Striking Cholestatic Giant Cell Hepatitis Resulting in Fulminant Liver Failure After Garcinia Cambogia Use.

Garcinia cambogia, a weight control herbal, can cause mild liver toxicity with nonspecific histologic changes. Herein, we reported a case of herbal-induced fulminant cholestatic giant cell hepatitis due to garcinia cambogia use. A 65-year-old woman with breast cancer treated 18 years earlier was admitted for obstructive jaundice for 2 weeks. She started using garcinia cambogia 3 months ago for weight loss. Physical exam showed scleral icterus. Serum studies excluded Wilson's disease, systemic infection including COVID-19 (coronavirus disease 2019), autoimmune hepatitis, and metabolic or toxicologic causes. An urgent liver biopsy showed severe giant cell hepatitis in absence of HSV-1/2, cytomegalovirus, HBsAg and HBcAg (immunostain), and EBV (in situ hybridization). Despite supportive therapy, the patient developed grade 2-3 hepatic encephalopathy and necessitated liver transplant. The explanted liver was markedly atrophy, in which the most striking histologic finding was diffuse distribution of multinucleated giant hepatocytes with syncytial pattern in a background of extensive zone-1 accentuated, geographic, hemorrhagic, confluent hepatocytic necrosis, along with remarkable hepatocytic and canalicular cholestasis. Marked hepatocellular and sinusoidal iron orverload present. The patient recovered uneventfully.

Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial.

Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.

A Rare Red Herring: Intrahepatic Splenosis Masquerading as Hepatocellular Carcinoma.

Splenosis is defined as viable splenic tissue that is autotransplanted into other compartments in the body. Intrahepatic splenosis is a rare diagnosis that can be difficult for clinicians to identify. The most common causes of splenosis include abdominal trauma and splenectomy. While most patients with intrahepatic splenosis are asymptomatic, in the presence of risk factors of hepatocellular carcinoma, it is paramount to rule out malignancy. In this report, we present a patient with imaging findings concerning for hepatocellular carcinoma, ultimately diagnosed with percutaneous biopsy and technetium-99m-tagged heat-damaged red blood cell scintigraphy-proven intrahepatic splenosis.

Persistently Elevated HBV Viral-Host Junction DNA in Urine as a Biomarker for Hepatocellular Carcinoma Minimum Residual Disease and Recurrence: A Pilot Study.

Hepatitis B virus (HBV)-host junction sequences (HBV-JSs) has been detected in the urine of patients with HBV infection. This study evaluated HBV-JSs as a marker of minimum residual disease (MRD) and tumor recurrence after treatment in HBV-hepatocellular carcinoma (HCC) patients. Archived serial urine DNA from two HBV-HCC with recurrence as confirmed by MRI and four HBV-related cirrhosis (LC) patients were used. Urinary HBV-JSs were identified by an HBV-targeted NGS assay. Quantitative junction-specific PCR assays were developed to investigate dynamic changes of the most abundant urinary HBV-JS. Abundant urinary HBV-JSs were identified in two cases of tumor recurrence. In case 1, a 78-year-old female with HBV- HCC underwent a follow-up MRI following microwave ablation. While MRI results were variable, the unique HBV-JS DNA, HBV-Chr17, steadily increased from initial diagnosis to HCC recurrence. In case 2, a 74-year-old male with HBV-HCC contained two HBV-JS DNA, HBV-Chr11 and HBV-TERT, that steadily increased after initial HCC diagnosis till recurrence. One LC examined had HBV-TERT DNA detected, but transiently in 3.5 years during HCC surveillance. HBV-JS DNA was persistently elevated prior to the diagnosis of recurrent HCC, suggesting the potential of urinary HBV-JS DNA to detect MRD and HCC recurrence after treatment.

Comparison of Magnetic Resonance-Based Elastography and Ultrasound Shear Wave Elastography in Patients With Suspicion of Nonalcoholic Fatty Liver Disease.

ABSTRACT: This study investigated the correlation between magnetic resonance elastography (MRE) and shear wave ultrasound elastography (SWE) in patients with clinically diagnosed or suspected nonalcoholic fatty liver disease (NAFLD). Subjects with or at risk of NAFLD identified by magnetic resonance imaging (MRI) proton density fat fraction (PDFF) were prospectively enrolled. For each patient, 6 valid 2-dimensional SWE measurements were acquired using a Logiq E10 scanner (GE HealthCare, Waukesha, WI). A reliability criterion of an interquartile range to median ratio of ≤15% was used for SWE to indicate quality dataset. Magnetic resonance elastography, and MR-fat quantification data were collected the same day as part of the patient's clinical standard of care. Magnetic resonance imaging PDFF was used as a reference to quantify fat with >6.4% indicating NAFLD. Pearson correlation and t-test were performed for statistical analyses. A total of 140 patients were enrolled, 112 of which met SWE reliability measurement criteria. Magnetic resonance elastography and 2-dimensional SWE showed a positive correlation across all study subjects ( r = 0.27; P = 0.004). When patients were grouped according to steatosis and fibrosis state, a positive correlation was observed between MRE and SWE in patients with fibrosis ( r = 0.30; P = 0.03), without fibrosis ( r = 0.27; P = 0.03), and with NAFLD ( r = 0.28; P = 0.02). No elastography technique correlated with liver fat quantification ( P > 0.52). Magnetic resonance elastography was significantly different between patients with and without fibrosis ( P < 0.0001). However, this difference was not apparent with SWE ( P = 0.09). In patients with suspected or known NAFLD, MRE, and SWE demonstrated a positive correlation. In addition, these noninvasive imaging modalities may be useful adjunct techniques for monitoring NAFLD.

The Early-Enhancing Hepatic Vein: Differentiating Focal Nodular Hyperplasia and Hepatic Adenoma With Pathologic Validation in MRI.

BACKGROUND: Focal nodular hyperplasia (FNH) and hepatic adenoma (HA) are two common benign liver lesions with different management options. In particular, resection is considered for large HA lesions to avoid possible bleeding complications or rarely malignant degeneration. PURPOSE: To determine whether early enhancement of a draining hepatic vein (EDHV) and absence of perilesional enhancement (PLE) on arterial phase MR images are useful for distinguishing FNH from HA. STUDY TYPE: Retrospective. POPULATION: A total of 34 patients: 16 with FNH and 18 with HA lesions. FIELD STRENGTH/SEQUENCE: A1.5 T, axial T1 fat-suppressed arterial postcontrast. ASSESMENT: Four abdominal radiologists blinded to pathologic diagnosis assessed for the presence or absence of EDHV in association with the lesion, definitively characterized by pathology. This was considered present if contrast could be identified in a hepatic vein contiguous with the lesion in question. Secondarily, PLE was evaluated. STATISTICAL TESTS: Fleiss's multirater kappa statistic, Chi-squared statistic, Phi-coefficient. Significance level P < 0.05. RESULTS: Considering all observations obtained from the four readers, an EDHV was identified with FNH 48.5% of the time. EDHV was seen with HA in 8.8% of cases. PLE was seen with significantly greater frequency in HA. The presence of an EDHV was associated with the absence of PLE. DATA CONCLUSION: In a lesion that may be either an FNH or HA, confident identification on arterial phase images of an EDHV should lead the reader to favor FNH, while the presence PLE should dissuade the reader from FNH. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Ultrasound-Based Machine Learning Approach for Detection of Nonalcoholic Fatty Liver Disease.

OBJECTIVES: Current diagnosis of nonalcoholic fatty liver disease (NAFLD) relies on biopsy or MR-based fat quantification. This prospective study explored the use of ultrasound with artificial intelligence for the detection of NAFLD. METHODS: One hundred and twenty subjects with clinical suspicion of NAFLD and 10 healthy volunteers consented to participate in this institutional review board-approved study. Subjects were categorized as NAFLD and non-NAFLD according to MR proton density fat fraction (PDFF) findings. Ultrasound images from 10 different locations in the right and left hepatic lobes were collected following a standard protocol. MRI-based liver fat quantification was used as the reference standard with >6.4% indicative of NAFLD. A supervised machine learning model was developed for assessment of NAFLD. To validate model performance, a balanced testing dataset of 24 subjects was used. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy with 95% confidence interval were calculated. RESULTS: A total of 1119 images from 106 participants was used for model development. The internal evaluation achieved an average precision of 0.941, recall of 88.2%, and precision of 89.0%. In the testing set AutoML achieved a sensitivity of 72.2% (63.1%-80.1%), specificity of 94.6% (88.7%-98.0%), positive predictive value (PPV) of 93.1% (86.0%-96.7%), negative predictive value of 77.3% (71.6%-82.1%), and accuracy of 83.4% (77.9%-88.0%). The average agreement for an individual subject was 92%. CONCLUSIONS: An ultrasound-based machine learning model for identification of NAFLD showed high specificity and PPV in this prospective trial. This approach may in the future be used as an inexpensive and noninvasive screening tool for identifying NAFLD in high-risk patients.

Reduced Rates of Post-Transplant Recurrent Hepatocellular Carcinoma in Non-Alcoholic Steatohepatitis: A Propensity Score Matched Analysis.

Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) has become the second leading cause of HCC-related liver transplantation in the United States. This study investigated post-transplant recurrence and survival for patients transplanted for NASH-related HCC compared to non-NASH HCC etiologies. Retrospective review of the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN) database identified 7,461 patients with HCC-1,405 with underlying NASH and 6,086 with non-NASH underlying diseases. After propensity score matching (PSM) to account for patient- and tumor-related confounders 1,175 remained in each group. Primary outcomes assessed were recurrence rate and recurrence-free survival. Recurrent malignancy at 5 years post-transplant was lower in NASH compared to non-NASH patients (5.80 vs. 9.41%, p = 0.01). Recurrence-free survival, however, was similar at 5 years between groups. Patients with NASH-related HCC were less likely to have post-transplant recurrence than their non-NASH counterparts, although recurrence-free survival was similar at 5 years.

Beyond the Liver Function Tests: A Radiologist's Guide to the Liver Blood Tests.

Liver blood tests (often also known as liver chemistries, liver tests, or the common misnomer liver function tests) are routinely used in diagnosis and management of hepatobiliary disease. Abnormal liver blood test results are often the first indicator of hepatobiliary disease and a common indication for abdominal imaging with US, CT, or MRI. Most of the disease entities can be categorized into hepatocellular or cholestatic patterns, with characteristic traits on liver blood tests. Each pattern has a specific differential, which can help narrow the differential diagnosis when combined with the clinical history and imaging findings. This article reviews the major liver blood tests as well as a general approach to recognizing common patterns of hepatobiliary disease within these tests (hepatocellular, cholestatic, acute liver failure, isolated hyperbilirubinemia). Examples of hepatobiliary disease with hepatocellular or cholestatic patterns are presented with characteristic test abnormalities and imaging findings. The commonly encountered scenario of chronic hepatitis with possible fibrosis is also reviewed, with discussion of potential further imaging such as elastography. The role of liver blood tests and imaging in evaluating complications of hepatic transplant is also discussed. Overall, integrating liver blood test patterns with imaging findings can help the radiologist accurately diagnose hepatobiliary disease, especially in cases where imaging findings may not allow differentiation between different entities. ©RSNA, 2021.

Predicting Long-Term Hepatocellular Carcinoma Response to Transarterial Radioembolization Using Contrast-Enhanced Ultrasound: Initial Experiences.

Conventional cross-sectional imaging done shortly after radioembolization of hepatocellular carcinoma (HCC) does not reliably predict long-term response to treatment. This study evaluated whether quantitative contrast-enhanced ultrasound (CEUS) can predict the long-term response of HCC to yttrium-90 (Y-90) treatment. Fifteen patients underwent CEUS at three time points: immediately following treatment and 1 and 2 wk post-treatment. Response 3-6 mo after treatment was categorized on contrast-enhanced magnetic resonance imaging by two experienced radiologists using the Modified Response Evaluation Criteria in Solid Tumors. CEUS data were analyzed by quantifying tumor perfusion and residual fractional vascularity using time-intensity curves. Patients with stable disease on magnetic resonance imaging had significantly greater fractional vascularity 2 wk post-treatment (65.15%) than those with partial or complete response (13.8 ± 9.9%, p = 0.007, and 14.9 ± 15.4%, p = 0.009, respectively). Complete responders had lower tumor vascularity at 2 wk than at post-operative examination (-38.3 ± 15.4%, p = 0.045). Thus, this pilot study suggests CEUS may provide an earlier indication of Y-90 treatment response than cross-sectional imaging.

US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial.

Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1-4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). Conclusion The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020.

Acute Liver Failure Requiring Liver Transplantation due to Acute Hepatitis A Virus Infection.

INTRODUCTION: Hepatitis A infection (HAV) is generally characterized by an acute icteric illness or may have a subclinical self-limited course, although rarely, can result in fulminant hepatitis and death. In 2019, the City of Philadelphia declared a public health emergency due to an HAV outbreak. We are reporting a series of four cases of acute liver failure (ALF) requiring liver transplantation (LT) due to acute HAV. METHODS: Chart review and case descriptions of four patients with acute HAV-related ALF who were expeditiously evaluated, listed as Status 1A, and who underwent LT between August 2019 and October 2019 at Thomas Jefferson University Hospital. RESULTS: All four patients presented with acute hepatocellular jaundice and had a positive HAV IgM, and all other causes of ALF were excluded. All four cases met the American Association for the Study of Liver Diseases (AASLD) criteria for ALF. Three of the four cases met King's College Criteria of poor prognosis for nonacetaminophen-induced ALF. All four patients underwent successful LT and were discharged six to twelve days postoperatively. One patient died of disseminated Aspergillus infection five months after LT, while the others have had excellent clinical outcomes shown by one-year follow-ups. All four explants had remarkably similar histological changes, revealing acute hepatitis with massive necrosis accompanied by a prominent lymphoplasmacytic inflammatory infiltrate and bile ductular proliferation. CONCLUSION: Although rare, patients presenting with acute HAV need close monitoring as they may rapidly progress to ALF. Early referral to a transplant center afforded timely access to LT and yielded overall good one-year survival. Widespread HAV vaccination for high-risk individuals is an essential strategy for preventing disease and curbing such future outbreaks.

Liver Cancer-Specific Serine Protease Inhibitor Kazal Is a Potentially Novel Biomarker for the Early Detection of Hepatocellular Carcinoma.

INTRODUCTION: Liver cancer-secreted serine protease inhibitor Kazal (LC-SPIK) is a protein that is specifically elevated in cases of hepatocellular carcinoma (HCC). We assessed the performance of LC-SPIK in detecting HCC, including its early stages, in patients with cirrhosis, hepatitis B virus (HBV), and hepatitis C virus (HCV). METHODS: We enrolled 488 patients, including 164 HCC patients (81 early HCC) and 324 controls in a blinded, prospective, case-control study. Serum LC-SPIK levels were determined by an enzyme-linked immunosorbent assay-based assay. The performance of serum LC-SPIK and α-fetoprotein (AFP), including area under the curve (AUC), sensitivity, and specificity, are compared. The performance of LC-SPIK was evaluated in an independent validation cohort with 102 patients. RESULTS: In distinguishing all HCC patients from those with cirrhosis and chronic HBV/HCV, LC-SPIK had an AUC of 0.87, with 80% sensitivity and 90% specificity using a cutoff of 21.5 ng/mL. This is significantly higher than AFP, which had an AUC of 0.70 and 52% sensitivity and 86% specificity using a standard cutoff value of 20.0 ng/mL. For early-stage HCC (Barcelona Clinic Liver Cancer stage 0 and A), LC-SPIK had an AUC of 0.85, with 72% sensitivity and 90% specificity, compared with AFP, which had an AUC of 0.61, with 42% sensitivity and 86% specificity. In addition, LC-SPIK accurately detected the presence of HCC in more than 70% of HCC patients with false-negative AFP results. DISCUSSION: The study provided strong evidence that LC-SPIK detects HCC, including early-stage HCC, with high sensitivity and specificity, and might be useful for surveillance in cirrhotic and chronic HBV/HCV patients, who are at an elevated risk of developing HCC.

A Rare Case of Wilson Disease in a 72-Year-Old Patient.

Wilson disease is an autosomal recessive disorder of abnormal copper metabolism that is prevalent in the younger population, rarely presenting in patients older than 40 years. Clinical presentation may be variable, and diagnosis is often aided by clinical and biochemical tests. We report the case of a 72-year-old woman who presented with acute liver failure initially of unclear etiology. Our patient was initially managed for presumed drug-induced liver injury but ultimately diagnosed with Wilson disease on the basis of clinical presentation, laboratory testing, liver biopsy, quantitative hepatic copper, and abnormal genetic testing.

Syphilis, The Great Mimicker, Presents As a Rare Case of Concurrent Hepatitis and Gastroparesis.

Syphilis has been called "the great mimicker" given its ability to affect a wide variety of organs and subsequently present with a vast array of symptoms. The variability in clinical presentation seen in syphilis can make the diagnosis challenging. We describe a unique presentation of syphilis manifesting as hepatitis and gastroparesis. To our knowledge, this is the first case report with simultaneous hepatic and gastric involvement.

Graft-versus-host disease, a rare complication after orthotopic liver transplantation.

Acute graft-versus-host disease (GVHD) after orthotopic liver transplantation (OLT) is a rare but fatal complication that poses a major diagnostic and therapeutic challenge. Our case highlights the need for further studies to develop therapeutic modalities to improve outcomes in patients who develop GHVD following OLT.

Hepatocellular carcinoma after locoregional therapy: Magnetic resonance imaging findings in falsely negative exams.

AIM: To elucidate causes for false negative magnetic resonance imaging (MRI) exams by identifying imaging characteristics that predict viable hepatocellular carcinoma (HCC) in lesions previously treated with locoregional therapy when obvious findings of recurrence are absent. METHODS: This retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study included patients who underwent liver transplantation at our center between 1/1/2000 and 12/31/2012 after being treated for HCC with locoregional therapy. All selected patients had a contrast-enhanced MRI after locoregional therapy within 90 d of transplant that was prospectively interpreted as without evidence of residual or recurrent tumor. Retrospectively, 2 radiologists, blinded to clinical and pathological data, independently reviewed the pre-transplant MRIs for 7 imaging features. Liver explant histopathology provided the reference standard, with clinically significant tumor defined as viable tumor ≥ 1.0 cm in maximum dimension. Fisher's exact test was first performed to identify significant imaging features. RESULTS: Inclusion criteria selected for 42 patients with 65 treated lesions. Fourteen of 42 patients (33%) and 16 of 65 treated lesions (25%) had clinically significant viable tumor on explant histology. None of the 7 imaging findings examined could reliably and reproducibly determine which treated lesion had viable tumor when the exam had been prospectively read as without evidence of viable HCC. CONCLUSION: After locoregional therapy some treated lesions that do not demonstrate any MRI evidence of HCC will contain viable tumor. As such even patients with a negative MRI following treatment should receive regular short-term imaging surveillance because some have occult viable tumor. The possibility of occult tumor should be a consideration when contemplating any action which might delay liver transplant.

From Child-Pugh to Model for End-Stage Liver Disease: Deciding Who Needs a Liver Transplant.

This article reviews the historical evolution of the liver transplant organ allocation policy and the indications/contraindications for liver transplant, and provides an overview of the liver transplant evaluation process. The article is intended to help internists determine whether and when referral to a liver transplant center is indicated, and to help internists to counsel patients whose initial evaluation at a transplant center is pending.