Negative Hepatitis Research Articles

Prevalence of occult hepatitis B virus infection and characterisation of hepatitis B surface antigen mutants among adults in western Croatia

Introduction and ObjectivesOccult hepatitis B virus (HBV) infection (OBI) is characterised by low levels of hepatitis B virus (HBV) DNA in the blood/liver of patients with negative hepatitis B surface antigen (HBsAg). This study aimed to determine the OBI prevalence and virological characteristics (viral genotypes and HBsAg mutants) in patients with an “anti-HBc only” serological profile. Materials and MethodsA total of 24 900 serum samples were routinely screened for hepatitis B markers over a five-year period. All anti-HBc-positive/HBsAg-negative/anti-HBs-negative sera were selected and analysed for the presence of HBV DNA. Mutational analyses of the HBs gene and polymerase gene sequences were performed. Results1749 (7.02%) sera were anti-HBc positive, and 113 (0.45%) sera had an “anti-HBc only” serological profile (HBsAg/anti-HBs negative). HBV DNA was detected in 12/113 (10.61%) “anti-HBc only” positive sera, representing 0.048% of all routinely tested samples. Due to extremely low viremia, HBV genome was successfully sequenced in only two sera where subgenotype D3 was confirmed. Mutational analyses of the S gene revealed multiple missense mutations. In addition to the M133I, Y134F, and G145R mutations, already associated with diagnostic escape, we also found nine novel OBI-related S-gene mutations - S136Y, F158L, K160N, E164G, S167L, A168V, L175S, S210I and F212C. ConclusionsWe detected multiple known and novel S gene mutations in 2/12 (16.6%) OBI cases, nevertheless, further studies are required to determine their role in the pathogenesis of OBI. Understanding the frequencies of clinically relevant HBV mutations may contribute to improvement of diagnostic protocols.

#5680 FIRST REPORT OF AN EVOLOCUMAB INDUCED NEPHROTIC SYNDROME

Abstract Background and Aims Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) reduce LDL-C and short-term risk of cardiovascular events by acting on the proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme produced in the liver. This article highlights the case of a 69 year-old man who developed nephrotic syndrome (NS) secondary to EVOLOCUMAB injection. To our knowledge, this is the first time that minimal change disease is described as associated with EVOLOCUMAB. Method Case Report describing a 69-year-old male with coronary artery disease who started EVOLOCUMAB injection every two weeks. Six weeks later, after the third dose of Evolocumab, he developed edema, and high blood pressure 180/90 mmHg. Laboratory tests showed a creatinine of 88 µmol/l and a GFR of 77 ml/min/m² associated with severe proteinuria of 9g/24H, normal level of anti-PLA2R, negative ANA (<1/80) and ANCA (<1/80), and negative hepatitis B and C serology. Results Kidney biopsy was obtained to investigate this nephrotic syndrome and showed minimal change disease. There was a mild focal mesangial prominence not exceeding three or four cells per segment by light microscopy (LM). Immunofluorescence was negative. EVOLOCUMAB was stopped and proteinuria dropped from 9g to 6g/25H, and stabilized at that level, so treatment with prednisone 1mg/kg was initiated, reducing proteinuria to 3g/24H one month later with clinical improvement. Conclusion The occurrence of reversible glomerular lesions reported here should be considered as a potential adverse effect when administrating a prolonged treatment of Evolocumab. We suggest performing urine test at least once a week, to detect early proteinuria in patients receiving this medication.

WED-148 - Significant disparities in risk of cirrhosis and hepatocellular carcinoma among non-cirrhotic, treatment naïve, e-antigen negative hepatitis B patients with low levels of serum alanine aminotransferase

WED-148 - Significant disparities in risk of cirrhosis and hepatocellular carcinoma among non-cirrhotic, treatment naïve, e-antigen negative hepatitis B patients with low levels of serum alanine aminotransferase

Man with episodic abdominal pain andjaundice.

A 51-year-old man without a past medical history presented to our emergency department with 2 months of intermittent epigastric pain radiating to the back, tan stools, fatigue, and weight loss. He denied current alcohol use. He appeared diffusely jaundiced. His abdomen was soft with mild epigastric tenderness and a negative Murphy sign. Serum analysis showed total bilirubin 13.7, aspartate transaminase 207, alanine transaminase 463, alkaline phosphatase 634, lipase > 4000, elevated carcinoembryonic antigen/carbohydrate antigen 19-9, and negative hepatitis panel. Imaging included point-of-care (POC) ultrasound (Figure 1, Video 1), computed tomography (CT; Figure 2), magnetic resonance imaging (MRI; Figure 3), and endoscopic retrograde cholangiopancreatograph (ERCP; Figure 4). Our patient had obstructive jaundice. POC ultrasound revealed a distended gallbladder with sludge without signs of acute cholecystitis. The dilated common bile duct >10 mm (normal < 6 mm) and dilated pancreatic duct >5 mm (normal < 3 mm) were consistent with the rare double duct sign. Dilatation without a clear etiology was confirmed on MRI and CT. ERCP revealed a duodenal ulcer with biopsy positive for invasive, poorly differentiated adenocarcinoma. Finally, a pancreaticoduodenectomy revealed a tumor of the pancreatic head. Etiologies of the double duct sign include neoplasms of the pancreatic head and ampulla of Vater and less commonly choledocholithiasis and chronic pancreatitis.1 Overall prevalence of associated malignancy varies from 58% to 100%.2 However, the presence of jaundice is strongly associated with malignancy whereas absence with benign conditions.3-5 Isodense culprit neoplasms are often not visualized on advanced imaging. As initial presentation of pancreatic cancer is insidious, the ominous presence of this sign should raise concerns for malignancy. The authors would like to thank Daniela Galan Alonso, MD, Department of Radiology, Jackson Memorial Hospital. Video.1 Point-of-care ultrasound of pancreas revealing double duct sign. Gallbladder (star), pancreatic duct (arrow), and common bile duct (circle). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Biologic Therapy Carries a Very Low Risk of Reactivation in Hepatitis B Surface Antigen-Negative Phase of Hepatitis B.

The risk of hepatitis B reactivation in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients exposed to biologic agents is not clear. We aimed to investigate the reactivation rate in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients after biologic therapy. Patients followed at gastroenterology, rheumatology, and dermatology clinics with a diagnosis of immune-mediated inflam matory diseases were screened. Immune-mediated inflammatory diseases patients exposed to biologic agents with a negative hepatitis B surface antigen and positive hepatitis B core immunoglobulin G antibody were included in the study. We screened 8266 immune-mediated inflammatory disease patients, and 2484 patients were identified as exposed to biologic agents. Two hundred twenty-one patients were included in the study. The mean age was 54.08 ± 11.69 years, and 115 (52.0%) patients were female. The median number of different biologic subtype use was 1 (range: 1-6). The mean biologic agent exposure time was 55 (range: 2-179) months. One hundred and fifty-two (68.8%) patients used a concomitant immunomodulatory agent, and 84 (38.0%) patients were exposed to corticosteroids during biologic use. No hepatitis B reactivation with a reverse seroconversion of hepatitis B surface antigen positivity was seen. Antiviral prophylaxis for hepatitis B was applied to 48 (21.7%) patients. Hepatitis B virus-DNA was screened in 56 (25.3%) patients prior to the biologic exposure. Two patients without antiviral prophylaxis had hepatitis B virus-DNA reactivation with a negative hepatitis B surface antigen during exposure to the biologic agent. We found 2 reactivations and no hepatitis B surface antigen seroconversion in our cohort. Antiviral prophylaxis for patients exposed to biologic agents may need to be discussed in more detail.

218 - COVID-19 and EBV co-infection leading to coombs negative hemolytic anemia and hepatitis in a healthy young adult

218 - COVID-19 and EBV co-infection leading to coombs negative hemolytic anemia and hepatitis in a healthy young adult

639. Vaccination in Kidney Transplant Candidates

Abstract Background Kidney transplant (KT) candidates have historically low immunization rates against recommended vaccines. A retrospective study of KT candidates was conducted to assess contemporary vaccination rates and vaccine uptake during pre-transplant evaluation. Methods All KT candidates ≥ 18 years referred to Transplant Infectious Disease Clinic for pre-transplant evaluation between January 1, 2020 and August 31, 2020 were retrospectively studied for history of prior vaccination against Tdap, 13 valent pneumococcal conjugate vaccine (PCV13), 23 valent pneumococcal polysaccharide vaccine (PPSV23), Hepatitis A and B (using Hepatitis A total IgG and Hepatitis B surface antibodies as surrogate markers) and recombinant zoster vaccine (RZV). Seropositivity (as a marker of immunity) against measles, mumps, rubella and varicella was also assessed. Results 109 KT candidates were evaluated (tables 1 &amp; 2). Rates of prior vaccination against Tdap, PCV13 and PPSV23 were 33%, 58%, and 67%. Only 5 (8%) of 61 patients ≥ 50 years of age had received 2 doses of RZV. Thirty (28%) had positive Hepatitis A total IgG and 72 (66%) patients had a positive Hepatitis B surface antibody. Among 37 patients with negative Hepatitis B surface antibody, most had received at least one dose of Hepatitis B vaccine (five were non responders, 19 had had initiated the vaccine series and one had waning antibody response). 79-96% patients had immunity against measles, mumps, rubella and varicella. Patients ≥ 50 years (vs under 50 years) had numerically higher immunization rates against PCV13 and PPSV23 (67% vs 46% and 74% vs 58%) and higher rates of immunity against measles, mumps, rubella and varicella (95% vs 73%; 85% vs 69%, 95% vs 81% and 100% vs 92% respectively). Dialysis patients had a higher Hepatitis B surface antibody compared to non-dialysis patients (78% vs 39%). Only 6 of 109 patients were fully immunized. Among 103 vaccine eligible patients, 99 (96%) agreed to get vaccinated. Table 1Baseline characteristics of kidney transplant candidates Table 2 Vaccination in kidney transplant candidates Conclusion KT candidates have low rates of prior immunization against Tdap, PCV13, PPSV23, Hepatitis A and B and RZV but high rates of serological immunity against measles, mumps, rubella and varicella. The vaccine uptake during pre-transplant evaluation was high and it provides an unique opportunity to improve immunization in this population. Disclosures All Authors: No reported disclosures.

Expression changes of Tim-3 as one of supplementary indicators for monitoring prognosis of liver pathological changes in chronic HBV infection

PurposeThis study was designed to analyze the liver tissue changes among the CHB patients who received treatment for at least 6 months and follow-up for at least 1 year, together with the correlation between the different disease condition and serum markers.MethodsOne-hundred and eighty-five CHB patients underwent antiviral therapy for at least 6 months were enrolled. In the 12-month follow-up, ultrasonography-guided biopsy was performed. The patients were grouped based on the serum markers and pathological changes in liver tissues. Then we determined the serum markers, virological tests and Tim-3 expression among these groups.ResultsAntiviral therapy significantly reduced liver inflammation indicators and serum Tim-3 level. However, the fibrosis process of liver tissue was not changed, and there are still disputes on the serum marker and hepatic lesion outcomes. Under normal liver function or negative hepatitis B e antigen (HBeAg) of CHB patients, there might be consensus between Tim-3 change and liver pathological outcome. According to the liver tissue inflammation and fibrosis conditions, Tim-3 was positively correlated with liver function indices. Besides, it was also related to fibrosis stage and inflammation grade.ConclusionThere were inconsistent changes between serum markers and liver tissue conditions after anti-viral therapy. Tim-3 expression was more suitable to indicate the changes of liver inflammatory and fibrosis response to some extent than ALT and AST. It may serve as a certain indicator to predict the CHB prognosis, which could be used as one of the monitoring indicators in liver pathological changes of chronic HBV infection, especially in monitoring liver tissue inflammation.

Obesity-Related Single-Nucleotide Polymorphisms and Weight Gain Following First-Line Antiretroviral Therapy.

We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH). Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models. A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020). Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.

Long-term outcome of lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients

BackgroundThe use of DTG-containing two-drug regimens is one of the most promising solutions to the need to ease the management of HIV treatment without harming its efficacy and safety. We report long- term results in patients switched, while virologically suppressed, to the combination of dolutegravir (DTG) plus lamivudine (3TC).MethodsThis is a prospective, clinical, uncontrolled cohort enrolling ART-experienced people living with HIV (PLWH) with HIV-RNA < 50 copies/ml for 6 months or longer, negative hepatitis B virus surface antigen, and without known M184V/I mutations. Kaplan-Meiers curves are used to describe persistency of virological suppression on therapy and a Cox regression model to evaluate baseline characteristics and the risk of stopping therapy.Results218 individuals switched their regimen since 2015. The mean estimated follow-up was of 64.3 months (95% CI 61.3–67.3) for approximately 1000 patient/years. After 5 years of follow-up, 77.1% were still on the DTG-3TC combination. No virologic failure was detected throughout the whole study period, and only 15 subjects presented single isolated viral blips above 50 copies/ml. Most patients stopped therapy because of reasons unrelated to study drugs (lost to follow-up; patients’ decision; moved to other Centers), but due to the unselected nature of the casuistry; 11 subjects died in the 5 years of follow-up mostly because of pre-existing co-morbidities (6 neoplastic diseases and 2 end-stage liver disease). The median baseline CD4 count was 669 cells/mcl (IQR 483–927). After 5 years it raised to 899 cells/mcl (IQR 646–1160) (P < 0.001) without a significant change of CD8 counts that lowered from 767 cells/mcl (IQR 532–1034) to 683 cells/mcl (IQR 538–988). Consequently, the CD4/CD8 ratio varied from 0.93 (IQR 0.60–1.30) to 1.15 (IQR 0.77–1.45) (P < 0.0001). A non-significant (P = 0.320) increment of mean creatinine, 0.06 mg/dl in magnitude, was observed over the whole follow-up.ConclusionThese long-term results over 5 years reinforce the durability and good tolerability of DTG-3TC. Our results continue to support the recommended switch use of this 2DR as a well-accepted treatment option for ART-experienced PLWH.

S3066 Interferon Therapy for Chronic Hepatitis Delta Viral Infection

Introduction: Hepatitis Delta Virus (HDV) infects those that are already infected with the Hepatitis B Virus (HBV), resulting in a serious infection that may damage hepatocytes. We present a patient that undergoes interferon therapy for chronic hepatitis delta infection with an emphasis on efficacy and side effects of treatment. Case Description/Methods: A 20 year old previously healthy African male presents with progressive fatigue. Bloodwork demonstrates elevated liver enzymes, thrombocytopenia, positive Hepatitis B surface antigen and core antibody, and is negative for hepatitis B e-antigen. HBV DNA levels are 30 IU/mL (reference range < 10 IU/mL). Six months later, liver enzymes remain elevated (AST 100 U/L, ALT 186 U/L). Liver biopsy confirms chronic hepatitis and moderate fibrosis with Metavir grade A3, stage F2, and is consistent with viral hepatitis infection. The biopsy also reveals schistosomiasis of the liver, for which the patient is treated with two series of Praziquantel 1800 mg, 3 times per day. Schistosomiasis resolve following treatment, yet liver enzymes remain elevated. Subsequent bloodwork is positive for HDV, with very high levels of HDV RNA at 14,000,000 IU/mL. The patient is started on tenofovir 300mg/day and peginterferon 180 mcg/week. This therapy is maintained for over 4 years, with side effects of headache and fatigue. Liver biopsy near end of treatment reveals mild portal inflammatory infiltrate composed predominantly of lymphocytes with scattered foci of lobular inflammation; Metavir grade 1, stage 0. Bloodwork at this time shows improvement in liver enzymes with AST 57 U/L and ALT 39 U/L. Patient stopped interferon due to side effects after four years of suppressive treatment. The most recent bloodwork shows HBV and HDV viral suppression via PCR, and negative Hepatitis B surface antigen. Liver surveillance via ultrasound reveals no evidence hepatocellular carcinoma during the duration of therapy. Discussion: Hepatitis delta virus (HDV) is a blood-borne virus that infects human hepatocytes. The replication of HDV depends upon a simultaneous infection with the Hepatitis B virus (HBV). Chronic HDV infections manifest as a rapidly progressing form of viral hepatitis, and can lead to cirrhosis with an increased risk of hepatocellular carcinoma. Currently, HDV has no approved treatment options from the United States Food and Drug Administration, and the only option for treatment is pegylated interferon-alpha.

S3283 A Tough Pill to Swallow: A Case Series of Statin-Induced Necrotizing Autoimmune Myopathy Manifesting as Dysphagia and Transaminitis

Introduction: Statins are commonly used to prevent cardiovascular disease. However, a small subset of patients may develop autoimmune myopathy, a form of inflammatory myositis characterized by proximal muscle weakness and in some cases, dysphagia. We present two cases highlighting statin-induced necrotizing autoimmune myopathy (SINAM), a rare entity affecting roughly 2 cases per 1 million people. Case Description/Methods: Two Hispanic men, aged 60 and 71, presented with dysphagia and transaminitis. They reported gradual onset of proximal muscle weakness and weight loss and were taking atorvastatin 20mg and 80mg, respectively. Case 1: Labs revealed ALP 58 IU/L, AST 238 U/L, ALT 407 U/L, CK 7228 U/L, normal CRP, ESR, and HMG CoA reductase (HMGCR) antibodies 257 U/mL. EGD was unrevealing. MRI of the pelvis/femur showed patchy, symmetric intramuscular edema in leg muscles (Figure 1). Muscle biopsy revealed myonecrosis consistent with immune-mediated necrotizing myopathy. Case 2: Labs revealed ALP 79 IU/L, AST 571 U/L, ALT 373 U/L, CK 8392 U/L, CRP 19.2 mg/L, ESR 67 mm/hr, and HMGCR antibodies 367 U/mL. Muscle biopsy was not pursued. Both cases revealed negative viral hepatitis, ANA, myositis panel, smooth muscle Ab, LKM-1 Ab, total IgG, ferritin, anti-mitochondrial Ab, and alpha-1 antitrypsin. Both patients were started on high-dose steroids. Case 1 patient had minimal improvement and was subsequently started on mycophenolate and rituximab. He remains under close monitoring. Case 2 patient had persistent severe weakness and dysphagia, therefore intravenous immunoglobulin (IVIG) and mycophenolate were added. However, dysphagia persists despite a consistent decrease in muscle enzymes. He remains hospitalized and is pending PEG tube placement. (Figure) Discussion: SINAM is a rare variant of idiopathic inflammatory myopathy characterized by proximal muscle weakness and myofiber necrosis after statin exposure. Diagnosis is made with positive antibodies to HMGCR and may avoid the need for muscle biopsy in the appropriate clinical context. Cessation of statin and initiation of glucocorticoids are first-line treatments. However, many cases are refractory to steroid monotherapy. Other therapies such as IVIG and immunosuppressants serve a role in refractory disease. Alternative lipid-lowering agents should be used, and statins must not be rechallenged. These cases emphasize that muscle weakness, dysphagia and transaminitis should be evaluated diligently as early recognition can lead to initiation of life-saving treatment.Figure 1.: A-D. MRI pelvis/femur showing bilateral patchy and symmetric intramuscular edema in leg muscles.

S3232 JAK2 Positive Budd-Chiari Syndrome and Risk in Liver Transplant

Introduction: Patients that present with Budd-Chiari Syndrome (BCS) may have underlying myeloproliferative neoplasms (MPN). Long-term prognosis is taken into consideration when evaluating for transplant. Here we present a complex patient with BCS secondary to MPN. Case Description/Methods: A 63-year-old male with new onset cirrhosis complicated by ascites and hepatic encephalopathy was hospitalized with three days of abdominal pain, distention, and diarrhea. He denied any new medications. He had no known personal or family history of liver or autoimmune diseases. He denied alcohol use. Initial laboratory evaluation included MELD-Na 15, undetectable acetaminophen, negative viral hepatitis serologies, and paracentesis was negative for infection with SAAG of 1.9. CT showed cirrhotic morphology, splenomegaly, and ascites. Ultrasound with doppler and CT venogram showed findings consistent with Budd-Chiari Syndrome (BCS). He was started on therapeutic heparin. The patient decompensated further with high MELD-Na and renal failure ultimately requiring renal replacement therapy and pressors. He was found to have a positive JAK2 V617F mutation. With leukocytosis and JAK2 mutation, bone marrow biopsy was obtained showing MPN consistent with myelofibrosis (MF). He was listed for transplant as MF was not deemed an absolute contraindication. Unfortunately, he decompensated further with variceal bleed and expired prior to transplant. Discussion: Considerations for our patient prior to transplant included the risk of leukemic transformation in setting of immunosuppression as well as increased thrombotic risk in the peri/post-operative setting. One study evaluated the prognosis of liver transplant with BCS and MPN and effects of immunosuppression. There was no difference in survival in BCS patients with or without MPN. Progression of MPN was not noted after transplant. The major concern was, however, was his thrombotic risk. One study identified portal vein thrombosis as an independent risk factor for graft loss in transplant recipients, independent of other factors. Listing the patient for transplant was controversial for these reasons. Hydroxyurea was initiated to mitigate these risks and bridge to transplant in this otherwise healthy, young, and high functioning patient. This case highlights the rapid decline of a complex patient with BCS secondary to myeloproliferative disease and the current data available to guide decision making in the transplant evaluation process.

S3111 An Unusual Case of Acute Liver Failure Secondary to Autoimmune Hepatitis (AIH) From Drug-Induced Liver Injury (DILI)

Introduction: A broad differential diagnosis and detailed workup is necessary in the evaluation of acute liver failure, as the below case demonstrates. Case Description/Methods: A 68-year-old Caucasian man presented to the ED complaining of chronic right lower quadrant pain, worsening over the last few weeks. He reported taking up to 20 tablets of naproxen a day. Review of systems was positive for diffuse pruritis of recent onset. Past medical history consisted of COPD, inguinal hernia status post mesh repair, knee osteoarthritis and a cholecystectomy. He endorsed daily tobacco use and minimal alcohol intake. Medications consisted of Albuterol inhaler and Naproxen. He had been diagnosed with a urinary tract infection one month prior that was treated with a ten-day course of Cephalexin. Exam was notable for diffuse excoriation and right upper/lower quadrant tenderness. Initial labs demonstrated creatinine 0.87, AST 2635, and ALT 887, with the remainder of his comprehensive metabolic panel being normal. Contrasted CT scan of the abdomen and pelvis revealed no abnormalities. A right upper quadrant ultrasound was notable for left sided intrahepatic biliary dilatation. Over the next day, his mentation worsened, with repeat labs notable for bicarbonate 13, creatinine 3.08, AST 12050, ALT 3950, total bilirubin 2.4 with direct bilirubin 1.5, INR 3.11 and ammonia 164. A broad infectious workup was unremarkable including negative viral hepatitis serologies. Smooth muscle antibody was weakly positive at a low titer of 1:20. Anti-nuclear and anti-mitochondrial antibodies were negative. Serum IgG level was normal. Endoscopic retrograde cholangiopancreatography revealed a severe left intrahepatic biliary stricture with resulting stent placement into the left hepatic duct. Bile duct brushing was negative for atypical cells. Liver biopsy demonstrated centrilobular necrosis and parenchymal collapse with focal bridging necrosis and mixed inflammatory infiltrate. A diagnosis of AIH secondary to DILI leading to acute liver failure was made, with either Naproxen or Cephalexin being the inciting drugs. Discussion: He was started on a prednisone taper and showed improvements in mental status and kidney and liver function on lab-work prior to discharge. Labs obtained on clinic follow-up one month after discharge revealed complete resolution of his kidney and liver injury. This case illustrates a rare clinical entity as neither Naproxen nor Cephalexin are classically associated with causing AIH or acute liver failure.

S3373 Atypical GBS as the Presenting Symptom of Celiac Disease: Recognizing Extra-intestinal Presentations of Celiac Disease

Introduction: Celiac disease (CD) is an immune-mediated enteropathy in response to gluten that occurs in 1% of the population. Classic presenting symptoms include bloating, weight loss, and diarrhea. But, extraintestinal symptoms such as dermatitis herpetiformis, iron deficiency anemia, asymptomatic liver abnormalities, and more rarely, neurologic symptoms can be seen. We present a case of a patient who presented with worsening polyneuropathy and hepatitis leading to a final diagnosis of CD. Case Description/Methods: A 44-year-old male with history of recent left-chest shingles complicated by paralysis of right face and left leg weakness was initially admitted for suspected atypical Guillain Barre Syndrome (GBS) and treated with prednisone and a 5-day course of intravenous immunoglobulin (IVIG). The patient was readmitted a few weeks later with worsening neurologic status. A thorough infectious workup was unremarkable. The patient was also noted to have abnormal liver enzymes on prior admission that initially improved, but were noted to be worse on readmission up to ALP 1103, AST 634 and ALT 689. Given no prior history of liver disease, patient underwent a thorough workup including negative viral hepatitis, normal liver US, abdominopelvic CT showed scattered hypoattenuating lesions in the liver, one measuring up to 2.2 cm. He underwent a liver biopsy which demonstrated acute hepatitis with findings concerning for autoimmune versus drug-induced hepatitis. Autoimmune hepatitis panel was negative, however, he was found to have a tissue transglutaminase IgA >250 U/mL. Finally, he underwent upper endoscopy with biopsies that demonstrated findings consistent with celiac disease. Liver enzymes improved with gluten avoidance, but neurologic impairments persisted. Discussion: Atypical extra-intestinal symptoms at presentation of CD can result in diagnostic delay and permanent neurological disability if not treated. CD has been found in as many as 9% of patients with elevated liver enzymes. It is imperative not only to recognize neurologic presentations of CD but also the spectrum of possible liver impairments. Adherence to a strict gluten-free diet has been shown to improve symptoms of both neuropathy and liver enzyme abnormalities, but must be instituted quickly.

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

S3253 A Case of Recurrent Ascites Secondary to Ventriculoperitoneal Shunt in a Patient With Idiopathic Intracranial Hypertension

Introduction: Idiopathic Intracranial Hypertension (IIH) is a rare diagnosis affecting approximately 0.9–3/100,000 adults, mostly females of childbearing age with obesity. Surgical intervention is usually indicated in cases that prove refractory to conservative measures (such as weight loss and acetazolamide) or in cases of progressive papilledema and visual deficit. Ventriculoperitoneal shunt (VPS) is the preferred internalized cerebrospinal fluid diversion method. Here, we present a case of VPS causing ascites in a woman with IIH. Case Description/Methods: A 33-year-old female smoker with obesity, hypertension, and IIH with VPS (Medtronic strata valve, set to 1.0., placed six years ago for headache and visual problems) presents to the ED with increased abdominal distention and discomfort along with shortness of breath. She underwent a paracentesis two weeks prior for new ascites. Paracentesis showed no malignant cells. She had no family history of gastrointestinal pathology, no risk factors for viral hepatitis, and negative hepatitis serologies. She started noticing re-accumulation of fluid that did not improve with prescribed furosemide. She had no other symptoms including fevers, chills, or neurological symptoms. Physical exam showed ascites with a normal neurologic exam. Liver function tests were normal. CT abdomen and pelvis showed an unremarkable liver and VPS catheter without kinking. Pelvic ultrasound was unrevealing except for an ovarian cyst. Repeat paracentesis showed SAAG (Serum Ascites Albumin Gradient) 0.8, WBC 650 cells/ul, and only 10% polymorphonuclear cells (PMN). Culture of peritoneal fluid was positive for Cutibacterium acnes. The patient completed an antibiotics course and underwent a removal of the distal (peritoneal) catheter of the VPS that led to resolution of her ascites. Discussion: We present a case of recurrent ascites resolution following VPS removal. Cerebrospinal fluid (CSF) ascites is one of the rarest intra-abdominal complications of VPS. Only 29 cases have been described in the literature and only six of them were in adults. In such cases, VPS are removed and Ventriculo-pleural or Ventriculo-atrial shunts are placed. While pathophysiology behind IIH is hypothesized to be due to inability of CSF to be reabsorbed by arachnoid granulations and extracranial lymphatics, there is no satisfactory explanation in the literature regarding the pathophysiology of CSF ascites due to VPS. It is suspected that our patient’s infected VPS caused device malfunction leading to ascites.

S1755 Intrahepatic Cholangiocarcinoma in a Patient With Alcoholic Liver Cirrhosis and Markedly Elevated Serum Alpha-Fetoprotein

Introduction: Intrahepatic cholangiocarcinoma (ICC) represents 5% of all primary liver malignancies, second only to hepatocellular carcinoma (HCC). Although risk factors such as primary sclerosing cholangitis, hepatolithiasis, and asbestos have been reported, the etiology of ICC is not well understood. An elevated serum AFP accompanied by a space-occupying solid lesion in a cirrhotic patient is typically indicative of HCC. In high-risk patients, such as those with chronic liver disease, AFP > 400 ng/mL has a high positive predictive value for HCC and a specificity of >95%. An elevated serum AFP greater than 20 ng/mL is seen in < 25% of ICC. Case Description/Methods: We present a patient with a past medical history of alcoholic liver cirrhosis Child-Pugh Class C presenting with acute change in mental status. On arrival, he was hemodynamically stable with classic stigmata of chronic liver disease on the exam. Non-contrast CT Head was non-revealing. Laboratory investigations revealed an obstructive pattern of transaminitis with a normal ammonia level, negative hepatitis panel, and serum AFP of 1955.8 ng/mL. EGD demonstrated portal hypertensive gastropathy. CT Abdomen/Pelvis demonstrated a large infiltrative heterogeneous mass involving the entire right hepatic lobe with a non-occlusive thrombus extending to the portal vein. Ultrasound-guided liver biopsy and immunohistochemical analysis demonstrated positive expression for cytokeratin 20, and CA 19-9. Neoplastic cells were negative for Hep-Par1, Glypican 3, and Arginase 1. The histological pattern (Figure) was consistent with poorly differentiated adenocarcinoma, most likely pancreaticobiliary in origin consistent with intrahepatic cholangiocarcinoma (ICC). Discussion: Elevated serum AFP accompanied by a space-occupying solid lesion in a cirrhotic patient is typically indicative of HCC. However, Xiong et al reported an increased risk by 3.92-fold of cholangiocarcinoma in patients with alcoholic liver disease. Even though, an increase in AFP has been reported in patients with ICC, an elevation higher than 20 ng/mL was seen in approximately 20% of the patients according to Wang et al. In our patient, surprisingly, the histopathological report showed findings consistent with ICC and negative hepatic markers, hence a high suspicious index should be held by clinicians for this entity upon approaching a patient with a solid liver mass associated with significantly elevated AFP levels.Figure 1.: On the left, histology of poorly differentiated adenocarcinoma composed of duct-like structures with high pleomorphism. H&E 400X. On the right, immunohistochemical study shows positive CA 19-9 stain of adenocarcinoma.

Clinical, Laboratory and Virological Characteristics of Patients with Positive Hepatitis B Surface Antigen

Background and Aim: Globally, Hepatitis B virus (HBV) infection is a major health issue contributing to various diseases such as hepatocellular carcinoma (HCC) and liver cirrhosis. Virus replication complex interaction with host immune system response causes dynamic interplay leading to HBV infection. In developing countries, HBV infection plays a significant role in higher rates of morbidities and mortalities. The present study aimed to assess the clinical, laboratory, and virological characteristics of patients with positive HBV surface antigen. Methodology: This cross-sectional study was carried out on 182 positive HBV surface antigen (HBsAg) in the department of Medicine, Social Security Hospital, Multan Road Lahore from April 2021 to March 2022. All the patients with positive HBsAg and negative hepatitis C were enrolled. Patients with a history of chronic liver disease, acute hepatitis B infection, and antiviral therapy were excluded. All patients underwent CBC, liver function tests, clinical evaluation, and abdominal ultrasonography examination, HBV serological marker’s assessment, HBV transmission risk factors, and HBV-DNA quantitative detection. SPSS version 25 was used for data analysis. Results: Out of 182 HBV infected patients, there were 162 (89%) males and 20 (11%) females. The overall mean age was 38.6 ± 8.6 years. The most prevalent complaint and common findings was arthralgia and hepatomegaly with reported incidence of 32 (17.6%) and 16 (8.8%) respectively. Based on ultrasonography imaging results, the incidence of normal liver, coarse liver, splenomegaly, and cirrhosis were found in 81.3% (n=148), 12.6% (n=23), 5.9% (n=11), and 6.6% (n=12) respectively. Based on laboratory results, normal alanine aminotransferase, normal aspartate aminotransferase, reduced serum albumin, and low platelet count were found in 76.9%, 84.8%, 4.9%, and 10.2% respectively. Regarding laboratory, clinical, and imaging characteristics, HBV-DNA positive and negative had no significant differences. Conclusion: The present study found that HBV infected patient’s clinical manifestations were fatigue, bleeding gums, abdominal pain and fatigue. Majority of patients had normal liver on liver function tests and ultrasonographic examination. Most patients had negative HBV infection antigen. Based on comparisons made between HBV-DNA negative and positive, no substantial variations were reported on laboratory, clinical, and imaging characteristics. Keywords: HBV antigen, Virological characteristics, HBV

HBsAg seroconversion in de novo hepatitis B virus-infected paediatric liver transplant recipients with anti-viral therapy.

We investigated the clinical characteristics and therapeutic strategies for paediatric liver transplant (PLT) recipients who experienced de novo hepatitis B virus infection and the features of HBsAg seroconversion. A total of 821 PLT were performed in HBV-free recipients between January 2013 and January 2019 in Paediatric Organ Transplant Center, Tianjin First Central Hospital. Twenty-one recipients developed de novo HBV infection, the clinical data were analysed. The overall incidence of de novo HBV infection was 2.5%. Only one recipient received an HBcAb-negative graft, 20 recipients received HBcAb-positive grafts. The incidence of de novo HBV infection in HBcAb-negative and HBcAb-positive graft recipients were 0.2% and 6.3%, respectively. Fifteen de novo HBV-infected recipients showed HBsAg seroconversion, the incidence of HBsAg seroconversion was 71.4%. The median time from the diagnosis of de novo HBV infection to HBsAg seroconversion was 15 (1, 73) months. Recipients with hepatitis B surface antigen (HBsAg) titre <1000 IU/L and negative hepatitis B e antigen (HBeAg) at the time of de novo HBV infection diagnosis were more likely to achieve HBsAg seroconversion. Nucleotide analogues were effective in treating recipients with de novo HBV infection. De novo HBV infection does not impact liver graft function as well as recipient and graft survival rate. De novo HBV infection does not impact PLT recipient outcomes under close monitoring and appropriate treatment. High incidence of HBsAg seroconversion can be achieved after anti-viral therapy.