Portal Tracts Research Articles

A Case of Acute Disseminated Histoplasmosis of the Liver in a Patient Receiving Amphotericin-B Therapy

Abstract Introduction/Objective Acute disseminated histoplasmosis (DH), caused by Histoplasma Capsulatum (HC), occurs primarily in immunocompromised hosts. It is characterized by an abrupt onset of symptoms (fever, malaise, hepatosplenomegaly, lymphadenopathy, anemia, leucopenia and thrombocytopenia) and a lack of granulomatous inflammatory response. If left untreated, death occurs within three months of the disease. The treatment of choice is a two-week course of Amphotericin-B (AmpB-Tx). Studies show a drop in fungal load in 85% of blood cultures and a drop of 1.6 U and 2.1 U in serum and urine antigen levels of histoplasmosis respectively, within 14 days of treatment thereby making it unlikely to see liver failure secondary to acute DH in a patient receiving AmpB-Tx. Methods/Case Report We present a case of a 41-year-old male, newly diagnosed with HIV (CD4=44; viral load=5,350,000) and DH on AmpB-Tx. At presentation, his liver function tests (LFT’s) were mildly elevated (Bilirubin =2.7mg/dL; ALP=259U/L; AST=271U/L; ALT=71U/L). On Day-9 of AmpB-Tx, he became somnolent and jaundiced with hepatosplenomegaly and ascites. His LFTs were markedly raised, showing an obstructive pattern (Bilirubin=16mg/dL; ALP=1578U/L; AST=261U/L; ALT=213U/L). On Day-11 of treatment, we received a liver biopsy for HIV cholangiopathy versus drug induced hepatotoxicity. The clinicians considered DH to be a less likely cause since the patient was already on AmpB-Tx. The liver biopsy showed hepatocytes with cholestasis, minimal acute portal inflammation and numerous portal tract and parenchymal macrophages laden with fungal organisms. Gomori-Methenamine-Silver stain confirmed the fungal organisms as being HC. This diagnosis prompted the continuation of AmpB-Tx past 14 days. The patient’s LFT’s reached maximum values of Bilirubin=18mg/dL; ALP=1680U/L; AST=355U/L; ALT=324U/L. After 25 days of AmpB-Tx, his LFT’s trended downwards with a resolution of his hepatic encephalopathy and jaundice. While a 14 day course was initially intended, AmpB-Tx was continued for a total of 28 days until a resolution of symptoms was achieved. Results (if a Case Study enter NA) NA. Conclusion Our case identifies a patient with progressive hepatic histoplasmosis in spite of AmpB-Tx. Keeping in mind and identifying such cases on pathology can alter the course of treatment for patients.

PSAT010 Severe Cholestatic Jaundice (Stauffer Syndrome) as a Rare Paraneoplastic Manifestation in Adrenocortical Carcinoma

Abstract Introduction Adrenocortical Carcinoma (ACC) is a rare and often aggressive malignancy arising from the adrenal cortex. Rarely, ACC can be associated with a paraneoplastic syndrome, such as tumor-associated hypoglycemia due to insulin-like growth factor-2 secretion, hyperreninemic hyperaldosteronism, erythropoietin-associated polycythemia, and leukocytosis due to chemokine release from the tumor. Stauffer syndrome is a paraneoplastic syndrome characterized by reversible cholestasis in the absence of liver metastases, most frequently described in the context of renal cell carcinoma. Our case is the first reported association between Stauffer syndrome and ACC. Clinical Case A 38-year-old man presented with nausea, vomiting, painless jaundice, pruritus, and weight loss. Laboratory evaluation revealed an elevated total bilirubin of 8.7 mg/dL (N<1.3), the INR was elevated secondary to the cholestasis from vitamin K insufficiency. Computed tomography (CT) scan revealed a 20.4 cm, heterogeneous left adrenal mass with central necrosis concerning for ACC. There was no evidence of liver metastases. Additional laboratory workup showed elevated DHEA-sulfate of 1764.2 ug/dL (N<568.9), ACTH of 18 pg/mL (N<7-63), cortisol of 18.30 mcg/dL (N<19.50), androstenedione of 247 ng/dL (N<150), estradiol of 123 pg/mL (N<41), testosterone of 237 ng/dL (N<871), aldosterone of 11 ng/dL (N<=21), and plasma renin activity of 14 ng/mL/hr (N<4.3). Plasma metanephrines and catecholamines were normal. The patient's condition deteriorated rapidly with progressive renal failure and uremia requiring intensive care unit admission for continuous renal replacement therapy and critical care optimization preoperatively. The patient's total bilirubin increased to 34.5 mg/dL, which prompted liver biopsy. This revealed no evidence of cirrhosis or hepatic metastasis. Therefore, severe cholestasis was attributed to Stauffer syndrome, a paraneoplastic cholestatic jaundice from the underlying adrenal mass. The patient underwent exploratory laparotomy with left adrenalectomy, left nephrectomy, left ureterolysis, and wedge liver biopsy. Histopathology showed a necrotic ACC with tumor invasion into the adrenal capsule, no lymphovascular invasion, margins uninvolved, and Ki-67 index of 40%. Kidney parenchyma exhibited diffuse pigment casts. The liver specimen contained diffuse bile deposits and minimal chronic inflammation in the portal tracts, consistent with Stauffer syndrome. Postoperatively, the patient had rapid improvement in his renal function, and bilirubin level normalized after several weeks. Mitotane therapy was deferred until the complete recovery of the liver function. Conclusion Our case highlights a unique presentation of paraneoplastic hepatic dysfunction with jaundice associated with newly diagnosed ACC. Although Stauffer syndrome is one of the most characteristic paraneoplastic syndromes associated with renal cell carcinoma and other malignancies, paraneoplastic hepatic dysfunction associated with ACC has not been previously reported. The patient had rapid improvement of hyperbilirubinemia after surgical resection of the tumor. Stauffer syndrome should be considered in patients with ACC with liver dysfunction and jaundice without evidence of liver metastases. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Quantitative analysis of tissue area of endoscopic ultrasound-guided liver biopsy specimens using 19-gauge fine-needle biopsy needle in patients with diffuse liver disease: A single-center retrospective study.

Endoscopic ultrasound-guided liver biopsy (EUS-LB) is a novel liver biopsy technique. We aimed to evaluate the efficacy and safety of EUS-LB in comparison with percutaneous liver biopsy (PLB). This retrospective study evaluated the safety and efficacy of EUS-LB using a 19-gauge fine needle biopsy (FNB) needle compared with PLB using a spring-loaded 16-gauge needle in patients with diffuse liver disease at our hospital from April 2017 to December 2020. The primary outcomes included the total hepatic tissue surface area and the total number of portal tracts. Secondary outcomes included the success and adverse event rates. Twenty patients each underwent EUS-LB and PLB. There was no statistical difference in the sum of liver tissue surface area (22 mm2 vs 22.6 mm2 , P= .910) and the total number of portal tracts (29 vs 25, P= .916). The success rate was 95% (19/20) for EUS-LB and 100% (20/20) for PLB (P= 1). There were two adverse events in the PLB group but none in the EUS-LB group (P= .487). Endoscopic ultrasound-guided liver biopsy using FNB has an optimal tissue yield and success rate and is safe compared to PLB. Thus, EUS-LB may be a new alternative to PLB.

Hepatocellular Adenoma in an Infant With Burn-McKeown Syndrome: Report of a Case.

Hepatocellular adenomas (HCA) in infants are exceedingly rare with only 5 cases reported to the best of our knowledge, all of them preceding the classification of HCA. Here we present an autopsy case of a 9-month-old girl with Burn-McKeown syndrome with an incidental liver nodule in the right lobe measuring 1.5cm in greatest dimension. The lesion was composed of an unencapsulated proliferation of hepatocytes with multiple unaccompanied arteries without well-formed portal tracts, and an intact reticulin framework without thickened hepatic plates, findings consistent with an HCA. Glutamine synthetase (GS), lipid fatty acid-binding protein (LFABP), c-reactive protein (CRP), serum amyloid-a (SAA), beta-catenin and CD34 immunostains were performed. GS was diffusely and strongly positive in the lesion, CD34 showed heterogenous staining of sinusoids within the lesion without a well-formed rim from the background liver and beta-catenin was negative for nuclear staining. CRP and SAA were considered negative, and LFABP was retained. Molecular testing showed no CTNNB1 variants and found two tier 3 variants involving CHEK2 and PTEN genes. These findings are consistent with an unclassified HCA (U-HCA) per the 2019 WHO Classification of Tumors, representing the youngest patient reported. This raises the possibility that some HCAs are congenital or develop very early in life, remaining undiagnosed until later in life.

EUS-guided versus percutaneous liver biopsy: A comprehensive review and meta-analysis of outcomes.

EUS-guided liver biopsy (EUS-LB) has gained momentum in recent years, especially with availability of newer needle designs. Given the emerging comparative data on EUS-LB with second-generation needles and percutaneous LB (PC-LB), we conducted a systematic review and meta-analysis to compare the safety and efficacy of the two techniques. We searched multiple databases from inception through November 2021 to identify studies comparing outcomes of EUS-LB and PC-LB. Pooled estimates were calculated using a random-effects model, and the results were expressed in terms of pooled proportions and odds ratio (OR) along with relevant 95% confidence intervals (CIs). Five studies with 748 patients were included in the final analysis. EUS-LB was performed in 276 patients and PC-LB in 472 patients. Across all studies, PC-LB had an overall higher diagnostic accuracy than EUS-LB, 98.6% confidence interval (CI: 94.7-99.7) versus 88.3% (49.6-98.3), OR: 1.65, P = 0.04. On assessing data from randomized controlled trials, there was no difference between the two. While pooled diagnostic adequacy and overall adverse events were not significantly different between PC-LB and EUS-LB, the former was superior in terms of the mean number of complete portal tracts (CPT) and total specimen length. PC-LB and EUS-LB produce similar results. PC-LB allows obtaining longer samples and more CPT. Further studies are needed to see if these trends hold up as more providers begin to perform EUS-LB.

Porto-sinusoidal vascular disorder.

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term.

S3139 Primary Hepatic Diffuse Large B Cell Lymphoma Presenting as a Picture of Acute Alcoholic Hepatitis

Introduction: Diffuse large B cell lymphoma (DLBCL) is a prevalent subcategory of Non-Hodgkin lymphoma (NHL) comprising around 25% of all NHL occurrences. Generally, 60% of cases will present with Stage III/IV advanced disease vs 40% with localized disease. While DLBCL can arise from any tissue, 40% of cases will come from extranodal extramedullary tissue; most commonly the stomach or GI. Interestingly, primary hepatic lymphoma is exceedingly rare with a reported incidence of 0.4% of all extranodal NHL and 0.016% for all NHL. The presentation can be vague and a mimicker of other disease with symptoms such as abdominal pain, bloating, nausea, vomiting, and B symptoms. Case Description/Methods: A 59-year-old female with no significant medical history presented for dizziness, fatigue, fever, shortness of breath, weight loss, night sweats, chills × 1 month. She drinks 18 beers/week and is employed at a bar. Initially found to have thrombocytopenia, transaminitis (AST > ALT), hepatosplenomegaly, hypotension, normocytic anemia, latent hepatitis B, and a pulmonary embolism. Her hepatitis was thought to be secondary to alcoholic hepatitis. Her MELD was 12 and Maddrey of -0.6. GI was consulted, further workup showed a past EBV and CMV infection. Quantiferon, HIV, mono, autoimmune and rheumatologic workup were negative. Ultimately a liver biopsy was positive for DLBCL. She was vaccinated for encapsulated organisms, treated for her Hepatitis B, and initiated on R-EPOCH regimen. She was transitioned to RCHOP and ultimately had no evidence of FDG presence on PET Scan and complete response to therapy. She was advised to have routine surveillance per NCCN guidelines (Figure 1). Discussion: Primary hepatic DLBCL is rare and not often diagnosed when a patient presents with acute hepatitis and known risk factors of alcohol use. However, our patient had multiple B-symptoms concerning for lymphoma. The only way to definitively diagnose DLBCL is by liver biopsy with the prevailing management of EPOCH chemotherapy. Early diagnosis and initiation of treatment is crucial due to its poor prognosis and advanced stage presentation. For this reason, a broad differential diagnosis must be considered when evaluating patients with alcoholic hepatitis. This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.Figure 1.: A, Markedly atypical lymphoid infiltrate involving both the hepatic sinusoids and portal tracts. The lymphocytes are large with vesicular chromatin, prominent nucleoli, and fairly abundant mitotic activity B, Immunohistochemical stains are performed. The atypical lymphocytes react with CD20, PAX5, and coexpress BCL-2 (90%) and C-MYC (60%).

S2954 COVID-19 Infection as a Trigger for Seronegative Autoimmune Hepatitis: A Case Report

Introduction: Autoimmune hepatitis (AIH) is an immune-mediated liver disease that commonly develops in a genetically predisposed patient after exposure to an environmental trigger. These triggers include viruses, immunization and drugs. Both COVID-19 infection and vaccination have been linked to the development of AIH. Case Description/Methods: A 58-year-old male patient, known to have vitiligo and mild rheumatic mitral stenosis presented to our hospital complaining of flu-like symptoms. The patient denied any history of alcohol intake, substance abuse, over-the-counter or herbal medications, or family history of liver or autoimmune disease. His chronic medications included aspirin and bisoprolol. He tested positive for COVID-19 PCR, so he was admitted for observation. Chest X-ray showed no abnormality, and he was not started on any medication. His laboratory investigations (Table 1) were remarkable for ALT of 271 and AST of 175 U/L. During hospitalization, liver enzymes were trending down but remained elevated. The hepatitis workup (Table 1) was notable for an elevated IgG level of 16.9 g/l (normal range 7-16). His radiological investigations included US abdomen that revealed mildly increased echotexture, MRI liver that was only remarkable for tiny cyst 2 mm, and liver elastography that showed a stiffness average of 5.77 kPa indicating mild stiffness. The patient was offered a liver biopsy, but he was reluctant. During follow-up, his LFTs remained elevated but were fluctuating (Figure 1a). On week 31, he finally agreed for liver biopsy that showed moderate interface and portal tract inflammatory cell infiltrate composed mainly of lymphocytes with occasional eosinophils (Figure 1b,c). The histopathological findings were suggestive of AIH. On week 34, he was started on prednisone 40 mg. LFTs on week 36 were completely normal. The prednisone was tapered over the following two months. Six months later, repeat LFTs were also normal. Discussion: Our patient had an elevation of LFTs after COVID-19 infection that persisted for weeks and promptly responded to steroids therapy. Drug-induced liver injury was less likely as he didn’t receive any hepatotoxic medications prior to or during his hospitalization. In our patient, the Revised Original Score for Autoimmune Hepatitis (AIH) was 17, indicating definite AIH. The proposed mechanism of AIH development after COVID-19 infection is the molecular mimicry between spike protein S1 and multiple human tissue proteins. More studies are needed to examine this association.Figure 1.: a: Trend of LFTs over time. b,c: histopathological images showing interface and portal tract inflammation. Abbreviations alphabetically: Bx: biopsy - d/c: discharge - Dx: diagnosis - f/u: followup - Rx: treatment Table 1. - shows extensive hepatitis workup Laboratory test result Reference ALT 271 0-40 U/L AST 175 0-37 U/L ALP 38.9 40-129 U/L Antinuclear ab Negative Negative Anti Mitochondrial ab Negative Negative Anti Mitochondrial M2 ab Negative Negative Anti Smooth Muscle ab Negative Negative Anti Liver Kidney Microsomes Negative Negative Hepatitis B Core ab Reactive non-reactive Hepatitis B Core Ab IgM non-reactive non-reactive Hepatitis B Surface Antigen Non-reactive Non-reactive Hepatitis B e Ab Non-reactive Non-reactive Hepatitis B e Antigen Non-reactive Non-reactive Hepatitis A Ab IgM Non-reactive Non-reactive Hepatitis C Ab Non-reactive Non-reactive Hepatitis E IgG Reactive Non-reactive Hepatitis E IgM Non-reactive Non-reactive Herpes Simplex virus Ab IgM Non-reactive Non-reactive Parvovirus Ab IgM Non-reactive Non-reactive Alpha-1 anti-trypsin 37 20-53 µmol/L Ceruloplasmin 33 14 to 40 mg/dL CMV PCR Negative Negative EBV PCR Negative Negative HBV PCR Negative Negative

Quantitative histologic evaluation reveals different degree of liver atrophy in cachectic and starved dogs.

Cases of neglect in dogs are among the forensic cases submitted most commonly for postmortem examination. Starvation is a form of primary protein-energy malnutrition in which the availability of food is severely restricted or absent; cachexia is a form of protein-energy malnutrition secondary to progressive metabolic derangement during chronic diseases. Despite both conditions leading to an emaciated appearance of the cadaver, discrimination between the two is crucial in forensic cases. We hypothesized that among emaciated dogs, the degree of liver atrophy in starved animals is higher than in cachectic ones, and that this can be investigated microscopically, regardless of the degree of cadaver decomposition. We studied 46 animals: 23 starved, 11 cachectic, and 12 control dogs. Portal tracts were identified by the presence of a bile duct and associated vascular structures recognizable by a thin rim of collagen still visible regardless of the degree of cadaver decomposition. The number of portal tracts per lpf (10×) was used as an indirect measure of atrophy. The number of portal tracts in starved dogs was significantly higher (p < 0.01) compared to both cachectic and control dogs, indicating a higher degree of liver atrophy in starvation. Measuring the density of portal tracts offers a reliable additional tool for discrimination between starvation and cachexia.

S3188 The Tale of an Ancient Herb: A Stress Reliever or a Liver Stressor

Introduction: Ashwagandha is found in several herbal products today. However, there is a paucity of literature regarding its safety. Our case serves to remind physicians about the potential liver toxicity of Ashwagandha and to illustrate how early recognition of drug-induced liver injury (DILI) and discontinuation of the offending substance can be lifesaving. Case Description/Methods: A 58-year-old man with a remote history of hepatitis B and C presented with nausea, vomiting, and right upper quadrant abdominal pain of one day duration. He reported using an herbal supplement called “Primal Male,” which contained Ashwagandha as a main ingredient, over the past two weeks. He was normotensive, tachycardic up to 120 beats per minute (bpm), and febrile. The initial laboratory studies were notable for elevated AST level of 954 U/L, ALT level of 860 U/L, and a normal alkaline phosphatase level of 101 U/L. He had a normal total bilirubin level and an international normalized ratio of 1.3. His complete blood count and renal function were unremarkable. His creatinine kinase (CK) level was also within the normal range. His drug test, alcohol level, and acetaminophen level were unremarkable. The viral panel did not suggest active viral infections. His autoimmune panel was negative. An abdominal CT scan did not reveal any acute abnormality. In the following days, his symptoms worsened, and he became more encephalopathic. His AST, ALT, total bilirubin, and INR levels continued to rise. He developed hypotension and received intravenous fluids and midodrine. He also completed a course of N-acetylcysteine treatment. On the fifth day of admission, he underwent a transjugular liver biopsy. Liver histology showed active lymphocytic hepatitis with moderate inflammation (primarily lymphocytes, abundant neutrophils, and occasionally eosinophils) around the portal tract. On the sixth day of hospitalization, he reported decreasing pain and was more hemodynamically stable. His liver enzymes also showed improvement. The cause of acute liver injury was suspected to be drug-induced liver injury from Ashwagandha use. He was counseled to avoid the use of the herbal supplement and other hepatotoxic products. One month later, his liver enzymes were in normal range. Discussion: DILI is a less common form of liver injury but is a leading cause of acute liver failure in the United States. Ashwagandha has been reported in a few cases of DILI. It is important to have an early suspicion of the offending agent and avoid further substance exposure.

S3098 Vanishing Bile Duct Syndrome in the Setting of Newly Diagnosed Hodgkin Lymphoma

Introduction: Vanishing bile duct syndrome (VBDS) is characterized by cholestatic liver disease in the setting of disappearing intra-hepatic bile ducts. It can resemble other forms of cholestatic liver disease; however, imaging and biochemical tests will be unrevealing. We describe a case of a woman with Hodgkin lymphoma (HL) who developed cholestatic hepatitis with loss of intra-hepatic bile ducts. Case Description/Methods: A 23-year-old woman with a history of HL who presented for evaluation and treatment of HL. Two months prior she had been treated for CMV-associated gastroenteritis and sepsis. Initial examination revealed jaundice and bilateral conjunctival icterus. Lab results showed total bilirubin of 18.1 mg/dL, ALT 363 U/L, AST 149 U/L, alkaline phosphatase (ALP) of 2392 U/L, direct bilirubin of 15.5 mg/dL, INR of 2.07, and cytomegalovirus (CMV) PCR at 670 IU/mL. Other acute viral hepatitis studies, tests for intrinsic liver disease, and autoimmune markers were negative. Computerized tomography (CT) of the abdomen and pelvis showed extensive lymphadenopathy, sclerotic changes throughout the skeleton, splenomegaly, and hepatomegaly without focal liver lesions. Magnetic resonance cholangiopancreatography (MRCP) of the abdomen showed no evidence of biliary ductal dilatation. Treatment for her HL was initiated, as well as foscarnet for her CMV viremia. Liver biopsy showed benign liver parenchyma with marked cholestasis and paucity of bile ducts, no cirrhosis, and no viral inclusions. The patient was initiated on ursodeoxycholic acid (UDCA) at 15 mg/kg/d without resolution of symptoms or cholestasis. Given no improvement in her cholestasis, the prospects of liver transplantation (LT) were discussed, but the patient was not a candidate (Figure 1). Discussion: Liver involvement in HL typically manifests as parenchymal invasion, external compression, or paraneoplastic destruction of bile ducts (VBDS). VBDS tends to signify a poor prognosis with patients frequently progressing to liver failure. The pathogenesis of VBDS in HL is not yet defined with current evidence suggesting an immune-mediated response. Typically, viral causes should be excluded. In this case, the patient did have CMV viremia. Given her prior treatment, low viral load, and absence of viral inclusions on liver biopsy, CMV was excluded as a cause. Treatment for VBDS revolves around treating the underlying cause. UDCA can be used as a temporizing measure, but, if no improvement is observed over time, patients are referred for liver transplant.Figure 1.: Parenchymal liver biopsy: (A) and (B) Lobular cholestasis. The hepatic lobules show cholestasis within the hepatocytes and bile canaliculi. (C) Paucity of intrahepatic bile duct. No bile duct is seen in the portal tract. (D) CK-7 positive hepatocytes in chronic cholestasis. The hepatocytes in this case stain positive for CK-7.

Melatonin attenuates thioacetamide-induced liver fibrosis in male rats through modulation of interleukin-6, interleukin-4, apoptosis and urokinase plasminogen activator receptor-associated protein/Endo180.

Liver fibrosis is a chronic progressive disease, its resolution still unclear, and the current study explored the role of melatonin in modulation of interleukin-6 (IL-6), interleukin-4 (IL-4), transforming growth factor beta1 (TGF-β1) and urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) pathway in thioacetamide (TAA)-induced hepatotoxicity. Thirty two adult Sprague-Dawley rats were divided into four groups: vehicle control group, TAA-induced liver fibrosis group that was left untreated, melatonin administration before and along with TAA and melatonin along with TAA group. TTA-induced massive liver necrosis, fibrosis around portal tract and increases serum levels of liver enzymes and total bilirubin when compared with control vehicle group. While both melatonin pretreatment and treatment retained liver parenchyma and liver enzymes quite similar to control group and reduced TAA-induced liver injury. Notably, melatonin pretreatment and treatment increased collagen degradation in TAA liver injury by19, 31.7-fold respectively evidence by collagen percentage area. Melatonin also decreased the amount of thiobarbituric acid reactive compounds and retained the reduced glutathione and superoxide dismutase to basal level quite similar to control group. Additionally, melatonin significantly (P value ≤0.05) decreased the levels of TGF-β1, epidermal growth factor (EGF), hydroxyproline, tissues IL-6, caspase-3, and receptor interacting serine/threonine kinase1 (RIPK1), fibrillin-1, and - smooth muscle actin in the liver tissues while significantly (P value ≤0.05) increasing the levels of IL-4 and uPARAP/Endo180. Due to its anti-inflammatory, anti-apoptotic, and antioxidant capabilities as well as its ability to decrease hepatic stellate cell activation and fibrogenesis, these data imply that melatonin has a powerful anti-fibrotic effect.

S3148 Seronegative Autoimmune Hepatitis: A Rare Manifestation of COVID-19

Introduction: Hepatic dysfunction is seen in 14-53% of patients with COVID-19, particularly in those with significant comorbidities. There have been reports of the development of autoimmune hepatitis (AIH) following COVID-19 vaccination and/or infection. AIH is usually associated with circulating autoantibodies but 10-20% of AIH patients are initially seronegative. We present the first reported episode to our knowledge of a case of seronegative AIH in the setting of concurrent COVID-19 infection. Case Description/Methods: A 39-year-old otherwise healthy female with a family history of mother with rheumatoid arthritis presented with 2 weeks of nausea, diarrhea, abdominal pain, and jaundice. She had significant transaminitis in the 1000 s and a conjugated hyperbilirubinemia. Despite previous vaccination and no respiratory symptoms, the patient tested positive for COVID-19. The patient denied taking hepatotoxic agents, and the workup was negative for acute viral hepatitis. The antinuclear, alpha-1-antitrypsin, ceruloplasmin, IgG, anti-smooth muscle, anti-mitochondrial, anti-neutrophil cytoplasmic, and anti-liver/kidney microsomal-1 antibodies were all unremarkable. Imaging was only remarkable for hepatic hemangiomas. Liver biopsy was ultimately performed showing active lymphoplasmacytic hepatitis with prominent regenerative changes and areas of confluent necrosis, consistent with autoimmune hepatitis. The patient’s symptoms and transaminitis improved following initiation of steroids (Figure 1). Discussion: We present a unique case of AIH as a manifestation of COVID-19 infection despite negative serology. Hepatic injury from COVID-19 is thought to be mediated by multitude of mechanisms including upregulation of ACE2 and DPP4 receptors, which are involved in RAS signaling pathways and regulation of the immune system. Further research is needed to better understand if there is a causal link between COVID-19 and hepatic autoimmune dysfunction and the underlying molecular mechanisms. Identifying autoimmune dysfunction following COVID-19 infection may allow us to recognize and treat these cases early on, leading to better hospitalization outcomes.Figure 1.: Liver biopsy showing marked interface activity and areas of confluent necrosis consistent with autoimmune hepatitis (AIH). A representative portal tract (PT) and central vein (CV) are illustrated.

S3190 The Great Masquerader: A Case of Syphilitic Hepatitis

Introduction: Syphilis, colloquially termed “the Great Imitator,” is a sexually transmitted infection caused by the spirochete treponema pallidum. Syphilis occurs in multiple stages. Tertiary syphilis occurs years after inoculation and presents with chronic granulomas, cardiovascular, and neurologic manifestations. Syphilitic hepatitis is a rare and often missed diagnosis in patients who have syphilis and who are often are co-infected with HIV or hepatitis B. Case Description/Methods: The diagnosis is made by both clinical presentations and positive serological markers, characteristic transaminitis, with no other alternative cause of hepatobiliary injury identified. Here, we highlight a case of an undomiciled 40-year-old male with HIV (on Genvoya) and chronic hepatitis B, who presented with tachycardia to 107. Physical examination was remarkable for a diffusely spread rash with erythema on the bilateral lower extremities, a small purulent boil on the right shin, left index finger and dry, itchy, distinct raised purple lesions on the scalp, eyebrows, upper and lower extremities, back, and shoulders. Laboratory findings were remarkable for a severely elevated alkaline phosphatase, mild transaminitis, and elevated total bilirubin, with negative pertinent imaging including a right upper quadrant sonogram, CT scan of the abdomen, and MRCP. Extensive additional work-up revealed elevated VDRL titers. Both a skin and liver biopsy were completed. Immunohistochemical stain of shave biopsy of a verrucous plaque on the scalp vertex and an excoriated papule of the left neck highlighted numerous spirochetes. Liver biopsy revealed hepatocellular necrosis with moderate mixed inflammation involving the portal tract and periportal hepatocytes, with immunohistochemical marker for spirochetes negative for organisms. However, given the patient’s clinical history of secondary syphilis involving the skin and lab abnormalities, it raised the differential diagnosis of syphilitic hepatitis (Figure). Discussion: With our case report and extensive research of the literature, we hope to shed light on the importance of certain infections, even those in decline, on the differential. Additionally, contemplation of coexisting infections often helps to contribute to diagnoses not otherwise common. Because of how rarely seen syphilitic hepatitis is, it is often a missed diagnosis, but we are hopeful our case report helps physicians with patients with similar presentations, especially patients with otherwise unexplained high alkaline phosphatase levels.Figure 1.: Skin Findings.

S3143 Rare Case of Plasma Cell Infiltration-Induced Cirrhosis

Introduction: Multiple myeloma (MM) is a type of malignancy that arises from the unorganized replication of plasma cells within the bone marrow. The overproduction of these cells damages systems throughout the body leading to early asymptomatic symptoms that can rapidly progress to systemic signs of disease. Liver involvement with MM is less common and generally occurs through plasma cell infiltration, light chain/amyloid deposition, and biliary obstruction. Though it can occur, the probability of it presenting near the time of diagnosis of MM is very rare and associated with poorer outcomes. Case Description/Methods: A 59-year-old male presented with generalized weakness, shortness of breath and weight gain. Physical exam showed sign of ascites and hepatomegaly. PMH was significant for esophageal cancer and a recent diagnosis of MM. No history of acute or chronic liver disease or cirrhosis risk factors. CT scan showed cardiomegaly, bilateral pleural effusions, pulmonary edema, and cirrhosis with abdominal ascites. Labs was unremarkable other than normocytic anemia. An echocardiogram showed mild reduced ejection fraction (47%) with speckle tracking suggestive of cardiac amyloidosis. Abdominal ultrasound confirmed appearance of cirrhosis, ascites, and right pleural effusion. Cirrhosis work up revealed negative hepatitis panel, normal alpha-1 antitrypsin, and normal ceruloplasmin. EGD was performed and ruled out extracellular vesicles (EV) but noted type I isolated gastric varices. Liver biopsy confirmed cirrhosis and showed portal tract damage with severe extensive plasma cell infiltration. Additionally, fragments of hepatic parenchymal showed disrupted lobular architecture by septal fibrosis and nodular formation. Immunohistochemistry was positive for CD3, CD20, CD5, BCL2, CD79a, and CD138 as well as increased lambda light chain compared to free kappa light chain. Despite extensive treatment including repeated thoracentesis and paracentesis, patient eventually developed in to decompensating liver cirrhosis (Figure 1). Discussion: In previous studies, plasma cell infiltration of the liver was seen in about 40% of cases of MM, but rarely lead to cirrhosis. This case is unique in that the patient had liver failure caused by cirrhosis and that it was some of the presenting symptoms. Whether due to masked signs or aggressive onset, the outcome for this diagnosis is poor and more specific factors observing liver function could have provided a more favorable outcome.Figure 1.: Cirrhosis secondary to plasma cell infiltration. Table 1. - Total Protein 5.0 g/dL Serum Ascites Albumin Gradient (SAAG) 1.9 g/dL Left Hepatic Vein Pressure 25 Hg Left Portal Vein Pressure 29 Hg Portosystemic Pressure Gradient 5 Hg EUS Guided Shear Wave Elastography of Liver 27 kPa

S3125 Overlapping Hepatotoxicity and Colitis Associated With Immune Checkpoint Inhibitors

Introduction: Immunotherapy with immune checkpoint inhibitors (ICIs) has become the standard of care for many solid-organ and hematologic malignancies. Gastrointestinal toxicities are common side effects that typically occur 6 weeks after starting ICI therapy. Overlapping hepatotoxicity and colitis associated with ICIs is rare and may be overlooked, resulting in high mortality. Case Description/Methods: A 73-year-old man with metastatic squamous cell carcinoma (SCC) of the head and neck presented with intermittent, diffuse abdominal discomfort, bloating and painless non-bloody diarrhea (up to 6 episodes daily) triggered by meals. Symptom onset was 6 weeks after starting pembrolizumab for head and neck SCC. Pembrolizumab therapy was held, and supportive therapy with proton pump inhibitors, antacids and antidiarrheals provided partial symptom relief. Laboratory work up showed elevated AST 132 U/L, ALT 220 U/L, ALP 851 U/L and normal total bilirubin. ANA was elevated with titer 1:80, with normal total IgG (699.5 mg/dL) and negative serologies for anti-smooth muscle antibody, CMV, EBV, and HSV. Abdominal CT with contrast showed a dilated common bile duct (CBD) of 11 mm and a new curvilinear filling defect in the distal CBD, without choledocholithiasis. MRCP revealed mildly dilated intrahepatic biliary ducts, CBD dilation (13 mm), and an ovoid 8mm soft tissue nodule in the periampullary duodenum. Upper endoscopy was nondiagnostic. At this time, the patient’s symptoms improved, but there was high suspicion of grade-2 ICI-associated hepatitis (ICIH). Percutaneous liver biopsy showed interlobular bile duct injury with intraepithelial lymphocytes and neutrophils and a neutrophilic ductular reaction consistent with ICIH. Serial lab work demonstrated improvement of liver enzymes, with AST 77 U/L, ALT 69 U/L and ALP 667 U/L at 60 days after initial labs. Diarrhea resumed, up to 6 episodes per day, consistent with the Common Terminology Criteria for Adverse Events diagnosis of ICI-related colitis (ICIC). Initial supportive therapy failed to improve diarrhea; thus, a prednisone taper was started, resolving the colitis. He declined the option to resume immunotherapy and transitioned to comfort care (Figure 1). Discussion: Overlapping ICIH and ICIC is rare and may have discordance between symptomatology and lab findings. Early recognition of overlapping ICIH and ICIC, supportive treatment, permanent cessation of the inciting ICI and switching it with alternative immunosuppressive therapy may improve patient outcomes and quality of life.Figure 1.: Panel A - CT chest/abdomen with contrast (coronal view) showing common bile duct dilation of 1.2 cm (yellow calipers) status post cholecystectomy. Panel B. Upper endoscopy showing prominent ampulla with free-flowing bile. Panel C. Histology of percutaneous, ultrasound-guided liver biopsy with H&E staining (10×) shows preserved lobular hepatic architecture with mixed inflammatory infiltrate including lymphocytes, histiocytes, and scattered eosinophils expanding the portal tracts. Table 1. - Immune Checkpoint Inhibitor Associated Hepatitis Grades, adapted from the American Society of Clinical Oncology, 2021 Grade Criteria 1 Asymptomatic (AST or ALT > ULN to 3.0 X ULN and/or total bilirubin > ULN to 1.5 X ULN) 2 Asymptomatic (AST or ALT > 3.0 to ≤ 5 X ULN and/or total bilirubin > 1.5 to ≤ 3 X ULN) 3 AST or ALT 5-20 X ULN and/or total bilirubin 3-10 X ULN, OR symptomatic liver dysfunction; fibrosis by biopsy; compensated cirrhosis; and reactivation of chronic hepatitis 4 AST or ALT > 20 X ULN and/or total bilirubin > 10 X ULN OR decompensated liver function (e.g., ascites, coagulopathy, encephalopathy, and coma) Abbreviations: AST, aspartate transferase; ALT, alanine transaminase; ULN, upper limit of normal.

S3091 Noncirrhotic Portal Hypertension in Turner’s Syndrome: A Case Report

Introduction: Turner's syndrome is one the most common chromosomal aneuploidies in humans. Although it can affect multiple organs, involvement of gastrointestinal (GI) organs is rare. Case Description/Methods: A 20-year-old female with history of Turner's syndrome with premature ovarian failure and mild mitral regurgitation was evaluated for easy fatigability and bruising. Laboratory assessment indicated pancytopenia. Peripheral blood smear showed a variety of red cell shape abnormalities and bone marrow biopsy showed normal cellular marrow. Computed tomography of the chest, abdomen and pelvis with and without contrast showed severe splenomegaly, tiny varices in the anterior mediastinum along the gastrohepatic ligament, and no portal vein thrombosis. Abdominal ultrasound examination revealed severe diffuse heterogeneity of the liver parenchyma with a slightly nodular hepatic contour and Fibroscan indicated mild steatosis S1 with advanced fibrosis F3. She underwent liver biopsy which showed focal mature fibrous expansion of some portal tracts, with delicate bridging fibrosis, as well as patchy increase in the number of small portal arteries with occasional increased thickness of arterial wall, subtle lobular parenchymal changes, suggestive of porto-sinusoidal vascular disease with no evidence of cirrhosis. Upper GI endoscopy revealed grade 2 esophageal varices and erythematous mucosa in stomach, suggestive of portal hypertension. Considering the definitive clinical signs of portal hypertension (gastroesophageal varices), the absence of cirrhosis on liver biopsy and histologic signs of porto-sinusoidal vascular disease, she was diagnosed with non-cirrhotic portal hypertension due to porto-sinusoidal vascular disease. She was started on propranolol for gastroesophageal varices and her heart rate is currently well-controlled. Follow-up abdominal ultrasound is negative for further changes in the liver size, morphology, or masses. Discussion: Turner’s syndrome might be associated with non-cirrhotic portal hypertension. High index of clinical suspicion can lead to early diagnosis and treatment of portal hypertension in individuals with Turner’s syndrome, reducing the burden of complications of portal hypertension such as cytopenia or bleeding.

Ultrasound Guidance vs Anatomical Landmark for Ankle Arthroscopic Portal Insertions: A Cadaveric Study

Category: Arthroscopy Introduction/Purpose: Ankle arthroscopy can be used for a variety of ankle pathology including soft tissue and bony impingement, loose bodies, osteochondral defects, ankle fractures, osteoarthritis and instability. However, complication rates associated with ankle arthroscopy range from 3.4 to 9%, with half of them consisting of neurovascular and tendon injuries due to arthroscopic portal placement. The purpose of the study is to determine the safety and efficacy of using ultrasound in topographic marking of the neurovascular structures and tendons in the foot and ankle and identification of a safe zone for arthroscopic portal creation, compared to using anatomical landmarks. Methods: Twelve cadaveric samples were divided into two groups of six. The first group underwent ultrasound assessment by a board certified radiologist, who identified zones of safety for ultrasound guided insertion of anteromedial, anterolateral and posteromedial arthroscopic portals. Ankle arthroscopy was then performed. The other group underwent similar ankle arthroscopy assessment utilizing conventional anatomical landmarks. Straws were used to delineate arthroscopy portal tracts. The cadaveric samples were then dissected. The following distances were measured between the portals and important anatomical structures: the anterolateral portal and superficial peroneal nerve (SPN) as well as extensor digitorum longus (EDL); anteromedial portal and the great saphenous vein (GSV) as well as tibialis anterior (TA); and the posteromedial portal and the flexor hallucis longus (FHL). Results: No neurovascular structures or tendons were injured in all twelve cadaveric samples. Compared with the non- ultrasonography group, the group that underwent ultrasonography assessment had statistically significant larger distance of the SPN, EDL and TA from the anterolateral and anteromedial arthroscopic portals (p values = 0.045, 0.046 and 0.025 respectively). No difference was found between the distance of the GSV from the anteromedial arthroscopic portal, as well as the distance of the FHL from the posteromedial arthroscopic portal. Conclusion: Ultrasound assessment and topographic identification of the safe zone for ankle arthroscopic portal creation is a safe and effective process that may reduce the risk of iatrogenic injury to neurovascular structures and tendons in anterior and posterior ankle arthroscopy.

S3114 Painless Jaundice With a Significantly Elevated CA 19-9: It Is Not Always Pancreaticobiliary Cancer

Introduction: Carbohydrate antigen 19-9 (CA 19-9) is often very high in pancreaticobiliary cancers but can be substantially elevated in benign diseases too. We present a case of painless jaundice with a significantly elevated CA 19-9 from vanishing bile duct syndrome (VBDS). Case Description/Methods: 65-year-old white male with history of obesity, hypertension, hyperlipidemia, prior cholecystectomy and no family history of pancreatic cancer presented with two weeks of painless jaundice and 10 pounds unintentional weight loss. Physical exam noted scleral icterus and jaundice with a T.Bili of 23 mg/dL (Table 1). CT scan showed intrahepatic bile duct dilation and a 10 mm common bile duct without a discrete mass. CA 19-9 was elevated to 1,480 U/mL, concerning for malignancy. ERCP found a low-grade main bile duct stricture which was stented. Bile duct brushings and fine needle aspiration of the pancreas were negative for malignancy. Biliary dilation was resolved on follow-up MRCP but his bilirubin remained high. Infectious and autoimmune workup was unremarkable. Repeat cholangiography and brushings confirmed no obstruction or malignancy (Fig. 1a). An infiltrative versus drug induced liver injury was suspected. EUS-guided liver biopsies revealed cholestasis with dilated bile canaliculi, hepatocytes with ballooning degeneration and a paucity of bile ductules. Cytokeratin-7 immunostaining demonstrated >50% ductopenia, confirming VBDS (Fig. 1b and c). Follow up at hepatology clinic determined triamterene-HCTZ, atorvastatin or omeprazole stopped during hospitalization to be the likely culprit. His CA 19-9, LFTs and symptoms improved over the following weeks (Table 1). Discussion: VBDS is an acquired cholestatic liver disease that may mimic the presentation of pancreatic cancer. CA 19-9 can be substantially elevated through T-cell mediated destruction of small bile ducts causing impaired excretion, inflammatory production, and decreased clearance. Severity of liver damage depends on the duration of injury and degree of bile duct loss at the time of diagnosis. Prompt diagnosis is important to prevent cirrhotic progression, improve outcomes, and avoid unnecessary treatments. Recognizing its association with an elevated CA 19-9 may help with this, but is scarcely reported in the literature. CA 19-9 is not typically checked in cases of VBDS but is likely commonly elevated. Providers should be aware of this association when faced with a patient with painless jaundice and a significantly elevated CA 19-9 but no obvious malignancy. Table 1. - LFT Trends During the Course of Presentation Normal Range Hospital Admission * 2 weeks 3 weeks ** 4 weeks *** 7 weeks 13 weeks Total bilirubin 0.2-1.3 mg/dL 23 22.7 22 19.7 4.7 1.3 Direct bilirubin 0.0-0.2 mg/dL >13 n/a 14.9 14.6 4.2 0.6 AST 0-45 U/L 107 134 172 200 121 27 ALT 0-50 U/L 190 130 163 182 120 35 ALP 40-150 U/L 267 179 187 168 132 109 CA 19-9 0-35 U/mL 1480 n/a n/a 85 49 n/a AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; CA19-9, carbohydrate antigen 19-9; n/a, not available. * ANA, anti-AMA, anti-SMA, anti-mitochondrial, anti-TTG, anti-LKM 1/2 IgG, and EBV IgG antibodies were negative. Serum IgA, A1AT, ceruloplasmin, TSH, iron levels, hepatitis panel, serum protein electrophoresis and acetaminophen levels were normal. Acetaminophen, multivitamin, iron, triamterene- HCTZ, omeprazole and atorvastatin were stopped on discharge. ** Three weeks post hospitalization. Repeat EUS/ERCP showed biliary decompression. VBDS diagnosed on liver biopsies. *** Seen in liver clinic. Started ursodiol 2000mg daily. Figure 1.: (A) ERCP with cholangiogram showing a low-grade distal biliary stricture without significant upstream dilation. (B) Liver biopsy with H&E stain, 500 μm magnification showing small portal tracts with no bile ducts (red circle); note marked cholestasis (arrows) in dilated canaliculi and lack of ductular reaction. Also visible at this magnification is the ballooning degeneration of hepatocytes. (C) Liver biopsy with cytokeratin 7 immunostain, 500 μm magnification. Small portal tracts with no terminal/small bile ducts. Early signs of ductular reaction seen by hepatocytes taking up CK7 stain (arrows).

S3119 Patient With Autoimmune Hepatitis Requiring Liver Transplant: Case Report and Literature Review

Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease caused by autoimmune-induced damage to the hepatocytes. AIH is known for elevated anti-smooth muscle antibodies (ASMA) and serum globulin levels. A liver biopsy is needed for the diagnosis. Despite its favorable prognosis, few cases can progress to fulminant liver failure. Case Description/Methods: 71-year-old male maintained on Descovy as preexposure prophylaxis for HIV for 1 year, was admitted 3 consecutive times over 1 month due to fatigue and jaundice. He was noted to have elevated transaminase and bilirubin levels. His presentation was suspected to be secondary to Descovy. Abdominal ultrasound was notable for hepatomegaly otherwise normal. He reported social alcohol consumption. He denied acetaminophen or new medication use. PE showed stable vital signs with jaundiced skin and hepatomegaly. The laboratory workup is shown below. Descovy was stopped and he was discharged. He was readmitted 1 week later for worsening symptoms. Workup showed positive ASMA for which he underwent a liver biopsy which was consistent with AIH. Infectious workup was unremarkable. He was started on a prednisone taper. Liver enzymes stabilized and he was discharged with plans to start azathioprine as an outpatient. However, he was admitted 2 weeks later for abdominal pain and encephalopathy. His labs showed worsening bilirubin, INR, and creatinine levels. CT head and abdomen were unremarkable. Doppler ultrasound demonstrated patent hepatic vasculature. He was placed on IV hydration, lactulose, and rifaximin. Due to concerns for hepato-renal syndrome, midodrine, octreotide, and albumin were added. He had a liver transplant evaluation which he underwent successfully. After prolonged hospitalization, he was discharged to post-acute rehab with a regimen consisting of tacrolimus, azathioprine, and prednisone (Figure 1). Discussion: The initial treatment for AIH is glucocorticoid therapy. Azathioprine can be added in moderate to severe cases or when there is a contraindication from using high-dose steroids. Few studies showed that tacrolimus can be effective in some cases that do not respond to steroids. Response to treatment is assessed by improvement of symptoms, laboratory tests, and liver histology. A liver transplant remains a rare indication in AIH and is reserved for patients who do not respond to immunosuppressants or progress to fulminant liver failure. The recurrence rate is reported to be 20-40% with a possibility of developing de novo AIH in a few cases.Figure 1.: Image A is showing portal tract with reactive bile ducts, abundant plasma cells, and interface hepatitis (H&E stain, 10×). Image B is showing Lobular aggregate of plasma cells adjacent to a central vein and involving hepatocytes which show reactive changes including ballooning (H&E stain, 20×). Table 1. - Test Admission #1 Admission #2 Admission #3 Post-transplant Reference range AST 481 952 264 32 5-45 U/L ALT 1048 1284 501 61 12-78 U/L ALP 236 184 166 66 46-116 U/L Total bilirubin 15.29 36.00 42.02 0.68 46-116 U/L Direct bilirubin 11.47 26.99 30.82 0.24 0.00 - 0.20 mg/dL Total protein 7.5 7.2 6 7 6.4-8.2 g/dL Albumin 3.3 2.7 2.1 3.7 3.5-5.0 g/dL PT 14.5 17.9 44 13.5 11.5-14.5 seconds INR 1.13 1.49 5.04 1.07 0.84-1.19 BUN 20 19 107 39 5-25 mg/dL Creatinine 1.28 1.39 4.03 4.37 0.6-1.3 mg/dL eGFR 56 51 13 12 ml/min/1.73sq.m Hemoglobin 17 16.5 16.7 11.3 12.0-17.0 g/dL WBC 7.89 8.74 16.2 6.13 4.31-10.16 thousands/uL Platelets 125 118 165 165 149-390 thousands/uL Sodium 134 132 131 139 136-145 mmol/L Potassium 3.7 3.7 5.3 4.4 3.5-5.3 mmol/L Chloride 100 100 103 103 100-108 mmol/L Calcium 8.9 9.2 9.2 10.1 8.3-10.1 mmol/L Ammonia 31 24 53 N/A 11 - 35 umol/L ASMA 40 0-19 U AMA < 20 0-20 U ANA Negative Negative IMMUNOGLOBULIN AIMMUNOGLOBULIN G IMMUNOGLOBULIN M 101112393 50-500 mg/dL650-2000 mg/dL40-270 mg/dL Acetaminophen < 2 10-20 ug/ml Urine drug screen Negative Negative Ceruloplasmin 22.2 16-31 mg/dL A1 antitrypsin 131 90-200 mg/dL Viral hepatitis panel Negative Negative HIV 1/2 AB-AG Negative Negative AST: Aspartate aminotransferase; ALT: alanine aminotransferase; ALP: alkaline phosphatase; INR: international normalized ratio; PT: prothrombin time; BUN: blood urea nitrogen; eGFR: estimated glomerular filtration rate; WBC: white blood count; ASMA: Anti-smooth muscle antibody; AMA: anti-mitochondrial antibody; ANA: antinuclear antibody.