research on models for linkage and treatment. Additionally, the CoP may be leveraged to build training materials and toolkits for antenatal providers, convene experts to formalize operational recommendations, and conduct surveys to understand needs of antenatal providers. Such actions are required to ensure equitable access to HCV treatment for women diagnosed with HCV in pregnancy and urgently needed to achieve the ambitious targets for HCV elimination by 2030.

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.

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.

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 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.

Influence of hepatitis C viral parameters on pregnancy complications and risk of mother-to-child transmission.

BACKGROUND & AIMS: With the World Health Organization plan for hepatitis C elimination by the year 2030, and recent guideline recommendations to screen all women during pregnancy for HCV, data on HCV in pregnancy are needed to determine the association of HCV viremia with adverse pregnancy outcomes and mother-to-child transmission (MTCT). METHODS: This retrospective cohort study was performed in Ontario, Canada, using population-based administrative healthcare data. Individuals were stratified based on whether they had active HCV viremia during pregnancy or resolved viremia at time of pregnancy. Peak HCV viral load was determined. Logistic regression was used to determine the association of viremia with adverse pregnancy outcomes; maternal HCV RNA levels were evaluated as a predictor of MTCT. RESULTS: We identified a total of 2,170 pregnancies in 1,636 women who were HCV RNA positive prior to pregnancy; 1,780 (82%) pregnancies occurred in women who were HCV RNA positive during pregnancy. Patients who were HCV RNA positive during pregnancy were more likely to have preterm delivery (18% vs. 12%, p = 0.002), intrahepatic cholestasis of pregnancy (4% vs. <2%, p = 0.003), and post-partum hemorrhage (9% vs. 5%, p = 0.013), and less likely to have gestational diabetes (6% vs. 10%, p = 0.008) than those with resolved infection. Only 511 (29%) infants had screening consistent with guidelines after birth; there was an estimated 3.5% risk of MTCT. HCV RNA ≥6.0 log10 IU/ml was significantly associated with MTCT (exact odds ratio 3.4, p = 0.04). CONCLUSION: Active HCV viremia among individuals with a history of HCV infection significantly increases adverse pregnancy outcomes. Few infants are screened for MTCT. Higher HCV RNA is associated with increased risk of MTCT. LAY SUMMARY: The prevalence of hepatitis C has increased in women of child-bearing age and has important implications for women who become pregnant and their infants. We evaluated the effect that hepatitis C has on pregnancy outcomes as well as the rate of hepatitis C transmission to infants in a large database with linked mother-infant records. We found that active hepatitis C during pregnancy increased the risk of pregnancy complications. We also identified very low rates of testing of infants born to mothers with hepatitis C, but found higher rates of hepatitis C transmission to infants in mothers with higher virus levels.

Cost-effectiveness of Antenatal Rescreening Among Pregnant Women for Hepatitis C in the United States.

To inform proposed changes in hepatitis C virus (HCV) screening guidelines in the United States, we assessed the cost-effectiveness of HCV antenatal rescreening for women without evidence of HCV during a prior pregnancy, using a previously published model. Universal HCV rescreening among pregnant women was cost-effective (incremental cost-effectiveness ratio, $6000 per quality-adjusted life-year) and should be recommended nationally.

Changing epidemiology, implications, and recommendations for hepatitis C in women of childbearing age and during pregnancy.

Despite the remarkable advances in HCV treatment brought about by the advent of direct-acting antivirals, HCV remains a global public health concern. One particular concern relates to the rising prevalence of HCV in women of childbearing age. Active HCV during pregnancy is associated with cholestasis of pregnancy as well as the risk of mother-to-child transmission. Guidelines are increasingly recommending universal screening during pregnancy, while the treatment of HCV during pregnancy is an area of ongoing research.

Burden of Future Liver Abnormalities in Patients With Intrahepatic Cholestasis of Pregnancy.

INTRODUCTION: There are limited data on the incidence, predictors, and time to future liver abnormalities in patients with intrahepatic cholestasis of pregnancy (ICP). METHODS: Single-center retrospective study of pregnant women with and without ICP who delivered from 2005 to 2009 evaluating incidence and time to future liver abnormalities. Women returning for care with liver function tests at a minimum of 6 months postpartum were included. Liver disease diagnoses and liver functions test abnormalities were compared. Time to development of alanine aminotransferase (ALT) >25 U/L, alkaline phosphatase (ALP) >140 U/L, and diagnosis of liver disease (through imaging or clinical evaluation) were compared between women with and without ICP using Kaplan-Meier methods and Cox regression models. RESULTS: A total of 255 women with ICP and 131 age-matched control subjects with delivery during the same period were identified. Subjects in both groups were similar in follow-up time, age at pregnancy, prepregnancy body mass index, and ethnicity (≥75% were Hispanic in both groups). On univariate analyses, ICP was associated with increased incidence of ALT >25 U/L P < 0.01 ALP >140 U/L (P < 0.01) and liver disease (P = 0.03). Adjusting for metabolic factors, ICP diagnosis was associated with risk of future liver abnormalities: postpartum ALT >25 U/L (hazard ratio [HR] 1.9, P < 0.01), ALP >140 U/L (HR 3.4, P < 0.01), and liver disease (HR 1.5, P = 0.05). DISCUSSION: In our cohort of urban women, ICP diagnosis predicted risk of future liver disease and abnormal liver tests. Women with pregnancies complicated by ICP may benefit from surveillance for postpartum liver abnormalities.

Adherence to pregnancy hepatitis B care guidelines in women and infants in the United States and evaluation of two interventions to improve care: A multicentre hospital-based study.

There has been an increase in hepatitis B (HBV) detection during pregnancy in the United States and an emphasis on measures to decrease mother-to-child transmission of HBV. We performed a multicentre retrospective study (2015-2018) evaluating care among all women with HBV during pregnancy. We determined rates and predictors of adherence to key maternal care measures including: (1) referral to HBV specialty care, (2) assessment of HBV DNA, and (3) initiation of antiviral therapy, and (4) rates of HBIG and HBV vaccine completion in infants. We evaluated two interventions to improve HBV care: (1) clinical decision support with best practice alert and (2) co-location of HBV care in obstetrics department. We identified 372 women with HBV during pregnancy. Patients had a median age of 33 (IQR 29, 36), were mostly of Asian (49%) or Black (36%) race, HBeAg-negative (83%) with HBV DNA ≤2000 IU/mL (65%) and maximum ALT ≤25 (66%). Regarding care measures, 62% were referred to an HBV specialist, 85% had HBV DNA checked during pregnancy and 68% with HBV DNA ≥200,000 were initiated on antiviral therapy. Co-located obstetric-liver diseases clinics appeared to improve adherence to maternal care measures. All infants received HBIG and the first HBV vaccine dose, 106 (81%) received the second, 94 (74%) received the 3rd dose, but fewer at the recommended time intervals. We identified clear gaps in adherence to HBV care measures for both mothers and infants. Co-location of HBV care in the obstetrics department shows promise in improving adherence to maternal care measures.

Factors Associated With Hepatitis B Exposure Among People Who Report Using Methamphetamine: National Health and Nutrition Examination Survey 2009-2016.

BACKGROUND: With the nation's focus on the opioid crisis, methamphetamine has made a comeback, potentially increasing risk for hepatitis B. We examined factors associated with hepatitis B virus (HBV) exposure among people who reported ever using methamphetamine in a nationally representative survey. METHODS: We used the National Health and Nutrition Examination Survey to examine factors associated with HBV exposure among participants who reported ever using methamphetamine using bivariate and multivariable logistic regression. RESULTS: Overall, 847 participants met the study inclusion criteria. In multivariable logistic regression, female sex (adjusted odds ratio, 3.83; 95% confidence interval, 1.65-8.90), living below the poverty threshold (3.17; 1.39-7.21), injection drug use (4.89; 1.95-12.26), active hepatitis C virus infection (3.39; 1.10-12.26), and identifying as men who have sex with men (28.21; 5.19-153.38) were significantly associated with HBV exposure. CONCLUSIONS: The odds of HBV exposure for female participants who reported using methamphetamine were 4 times than that for male participants. Poverty, injection drug use, and hepatitis C virus infection were also associated. As methamphetamine use increases, it is critical to identify those at risk of acquiring HBV infections in order to target testing and vaccination.

Trends in Hepatitis B Infection and Immunity Among Women of Childbearing Age in the United States.

BACKGROUND: The current opioid injection drug use epidemic has been associated with an increase in hepatitis C virus infections among women of childbearing age in the United States, but changes in hepatitis B virus (HBV) infections have not been studied. METHODS: A retrospective analysis of HBV statuses among women of childbearing age nationally and by state was conducted, utilizing the Quest Diagnostics database. Rates of HBV in women born before and after the implementation of universal HBV vaccination recommendations were determined. RESULTS: We identified 8 871 965 women tested for HBV from 2011-2017. Nationally, the annual rate of acute HBV infections was stable, but rates increased in Kentucky, Alabama, and Indiana (P < .03). The national prevalence of new, chronic HBV diagnoses decreased significantly, from 0.83% in 2011 to 0.19% in 2017 (P < .0001), but increased in Mississippi, Kentucky, and West Virginia (P ≤ .05). A declining prevalence of HBV seroprotection was evident over time, especially within the birth-dose cohort (which dropped from 48.5% to 38.5%; P < .0001). CONCLUSIONS: National rates of newly diagnosed acute and chronic HBV infections declined or were stable overall, but increased significantly in specific Appalachian states. The HBV vaccine is effective in decreasing infections, but seroprotection wanes over time. These trends in new infections may be related to increased injection drug use and highlight potential gaps in HBV vaccine protection.

Liver transplant for hepatocellular carcinoma in the United States: Evolving trends over the last three decades.

Hepatitis C virus infection has been the most common etiology in HCC-related liver transplantation (LT). Since 2014, direct-acting antivirals (DAAs) have dramatically improved HCV cure. We aimed to study the changing pattern of etiologies and impact in outcome in HCC-related LT according to HCV treatment-era through retrospective analysis of the Scientific Registry of Transplant Recipients (SRTR) database (1987-2017). A total of 27 855 HCC-related liver transplants were performed (median age 59 years, 77% male). In the DAA era (2014-2017) there has been a 14.6% decrease in LT for HCV-related HCC; however, HCV remains the most common etiology in 50% of cases. In the same era, there has been a 50% increase in LT for NAFLD-related HCC. Overall survival was significantly worse for HCV-related HCC compared to NAFLD-related HCC during pre-DAA era (2002-2013; P = .031), but these differences disappeared in the DAA era. In addition, HCV patients had a significant improvement in survival when comparing the DAA era with IFN era (P < .001). Independent predictors of survival were significantly different in the pre-DAA era (HCV, AFP, diabetes) than in the DAA era (tumor size). HCV-related HCC continues to be the main indication for LT in the DAA era, but patients' survival has significantly improved and is comparable to that of NAFLD-related HCC.

Outcomes of liver transplantation for acute fatty liver disease of pregnancy.

Acute fatty liver of pregnancy (AFLP) often resolves after pregnancy delivery but can progress to acute liver failure necessitating liver transplantation. We performed a retrospective review of the national Scientific Registry of Transplant Recipients (SRTR) data to identify all women in the United States undergoing liver transplantation (LT) for acute liver failure (ALF) from AFLP from 1991 to 2015, and compared to outcomes in women of childbearing age undergoing transplant for ALF from acetaminophen and ALF from other etiologies. Women with AFLP were likely to be on life support at time of LT and had high rates of renal dysfunction (median Cr 2.1, IQR 1.2-2.3), and hyperbilirubinemia (median bilirubin 17.1, IQR 11.0, 19.9). Although their early and late LT survival outcomes were comparable to the other indications for LT, cumulative 5-year graft survival was numerically lower among AFLP patients (54%, 95% CI, 27-76) compared to APAP (70%, 95% CI, 63-77) and "Other ALF" (76%, 95% CI, 72-80) groups. In conclusion, although AFLP is a rare indication for LT, AFLP patients were as sick or sicker than other women of childbearing age undergoing LT for ALF. Worsened graft survival may be related to higher rates of rejection in the AFLP group.

Noninvasive Tests for Prognosticating Outcomes in Patients With Chronic Liver Disease in Pregnancy: Ready for Prime Time?

Rates of cirrhosis and pregnancy in women of reproductive age are increasing, making pregnancy-specific prognostic markers of disease severity increasingly important. Gonsalkorala et al. describe albumin-bilirubin score and aspartate aminotransferase-to-platelet ratio index as superior prognostic tools to the Model for End-Stage Liver Disease (MELD) score in predicting live births and gestation beyond 37 weeks in pregnant women with cirrhosis, among 165 pregnancies in women with chronic liver disease. However, further efforts are needed to identify diagnostic and prognostic tools during pregnancy, as well as to refine and implement a multidisciplinary team-centered approach to the care of women with chronic liver disease during pregnancy.

Direct-acting antiviral treatment for patients with hepatocellular carcinoma.

PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) affects a significant portion of patients with hepatitis C. The use of direct-acting antiviral (DAA) agents has transformed the disease outcomes in this patient group. RECENT FINDINGS: Hepatitis C virus (HCV) response to DAAs can be affected by the presence of HCC, whereas DAA therapy may affect the risk of HCC recurrence in patients with a history of HCC. SUMMARY: Emerging data are demonstrating lower sustained virologic response (SVR) rates in patients with HCC compared with patients without HCC. Conflicting studies have also suggested that rates of HCC recurrence in patients with a history of HCC can potentially be increased or decreased on DAA therapy. This review will provide a brief overview of these data and inform practitioners on important considerations to make when prescribing DAA therapy for patients with HCV and HCC.