Utility and impact of magnetic resonance elastography in the clinical course and management of chronic liver disease.

We aimed to characterize scenarios where magnetic resonance elastography (MRE) of the liver was ordered and its impact on clinical course and management. 96 consecutive MRE examinations and subsequent encounters over 14 months were reviewed. Indication for MRE of the liver and subsequent management were abstracted from the medical record. In all cases, non-invasive assessment of liver fibrosis was the primary indication and at least one additional rationale was noted. There was a significant decrease in recommendations to undergo liver biopsy after MRE. Additionally, a greater percentage of those recommended to undergo biopsy completed the procedure after discussion of the results. Given the significant cost and rare but serious risks of liver biopsy, MRE of the liver provides an attractive, safer alternative that may have a comparable impact on management, or select cases where biopsy is essential to guide management. We demonstrate the versatility of MRE in real-world hepatology practice, including its utility as a non-invasive surrogate for liver biopsy.

Novel autoantibody targets identified in patients with autoimmune hepatitis (AIH) by PhIP-Seq reveals pathogenic insights.

Autoimmune hepatitis (AIH) is a severe autoimmune disease, characterized by the presence of autoantibodies. However, the role of autoantibodies in the pathophysiology of AIH remains uncertain. Here, we employed Phage Immunoprecipitation-Sequencing (PhIP-Seq) to identify novel autoantibodies in AIH. Using these results, a logistic regression classifier was able to predict which patients had AIH, indicating the presence of a distinct humoral immune signature. To further investigate the autoantibodies most specific to AIH, significant peptides were identified relative to a broad array of controls (298 patients with non-alcoholic fatty liver disease (NAFLD), primary biliary cholangitis (PBC), or healthy controls). Top ranked autoreactive targets included SLA, the target of a well-recognized autoantibody in AIH, and disco interacting protein 2 homolog A (DIP2A). The autoreactive fragment of DIP2A shares a 9-amino acid stretch nearly identical to the U27 protein of HHV-6B, a virus found in the liver. In addition, antibodies against peptides derived from the leucine rich repeat N-terminal (LRRNT) domain of the relaxin family peptide receptor 1 (RXFP1) were highly enriched and specific to AIH. The enriched peptides map to a motif adjacent to the receptor binding domain, which is required for RXFP1 signaling. RXFP1 is a G protein-coupled receptor that binds relaxin-2, an anti-fibrogenic molecule shown to reduce the myofibroblastic phenotype of hepatic stellate cells. Eight of nine patients with antibodies to RXFP1 had evidence of advanced fibrosis (F3 or greater). Furthermore, serum from AIH patients positive for anti-RFXP1 antibody was able to significantly inhibit relaxin-2 signaling in the human monocytic cell line, THP1. Depletion of IgG from anti-RXFP1 positive serum abrogated this effect. These data provide supporting evidence that HHV6 plays a role in the development of AIH and point to a potential pathogenic role for anti-RXFP1 IgG in some patients. Identification of anti-RXFP1 in patient serum may enable risk stratification of AIH patients for fibrosis progression and lead to the development of novel strategies for disease intervention.

Racial differences in prevalence and severity of non-alcoholic fatty liver disease.

The aim of this review is to assess the evidence regarding racial differences in the prevalence and severity of nonalcoholic fatty liver disease (NAFLD). We reviewed the published literature that reported prevalence, severity, and genetic associations of NAFLD in different ethnic groups. The metabolic syndrome (MetS) has been associated with NAFLD, but each component of the MetS is present in various races in different percentages and their effect on NAFLD appears to be dissimilar. An elevated triglyceride (TG) level seems to have the strongest association with NAFLD. The latter is more prevalent in Hispanic patients; Blacks have lower TG levels and a lower NAFLD prevalence, compared to Caucasians or Hispanics. The severity of liver fibrosis is lower in some, but not all biopsy-based studies of Black patients. No study has evaluated the severity of liver disease controlling for the individual components of MetS, especially TG. Important racial differences in the prevalence of selected genetic polymorphisms, particularly PNPLA-3 and MBOAT7 have been documented, together with their effects on the prevalence of liver steatosis and fibrosis. Data on overall and liver mortality have found no significant differences according to race/ethnicity, with the possible exception of one paper reporting lower cirrhosis mortality in Black patients. We conclude that NAFLD is more prevalent in Hispanics and less in Blacks. This is supported by differences in key genetic polymorphisms associated with hepatic fat storage. However, there is presently insufficient evidence to firmly conclude that race, per se, plays a role in the development of liver fibrosis and its complications. Further studies, appropriately controlled for diet, exercise, and individual MetS parameters are needed.