Utility of a Low-Cost 3-D Printed Microscope for Evaluating Esophageal Biopsies.

In this manuscript we assessed the utility of a low-cost 3D printed microscope to evaluate esophageal biopsies. We conducted a comparative analysis between the traditional microscope and our 3-D printed microscope, utilizing a set of esophageal biopsy samples obtained from patients undergoing screening endoscopy. Two pathologists independently examined 30 esophageal biopsies by light microscopy and digital images obtained using a low-cost 3D printed microscope (Observer 1 and 2). The glass slide consensus diagnosis was compared to the findings of 2 additional pathologist who independently just reviewed the digital images (Observer 3 and 4). The intra-observer agreement was substantial to almost perfect for observer 1 (k:0.64) and 2 (k:0.84). All four observers had 100% sensitivity and negative predictive value, whereas specificity ranged from 59% to 100% and positive predictive value ranged from 21% to 100%. The PPV and specificity were lower for the two Observers (3 and 4) who just examined the digital images. Overall, our results suggest that telepathology may be used with high sensitivity and specificity, utilizing the pictures produced by our 3D-printed microscope.

MUC1 Expressions and Its Prognostic Values in US Gastric Cancer Patients.

This study aims to evaluate the prognostic value of MUC expression in US GC patients. A total of 70 tumor specimens were collected from GC patients who underwent surgery or endoscopic resection between 2013 and 2019 at a tertiary referral center in the US. MUC expression status including MUC1, MUC2, MUC5AC, and MUC6 was evaluated by immunohistochemical staining. The positive rates of MUC1, MUC2, MUC5AC, and MUC6 were 71.4%, 78.6%, 74.3%, and 33.3%, respectively. Patients with positive MUC1 expression had a significantly higher rate of aggressive pathologic features including diffuse-type cancer (42.0% vs. 0%; p < 0.001), advanced GC (80.0% vs. 30.0%, p < 0.001), lymph node metastasis (62.0% vs. 20.0%; p = 0.001), and distant metastasis (32.0% vs. 5.0%; p = 0.017) compared with those with negative MUC1 expression. However, the differences in the pathologic features were not observed according to MUC2, MUC5AC, and MUC6 expression status. In early gastric cancer (EGC), patients with a high level of MUC1 expression showed a higher rate of lymphovascular invasion (71.4% vs. 21.4%; p = 0.026) and EGC meeting non-curative resection (85.7% vs. 42.9%; p = 0.061) than those with negative MUC1. In US GC patients, MUC1 expression is associated with aggressive pathological features, and might be a useful prognostic marker.

Liver Explants of Biliary Atresia Patients Transplanted in Adulthood Show Features of Obliterative Portal Venopathy: Case Series and Guidelines for Pathologic Reporting of Adult Explants.

CONTEXT.­: Biliary atresia (BA) patients can have portal vein (PV) abnormalities. OBJECTIVE.­: To investigate the explant pathology of BA patients transplanted in adulthood with a focus on portal venous abnormalities. DESIGN.­: Adult BA liver explants were reviewed, along with prior biopsies, Kasai portoenterostomy (KP), and relevant medical records. RESULTS.­: Three explants were identified; all patients were female, with age at diagnosis, KP, and liver transplantation (LT) as follows: (1) less than 1 week, 8 days, and 25 years; (2) 15 weeks, 16 weeks, and 32 years; and (3) 7 weeks, 8 weeks, and 33 years, respectively, with normalization of conjugated bilirubin within 6 months of KP and development of portal hypertension (PHTN) within 3 years of KP for all 3. The first 2 had recurrent cholangitis. Duration of pre-LT PHTN was 22, 29, and 30 years, and that of pre-LT cholangitis was 9, 3, and 0 years, respectively. All 3 explants showed hilar and extrahepatic fibromyxoid intimal hyperplasia of the PV with parenchymal hepatoportal sclerosis. Cholestasis was limited to those with a history of cholangitis. Patient 3, without cholangitis, showed delicate septal fibrosis with peripheral accentuation without biliary cirrhosis. CONCLUSIONS.­: In the context of a functioning KP, cholestasis and biliary cirrhosis are likely related to recurrent cholangitis, which may or may not occur after KP. In the absence of biliary cirrhosis, PHTN may be secondary to obliterative venopathy. Adult BA explants should be sampled thoroughly, with a focus on hilar/perihilar connective tissue to include PV branches. Explants may not show biliary cirrhosis and should be reported with appropriate clinicopathologic correlation.

Interobserver Variability and Challenges in Intraoperative Frozen Section Evaluation of Pancreatic Margins in Pancreatectomy Specimens.

OBJECTIVE: Frozen-section evaluation of the pancreatic margin is challenging. We aimed to determine interobserver variability among gastrointestinal pathologists for the assessment of frozen sections of pancreatic margins with marked chronic pancreatitis and to determine the challenging histological features in discrepant cases. METHODS: We identified 45 patients who underwent pancreas resection for pancreatic ductal adenocarcinoma and showed marked chronic pancreatitis at pancreatic margin. Deidentified first levels of frozen-sections of the pancreatic margins from all cases were independently reviewed by 5 experienced gastrointestinal pathologists for the presence of carcinoma and/or high-grade dysplasia. RESULTS: Interobserver agreement among pathologists was calculated as kappa coefficients ([Formula: see text]). A consensus diagnosis for discordant cases was obtained after group review and discussion. Interobserver agreement for adenocarcinoma diagnosis was 87%, and there was "substantial agreement" (Fleiss [Formula: see text]=0.78, P<0.01) and "almost perfect agreement" (Brennan-Prediger [Formula: see text]=0.86, P<0.01). Using the final diagnosis based on frozen and permanent sections as the gold standard and the concordant read of at least 3 of 5 pathologists for comparison, the diagnosis of adenocarcinoma was made in frozen-sections of pancreas margins, with accuracy 98%, sensitivity 83%, specificity 100%, negative predictive value 97%, positive predictive value 100%, false negative rate 9%, and false positive rate 0%. CONCLUSIONS: We showed excellent interobserver agreement among gastrointestinal pathologists for diagnosis of adenocarcinoma on frozen sections of pancreatic margins with marked chronic pancreatitis. Missed adenocarcinoma at the margin was mainly caused by freezing or cautery artifacts or by overlooking a tiny focus of perineural invasion in a background of marked chronic pancreatitis. The evaluation of deeper levels led to perfect agreement.

Perineural Invasion by an Intraductal Papillary Mucinous Neoplasm of Pancreas: A Case Report of an Unusual and Unreported High-Risk Feature of Malignant Progression.

Perineural invasion is a frequent histological finding in pancreatic adenocarcinoma. However, perineural invasion by intraductal papillary mucinous neoplasm (IPMN), a precursor lesion of pancreatic adenocarcinoma, has not been reported so far. We report a unique case of perineural invasion by IPMN in a 60-year-old female who underwent pancreatoduodenectomy for high-risk features of IPMN. Histological evaluation showed increased nerve density in the connective tissue of IPMN with multiple foci of perineural invasion by IPMN. In addition, there was a discrete 2 mm focus of invasive carcinoma that did not show perineural invasion. Chemotherapy was started and the patient is disease-free at 29 months follow up. The case illustrates previously unreported neuroplastic alterations and neutrotropism in benign neoplastic component of a malignant IPMN.

Prevalence and clinical significance of portal inflammation, portal plasma cells, interface hepatitis and biliary injury in liver biopsies from patients with non-alcoholic steatohepatitis.

The significance of portal tract histological changes in non-alcoholic fatty liver disease (NAFLD) remains unclear. In 2019, CymaBay Therapeutics halted clinical trials of seladelpar (a PPARδ agonist) because initial end-of-treatment liver biopsies of patients with non-alcoholic steatohepatitis (NASH) showed concerning features of portal inflammation with plasma cells, interface hepatitis and focal bile duct abnormalities. Adjudication concluded that these findings were present in the initial, as well as the subsequent biopsies. Thus, this study's aim was to determine the prevalence and clinical significance of portal inflammation, portal plasma cells, interface hepatitis and features of bile duct damage in liver biopsies of adult patients with NAFLD. The pathology database was searched for cases of NAFLD, including steatosis alone and NASH, from January 2016 to October 2020. Liver biopsies were selected from age and sex matched adult patients with diagnoses of steatosis alone (n=10), NASH fibrosis stage 1 (n=10), stage 2 (n=10), stage 3 (n=10), and stage 4 (n=10). There were 24 males and 26 females with a mean age of 48 years (range 20-79). Exclusion criteria included age <18 years, daily alcohol intake >14 drinks per week, elevation of alkaline phosphatase level, comorbid chronic liver disease, or liver biopsy performed as part of a clinical trial for NASH. Control liver biopsies were selected from age and sex matched persons without significant steatosis and normal liver biochemical tests (n=10). Histological parameters were evaluated in 10 portal tracts or 10 septal areas in each liver biopsy. Portal inflammation and interface hepatitis were graded on a scale of 0-4. Portal plasma cells and bile duct damage were scored from 0-3. Ductular proliferation was assessed by CK7 immunostain and graded from 0-4. NASH biopsies with advanced fibrosis (stage 3 and 4) showed portal inflammatory infiltrates (score 2-3) with readily identifiable plasma cells (score 2), and mild to moderate interface hepatitis (score 2-3). All cases and controls showed focal, mild cholangiocyte changes, characterised by cytoplasmic vacuolation, segmental loss of nuclei, nuclear disarray and apoptosis. NASH patients with advanced fibrosis had frequent and diffuse cholangiocyte changes, along with focal lymphocytic cholangitis and moderate to marked ductular reaction (score 3-4). Histopathological features of advanced NASH frequently include increased portal inflammation with plasma cells, interface hepatitis, cholangiocyte injury and prominent ductular reaction.

Clinicopathologic correlations of superficial esophageal adenocarcinoma in endoscopic submucosal dissection specimens.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a novel endoscopic treatment for early esophageal adenocarcinoma (EAC). The western pathologists' experience with ESD specimens remains limited. This study aimed to correlate histopathologic features of Barrett's esophagus (BE)-associated adenocarcinoma in ESD resections with clinical outcomes to determine whether they aid future management decisions. METHODS: We retrospectively evaluated 49 consecutive ESD resection specimens from 42 patients with BE-associated adenocarcinoma (24 intramucosal and 18 submucosal EAC) at a single tertiary referral center. Pathologic evaluation included presence of dysplasia, invasive adenocarcinoma, peritumoral inflammation, desmoplasia, lymphovascular and perineural invasion; tumor differentiation, depth of invasion, morphology, and budding; and margin status for dysplasia or carcinoma. Follow up data included endoscopic biopsies in 35 patients and pathology reports of esophagectomies in 11 patients. Poor outcomes were defined as recurrence or residual invasive adenocarcinoma at esophagectomy, metastasis on imaging, or R1 resection in patients undergoing ESD for tumor debulking. RESULTS: Two patients (8%) with intramucosal adenocarcinoma and 9 patients (50%) with submucosal adenocarcinoma had poor outcomes. Histopathologic features associated with poor outcomes included poor differentiation, lymphovascular invasion, submucosal invasion > 500 µm, tumor budding, and tubuloinfiltrative histologic pattern. Four patients had positive deep margin away from the deepest tumor invasion and did not show residual tumor on follow up. CONCLUSIONS: Our results validated European Society of Gastroenterology (ESGE) guidelines of high-risk pathologic features for additional therapy in esophageal adenocarcinoma and identified tumor budding frequently in association with other high-risk features. Positive deep margin distant from deepest tumor invasion could be procedural and warrants endoscopic correlation for management.

Clinical Translation and Evaluation of a Handheld and Biocompatible Mass Spectrometry Probe for Surgical Use.

BACKGROUND: Intraoperative tissue analysis and identification are critical to guide surgical procedures and improve patient outcomes. Here, we describe the clinical translation and evaluation of the MasSpec Pen technology for molecular analysis of in vivo and freshly excised tissues in the operating room (OR). METHODS: An Orbitrap mass spectrometer equipped with a MasSpec Pen interface was installed in an OR. A "dual-path" MasSpec Pen interface was designed and programmed for the clinical studies with 2 parallel systems that facilitated the operation of the MasSpec Pen. The MasSpec Pen devices were autoclaved before each surgical procedure and were used by surgeons and surgical staff during 100 surgeries over a 12-month period. RESULTS: Detection of mass spectral profiles from 715 in vivo and ex vivo analyses performed on thyroid, parathyroid, lymph node, breast, pancreatic, and bile duct tissues during parathyroidectomies, thyroidectomies, breast, and pancreatic neoplasia surgeries was achieved. The MasSpec Pen enabled gentle extraction and sensitive detection of various molecular species including small metabolites and lipids using a droplet of sterile water without causing apparent tissue damage. Notably, effective molecular analysis was achieved while no limitations to sequential histologic tissue analysis were identified and no device-related complications were reported for any of the patients. CONCLUSIONS: This study shows that the MasSpec Pen system can be successfully incorporated into the OR, allowing direct detection of rich molecular profiles from tissues with a seconds-long turnaround time that could be used to inform surgical and clinical decisions without disrupting tissue analysis workflows.

Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology.

Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry-based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.

Sequencing of a central nervous system tumor demonstrates cancer transmission in an organ transplant.

Four organ transplant recipients from an organ donor diagnosed with anaplastic pleomorphic xanthoastrocytoma developed fatal malignancies for which the origin could not be confirmed by standard methods. We identified the somatic mutational profiles of the neoplasms using next-generation sequencing technologies and tracked the relationship between the different samples. The data were consistent with the presence of an aggressive clonal entity in the donor and the subsequent proliferation of descendent tumors in each recipient. Deleterious mutations in BRAF, PIK3CA, SDHC, DDR2, and FANCD2, and a chromosomal deletion spanning the CDKN2A/B genes, were shared between the recipients' lesions. In addition to demonstrating that DNA sequencing tracked a donor/recipient cancer transmission, this study established that the genetic profile of a donor tumor and its potential aggressive phenotype could have been determined before transplantation was considered. As the genetic correlates of tumor invasion and metastases become better known, adding genetic profiling by DNA sequencing to the data considered for transplant safety should be considered.

Short-term clinical outcomes of non-curative endoscopic submucosal dissection for early esophageal adenocarcinoma.

OBJECTIVES: Few Western studies highlighted the outcomes of endoscopic submucosal dissection (ESD) for early esophageal adenocarcinoma (EAC). Data regarding the outcomes of noncurative ESDs remains scarce. In this study, we share our experience with ESD for early EAC with a focus on noncurative ESDs. METHODS: A retrospective single-center analysis of consecutive patients who underwent ESD for early EAC from August 2015 through February 2020. Primary outcomes included the clinical outcomes of noncurative ESDs along with overall en bloc, R0 and curative resection rates. Secondary outcomes included comparing results between T1a and T1b tumors. RESULTS: Final group included 23 T1a and 17 T1b EAC patients. Patients' median Charlson comorbidity index was five. En bloc resection rate was (97.5%). Compared to the T1b group, the T1a group had a statistically significantly higher R0 (78.3 vs. 41.2%; P = 0.0235), curative (73.9 vs. 11.8%; P = 0.0001) and accumulative endoscopic curative resection rates (82.6 vs. 23.5%; P = 0.0003). A study flowchart is presented in (Fig. 1). Out of the 21 noncurative ESDs, 10 patients (47.6%) underwent R0 esophagectomy, 6 patients (28.6%) are undergoing surveillance endoscopies without additional therapy, 3 patients (14.3%) underwent repeat curative ESD and 1 patient (4.76%) is receiving chemotherapy with surveillance endoscopy. Over median endoscopic follow-up of 22.5 months (IQR, 14.25-30.75), 2 out of 10 patients with noncurative ESDs had recurrent disease. CONCLUSIONS: ESD achieved a higher curative resection rate in T1a EAC when compared to T1b. Despite a lower curative resection rate in T1b EAC, certain patients might benefit from a conservative multimodal therapy.

Ampullary Carcinosarcoma with Enteroblastic Differentiation: A Case Report.

Adenocarcinoma with enteroblastic differentiation is an extremely rare tumor with poor prognosis and unique pathologic features. The tumor appears to be relatively more common in stomach, with rare cases reported in esophagus, colon, rectum and ampulla. Underrecognition by pathologists may be a contributing factor towards underreporting of this tumor. Combination of carcinosarcoma and enteroblastic differentiation has not been reported so far.We report a unique case of ampullary carcinosarcoma with enteroblastic differentiation in a 59-year-old female, diagnosed in the pancreatoduodenectomy specimen. The carcinomatous component showed features of enteroblastic differentiation characterized by tubular architecture with clear cytoplasm, solid component with trabecular architecture and immunohistochemical expression of SALL4 and AFP. The patient was treated with adjuvant Folfirinox chemotherapy and is disease free at 17 months follow up.

Lactoferrin amyloid presenting as a mural nodule in a pancreatic cystic lesion prompting pancreatoduodenectomy: a case report.

BACKGROUND: Amyloid deposition in pancreas is rare. Lactoferrin amyloid deposition has not been reported in pancreas, till date. Presence of enhancing mural nodule in a cyst on imaging is a worrisome feature for malignancy, and warrants surgical resection in a surgically fit candidate, as per Fukuoka guidelines for management of cystic lesions in pancreas. CASE REPORT: We report a case of localized amyloidosis presenting as a mural nodule in a 1.6 cm cyst located in the head of pancreas, which led to pancreatoduodenectomy in a 69 year old woman. Histological evaluation revealed a simple mucinous cyst with localized lactoferrin amyloid deposition corresponding to the mural nodule identified on imaging. CONCLUSIONS: We report the first case of localized lactoferrin amyloid deposition in pancreas that presented as a mural nodule in a cystic lesion and prompted pancreatoduodenectomy. This unique case illustrates that on rare occasion mural nodule in a cyst can be benign. It adds amyloid deposition to the differential diagnosis of mural nodules in pancreatic cystic lesions seen on imaging.

Clinicopathologic Features and Diagnostic Implications of Pyloric Gland Metaplasia in Intestinal Specimens.

Pyloric gland metaplasia (PGM) is a histopathologic change usually seen after inflammatory injury and, although described in association with inflammatory bowel disease (IBD) and particularly Crohn disease (CD), its significance is still debated. We evaluated long-term correlates of PGM in a large cohort of 601 intestinal specimens, 227 (37.8%) biopsies, and 374 (62.2%) resections, from 567 different patients, 328 (57.8%) male and 239 (42.2%) female, with a mean age of 43.4±15.8 years. During mean clinical follow-up of 83.5±48.1 months, 511 (90.1%) patients were diagnosed with IBD, 457 (89.4%) with CD, and 53 (10.4%) with ulcerative colitis. In multivariate analysis, IBD patients with PGM were younger (P<0.001) and more often had severely active inflammation (P=0.002) compared with non-IBD patients, whereas, among IBD patients, those with ulcerative colitis were more likely to have PGM in a biopsy (P<0.001) or in the colorectum (P=0.009), compared with CD patients. Kaplan-Meier analyses showed that incidental PGM in a biopsy was more likely to predict IBD in patients younger than 50 years (P<0.001) and those without a history of bowel surgery (P<0.001) and also more likely to signify CD in patients younger than 50 years (P=0.004), those without a history of bowel surgery (P=0.020), and when identified in the small intestine (P=0.032). In conclusion, intestinal PGM warrants a high suspicion for IBD and specifically CD, however, it should be interpreted with caution, especially in older patients or those with a history of prior intestinal surgery and in colorectal biopsies or specimens lacking severely active inflammation.

Drug-Induced Liver Injury Associated With Alpha Bolic (RAD-140) and Alpha Elite (RAD-140 and LGD-4033).

We report a 52-year-old man who developed drug-induced liver injury after taking Alpha Bolic (contains RAD-140) and Alpha Elite (contains both RAD-140 and LGD-4033) supplements. Liver biopsy demonstrated diffuse centrilobular canalicular cholestasis, prominent ductular reaction, and mild lobular inflammation with rare non-necrotizing epithelioid granuloma suggestive of drug-induced liver injury. Liver enzymes returned to normal levels approximately 3 months after the patient stopped both supplements. We present the mechanism of drug-induced liver injury associated with 2 selective androgen receptor modulators, including RAD-140 and LGD 4033.

Ligandrol (LGD-4033)-Induced Liver Injury.

We described a 32-year-old man who developed severe drug-induced liver injury after using Ligandrol (LGD-4033). The diagnosis was confirmed by a liver biopsy that showed cholestatic hepatitis with a mild portal, periportal, and perisinusoidal fibrosis. Ligandrol is a selective androgen receptor modulator that is available over the counter and via the internet.

Biliary Atresia Patients With Successful Kasai Portoenterostomy Can Present With Features of Obliterative Portal Venopathy.

OBJECTIVE: Study of liver explants of biliary atresia (BA) patients with successful Kasai portoenterostomy (KP). METHODS: Pathology and medical records of BA liver explants from January 2009 to June 2018 with successful KP were reviewed along with appropriate controls. RESULTS: Fourteen out of 68 (20.6%) BA patients with LT had a successful KP. Median age at BA diagnosis, KP and LT was 60.5 days, 61 days, and 10 years, respectively, with conjugated bilirubin (c-bil) normalizing at 12.5 weeks after KP. Advanced fibrosis was diffuse in 2/14 (14.3%) explants, limited to periphery in 11/14 (78.6%) and absent in 1. Hilar partial nodular transformation (PNT) was seen in 11 explants (78.6%) and diffuse nodular regenerative hyperplasia (NRH) in 2 (14.3%). Areas of PNT and NRH showed diffuse portal sclerosis (100%), complete and incomplete portal vein (PV) stenosis (100%), PV herniation (100%), hypervascular portal tracts (20%), periportal abnormal vessels (100%), abundant lymphatic collaterals (100%), mild medial hepatic arterial hypertrophy (100%), and delicate fibrous septae (100%). Extrahepatic PVs showed variable luminal occlusion with mean PV intima to full thickness ratio of 0.6 +/- 0.11; significantly higher than age-matched noncirrhotic (n = 27, 0.08 +/- 0.09; P < 0.0001) and cirrhotic controls (n = 19, 0.34 +/- 0.2; P = 0.0015); and comparable to BA patients with failed KP (P = 0.82) and without KP (P = 0.04). CONCLUSIONS: BA patients with successful KP can present with obliterative portal venopathy (OPV). In the context of optimal bile drainage, portal hypertension may not be because of advanced parenchymal fibrosis but possibly because of OPV. Vascular abnormalities of the PV system should be investigated in BA patients.

Autoimmune Hepatitis Refractory to Treatment Due to Underlying Grave's Disease.

A 24-year-old Hispanic woman presented to our facility with a two-week history of abdominal pain, nausea, vomiting, diarrhea, jaundice, and scleral icterus. Initial laboratory workup revealed elevated transaminases, direct hyperbilirubinemia, and positive anti-smooth muscle antibody. Liver biopsy confirmed the diagnosis of autoimmune hepatitis and our patient was started on oral prednisone therapy. Her liver enzymes initially began to normalize but then spontaneously started up-trending. She was subsequently readmitted to the hospital for further management, at which time she also complained of palpitations, heat intolerance, and sweating. Laboratory workup revealed hyperthyroidism secondary to Grave's disease. Our patient was not a candidate for methimazole or propylthiouracil treatment due to her hepatic dysfunction, so she was started on hydrocortisone due to its secondary effect of decreased conversion of thyroxine to triiodothyronine. She achieved biochemical remission of her autoimmune hepatitis on this regimen and was transitioned back to oral prednisone therapy. Her liver enzymes normalized once she underwent radioactive iodine ablation of her thyroid. This clinical course suggests that autoimmune hepatitis with concurrent Grave's disease may be refractory to treatment until the underlying hyperthyroid state is corrected.