Lobular Activity Research Articles

Clinical and Pathological Features of Immune Checkpoint Inhibitor-induced Liver Injury in Comparison with Drug-induced Liver Injury and Autoimmune Hepatitis.

Immune checkpoint inhibitors may cause various types of organ damage as immune-related adverse events, of which, liver damage is the most common. Herein, we evaluated the clinicopathological features of immune checkpoint inhibitor-related liver injury and investigated the differences between immune checkpoint inhibitor-related liver injury and drug-induced liver injury or autoimmune hepatitis. We selected patients with ≥ grade 3 liver injury who were diagnosed with immune checkpoint inhibitor-related liver injury (n=15). Liver biopsies were performed in 10 of the 15 cases. We also selected cases in which a liver biopsy was performed and drug-induced liver injury (n=7) or autoimmune hepatitis [n=21: acute exacerbation (n=13) was diagnosed and cases of acute onset (n=8), in which liver function test results corresponded to ≥ grade 3]. Portal fibrosis and periportal activity scores were significantly higher in the acute exacerbation autoimmune hepatitis group than in the other groups. Portal and lobular activity were not different between the groups. Plasma cell infiltration showed a higher trend in the autoimmune hepatitis group than in the other groups. Granuloma formations were seen in 90% of immune checkpoint inhibitor-related liver injury cases. The CD4/8 ratio was significantly lower in the immune checkpoint inhibitor-related liver injury group than in the other groups. Patients with bile duct injury had poorer response to corticosteroid therapy than those without. There are some obvious differences among immune checkpoint inhibitor-related liver injury, drug-induced liver injury, and autoimmune hepatitis in liver histology. Liver biopsy is helpful for the diagnosis and severity evaluation of liver injury.

Abstract 13902: Using a Proteomics-Based Cardiovascular Risk Test to Identify Systemic Changes in a Clinical Trial of Nonalcoholic Fatty Liver Disease

Background: Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular outcomes. Assessment of the impact of NASH therapy on cardiovascular risk is an important element of NASH drug development but is challenging particularly in early phase trials. Aptamer-based proteomic profiles (Somalogic®) in serum have been used to develop and validate a risk score as a surrogate for cardiovascular (CV) risk. Hypothesis: Improvement in NASH histology will result in improved proteomic cardiovascular risk scores. Methods: A post-hoc analysis of proteomic profiles of serum samples, using the Somalogic® platform, from the Pioglitazone vs. Vitamin E vs. Placebo for Treatment of Nonalcoholic Fatty Liver Disease (PIVENS) trial was conducted. PIVENS was a 96-week trial of nondiabetic participants with (NASH). We applied the proteomic CV risk scores to samples from baseline, on therapy and end of treatment visits (n=7) visits and received liver histology results at baseline and 96 weeks on N = 209 (84.6%) study participants. Generalized linear and mixed models were used to assess the association between CV risk score, treatment arm and change in liver biopsy results. Results: Baseline scores were similar across groups (mean 0.19, SD 0.14). There was no association between treatment arms and changes in scores during therapy and end of treatment. However, improvement in histological markers of activity (lobular inflammation and NAFLD activity score) and fibrosis were associated with improved cv risk scores (Figure) (p< 0.05 for all). Conclusions: Improvement in hepatic inflammation, NAFLD activity score and fibrosis were associated with improved proteomic CV risk scores regardless of treatment provided. Additional prospective validation of these findings is warranted. Proteomic profiling can potentially be used to track changes in cardiovascular risk profile changes in response to therapy in the short term NASH treatment trials.

S3241 A Case of Autoimmune Hepatitis in the Setting of the Janssen COVID-19 Vaccine

Introduction: Autoimmune hepatitis (AIH) is an inflammatory autoimmune condition that can result in chronic liver disease, it can be caused by the interaction of hereditary, epigenetic, immune, and environmental triggers. Vaccine related AIH is an uncommon phenomenon that has been reported in the presence of other vaccinations.. We present a unique case of AIH in the setting of the Janssen SARS-CoV-2 vaccine (JJ). Case Description/Methods: A 45-year-old female with a history ofHTN, DM, GERD, and obesity presented from her primary care physician’s office with abnormal liver chemistries in a hepatocellular pattern. Her hepatic profile showed AST 1119, ALT 988, AP 130, and total bilirubin of 1.5 (R-factor 22.8). Given the magnitude and rapidity of the elevated chemistries a broad serologic workup was initiated. She was negative for hepatitis A, B, and C, as well as HSV 1/2, EBV, CMV, HIV, VZV, and adenovirus. Her ferritin and iron studies did not suggest iron overload. Her ceruloplasmin and alpha 1 antitrypsin levels were within acceptable ranges. Her ANA was negative; her smooth muscle antibody was positive (1:320), IgG was elevated to 3,451 mg/dL. Her urine toxin screen was negative. She had chronically been on HCTZ and took occasionally seamoss supplements. She denied using tylenol or any other over the counter or herbal supplements. In the past month she had received a single dose of the Janssen SARS CoV-2 vaccination (Johnson and Johnson). Her liver chemistries prior were AST 17, ALT 14, AP 52, and total bilirubin of 0.3. She subsequently underwent a liver biopsy which showed moderate (grade 3) lobular inflammatory activity, mild (grade 2) periportal activity, and mild (stage 2) fibrosis with an abundance of plasma cells consistent with autoimmune hepatitis. Treatment was initiated with oral prednisone with a resulting improvement in her liver chemistries (Figure). Discussion: Autoimmune hepatitis in the setting of recent administration COVID 19 vaccine administration has been rarely reported. We present a unique case of COVID vaccine induced autoimmune hepatitis from a non-mRNA based vaccine. It has been suggested that possible mechanisms may include molecular mimicry or bystander activation of dormant autoreactive T-helper cells for both tissue-specific and non-tissue-specific reactions. We aim to shed light to this interesting paradigm and to spark the scientific discourse to further delineate potential mechanisms leading to this uncommon complication.Figure 1.: Liver biopsy which showed moderate (grade 3) lobular inflammatory activity, mild (grade 2) periportal activity, and mild (stage 2) fibrosis with an abundance of plasma cells consistent with autoimmune hepatitis.

S3280 A Rare Case of Isolated ALECT-2 Hepatic Amyloidosis

Introduction: Amyloidosis is a rare disease that is defined by deposition of extracellular fibrils from immunoglobulin light chains which results in organ dysfunction. Many patients with primary systemic amyloid have hepatic involvement. Hepatic amyloid deposition is characterized by mild hepatomegaly and occasional elevated liver enzymes. Ultrasound may reveal a heterogenous echogenicity of the liver and Computed Tomography (CT) may reveal decreased parenchymal attenuation. Biopsy is the gold standard for diagnosis, seen as extracellular amorphous material, and Congo red staining will reveal apple-green birefringence under polarized light. Whereas amyloidosis is most often systemic, there are rare cases of isolated hepatic amyloid deposition. Leukocyte cell-derived chemotaxin 2 (ALECT-2) is a novel amyloid subtype, previously thought to be found in renal amyloid with a predominance in Hispanic patients but has recently been reported in the liver. We present a rare case of isolated hepatic amyloidosis without systemic involvement. Case Description/Methods: A 53-year-old Hispanic female with history of diabetes mellitus, hyperlipidemia, and nonalcoholic fatty liver disease presented to hepatology clinic for liver enzyme elevation. Lab studies were significant for AST 36 U/L, ALT 67 U/L, Alkaline Phosphatase, total bilirubin 2.7 mg/dL, positive anti-smooth muscle antibody (22 U), immunoglobulin G 1049 mg/dL, normal anti-nuclear antibody screen and normal anti-mitochondrial antibody. CT showed post cholecystectomy changes, a calcified granuloma in the right hepatic lobe, but otherwise normal liver. Liver biopsy showed focal amyloid deposition, mild steatosis, mild lobular activity, and rare ballooning hepatocytes without fibrosis. Positron emission tomography-CT, bone marrow biopsy, urine and serum protein electrophoresis were unremarkable. Further amyloid testing showed leukocyte chemotactic factor-2 (ALECT-2) amyloidosis. A referral for second opinion and experimental treatment options was recommended, however the patient declined. The patient has had stable lab values over the last two years with observation. Discussion: This is a rare case of isolated hepatic amyloidosis, highlighting the need for maintaining a broad differential diagnosis in a patient presenting with elevated liver enzymes. Given the rare nature of this condition, it is important to demonstrate this patient’s presentation and two-year outcomes with observation, given lack of available treatment regimens.

Two-dimensional Shear-Wave Elastography and US Attenuation Imaging for Nonalcoholic Steatohepatitis Diagnosis: A Cross-sectional, Multicenter Study.

Background Multiparametric US examination may have potential in the comprehensive evaluation of nonalcoholic fatty liver disease (NAFLD), but multicenter studies are lacking. Purpose To evaluate the diagnostic performance of multiparametric US with the attenuation coefficient (AC) from attenuation imaging (ATI) and liver stiffness (LS) and dispersion slope (DS) from two-dimensional (2D) shear-wave elastography (SWE) in a multicenter study of patients with NAFLD. Materials and Methods This prospective study enrolled consecutive participants between December 2019 and June 2021 with suspected nonalcoholic steatohepatitis (NASH) who were scheduled to undergo liver biopsy in five tertiary hospitals. Before the procedure, all participants underwent US with ATI and 2D SWE according to the study protocol. Multivariable linear regression analyses were performed to determine the significant determinant factors for AC, LS, and DS. Diagnostic performance was decided based on the areas under the receiver operating characteristic curve (AUCs). Results A total of 132 participants (median age, 38 years; IQR, 27-54 years; 69 women) were evaluated. Among the participant characteristics, including pathologic findings, demographic characteristics, body mass index, and serum markers, hepatic steatosis for AC (P < .001), lobular inflammatory activity for DS (P = .007), and both fibrosis (P = .01) and lobular inflammatory activity (P = .04) for LS were significant determinant factors. At histopathologic examination, 53 of the 132 participants (40.2%) had NASH. The risk score system obtained using unweighted sum of scores from AC and DS showed the best diagnostic performance in the detection of NASH (AUC = 0.94; 95% CI: 0.89, 0.98; P < .05 for all), as compared with serum markers or other US parameters alone (AUC ≤ 0.88). Conclusion US attenuation imaging and two-dimensional shear-wave elastography were useful for assessing hepatic steatosis, lobular inflammation, and fibrosis. The risk score system obtained using the attenuation coefficient and dispersion slope showed the best diagnostic performance fo r nonalcoholic steatohepatitis. cris.nih.go.kr no. KCT0004326 © RSNA, 2022 Online supplemental material is available for this article.

Letter to the editor: Liver transplantation following severe acute respiratory syndrome‐coronavirus‐2 vaccination–induced liver failure

Several case reports have described development of liver injury following severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccination in Hepatology.[1, 2] These cases showed autoimmune hepatitis (AIH) features, and all cases responded well to corticosteroid therapy. Herein, we present a patient who underwent liver transplantation due to fulminant liver failure following vaccination with the BioNTech vaccine. A 53-year-old previously healthy man received a first dose of BioNTech vaccine on the June 5, 2021. Ten days after vaccination, he developed mild abdominal pain, erythematous skin eruption, and pruritus. Initial laboratory findings were alanine aminotransferase (ALT) 333 (upper limit of normal [ULN] 55 U/L), aspartate aminotransferase (AST) 168 (ULN 34 U/L), alkaline phosphatase 102 (ULN 150 U/L), and total bilirubin 0.8 (ULN 1.2 mg/dl). The patient’s symptoms were considered to be a hypersensitivity reaction. Oral antihistaminic therapy and topical steroids did not lead to clinical improvement. On day 18 after vaccination, prednisolone 32 mg/day for 10 days followed by 16 mg/day for 20 days was commenced. One week into the steroid course, symptoms significantly improved, and aminotransferases decreased (Figure 1). The patient was reluctant to receive a second vaccine dose for fear of additional side effects but had travel plans and needed a full vaccination chart. He, therefore, scheduled a second Pfizer-BioNTech vaccine dose 6 weeks after the first dose. Following the second vaccination, similar symptoms reoccurred after a few days. The dose of prednisolone was increased to 32 mg/day, gradually tapered, and discontinued in mid-August 2021. One month after, he developed abdominal pain, myalgia, fatigue, and jaundice. The symptoms and laboratory findings did not improve over 10 days, and he was referred to a tertiary liver transplant center. At admission, ALT was 485, AST was 629, total bilirubin was 6.6 mg/dl, and the international normalized ratio was 1.36. Serum IgG levels were 28.3 (7.0–16.4 g/L). Viral serology was negative for hepatitis A–E, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus. Antinuclear antibodies, smooth muscle actin, antimitochondrial antibodies, anti–liver–kidney microsome 1, liver cytosolic antigen 1, and anti–soluble liver antigen were all negative; and ceruloplasmin was normal. The liver biopsy showed portal inflammation with interface activity and significant lobular necroinflammatory activity, hepatocellular rosette formation and emperipolesis that are typical components of AIH. Treatment with prednisolone (40 mg/day, i.v.) and plasma exchange did not improve the liver function. The patient developed HE and underwent living donor liver transplantation. One month after liver transplantation, he was alive with significantly improved laboratory findings. We presented a report of severe outcome of liver injury that developed after SARS-CoV-2 vaccination. We are aware that it is difficult to establish a definitive causality between SARS-CoV-2 vaccine and hepatitis. However, our case demonstrates strong evidence of vaccine-induced immune-mediated liver injury. The patient developed liver injury after a first dose of Pfizer-BioNTech vaccine which on reexposure led to severe liver injury. Our case, along with other reports, suggests that AIH-like hepatitis may develop after SARS-CoV-2 vaccination. Early diagnosis and effective management seem to be very important in this emerging condition. Nothing to report. Cumali Efe, Murat Harputluoğlu, and Sezai Yilmaz conceptualized the study. Cumali Efe, Murat Harputluoğlu, and Neşe Karadağ Soylu collected and analyzed data. All authors approved the final version of the manuscript. All data that support the findings of this study are presented in the text.

Kolaviron pre-treatment suppresses 7, 12 dimethylbenzanthracene-induced alterations in estrogen receptor-α, CYP 1A1, oxidative stress and inflammation in female Wistar rats.

Due to the need to develop locally available, cheaper, and efficacious treatment regimens for breast cancer, the chemopreventive effect of kolaviron (KV), an extract of Garcinia kola seeds was examined. Fifty (50) female Wistar rats (120-180g) were assigned to five groups (control group, 7, 12 dimethylbenzanthracene [DMBA] groups, tamoxifen group) of 10 rats each. They were pre-treated with KV thrice a week for four weeks except control. Estrogen receptor-α (ER-α) levels were determined in the pre-treated rats before induction of mammary carcinogenesis. After the four weeks pre-treatment period, 80mg/kg of DMBA was used for induction. A hundred and fifty (150) days after induction, the rats were sacrificed humanely. Significantly higher levels of ER-α, formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, increased cytokines (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]), CYP1A1 activity and malondialdehyde (MDA) with a corresponding decrease in superoxide dismutase (SOD), catalase and glutathione peroxidase were observed in DMBA-induced rats. Pre-treatment with KV at 200mg/kg body weight significantly (p<.05) decreased ER-α levels by 19.01% and 37.52%, [IL-6] by 36.37% and 20.55%, TNF-α by 42.2% and 12.33% in serum and mammary tissue respectively. Also, a significant (p<.05) decrease in serum CYP1A1 activity, MDA with concomitant increase in SOD, catalase and glutathione peroxidase activities were observed in serum and mammary tissue respectively. Collectively, the results suggest that KV could be further explored in targeting chemoprevention of DMBA-induced mammary damage. PRACTICAL APPLICATIONS: Garcinia kola is widely cultivated in West and Central Africa with kolaviron (KV) as its major constituents. The seeds which have a bitter astringent taste are widely consumed by people in the region. Locals claim that consumption of the seeds provides relief for the management of several ailments including cancer. However, scientific investigations that provide a basis for these claims are still needed. This study provides evidence that points to the ameliorative potential of KV on breast cancer model. The results will be beneficial to local communities who hitherto had no knowledge on the potential of G. kola in chemoprevention. The results from this study will also attract further research attention from the international scientific community to examine the anti-cancer benefits of G. kola. This will also be beneficial to the global community due to the increasing number of breast cancer cases recorded annually.

Histologic Changes in Core-Needle Liver Biopsies From Patients With Acute-on-Chronic Liver Failure and Independent Histologic Predictors of 28-Day Mortality.

The histologic features in patients with acute-on-chronic liver failure (ACLF) are evolving, and histologic indicators of patients' poor prognosis are not yet fully established. To evaluate the independent histologic predictors of 28-day mortality in ACLF patients on core-needle liver biopsies. Core-needle biopsies from patients with a diagnosis of ACLF (n = 152) as per the European Association for the Study of the Liver criteria were included during 8 years. Liver biopsies from 98 patients with compensated chronic liver disease were included as disease controls for histologic comparison. Features of ongoing changes, such as hepatic necrosis, hepatic apoptosis, cholestasis, hepatocyte degeneration, bile ductular proliferation, Mallory-Denk bodies, steatosis, and extent of liver fibrosis, were analyzed for predicting short-term mortality (28 days). A P value of <.05 was considered significant. In our cohort of ACLF patients, the following etiologies for acute decompensation were identified: alcohol, 47 of 152 (30.9%); sepsis, 24 of 152 (15.7%); hepatotropic viruses, 20 of 152 (13.1%); drug-induced liver injury, 11 of 152 (7.2%); autoimmune flare, 9 of 152 (5.9%); mixed etiologies, 5 of 152 (3.2%); and cryptogenic, 36 of 152 (23.6%). On histologic examination, hepatic necrosis (P < .001), dense lobular inflammation (P = .03), cholestasis (P < .001), ductular reaction (P = .001), hepatocyte degeneration (P < .001), and absence of advanced fibrosis stages (P < .001) were identified significantly more othen in ACLF patients than in disease controls on univariate analysis. On multivariate Cox regression analysis, the absence of advanced Ishak histologic activity index fibrosis stages (P = .02) and the presence of dense lobular inflammation (P = .04) were associated with increased 28-day mortality in ACLF patients. After adjusting the clinical causes of acute decompensation, only dense lobular inflammation was found as an independent predictor of short-term mortality (P = .04) in ACLF patients. Dense lobular necroinflammatory activity is a clinically independent histologic predictor of 28-day short-term mortality in patients with ACLF.

Liver Pathology and SARS-CoV-2 Detection in Formalin-Fixed Tissue of Patients With COVID-19.

ObjectivesThe novel coronavirus, severe acute respiratory syndrome coronavirus 2, causing coronavirus disease 2019 (COVID-19) remains a global health threat and a significant source of human morbidity and mortality. While the virus primarily induces lung injury, it also has been reported to cause hepatic sequelae.MethodsWe aimed to detect the virus in formalin-fixed tissue blocks and document the liver injury patterns in patients with COVID-19 compared with a control group.ResultsWe were able to detect viral RNA in the bronchioalveolar cell blocks (12/12, 100%) and formalin-fixed, paraffin-embedded tissue of the lung (8/8, 100%) and liver (4/9, 44%) of patients with COVID-19. Although the peak values of the main liver enzymes and bilirubin were higher in the patients with COVID-19 compared with the control group, the differences were not significant. The main histologic findings were minimal to focal mild portal tract chronic inflammation (7/8, 88%, P < .05) and mild focal lobular activity (6/8, 75%, P = .06).ConclusionsWe found that most patients who died of COVID-19 had evidence of mild focal hepatitis clinically and histologically; however, the virus was detected in less than half of the cases.

Pathological predictive factors for late recurrence of hepatocellular carcinoma in chronic liver disease.

Late recurrence of hepatocellular carcinoma (HCC) is regarded as de novo HCC from chronic hepatitis. This study investigated clinicopathological and molecular factors to develop a nomogram for predicting late HCC recurrence (>2years after curative resection). The training and validation cohorts included HCC patients with a major aetiology of hepatitis B who underwent curative resection. Clinicopathological features including lobular and porto-periportal inflammatory activity, fibrosis and liver cell change were evaluated. Proteins encoded by genes related to late recurrence were identified using a reverse phase protein array of 95 non-tumourous liver tissues. Immunoexpression of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), plasminogen activator inhibitor-1, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) and spleen tyrosine kinase (SYK) was measured. Late recurrence occurred in 74/402 (18%) and 47/243 (19%) in the training and validation cohorts respectively. Cirrhosis, moderate/severe lobular inflammatory activity, and expression of pSTAT3, pERK1/2, and SYK proteins correlated to the gene signature of hepatocyte injury and regeneration were independently associated with late recurrence, with odds ratios (95% confidence intervals) of 2.0 (1.2-3.3), 21.1 (4.3-102.7) and 6.0 (2.1-17.7) respectively (P<.05 for all). A nomogram based on these variables (histological parameters and immunohistochemical marker combinations) showed high reliability in both the training and validation cohorts (Harrell's C index: 0.701 and 0.716; 95% confidence intervals: 0.64-0.76 and 0.64-0.79 respectively). The combination of pSTAT3, pERK1/2 and SYK immunoexpression with high lobular inflammatory activity and cirrhosis (fibrosis) predicts late HCC recurrence.

S2394 The Truth Behind the Transaminitis

INTRODUCTION: Abnormal liver enzyme tests are a common finding in the clinical setting but the differential is broad and requires critical thinking. Often, the etiology is unclear in medically complex patients as the cause may be multifactorial. Sarcoidosis is a systemic autoimmune condition and many clinicians are familiar with its pulmonary involvement but about 30% of affected patients have extrapulmonary manifestations. Clinically significant gastrointestinal disease occurs in less than 1% of sarcoidosis patients but the liver can be involved in up to 65% of affected individuals. Accurate assessment and diagnosis can be difficult and requires one to always be open to a broad differential. CASE DESCRIPTION/METHODS: Our case involved a 47-year-old female with history of hashimoto’s disease, multiple sclerosis on tecfidera, and pulmonary sarcoidosis in remission. Incidental elevation of AST, ALT, and alkaline phosphatase were noted on labs when she was admitted after a car accident. Initial liver biopsy was nondiagnostic and lab work revealed normal ferratin, negative ASMA, AMA, A1AT, hepatitis C antibody and acute hepatitis panel but ANA was positive. Due to report of right upper quadrant abdominal pain at that time, she underwent MRI of the abdomen/pelvis and the common bile duct was noted to be 7 mm. She had an ERCP at that time with a sphincterotomy and though the pain resolved, her labs persisted. Tecfidera was another confounder as it also causes transaminitis. However, a medication interruption showed no improvement. Since a clear diagnosis was not found, her team trialed her on steroids for presumed autoimmune hepatitis and her labs improved. When her taper ended, she was readmitted for transaminitis and repeat liver biopsy at that time showed portal and periportal granuloma with associated lymphohistiocytic lobular necroinflammatory activity, which was more consistent with hepatic sarcoidosis. She was started on budesonide with imuran and her labs normalized. DISCUSSION: Though the patient had a remote history of sarcoidosis, she also had a number of other possible causes for her transaminitis and prior to the second biopsy, the working diagnosis of autoimmune hepatitis was supported by a positive ANA and improvement following steroids. This case highlights the importance of keeping a broad, evolving differential while merging clinical assessment with critical interpretation of laboratory data.

Approach to the patient with acute severe autoimmune hepatitis.

SummaryAutoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.

Use of SARS-CoV-2-infected deceased organ donors: Should we always "just say no?"

In the context of a rapidly evolving pandemic, multiple organizations have released guidelines stating that all organs from potential deceased donors with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection should be deferred, including from otherwise medically eligible donors found to have mild or asymptomatic SARS‐CoV‐2 discovered on routine donor screening. In this article, we critically examine the available data on the risk of transmission of SARS‐CoV‐2 through organ transplantation. The isolation of SARS‐CoV‐2 from nonlung clinical specimens, the detection of SARS‐CoV‐2 in autopsy specimens, previous experience with the related coronaviruses SARS‐CoV and MERS‐CoV, and the vast experience with other common RNA respiratory viruses are all addressed. Taken together, these data provide little evidence to suggest the presence of intact transmissible SARS‐CoV in organs that can potentially be transplanted, specifically liver and heart. Other considerations including ethical, financial, societal, and logistical concerns are also addressed. We conclude that, for selected patients with high waitlist mortality, transplant programs should consider accepting heart or liver transplants from deceased donors with SARS‐CoV‐2 infection.

Liver histology in children with glycogen storage disorders type VI and IX

BackgroundGlycogen storage diseases (GSD) type VI and IX are caused by liver phosphorylase system deficiencies and the two types are clinically indistinguishable. AimAs the role of liver biopsy is increasingly questioned, we aim to assess its current value in clinical practice. MethodsWe retrospectively reviewed children with diagnosis of GSD VI and IX at a paediatric liver centre between 2001 and 2018. Clinical features, molecular analysis and imaging were reviewed. Liver histology was reassessed by a single histopatologist. ResultsTwenty-two cases were identified (9 type VI, 9 IXa, 1 IXb and 3 IXc). Features at presentation were hepatomegaly (95%), deranged AST (81%), short stature (50%) and failure to thrive (4%). Liver biopsy was performed in 19 patients. Fibrosis varied in GSD IXa with METAVIR score between F1-F3 and ISHAK score of F2-F5. METAVIR score was F2-F3 in GSD VI and F3-F4 in GSD IXc. Hepatocyte glycogenation, mild steatosis, lobular inflammatory activity and periportal copper binding protein staining were also demonstrated. ConclusionsAlthough GSD VI and IX are considered clinically mild, chronic histological changes of varying severity could be seen in all liver biopsies. Histopathological assessment of the liver involvement is superior to biochemical parameters, but definitive classification requires a mutational analysis.

Accuracy of Two-Dimensional Shear Wave Elastography and Attenuation Imaging for Evaluation of Patients With Nonalcoholic Steatohepatitis

We evaluated the accuracy of a multiparametric approach using attenuation imaging and 2-dimensional shear wave elastography (2D-SWE) for the detection of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We studied 102 patients with increased levels of liver enzymes or suspicion of NAFLD, examined by attenuation imaging and 2D-SWE, immediately before biopsy collection and analysis (reference standard), from January 2018 to July 2019. We collected data on the attenuation coefficient (dB/cm/MHz) from attenuation imaging, liver stiffness measurements, and shear wave dispersion slope (SWDS, [m/s]/kHz) from 2D-SWE. Multivariate linear regression analysis was performed to identify factors associated with each parameter. Diagnostic performance was determined from area under the receiver operating curve (AUROC) values. The attenuation coefficient was associated with steatosis grade (P < .01) and identified patients with steatosis grades S1 or higher, S2 or higher, and S3 or higher, with AUROC values of 0.93, 0.88, and 0.83, respectively. Liver stiffness associated with fibrosis stage (P < .01) and lobular inflammatory activity was the only factor associated with SWDS (P < .01). SWDS detected inflammation grades I1 or higher, I2 or higher, and I3 or higher with AUROC values of 0.89, 0.85, and 0.78, respectively. We developed a risk scoring system to detect steatohepatitis based on the attenuation coefficient (score of 1 for 0.64 < attenuation coefficient ≤ 0.70; score of 2 for 0.70 < attenuation coefficient ≤ 0.73; and score of 3 for attenuation coefficient >0.73) and SWDS (score of 2 for 10.5 [m/s]/kHz < SWDS ≤ 11.7 [m/s]/kHz; and score of 3 for SWDS >11.7 [m/s]/kHz), using an unweighted sum of each score. Based on histopathology analysis, 55 patients had steatohepatitis. Risk scores correlated with NAFLD activity score (rho= 0.73; P < .01). Our scoring system identified patients with steatohepatitis with an AUROC of 0.93-this valuewassignificantly higher than that of other parameters (P < .05), except SWDS (AUROC, 0.89; P= .18). In the evaluation of patients with suspected NAFLD, the attenuation coefficient can identify patients with steatosis and liver stiffness can detect fibrosis accurately. SWDS was associated significantly with lobular inflammation. We developed a risk scoring system based on the attenuation coefficient and SWDS that might be used to detect steatohepatitis.

Current Knowledge and Research Priorities in the Digestive Manifestations of COVID-19

Current Knowledge and Research Priorities in the Digestive Manifestations of COVID-19

Early Rehabilitation for Critically Ill Patients With COVID-19: More Benefits Than Risks.

Early Rehabilitation for Critically Ill Patients With COVID-19: More Benefits Than Risks.

High Prevalence of Concurrent Gastrointestinal Manifestations in Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Early Experience From California

High Prevalence of Concurrent Gastrointestinal Manifestations in Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Early Experience From California

AGA Rapid Recommendations for Gastrointestinal Procedures During the COVID-19 Pandemic

Abbreviations used in this paper AGAAmerican Gastroenterological AssociationCDCCenters for Disease Control and PreventionCIconfidence intervalCOVID-19coronavirus disease 2019GIgastrointestinalGRADEGrading of Recommendations Assessment, Development and EvaluationMERS-CoVMiddle East respiratory syndrome–related coronavirusORodds ratioPAPRpowered air-purifying respiratorPPEpersonal protective equipmentRRrisk ratioSARS-CoV-2severe acute respiratory syndrome coronavirus 2WHOWorld Health Organization

3165 The Great Masquerade

INTRODUCTION: Syphilis is a sexually transmitted infection caused by T. pallidum. It is often described as “the great imitator,” affecting multiple organ systems, and has a wide variation in its clinical presentation. Syphilitic hepatitis is a rare and occurs in 0.2-3% of cases of secondary syphilis. We present a case of mixed hepatocellular and cholestatic hepatitis that led to the diagnosis of syphilis in a patient who presented with non-specific symptoms. CASE DESCRIPTION/METHODS: A 39-year-old homosexual male was referred for evaluation of worsening jaundice following a course of acyclovir for genital herpes 3 months prior. He reported non-specific symptoms including acute diarrhea, abdominal pain, myalgia, rash and weight loss with no change in mental status. He had no pertinent past medical or family history and denied any exposure to IV drugs or blood transfusions. Clinical exam showed scleral icterus, a soft and non-tender abdomen and macular rash in the extremities. Laboratory evaluation showed AST 209, ALT 617 and ALP 1195 (peaked at 2170). INR was 1.0 and albumin was 3.1. Viral hepatitis A, B, C, EBV and HIV testing were negative. F-actin IgG was positive (36) and ANA negative. MRI abdomen showed hepatomegaly without evidence of biliary obstruction. Liver biopsy showed moderate portal/periportal edema; mixed acute and chronic inflammation and pericholangitis with cholestasis. Syphilis immunostaining and Warthin-Starry staining were negative. Our patient was initially treated as presumed autoimmune hepatitis with prednisone. He had significant clinical and LFT improvement over 3-4 weeks but developed new-onset arthralgia in the midst of treatment. Rheumatological workup revealed positive rapid plasma reagin with T. pallidumreactivity. He completed a course of benzathine penicillin, following which he had complete resolution of his symptoms and normalisation of his LFTs. DISCUSSION: SH presents a diagnostic challenge in view of its infrequency and there are currently no standardised diagnostic criteria. Liver chemistry typically demonstrates a cholestatic picture with a disproportionately elevated ALP, likely secondary to pericholangiolar inflammation. However, in our patient, there was also moderate lobular activity with plasma cells, corresponding to a moderately elevated ALT. It is imperative that clinicians have a high index of suspicion for syphilis in view of the morbidity and mortality associated with a missed or late diagnosis and the availability of an effective treatment.