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BACKGROUND: Steatohepatitis is common in persons living with HIV and may be associated with gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis in persons living with HIV. In the Womens Interagency HIV Study, we examined the associations of HIV and circulating biomarkers linked to MT and gut damage using the FibroScan-aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis with advanced fibrosis. METHODS: Among 883 women with HIV and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut damage (kynurenine and tryptophan ratio, intestinal fatty acid-binding protein, soluble CD14, and soluble CD163) with a log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. RESULTS: HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in women with HIV than women without HIV (P < .001 for each). MT biomarkers mediated 13% to 32% of the association of HIV and FAST score. CONCLUSIONS: Biomarkers linked to MT and gut damage are associated with a higher FAST score and mediate the association of HIV with a higher FAST score. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

Background and aimsFrailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality.Approach and resultsAdults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0-4.8) for 3-month mortality, 4.2 (95% CI, 4.1-4.4) for 6-month mortality, and 4.2 (95% CI, 4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79.ConclusionsLFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.

We sought to identify specific gaps in preventive care provided to outpatients with cirrhosis and to determine factors associated with high quality of care (QOC), to guide quality improvement efforts. Outpatients with cirrhosis who received care at a large, academic tertiary health care system in the United States were included. Twelve quality indicators (QIs), including preventive care processes for ascites, esophageal varices, hepatic encephalopathy, hepatocellular carcinoma (HCC), and general cirrhosis care, were measured. QI pass rates were calculated as the proportion of patients eligible for a QI who received that QI during the study period. We performed logistic regression to determine predictors of high QOC (≥ 75% of eligible QIs) and receipt of HCC surveillance. Of the 439 patients, the median age was 63 years, 59% were male, and 19% were Hispanic. The median Model for End-Stage Liver Disease-Sodium score was 11, 64% were compensated, and 32% had hepatitis C virus. QI pass rates varied by individual QIs, but were overall low. For example, 24% received appropriate HCC surveillance, 32% received an index endoscopy for varices screening, and 21% received secondary prophylaxis for spontaneous bacterial peritonitis. In multivariable analyses, Asian race (odds ratio [OR]: 3.7, 95% confidence interval [CI]: 1.3-10.2) was associated with higher QOC, and both Asian race (OR: 3.3, 95% CI: 1.2-9.0) and decompensated status (OR: 2.1, 95% CI: 1.1-4.2) were associated with receipt of HCC surveillance. A greater number of specialty care visits was not associated with higher QOC. Conclusion: Receipt of outpatient preventive cirrhosis QIs was variable and overall low in a diverse cohort of patients with cirrhosis. Variation in care by race/ethnicity and illness trajectory should prompt further inquiry into identifying modifiable factors to standardize care delivery and to improve QOC.

Purpose of reviewIn this review article we evaluate sex differences in the natural history of NAFLD and highlight distinct risk profiles of women with NAFLD, as well as unique treatment considerations and research gaps.Summary of findingsReproductive factors, such as menopausal status should be considered when evaluating NAFLD risk in women, as well as additional reproductive risk factors such as age at menarche, presence of polycystic ovary syndrome, and gestational diabetes. Women do appear to have lower risk for hepatocellular carcinoma from NASH, as well as lower mortality from NASH cirrhosis than men, although among women, NASH is now the leading indication for liver transplant. Data on sex differences in biomarker development and clinical trials are lacking, and researchers should be encouraged to evaluate biomarker performance by sex, and specifically report clinical trial endpoints in women.

Cholestatic liver diseases (CLDs) encompass a variety of disorders of abnormal bile formation and/or flow. CLDs often lead to progressive hepatic insult and injury and following the development of cirrhosis and associated complications. Many such complications are clinically silent until they manifest with severe sequelae, including but not limited to life-altering symptoms, metabolic disturbances, cirrhosis, and hepatobiliary diseases as well as other malignancies. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common CLDs, and both relate to mutual as well as unique complications. This review provides an overview of PSC and PBC, with a focus on preventive measures aimed to reduce the incidence and severity of disease-related complications.

Hemobilia refers to bleeding from and/or into the biliary tract and is an uncommon but important cause of gastrointestinal hemorrhage. Reports of hemobilia date back to the 1600s, but due to its relative rarity and challenges in diagnosis, only in recent decades has hemobilia been more critically studied. The majority of cases of hemobilia are iatrogenic and caused by invasive procedures involving the liver, pancreas, bile ducts and/or the hepatopancreatobiliary vasculature, with trauma and malignancy representing the two other leading causes. A classic triad of right upper quadrant pain, jaundice, and overt upper gastrointestinal bleeding has been described (i.e. Quincke's triad), but this is present in only 25%-30% of patients with hemobilia. Therefore, prompt diagnosis depends critically on having a high index of suspicion, which may be based on a patient's clinical presentation and having recently undergone (peri-) biliary instrumentation or other predisposing factors. The treatment of hemobilia depends on its severity and suspected source and ranges from supportive care to advanced endoscopic, interventional radiologic, or surgical intervention. Here we provide a clinical overview and update regarding the etiology, diagnosis, and treatment of hemobilia geared for specialists and subspecialists alike.

BackgroundHepatic steatosis is increasing worldwide. Whether HIV and its associated metabolic perturbations exacerbate steatosis is unclear. Sex differences in adipose tissue distribution may also affect steatosis risk. We examined the contribution of HIV and sex to steatosis.MethodsUsing MRI and spectroscopy, visceral adipose tissue (VAT) and liver fat fraction (LFF) were measured in 121 HIV-infected and 107 uninfected men and women without viral hepatitis. Differences in LFF by HIV status and sex were evaluated using multivariable linear regression, adjusting for demographic, lifestyle, VAT, homeostasis model assessment-estimated insulin resistance, and HIV-related factors.ResultsHIV-infected women had lower LFF than uninfected women (demographic-adjusted mean: 1.9 vs. 3.1%; P = 0.028); LFF was similar in HIV-infected and uninfected men (4.6 vs. 4.1%; P = 0.78). HIV-infected and uninfected women had less VAT than men (median: 139 and 161 vs. 201 cm and 188 cm, respectively). After adjustment, HIV-infected women had 34% [95% confidence interval (CI): -54%, -5.5%] lower LFF than uninfected women, whereas there was little difference in men (-5.5%; 95% CI: -26%, 21%). Among HIV-infected persons, greater VAT and homeostasis model assessment-estimated insulin resistance were associated with greater LFF. HIV-related factors (CD4 cell count, HIV RNA level, or antiretroviral therapy use) had little association with LFF. Although HIV-infected men had 81% (95% CI: 32%, 148%) greater LFF than HIV-infected women, the association was attenuated after multivariable adjustment (25%; 95% CI: -9.1%, 73%).ConclusionContrary to expectation, HIV infection is not associated with greater steatosis compared with uninfected adults. It is possible that less fat is stored in the liver to maintain subcutaneous fat (which is reduced in HIV) and the effect is magnified in HIV-infected women, who also have less VAT.

Purpose of reviewTo review the experience to date and unique challenges associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected patients.Recent findingsThe prevalence of cirrhosis and hepatocellular carcinoma is rising among HIV-infected individuals. With careful patient selection and in the absence of HCV infection, HIV-infected and HIV-uninfected liver transplant recipients have comparable posttransplant outcomes. However, in the presence of HCV infection, patient and graft survival are significantly poorer in HIV-infected recipients, who have a higher risk of aggressive HCV recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be improved with careful recipient and donor selection and with the availability of new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does not adversely impact treatment success in nontransplant populations. Therefore, there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected transplant patients and will result in improved outcomes. Careful attention to drug-drug interactions with HIV antiretroviral agents, DAAs, and posttransplant immunosuppressants is required.SummaryLiver transplant outcomes are poorer in HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new HCV DAAs offer tremendous potential to improve outcomes in this challenging population.

Abstract Background Individuals who carry deleterious BRCA mutations face significantly elevated risks of breast, ovarian, and other cancers. These individuals are also responsible for informing relatives of their increased risk for carrying the family BRCA mutation. Few interventions have been developed to facilitate this family communication process. Methods We developed the Sharing Risk Information Tool (ShaRIT), a personalized educational intervention, to support BRCA carriers as they discuss BRCA positive results and their implications with relatives. We conducted a pilot study of 19 BRCA carriers identified through the University of California San Francisco Cancer Risk Program. Our study had two aims: 1) to assess the feasibility and acceptability of ShaRIT, and 2) describe characteristics associated with increased family communication and BRCA testing. Participants in our study were divided into two groups: those who had not received ShaRIT as part of their genetic counseling protocol (control group, n = 10) and those who received ShaRIT (n = 9). Results All 9 women who received ShaRIT reported that it was a useful resource. Characteristics associated with increased sharing and testing included: female gender, degree of relationship, and frequency of communication. Increased pedigree knowledge showed a trend toward higher rates of sharing. Conclusions Both participants and genetic counselors considered ShaRIT a well-received, comprehensive tool for disseminating individual risk information and clinical care guidelines to Hereditary Breast and Ovarian Cancer Syndrome families. Because of this, ShaRIT has been incorporated as standard of care at our institution. In the future we hope to evaluate the effects of ShaRIT on family communication and family testing in larger populations of BRCA positive families.

Food insecurity (FI) is a risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis in the general population, but its impact on liver disease in people with HIV (PWH) is unknown. We examined the association of FI with prevalence of NAFLD and fibrosis in a diverse cohort of PWH. PWH aged ≥ 18 years on antiretroviral therapy, HIV RNA <200 copies/mL, and without other known liver diseases were screened for NAFLD (controlled attenuated parameter ≥263 decibels/meter) and advanced fibrosis (liver stiffness measurement ≥11 kilopascals) by vibration controlled transient elastography at 8 U.S. centers. Participants were categorized as food insecure using the Six-Item Short Form Household Food Security Survey. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of NAFLD and advanced fibrosis by FI status. Among 654 PWH, NAFLD was present in 348 (53%) and advanced fibrosis in 41 (6%). FI was present in 203 of participants (31%), including 97/348 with NAFLD (28%) and 18/41 with advanced fibrosis (44%). In multivariable analysis, FI was associated with lower odds of NAFLD (OR, 0.57; 95% CI, 0.37–0.88) and a greater, but nonsignificant, odds of advanced fibrosis (OR, 1.38; 95% CI, 0.65–2.90). We identified a significant interaction between FI and diabetes (P =.02) on fibrosis risk, with greater odds of fibrosis among food insecure PWH and diabetes (OR, 3.83; 95% CI, 1.15–12.73) but not among food insecure nondiabetics (OR, 1.12; 95% CI, 0.47–2.98). FI is highly prevalent among PWH and associated with lower odds of NAFLD, and among PWH with diabetes, there is greater odds of advanced fibrosis. FI may contribute to hepatic fibrosis through mechanisms other than steatosis in PWH. [ABSTRACT FROM AUTHOR]

Objective: Bile duct dilation (BDD) of unclear etiology is a common indication for further imaging via endoscopic ultrasound (EUS). We aimed to assess the yield of EUS in determining BDD etiology in patients with prior non‐diagnostic imaging studies. Methods: A retrospective chart review was performed at a single, tertiary‐care university hospital for patients referred for EUS for BDD with or without pancreatic duct dilation (PDD). EUS‐guided fine needle aspiration (FNA) was performed if a focal lesion was identified. Cases with an etiology of BDD diagnosed or strongly suggested by prior imaging were excluded. EUS findings believed to represent a structural cause for BDD included a wide range of pancreaticobiliary and luminal pathology as well as patients' clinical factors. Results: In total, 307 patients were identified. Findings to explain BDD were found by EUS in 213 patients for a diagnostic yield of 69.4%. Patients with jaundice were significantly more likely to receive a diagnosis by EUS than those without (78.8% vs 55.3%, P < 0.01). Notably, 8.1% of patients with normal liver function test (LFT) had a EUS‐diagnosed malignancy. Patients' age, narcotic use, concurrent PDD and prior cholecystectomy did not appear to influence the EUS yield. Conclusions: EUS continues to play a substantial role in evaluating BDD of unclear etiology, most notably in patients with jaundice. In addition, given that 8.1% of asymptomatic patients without jaundice or abnormal LFT had malignancy diagnosed on EUS, the use of EUS for BDD of unclear etiology remains warranted. [ABSTRACT FROM AUTHOR]