Improving the Diagnostic Accuracy of RECAM in North American Patients with Suspected Idiosyncratic Drug-Induced Liver Injury: Improving RECAM accuracy.

BACKGROUND: The RECAM is an updated, electronic version of the RUCAM to diagnose DILI. The primary aim of this study was to compare RECAM versus RUCAM in patients with suspected DILI. METHODS: Patient encounters from 10/1/2015 to 9/30/2019 were searched for suspected DILI using ICD-10 K71 codes for toxic liver disease. DILIN expert opinion scores were assigned to each case (1/2/3= probable DILI, 4/5= non-DILI). RECAM and RUCAM scores were compared with DILIN expert opinion scores. RESULTS: Among 766,930 encounters searched, 120 unique patients met inclusion criteria with 72 (60%) adjudicated as probable-DILI. The most frequent suspect drugs were antimicrobials (38.3%), antineoplastics (8.3%), and antirheumatic drugs (8.3%). Mean age was 49.2 + 15.6 years and 50% were female with 45.8% having hepatocellular injury. RUCAM had better agreement with DILIN expert opinion for probable-DILI versus RECAM (66.7% vs. 44.4%, p=0.018). Both had 100% agreement with DILIN expert opinion for non-DILI. Frequently missing laboratory data included HCV RNA (64.3%) and anti-HEV IgM testing (70%), leading to loss of up to 6 points in RECAM scoring but not impacting RUCAM scores. A modified RECAM that made HCV RNA and anti-HEV IgM optional had better agreement with DILIN expert opinion compared to RUCAM (79.2% vs. 66.7%, p=0.09). CONCLUSION: Among 120 suspected DILI cases, RUCAM had better agreement with DILIN expert opinion scores versus RECAM. Making HCV RNA and anti-HEV IgM testing optional significantly improved agreement between RECAM and DILIN expert opinion. Future modifications to RECAM are needed to improve causality assessment in North American patients with suspected DILI.

Viral hepatitis in pregnancy.

Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy.

Derivation and Internal Validation of a Clinical Prediction Tool to Predict Nonalcoholic Fatty Liver Disease in Patients With Crohn's Disease.

BACKGROUND: Crohn's disease (CD) patients have more than double the risk of nonalcoholic fatty liver disease (NAFLD) compared with the general population after considering traditional risk factors. NAFLD remains underappreciated because routine imaging and liver biochemistries are neither sensitive nor specific for the diagnosis. Here we developed a Clinical Prediction Tool for NAFLD in CD (CPN-CD) using readily accessible parameters to diagnose NAFLD, as determined by magnetic resonance proton density fat fraction (PDFF). METHODS: A total of 311 consecutive CD patients who underwent magnetic resonance enterography from June 1, 2017, to May 31, 2018, were screened for NAFLD, defined as a PDFF >5.5% after excluding other liver diagnoses. CPN-CD was derived using binary multivariate logistic regression and internally validated with a 10-fold cross-validation. CPN-CD was compared with the Hepatic Steatosis Index (HSI) by the C-statistic and categorical Net Reclassification Improvement (NRI). RESULTS: CPN-CD included age, sex, ethnicity/race, serum alanine aminotransferase, body mass index, known cardiometabolic diagnoses, CD duration, and current use of azathioprine/6-mercaptopurine. At <20% risk, NAFLD could be excluded with a sensitivity of 86% (negative predictive value, 86%). At ≥50% risk, NAFLD was diagnosed with a specificity of 87% (positive predictive value, 75%). CPN-CD exhibited good discrimination (C-statistic 0.85) compared with fair discrimination of the HSI (C-statistic, 0.76). CPN-CD was superior to the HSI by net reclassification improvement (+0.20; P < 0.001) and decision curve analysis. CONCLUSIONS: CPN-CD outperforms HSI in detecting NAFLD in patients with CD. Future directions include external validation, outcome validation, and testing generalizability to patients with ulcerative colitis.

Crohn's Disease Is Associated With an Increased Prevalence of Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study Using Magnetic Resonance Proton Density Fat Fraction Mapping.

Nonalcoholic fatty liver disease (NAFLD) commonly coexists with Crohn's disease (CD); however, it remains unclear if it is more prevalent than would be expected as ultrasound surveys of CD patients report a very wide range of prevalence (9%-40%).1-3 To address this uncertainty, we performed a prospective, cross-sectional survey of NAFLD in CD patients by generating magnetic resonance proton density fat fraction (MR-PDFF) maps as compared with 2 control populations. MR-PDFF provides a quantitative, sensitive and specific (97% and 100%, respectively) radiographic surrogate for liver fat.4.

Serum alpha-fetoprotein level per total tumor volume as a predictor of recurrence of hepatocellular carcinoma after resection.

BACKGROUND: Alpha-fetoprotein has been used as a predictor of recurrence for hepatocellular carcinoma and disease-free survival post-resection. Studies in East Asia have shown that serum alpha-fetoprotein per total tumor volume ratio is a better prognostic indicator than alpha-fetoprotein alone. Similar studies in the United States evaluating serum alpha-fetoprotein to total tumor volume ratio have not been conducted. Its relevance is incompletely understood. METHODS: Consecutive patients undergoing resection for hepatocellular carcinoma at a single tertiary center between 2000 and 2013 were identified for inclusion in this retrospective cohort study. Patient demographics, associated liver disease, Child-Pugh and Model for End-Stage Liver Disease scores, preoperative imaging, surgical pathology, alpha-fetoprotein at diagnosis, last alpha-fetoprotein before surgery, and peak alpha-fetoprotein levels were recorded. Actual tumor volume by imaging volumetrics was used when available (n = 70). For the remaining cases, total tumor volume was calculated using the sum of the volumes of all the tumors ((4/3)πr3) where "r" is the mean radius of each lesion. Peak serum alpha-fetoprotein was used to calculate the alpha-fetoprotein to total tumor volume ratio. RESULTS: A total of 124 patients resected for hepatocellular carcinoma between 2000 and 2013 were identified. Overall 1-, 3-, and 5-year survival post resection was 76%, 53%, and 35%, respectively. On multivariate analysis, peak alpha-fetoprotein to total tumor volume ratio > 20 (P < .001, HR = 3.72, 95% CI [1.82-7.58]) and lymphovascular space invasion (P = .002, HR = 3.30, 95% CI [1.57-6.94]) were found to affect hepatocellular carcinoma recurrence-free survival. CONCLUSION: A variety of prognostic values predict the recurrence of hepatocellular carcinoma postresection. Peak preoperative alpha-fetoprotein to total tumor volume > 20 and lymphovascular space invasion has been shown to predict recurrence of hepatocellular carcinoma. Our study confirms findings from East Asian studies. But larger series are needed to establish this correlation in patients with hepatocellular carcinoma not treated by resection.

Erdheim-Chester Disease presenting with histiocytic colitis and cytokine storm.

BACKGROUND: Non-Langerhans histiocytosis is a group of inflammatory lymphoproliferative disorders originating from non-clonal expansion of hematopoietic stem cells into cytokine-secreting dendritic cells or macrophages. Erdheim-Chester Disease (ECD) is a rare type of non-Langerhans cell histiocytosis characterized by tissue inflammation and injury caused by macrophage infiltration and histologic findings of foamy histiocytes. Often ECD involves the skeleton, retroperitoneum and the orbits. This is the first report documenting ECD manifesting as segmental colitis and causing cytokine-release syndrome. CASE PRESENTATION: A 68-year old woman presented with persistent fever without infectious etiology and hematochezia. Endoscopy showed segmental colitis and pathology revealed infiltration of large foamy histiocytes CD3-/CD20-/CD68+/CD163+/S100- consistent with ECD. The patient was empirically treated with steroids but continued to have fever and developed progressive distributive shock. CONCLUSION: This case report describes the differential diagnosis of infectious and immune-mediated inflammatory and rheumatologic segmental colitis. Non-Langerhans histiocytosis and ECD are rare causes of gastrointestinal inflammation. Prompt diagnosis is imperative for the appropriate treatment to prevent hemodynamic compromise due to distributive shock or gastrointestinal bleeding. Importantly, gastrointestinal ECD might exhibit poor response to steroid treatment and other potential treatments including chemotherapy, and biologic treatments targeting IL-1 and TNF-alpha signalling should be considered.

Neuroglobin expression in the cochlea of rat pups exposed to chronic very mild carbon monoxide (25ppm) in air during and after the prenatal period.

The distribution of neuroglobin (Ngb) was investigated in the normal rat cochlea using immunohistochemistry and non-radioactive insitu hybridization. We also determined whether chronic, very mild CO exposure at 25ppm in air over the gestational and postnatal period alters the expression of Ngb. Pregnant rats were exposed chronically to CO from gestational days 5-20. Four groups were made as follows: prenatal exposure to CO only; prenatal exposure to CO followed by postnatal exposure from postnatal days (5) P5 to P20; rat pups were exposed to CO from P5 to P20; controls (air without CO). In normal adult rats and control group pups, Ngb was found in spiral ganglia neurons, fibrocytes of the spiral ligament, and supporting cells of the organ of Corti. Ngb was not present in the stria vascularis and the inner and outer hair cells. At P20 Ngb immunoreactivity and transcript expression decreased in spiral ganglia neurons and the spiral ligament in the prenatal and pre- and postnatal groups. This decrease was not observed in the postnatal group. Ngb-IR did not decrease in supporting cells in any CO group. Cytochrome-C immunoreactivity followed Ngb distribution in normal controls and CO treated groups. A decrease in Ngb in spiral ganglia neurons and rat spiral ligament, but not in supporting cells, following CO exposure supports the idea that chronic, mild exposure to CO may create a vulnerable cellular environment predisposed to adverse cochlear development.