Acquisition of epithelial plasticity in human chronic liver disease.

For many adult human organs, tissue regeneration during chronic disease remains a controversial subject. Regenerative processes are easily observed in animal models, and their underlying mechanisms are becoming well characterized1-4, but technical challenges and ethical aspects are limiting the validation of these results in humans. We decided to address this difficulty with respect to the liver. This organ displays the remarkable ability to regenerate after acute injury, although liver regeneration in the context of recurring injury remains to be fully demonstrated. Here we performed single-nucleus RNA sequencing (snRNA-seq) on 47 liver biopsies from patients with different stages of metabolic dysfunction-associated steatotic liver disease to establish a cellular map of the liver during disease progression. We then combined these single-cell-level data with advanced 3D imaging to reveal profound changes in the liver architecture. Hepatocytes lose their zonation and considerable reorganization of the biliary tree takes place. More importantly, our study uncovers transdifferentiation events that occur between hepatocytes and cholangiocytes without the presence of adult stem cells or developmental progenitor activation. Detailed analyses and functional validations using cholangiocyte organoids confirm the importance of the PI3K-AKT-mTOR pathway in this process, thereby connecting this acquisition of plasticity to insulin signalling. Together, our data indicate that chronic injury creates an environment that induces cellular plasticity in human organs, and understanding the underlying mechanisms of this process could open new therapeutic avenues in the management of chronic diseases.

FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2.

Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.

Convergent somatic mutations in metabolism genes in chronic liver disease.

The progression of chronic liver disease to hepatocellular carcinoma is caused by the acquisition of somatic mutations that affect 20-30 cancer genes1-8. Burdens of somatic mutations are higher and clonal expansions larger in chronic liver disease9-13 than in normal liver13-16, which enables positive selection to shape the genomic landscape9-13. Here we analysed somatic mutations from 1,590 genomes across 34 liver samples, including healthy controls, alcohol-related liver disease and non-alcoholic fatty liver disease. Seven of the 29 patients with liver disease had mutations in FOXO1, the major transcription factor in insulin signalling. These mutations affected a single hotspot within the gene, impairing the insulin-mediated nuclear export of FOXO1. Notably, six of the seven patients with FOXO1S22W hotspot mutations showed convergent evolution, with variants acquired independently by up to nine distinct hepatocyte clones per patient. CIDEB, which regulates lipid droplet metabolism in hepatocytes17-19, and GPAM, which produces storage triacylglycerol from free fatty acids20,21, also had a significant excess of mutations. We again observed frequent convergent evolution: up to fourteen independent clones per patient with CIDEB mutations and up to seven clones per patient with GPAM mutations. Mutations in metabolism genes were distributed across multiple anatomical segments of the liver, increased clone size and were seen in both alcohol-related liver disease and non-alcoholic fatty liver disease, but rarely in hepatocellular carcinoma. Master regulators of metabolic pathways are a frequent target of convergent somatic mutation in alcohol-related and non-alcoholic fatty liver disease.

Pervasive lesion segregation shapes cancer genome evolution.

Cancers arise through the acquisition of oncogenic mutations and grow by clonal expansion1,2. Here we reveal that most mutagenic DNA lesions are not resolved into a mutated DNA base pair within a single cell cycle. Instead, DNA lesions segregate, unrepaired, into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterize this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multiallelic and combinatorial genetic diversity. The phasing of lesions enables accurate measurement of strand-biased repair processes, quantification of oncogenic selection and fine mapping of sister-chromatid-exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes.

Somatic mutations and clonal dynamics in healthy and cirrhotic human liver.

The most common causes of chronic liver disease are excess alcohol intake, viral hepatitis and non-alcoholic fatty liver disease, with the clinical spectrum ranging in severity from hepatic inflammation to cirrhosis, liver failure or hepatocellular carcinoma (HCC). The genome of HCC exhibits diverse mutational signatures, resulting in recurrent mutations across more than 30 cancer genes1-7. Stem cells from normal livers have a low mutational burden and limited diversity of signatures8, which suggests that the complexity of HCC arises during the progression to chronic liver disease and subsequent malignant transformation. Here, by sequencing whole genomes of 482 microdissections of 100-500 hepatocytes from 5 normal and 9 cirrhotic livers, we show that cirrhotic liver has a higher mutational burden than normal liver. Although rare in normal hepatocytes, structural variants, including chromothripsis, were prominent in cirrhosis. Driver mutations, such as point mutations and structural variants, affected 1-5% of clones. Clonal expansions of millimetres in diameter occurred in cirrhosis, with clones sequestered by the bands of fibrosis that surround regenerative nodules. Some mutational signatures were universal and equally active in both non-malignant hepatocytes and HCCs; some were substantially more active in HCCs than chronic liver disease; and others-arising from exogenous exposures-were present in a subset of patients. The activity of exogenous signatures between adjacent cirrhotic nodules varied by up to tenfold within each patient, as a result of clone-specific and microenvironmental forces. Synchronous HCCs exhibited the same mutational signatures as background cirrhotic liver, but with higher burden. Somatic mutations chronicle the exposures, toxicity, regeneration and clonal structure of liver tissue as it progresses from health to disease.

Spleen Size Does Not Correlate With Histological Stage of Liver Disease in People With Nonalcoholic Fatty Liver Disease.

Splenomegaly in the context of liver disease is classically associated with advanced cirrhosis and portal hypertension.1 More recently, we observed an increasing number of patients with splenomegaly and nonalcoholic fatty liver disease (NAFLD), but in whom intensive work-up revealed no evidence of advanced liver disease or portal hypertension. In this study, we found no correlation between spleen size and histological stage of NAFLD, and a strong correlation between body weight, height and serum high density lipoprotein (HDL) levels.

Perceived Need and Acceptance of a Future Chlamydia Vaccine Among Health Care Providers.

BACKGROUND: Chlamydia vaccination is a potentially important strategy to prevent infections and reduce the global burden of disease. Ideally, chlamydia immunization programs would require vaccinating adolescents before they engage in sexual activity. Communication by health care providers (HCPs) has been shown to have an impact on vaccine acceptance. Therefore, it is imperative to understand their opinions on chlamydia vaccines and factors that would promote strong vaccine recommendations to patients to promote uptake. METHODS: Semi-structured interviews with adolescent HCPs were conducted and focused on perceived need for chlamydia vaccine. Additional topics included vaccine characteristics, such as efficacy, cost, and booster vaccines, and potential vaccine recommendation strategies. RESULTS: From January to July 2021, 22 interviews were completed. Health care providers discussed how chlamydia vaccines are needed, especially in settings with high prevalence rates. Health care providers thought a chlamydia vaccine would need to be very efficacious in preventing infections and related sequalae and cost-effective. However, there were concerns about low completion rates if this vaccine required multiple doses or boosters. In addition, vaccine misinformation was prevalent among HCPs regarding potential benefits of vaccination. CONCLUSIONS: Health care providers' perceptions that an adolescent chlamydia vaccine would be beneficial offers great promise for future promotion. However, there is need for targeted education programs about chlamydia and the benefits of vaccination for HCPs. These programs will be especially important in order for HCPs to effectively communicate about the benefits of vaccination to parents and adolescents provide strong vaccine recommendations.

Chlamydia Vaccination: Parent Opinions and Implications for Future Promotion Programs.

BACKGROUND: Chlamydia vaccines are currently under development and have the potential to lower the incidence of infection and disease, which are highest among adolescents and young adults. Ideally, a chlamydia vaccine would be administered to adolescents before sexual debut, a time when parents are the primary vaccine decision makers. This study explores parent opinions about an adolescent chlamydia vaccine to understand barriers and facilitators to uptake. METHODS: Semistructured interviews were conducted with parents of adolescents. Topics included conversations parents have with their children about chlamydia, opinions on chlamydia vaccine development, and vaccine characteristics, such as efficacy and cost. Interviews were analyzed using a thematic analysis approach. RESULTS: From March to April 2021, 21 interviews were completed. Few parents discuss chlamydia with their children and sex education was seen as limited. Overall, 16 parents indicated that a chlamydia vaccine is needed. However, there were mixed opinions about vaccinating their own children, related to the need to vaccinate at a young age, vaccine efficacy, and confusion about benefits of vaccination. Finally, healthcare provider recommendations were seen as important before deciding to vaccinate a child. CONCLUSIONS: Although parents think that chlamydia vaccines are needed, lack of awareness about infections and potential benefits of vaccination could serve as barriers to uptake. Healthcare provider recommendations can help to improve knowledge and vaccine uptake. However, there is a need for multilevel approaches to improve chlamydia awareness and ensure that vaccination initiation and completion rates remain high.

ABCB4 Mutations in Adults Cause a Spectrum Cholestatic Disorder Histologically Distinct from Other Biliary Disease.

BACKGROUND: Mutations in the ABCB4 gene are associated with failure of bile acid emulsification leading to cholestatic liver disease. Presentations range from progressive familial intrahepatic cholestasis type 3 (PFIC3) in childhood, to milder forms seen in adulthood. AIMS: We sought to characterize adult disease with particular reference to histology which has been hitherto poorly defined. METHODS: Four unrelated adults (three female, mean age 39 years) and three sisters presenting with cholestatic liver disease in adulthood, associated with variants in the ABCB4 gene, were identified. Clinical review and detailed blinded histopathological analysis were performed. RESULTS: Two novel pathogenic ABCB4 variants were identified: c.620 T > G, p.(Ile207Arg) and c.2301dupT, p.(Thr768TyrfsTer26). Sub-phenotypes observed included low-phospholipid-associated cholelithiasis syndrome (LPAC), intrahepatic cholestasis of pregnancy (ICP), drug-induced cholestasis, idiopathic adulthood ductopenia, and adult PFIC3. Of note, 5/7 had presented with gallstone complications (4 meeting LPAC definition) and 4/6 females had a history of ICP. Considerable overlap was observed phenotypically and liver transplantation was required in 3/7 of patients. Histologically, cases generally demonstrated ductopenia of the smaller tracts, mild non-ductocentric portal inflammation, bilirubinostasis, significant copper-associated protein deposition, and varying degrees of fibrosis. CONCLUSIONS: Adults with ABCB4 mutations may harbor a spectrum of cholestatic disease phenotypes and can progress to liver transplantation. We observed a distinct histological pattern which differs from classical biliary disease and describe two novel pathogenic ABCB4 variants. ABCB4 sequencing should be considered in patients with relevant cholestatic phenotypes and/or suggestive histology; accurate diagnosis can guide potential interventions to delay progression and inform family screening.

Life after breast cancer: 'Being' a young African American survivor.

Objective: In the United States, 26,534 young women (≤45 years) were diagnosed with breast cancer in 2017. Young African American (AA) women have higher incidence and mortality rates than Whites and Hispanics. Yet, few published studies describe survivorship (life after breast cancer diagnosis) experiences among this group. Here, we explore the lived experience of young AA breast cancer survivorship (via quality of life [QOL]).Design: This phenomenological study was framed by the QOL Applied to Breast Cancer model. Fifteen young AA survivors from the Southern U. S. participated in two semi-structured interviews. Methods of transcendental phenomenology were used for data collection and analysis.Results: Five themes emerged from participants' (mean age = 35 years; survivorship = 4 years) descriptions of survivorship experience: (1) actively managing spiritual self, (2) actively managing physical self, (3) actively managing psychological self, (4) actively managing social self, and (5) seeking survivorship knowledge. Participants perceived survivorship as a labile 'new normal' and 'ongoing struggle,' in which spirituality and survivorship knowledge were key to restructuring their lives.Conclusions: Survivorship among young AA survivors was more fluid and complex than the QOL model explained. Findings describe young AA breast cancer survivorship and indicate areas of potential strengths and distress. Healthcare providers and ancillary staff must exercise cultural competence to assess and anticipate young AA survivors' needs and concerns. Implementing targeted survivorship interventions, accounting for cultural contexts (e.g. high spirituality) and need for age-specific survivorship information, may improve QOL among young AA survivors.

Development and prognostic relevance of a histologic grading and staging system for alcohol-related liver disease.

BACKGROUND & AIMS: The SALVE Histopathology Group (SHG) developed and validated a grading and staging system for the clinical and full histological spectrum of alcohol-related liver disease (ALD) and evaluated its prognostic utility in a multinational cohort of 445 patients. METHODS: SALVE grade was described by semiquantitative scores for steatosis, activity (hepatocellular injury and lobular neutrophils) and cholestasis. The histological diagnosis of steatohepatitis due to ALD (histological ASH, hASH) was based on the presence of hepatocellular ballooning and lobular neutrophils. Fibrosis staging was adapted from the Clinical Research Network staging system for non-alcoholic fatty liver disease and the Laennec staging system and reflects the pattern and extent of ALD fibrosis. There are 7 SALVE fibrosis stages (SFS) ranging from no fibrosis to severe cirrhosis. RESULTS: Interobserver κ-value for each grading and staging parameter was >0.6. In the whole study cohort, long-term outcome was associated with activity grade and cholestasis, as well as cirrhosis with very broad septa (severe cirrhosis) (p <0.001 for all parameters). In decompensated ALD, adverse short-term outcome was associated with activity grade, hASH and cholestasis (p = 0.038, 0.012 and 0.001, respectively), whereas in compensated ALD, hASH and severe fibrosis/cirrhosis were associated with decompensation-free survival (p = 0.011 and 0.001, respectively). On multivariable analysis, severe cirrhosis emerged as an independent histological predictor of long-term survival in the whole study cohort. Severe cirrhosis and hASH were identified as independent predictors of short-term survival in decompensated ALD, and also as independent predictors of decompensation-free survival in compensated ALD. CONCLUSION: The SALVE grading and staging system is a reproducible and prognostically relevant method for the histological assessment of disease activity and fibrosis in ALD. LAY SUMMARY: Patients with alcohol-related liver disease (ALD) may undergo liver biopsy to assess disease severity. We developed a system to classify ALD under the microscope by grading ALD activity and staging the extent of liver scarring. We validated the prognostic performance of this system in 445 patients from 4 European centers.

Pilot study of a noninvasive real-time optical backscatter probe in liver transplantation.

Transplantation of severely steatotic donor livers is associated with early allograft dysfunction and poorer graft survival. Histology remains the gold standard diagnostic of donor steatosis despite the lack of consensus definition and its subjective nature. In this prospective observational study of liver transplant patients, we demonstrate the feasibility of using a handheld optical backscatter probe to assess the degree of hepatic steatosis and correlate the backscatter readings with clinical outcomes. The probe is placed on the surface of the liver and emits red and near infrared light from the tip of the device and measures the amount of backscatter of light from liver tissue via two photodiodes. Measurement of optical backscatter (Mantel-Cox P < 0.0001) and histopathological scoring of macrovesicular steatosis (Mantel-Cox P = 0.046) were predictive of 5-year graft survival. Recipients with early allograft dysfunction defined according to both Olthoff (P = 0.0067) and MEAF score (P = 0.0097) had significantly higher backscatter levels from the donor organ. Backscatter was predictive of graft loss (AUC 0.75, P = 0.0045). This study demonstrates the feasibility of real-time measurement of optical backscatter in donor livers. Early results indicate readings correlate with steatosis and may give insight to graft outcomes such as early allograft dysfunction and graft loss.

Management of Return to School Following Brain Injury: An Evaluation Model.

Traumatic brain injury (TBI) affects children's ability to succeed at school. Few educators have the necessary training and knowledge needed to adequately monitor and treat students with a TBI, despite schools regularly serving as the long-term service provider. In this article, we describe a return to school model used in Oregon that implements best practices indicated by the extant literature, as well as our research protocol for evaluating this model. We discuss project aims and our planned procedures, including the measures used, our quasi-experimental design using matched controls, statistical power, and impact analyses. This project will provide the evidential base for implementation of a return to school model at scale.

Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology.

Liver biopsy is required when clinically important information about the diagnosis, prognosis or management of a patient cannot be obtained by safer means, or for research purposes. There are several approaches to liver biopsy but predominantly percutaneous or transvenous approaches are used. A wide choice of needles is available and the approach and type of needle used will depend on the clinical state of the patient and local expertise but, for non-lesional biopsies, a 16-gauge needle is recommended. Many patients with liver disease will have abnormal laboratory coagulation tests or receive anticoagulation or antiplatelet medication. A greater understanding of the changes in haemostasis in liver disease allows for a more rational, evidence-based approach to peri-biopsy management. Overall, liver biopsy is safe but there is a small morbidity and a very small mortality so patients must be fully counselled. The specimen must be of sufficient size for histopathological interpretation. Communication with the histopathologist, with access to relevant clinical information and the results of other investigations, is essential for the generation of a clinically useful report.

Adolescents' perceptions of sexual health education programs: An integrative review.

INTRODUCTION: Adolescents are key stakeholders in sexual health education, yet they are rarely consulted when developing sexual health programs. Their voices are integral to improving the delivery of relevant and appropriate school-based sexual health education to promote safer adolescent sexual behaviors. METHODS: An integrative review was conducted utilizing three databases: Cumulative Index of Nursing and Allied Health Literature (CINAHL) Complete, PubMed, and Education Resources Information Center (ERIC). The PRISMA and matrix method were used to search the literature and synthesize the findings from 16 articles regarding adolescent perceptions of school-based sexual health education. RESULTS: The main themes that emerged from this review included: (a) factors influencing adolescent perceptions of sexual health education programs, (b) characteristics of good sexual health education programs, and (c) areas of improvement in sexual health education programs. CONCLUSION: Adolescents overwhelmingly requested honest, comprehensive content delivered by nonjudgmental, well-educated health professionals in a comfortable environment.

Neighborhood Disorder, Family Functioning, and Risky Sexual Behaviors in Adolescence.

Adolescent risky sexual behaviors can result in negative consequences such as sexually transmitted infection. However, much research effort has been placed on understanding individual characteristics, rather than the role of neighborhood environment. This study addressed the prospective effects of neighborhood and family functioning in preadolescence on risky sexual behaviors. Participants included 4179 youth (Mage = 11.01 years, range 8.64-13.83; 51% female) and their caregivers. Using objective and self-reported measures of neighborhood and family functioning, results from multilevel regression analyses indicated that youth residing in disordered neighborhoods or had poorer family functioning in preadolescence were more likely to initiate sexual intercourse at younger ages 5 years later. Specifically, neighborhood poverty and decay were linked to early sexual initiation, whereas neighborhood social and family processes were protective against early sexual initiation. Males were more likely to engage in risky sexual behaviors in neighborhoods with greater poverty or decay; neighborhood poverty was linked with sexual initiation in White but not African American youth. Finally, parental monitoring moderated relationships between neighborhood social resources and contraceptive use, with neighborhood social resources linked with greater contraceptive use at low levels of parental monitoring, but lower contraceptive use at high levels of parental monitoring. These findings underscore the importance of neighborhood and family contexts in adolescents' risky sexual behavior, suggesting that males and White youth are more vulnerable to the effects of neighborhood poverty and that more research is needed on the possible counterproductive function of parental monitoring in neighborhoods with greater social resources.

Barriers to HIV Testing: Patient and Provider Perspectives in the Deep South.

Although CDC guidelines call for universal, "opt-out" HIV testing, barriers to testing continue to exist throughout the United States, with the rural South particularly vulnerable to both HIV infection and decreased awareness of status. Therefore, the objectives of this study were to evaluate uptake of "opt-out" HIV testing and barriers to testing within the primary care setting in the South. A concurrent triangulation design guided the collection of quantitative data from patients (N = 250) and qualitative data from providers (N = 10) across three primary health clinics in Alabama. We found that 30% of patients had never been tested for HIV, with the highest ranked barrier among patients being perceived costs, access to specialty care, and not feeling at risk. Significant differences existed in perceived barriers between patients and providers. Increased provider-patient engagement and the routine implementation of "opt-out" HIV testing would effectively reveal and mitigate barriers to testing, thus, increasing awareness of status.

Preliminary Efficacy of Online Traumatic Brain Injury Professional Development for Educators: An Exploratory Randomized Clinical Trial.

OBJECTIVE: To examine the efficacy of an online traumatic brain injury (TBI) professional development intervention, In the Classroom After Concussion: Best Practices for Student Success. DESIGN: A randomized controlled trial with a sample of 100 general educators, who were randomly assigned to the In the Classroom Web site (treatment group) or the LEARNet Web site (control group). Participants completed the pretest, accessed the In the Classroom or LEARNet site and the posttest and completed follow-up assessments 60 days after posttest. MEASURES: (1) Knowledge of effective strategies for working with students with TBI; (2) knowledge application; (3) self-efficacy in handling situations presented in text and video scenarios, and (4) a standardized self-efficacy measure. RESULTS: On the posttest assessment, In the Classroom educators showed significantly greater gains in knowledge (P < .0001, d = 1.36 [large effect]), TBI knowledge application (P = .0261, d = 0.46), and general self-efficacy (P = .0106, d = 0.39) than the LEARNet controls. In the Classroom educators maintained significant gains in knowledge (P = .001, d = 0.82) and general self-efficacy (P = .018, d = 0.38) but not in TBI knowledge application (P = .921, d = 0.02). CONCLUSION: Given the prevalence of TBI, it is important to develop evidence-based, cost-effective approaches to knowledge transfer and exchange in TBI professional development. In the Classroom is one such approach.

n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects. Based on knowledge of their complementary molecular targets, we aimed to demonstrate that the combination of n-3 LC-PUFA (n-3) and flavan-3-ols (FLAV) prevents NAFLD. In a high-fat high-fructose (HF/HFr) fed C57Bl/6J mouse model, the independent and interactive impact of n-3 and FLAV on histologically defined NAFLD, insulin sensitivity, weight gain, intestinal and hepatic gene expression, intestinal bile acids were examined. Only the combination of FLAV and n-3 (FLAVn-3) prevented steatosis as evidenced by a strong reduction in hepatocyte ballooning. While FLAV reduced body (-28-30%), adipose tissue (-45-50%) weights and serum insulin (-22-25%) as observed following an intra-peritoneal glucose tolerance test, n-3 downregulated the expression of Srebf1 and the lipogenic genes (Acaca, Fasn). Significant impacts of interventions on intestinal bile acid metabolism, farnesoid X receptor (Fxr) signalling in the intestine and liver, and hepatic expression of fatty acid transporters (Fabp4, Vldlr, Cd36) were also evident. FLAVn-3 may be a novel intervention for NAFLD. Future research should aim to demonstrate its efficacy in the prevention and treatment of human NAFLD.

Liver transplantation in adults with liver disease due to common variable immunodeficiency leads to early recurrent disease and poor outcome.

Common variable immunodeficiency (CVID) is the most common form of primary immunodeficiency characterized by antibody deficiency, recurrent bacterial infections, and autoimmunity. Advanced chronic liver disease occurs in a subset of patients with CVID and manifests with various histological features, such as nodular regenerative hyperplasia, inflammation, fibrosis, and cholangiopathy. We present a case series characterizing the outcomes in adult patients transplanted for primary CVID-related liver disease. We discuss the unique transplantation challenges faced in this primary immunodeficiency group including susceptibility to infections and early disease recurrence. There is a statistically significant decrease in 3-year and 5-year survival after liver transplantation in those with CVID-related liver disease (55% at 3 and 5 years) compared with all-comers (89% at 3 years, 81% at 5 years), prompting a need for discussion of suitability of transplantation in this group of patients as well as methods for reducing posttransplantation risk such as scrupulous search for infectious agents and reduction of immunosuppression. Liver Transplantation 24 171-181 2018 AASLD.