Needle Biopsy Of Liver Research Articles

Evaluation of the histologic and immunohistochemical (CD34, glutamine synthetase) findings in idiopathic non-cirrhotic portal hypertension (INCPH)

AimIdiopathic non-cirrhotic portal hypertension (INCPH) is a vascular disorder of uncertain origin. Diagnosis can be challenging on liver biopsy. Despite diverse histomorphologic findings documented in literature, studies on the frequency of these findings are lacking. This study aims to assess both the histomorphologic features and the immunoexpression patterns of CD34 and glutamine synthetase (GS) in liver biopsies and searched for their contribution to the pathologic diagnosis of INCPH.Materials and methodsHematoxylin–eosin, CD34, and GS-stained liver needle biopsy sections of 16 patients clinically diagnosed with INCPH were retrospectively analyzed. Histologic findings such as portal vein narrowing, obliteration, or loss were grouped as major findings, while portal vein herniation, hypervascularized portal tracts, and periportal abnormal vessels were grouped as minor findings, and their frequency were evaluated. Periportal endothelial CD34 stained areas were measured via ocular micrometer. The distribution of GS immunoexpression was evaluated. Eighteen healthy liver donor biopsies were evaluated as controls.ResultsIn INCPH cases, 58% of portal tracts showed major findings, compared to 15% in the control group (p < 0.001). Minor findings were observed in 16% of INCPH cases and 7% of controls (p = 0.014). The number of portal tracts with histologic findings is significantly higher in INCPH than in control liver biopsies. Abnormal portal tract distribution, like being close to each other, was seen in 75% of INCPH cases but not in controls (p < 0.001). Nodular regenerative hyperplasia (NRH) was present in 31% of cases. Periportal CD34 expression was higher in INCPH, and affected areas were larger than in controls (p < 0.001). Irregular GS staining, i.e. GS staining with patchy distribution in zone 3, and/or periportal and zone 2 hepatocytes, was found in 62% of INCPH cases, while controls showed the usual pattern (p < 0.001).ConclusionIn the biopsy diagnosis of INCPH, in addition to the presence of major histologic findings and the amount of portal tracts displaying these features, the expression of endothelial CD34 in periportal areas, and irregular hepatocellular GS expression can also be considered as supporting feature.

Severe Acute Hepatitis of Unknown Etiology in Pediatric Patients: Multidisciplinary Clinical Approach

Introduction: In mid-2022, the World Health Organization (WHO) declared a moderate-risk outbreak due to an increase in severe acute hepatitis cases of unknown etiology in children. Several reports suggested a viral infection link, with the outbreak spanning over 35 countries. By June 2022, Mexico reported 69 probable cases across 5 entities to the WHO. Case Presentation: A 4-year-old boy presented with vomiting, jaundice, choluria, and hepatomegaly. A multidisciplinary approach was employed, using an algorithm developed exclusively for clinical, epidemiological, and biochemical follow-up. Despite the negative identification of any associated microorganism and the absence of antibodies, liver function tests remained elevated. A fine needle liver biopsy was performed for diagnostic support, followed by histopathological study and sequencing and analysis of the complete high-depth transcriptome. Transcriptome analysis identified dysbiosis-related intestinal microbiota, including increased enterogenic and opportunistic pathogenic bacteria of the genus Clostridium, as well as HERV-K113, implicated in autoimmune disease development. Conclusions: The study's findings suggest possible immune-mediated mechanisms involving dysbiosis of the gut microbiota and the potential role of HERV-K113. Management and control of acute liver disease depend on specific causes, with the main challenge being early determination and implementation of optimal management strategies. The exact pathological mechanisms underlying pediatric acute hepatitis of unknown etiology remain elusive, warranting further studies to confirm or refute these hypotheses and elucidate the underlying pathological mechanisms

Comparison of diagnostic outcomes, safety, and cost of Franseen-tip 19G versus 22G needles for endoscopic ultrasound-guided liver biopsies.

Background and study aims Favorable outcomes were noted with refinement in newer endoscopic ultrasound-guided liver biopsy (EUS-LB) needle tips. Still, the overall usefulness and benefit are yet to be well explored. Patients and methods This was a retrospective analysis of patients with EUS-LB (Franseen-tip 19G versus 22G FNB needle) over 2 years. EUS-LB was obtained in a one-pass, two-actuation, modified wet suction technique. Diagnostic yield, fragmentation rate, aggregate specimen length (AL), number of complete portal tracts (CPT), length of longest intact core (LIC), adverse events (AEs) (early), and cost of the procedure (1USD = 82 INR) were compared. Results Fifty-four patients (33 [61.1%], female) successfully underwent EUS-LB with a median age of 46 years (interquartile range [IQR] 34-54); the majority 32 (59.2%) underwent 19G biopsies. There was a significantly increased median (IQR) AL in the 19G compared with 22G (20 mm [19-21] vs. 15 [14-15], P < 0.001), respectively. Similarly, significantly lengthier median LIC and CPT were seen, respectively. A nonsignificant diagnostic yield was noted (100% vs. 90.9%, P = 0.082), respectively. The fragmentation rate was higher in 22G FNB needles (36.4% [95% CI 16-56] vs. 12.5% [95% CI 1-24], respectively; P = 0.038). Seven patients (12.9%) had mild AEs with no difference between groups. The average procedure cost with 19G was INR 63000 (768$), and with 22G needle was INR 54500 (664$). Conclusions The Franseen-tip 19G outperforms 22G with a significantly lower fragmentation rate, longer AL, LIC, and a higher number of CPT with a marginal increase in the procedure cost, without any difference in diagnostic yield and safety.

Enteroblastic cholangiocarcinoma: An uncommon, underrecognized subtype of bile duct cancer

Enteroblastic carcinoma is clinically characterized by an elevated serum level of alpha-fetoprotein (AFP) and is histologically characterized by cancer cells with a clear cytoplasm and ‘blastic’ coarse chromatin. It sometimes has an element of hepatoid carcinoma; therefore, these two neoplasms are often regarded as sister entities. Although hepatoid carcinoma in the biliary tree has been reported, enteroblastic cholangiocarcinoma is extremely uncommon. In the present study, four cases of enteroblastic cholangiocarcinoma were examined. Tumors were located inside the liver (n = 2) or common bile duct (n = 2). The two intrahepatic cases had a history of primary sclerosing cholangitis, and serum AFP levels were elevated in both. One unresectable case was diagnosed by needle liver biopsy, while the remaining three underwent surgical resection. Histologically, all cases showed similar microscopic features. Cuboidal or polygonal cancer cells with the characteristic clear cytoplasm and subnuclear vacuoles were arranged in a papillary, micropapillary, tubular, or solid architecture. One case had an element of pancreatobiliary-type adenocarcinoma, while a hepatoid carcinoma element was not observed in any cases. All cases were positive for AFP, glypican 3, and SALL4, with SALL4 being the most widely expressed. Heppar-1 and arginase-1 were negative, except for one case, which was positive for Heppar-1. In conclusion, enteroblastic cholangiocarcinoma is an uncommon subtype of biliary tract malignancy. These cases may have been categorized as ‘clear cell’ cholangiocarcinoma. Although enteroblastic cholangiocarcinoma seems to occur more commonly in extrahepatic regions, including the gallbladder, it may also develop in the liver, particularly in patients with primary sclerosing cholangitis.

Performance of non-invasive tests for liver fibrosis resolution after bariatric surgery

Background & aimsThe value of non-invasive tests for monitoring the resolution of significant liver fibrosis after treatment is poorly investigated. We compared the performances of six non-invasive tests to predict the resolution of significant fibrosis after bariatric surgery. MethodsParticipants were individuals with obesity submitted to needle liver biopsy at the time of bariatric surgery, and 12 and/or 60 months after surgery. We calculated the fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), AST to platelet ratio index (APRI), Hepatic fibrosis score (HFS), Fibrotic NASH index (FNI), and Liver risk score (LRS) at each time point, and compared their performances for predicting significant fibrosis (F ≥ 2) and its resolution following surgery. ResultsAt baseline, 2436 patients had liver biopsy, including 261 (10.7 %) with significant fibrosis. Overall, 672 patients had pre- and post-operative biopsies (564 at M12 and 328 at M60). The fibrosis stage decreased at M12 and M60 (p < 0.001 vs M0). Resolution of significant fibrosis occurred in 58/121 (47.9 %) at M12 and 32/50 (64 %) at M60. The mean value of all tests decreased after surgery, except for FIB-4. Performances for predicting fibrosis resolution was higher at M60 than at M12 for all tests, and maximal at M60 for FNI and LRS: area under the curve 0.843 (95%CI 0.71–0.95) and 0.92 (95%CI 0.84–1.00); positive likelihood ratio 3.75 (95 % CI 1.33–10.59) and 4.58 (95 % CI 1.65–12.70), respectively. ConclusionsResults showed the value and limits of non-invasive tests for monitoring the evolution of liver fibrosis after an intervention. Following bariatric surgery, the best performances to predict the resolution of significant fibrosis were observed at M60 with tests combining liver and metabolic traits, namely FNI and LRS.

Improved assessment of donor liver steatosis using Banff consensus recommendations and deep learning algorithms

The Banff Liver Working Group recently published consensus recommendations for steatosis assessment in donor liver biopsy, but few studies reported their use and no automated deep-learning algorithms based on the proposed criteria have been developed so far. We evaluated Banff recommendations on a large monocentric series of donor liver needle biopsies by comparing pathologists' scores with those generated by convolutional neural networks (CNNs) we specifically developed for automated steatosis assessment. We retrospectively retrieved 292 allograft liver needle biopsies collected between January 2016 and January 2020 and performed steatosis assessment using a former intra-institution method (pre-Banff method) and the newly introduced Banff recommendations. Scores provided by pathologists and CNN models were then compared, and the degree of agreement was measured with the intraclass correlation coefficient (ICC). Regarding the pre-Banff method, poor agreement was observed between the pathologist and CNN models for small droplet macrovesicular steatosis (ICC: 0.38), large droplet macrovesicular steatosis (ICC: 0.08), and the final combined score (ICC: 0.16) evaluation, but none of these reached statistically significance. Interestingly, significantly improved agreement was observed using the Banff approach: ICC was 0.93 for the low-power score (p <0.001), 0.89 for the high-power score (p <0.001), and 0.93 for the final score (p <0.001). Comparing the pre-Banff method with the Banff approach on the same biopsy, pathologist and CNN model assessment showed a mean (±SD) percentage of discrepancy of 26.89 (±22.16) and 1.20 (±5.58), respectively. Our findings support the use of Banff recommendations in daily practice and highlight the need for a granular analysis of their effect on liver transplantation outcomes. We developed and validated the first automated deep-learning algorithms for standardized steatosis assessment based on the Banff Liver Working Group consensus recommendations. Our algorithm provides an unbiased automated evaluation of steatosis, which will lay the groundwork for granular analysis of steatosis's short- and long-term effects on organ viability, enabling the identification of clinically relevant steatosis cut-offs for donor organ acceptance. Implementing our algorithm in daily clinical practice will allow for a more efficient and safe allocation of donor organs, improving the post-transplant outcomes of patients.

Abstract 12705: Identification and Characterization of Solbinsiran, a GalNAc Conjugated siRNA Targeting Angiopoietin-Like 3

Introduction: While statins play an important role in reducing LDL-C levels and the risk of ASCVD events, residual risk from apolipoprotein B (apoB)-containing lipoprotein particles persists among patients with or at high risk of ASCVD. Hypothesis: Blocking ANGPTL3 activity or preventing its expression is a therapeutic approach to reduce apoB-containing lipoprotein particles. Solbinsiran (LY3561774), a novel Dicer-substrate small interfering RNA oligonucleotide, was designed to reduce the levels of ANGPTL3 protein expression. Methods: Nucleotide base sequences of a library of anti-ANGPTL3 siRNAs were selected using an in silico RNAi prediction algorithm on ANGPTL3 mRNA sequences conserved in humans and cynomolgus monkeys. Through a large-scale in vitro screen of the anti-ANGPTL3 library in human cells, the candidate solbinsiran sequence was identified as an efficacious siRNA. Solbinsiran in vivo efficacy was measured by RT-qPCR of liver from CD-1 female mice overexpressing human ANGPTL3 . The degree and durability of ANGPTL3 mRNA knockdown and circulating protein level reduction by solbinsiran was evaluated in cynomolgus monkeys administered single dose subcutaneous injections of either PBS or 3 mg/kg solbinsiran. Blood samples to measure ANGPTL3 protein were collected on Study Days -8, -5, and 0, and weekly after dosing until Day 113. Ultrasound-guided core needle liver biopsies were collected on Study Days 5, 28, 56, 84, and 113. Total RNA derived from the liver biopsy samples to measure ANGPTL3 mRNA was subjected to RT-qPCR analysis. Results: When given a single dose at 1 mg/kg subcutaneously, solbinsiran reduced human ANGPTL3 mRNA by 65% in hepatocytes as compared to vehicle-treated mice. A single dose of solbinsiran reduced liver ANGPTL3 mRNA expression by up to 72.9% (p&lt;0.0001) and serum ANGPTL3 protein expression by 68.6% (p&lt;0.001). Solbinsiran also displayed a long duration of activity, as indicated by a greater than 50% mRNA knockdown remaining 12 weeks after a single dose. Conclusions: These data supported the advancement of solbinsiran to Phase 1 clinical testing in participants with mixed dyslipidemia (ClinicalTrials.gov Identifier: NCT04644809).

PSV-10 Effects of Rumen-Bypass Protein Supplement on Growth Performance, Hepatic Mitochondrial Function and Immune Gene Expression of Beef Steers with Divergent Residual Feed Intake Phenotype

Abstract We examined the effects of rumen-bypass protein supplement on growth performance, hepatic mitochondrial Electron Transport Chain (ETC) activities, and mRNA expression of innate and adaptive immune genes of beef steers with divergent residual feed intake (RFI) phenotype. Thirty-nine crossbred beef steers (average BW = 492 ± 36 kg) were used in a generalized randomized block design with a 2 × 2 factorial arrangement of treatments for a 42-d experimental period. The factors evaluated were 1) RFI classification [low-RFI (-2.12kg/d) vs. high-RFI (2.02kg/d)], and 2) feed additive: rumen-bypass protein supplement (RCP; 227 g· steer-1· day-1) vs. Control diet (CON; 0 g/d), resulting in four treatments: Low-RFI-CON (n = 10), low-RFI-RCP (n = 9), high-RFI-CON (n = 10), and high-RFI-RCP (n = 10). The rumen-bypass protein supplement (84% CP) is a blend of hydrolyzed feather meal, porcine blood meal, and DL-methionine hydroxy analogue. The beef steers were stratified by BW and randomly assigned to treatments and housed in four pens equipped with two GrowSafe feed bunks each to measure individual DMI. Body weight was measured every 7 days. Liver tissue was sampled on d 42 from all animals using a liver biopsy needle for mRNA expression analysis of 84 immune genes and analysis of mitochondrial ETC activities of complexes I – V. No effects of supplemental feed additive or RFI × feed additive interactions were observed (P &amp;gt; 0.05) for ADG and DMI. Compared with high-RFI, low-RFI beef steers tended to have less DMI (13.6 vs 12.9 kg/d; P = 0.09) but ADG was similar for the two RFI groups. Feed additive × RFI interactions were observed (P ≤ 0.05) for mitochondrial activities of Complexes IV, V, and mRNA expressions of some immune genes. Supplemental RCP increased Complex IV (39.2 nmol/min/mg) activity and reduced that of Complex V (94.1 nmol· min-1· mg-1) in high-RFI beef steers whereas the activity of Complex IV (13.1 nmol· min-1· mg-1) was reduced and that of Complex V (120 nmol· min-1· mg-1) was increased in low-RFI beef steers. Supplemental RCP increased (P &amp;lt; 0.05) the mRNA expression of TLR2 [fold change (FC) = 1.17 vs 0.98], TLR3 (FC = 1.49 vs 0.97), NFKB1 (FC = 1.02 vs 0.90), and IL23A (FC = 1.35 vs 1.07) in high-RFI beef steers but the expression of these genes were not altered in low-RFI beef steers. In conclusion, RCP supplementation did not affect the growth performance and the observed effects on hepatic immune gene expression and activities of mitochondrial ETC complexes are dependent on the RFI phenotype of the beef steers. Further research should explore the mechanism responsible for the interactions between RCP supplementation and RFI status.

Is M30 staining a reliable marker predicting graft rejection and fibrosis in protocolar liver biopsies in post-liver transplant pediatric patients?

Liver transplantation is currently a treatment of choice in patients with end-stage liver disease. Acute cellular rejection (ACR), antibody-mediated rejection (AMR), and chronic rejection (ChR) are major causes of graft injury. Therefore, new markers predicting graft rejection are investigating. Apoptosis has been recently proposed as one of the mechanisms contributing to liver fibrosis in liver grafts. Coarse needle liver biopsy is still a gold standard in monitoring post-transplant pathologies. The aim of this study was to assess the utility of immunohistochemical (IHC) staining for M30 (cytokeratin 18), as a prognostic marker of rejection in pediatric recipients of liver transplant and predicting marker of liver fibrosis and worse follow-up. The study enrolled 55 biopsies from 55 patients aged 2.37 to 18.9 years (median 13.87 years) who underwent protocolar liver biopsies taken 1-17 years after liver transplantation (median 8.36 years). The control group (positive control group) consisted of 26 biopsies from 16 patients in whom acute ACR was diagnosed. IHC staining for M30 (cytokeratin 18) and histochemical Azan staining were performed in all liver specimens. The following changes were re-evaluated in each specimen: features of ACR (the severity was assessed using RAI/Rejection Activity Index/Scale, which ranges from 3-9 points and include 3 histopathological changes suggestive of rejection), AMR or ChR; severity of fibrosis (Ishak Scale); presence of cholestasis and steatosis. Clinical parameters including laboratory tests of liver function (AST, ALT, GGTP, bilirubin) were also evaluated. M30 expression correlated with presence of acute cellular rejection. However, no relationship was found between M30 expression and severity of fibrosis. M30 staining, marker of apoptosis, seems to be a promising marker predicting acute cellular rejection.

The Role of Immunohistochemistry in the Differential Diagnosis between Intrahepatic Cholangiocarcinoma, Hepatocellular Carcinoma and Liver Metastasis, as Well as Its Prognostic Value.

Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (n = 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation.

Visualizing in situ viral replication across the natural history of chronic HBV infection.

Chronic HBV infection evolves through different phases. Interactions between viral replication and the host immune response in the liver underlie the pathogenesis of this disease. The aim of this study was to directly visualize the HBV replication intermediates at a single-cell resolution inscribed on morphological changes corresponding to disease activity. A set of archived formalin-fixed paraffin-embedded liver needle biopsies from treatment-naïve patients were collected and categorized into phases according to the American Association for the Study of the Liver Diseases (AASLD) guidelines. HBV RNA and DNA were detected using in situ hybridization assays. The hepatocytes were ubiquitously infected in subjects with immune tolerance, and their percentage was gradually decreased in immune-active and inactive chronic hepatitis B phases. HBV-infected hepatocytes were prone to localize close to fibrous septa. The subcellular distribution of signals was able to distinguish hepatocytes with productive infection from those harboring HBV integrants and transcriptionally inactive covalently closed circular DNAs. A smaller number of hepatocytes with productive infection and more harboring transcriptionally inactive covalently closed circular DNA or HBV integrants became apparent in the inactive chronic hepatitis B phase. An atlas of in situ characteristics of viral-host interactions for each phase is described, which sheds light on the nature of viral replication and disease pathogenesis among the phases of chronic HBV infection.

Assessment of the possible impact of hepatitis viruses on the development and course of autoimmune liver diseases

Despite the well-studied pathogenesis, the etiology of autoimmune liver disease (AILD) remains unknown. To determine the significance of hepatitis A, B, C and E viruses in the development and progression of AILD. A single-center case-control study included 139 patients with AILD: autoimmune hepatitis - AIH (n=46), primary biliary cholangitis - PBS (n=74), primary sclerosing cholangitis - PSC (n=19). Median age 56 years, IQR 48-65 years. 125 patients - without liver disease - control group (median age 55 years, IQR 46-65 years). Testing of blood serum samples for anti-HAV IgG, anti-HEV IgG, HBsAg, anti-HBc IgG, anti-HCV was carried out by solid-phase ELISA. All patients underwent fibroelastography. Needle liver biopsy - 70 patients: AIH (n=37), PBC (n=28) and PSC (n=5). Ab(IgG) to HAV and HBV were detected in patients with AILD significantly more often than in the control group (74.8% vs 54.4%; p<0.001). An increased risk of developing AILD was established in patients with the presence of antibodies to HAV, HBV and HEV (OR 2.491, CI 95% [1.481-4.190]). The highest risk of developing PBC was found in patients with antibodies to HAV and HBV (OR 3.008, 95% CI [1.633-5.542] and OR 2.515, 95% CI [1.242-5.093]). In patients with severe liver fibrosis (F3-F4 according to METAVIR), antibodies to HAV and HBV were detected significantly more often than in patients with F0-F2 [85% vs 65%; p=0.008]. In our work, we have demonstrated the relationship of past hepatitis A, B, E and AILD, as well as the high risk of developing severe fibrosis in patients with AILD and markers of hepatitis A and B viruses indicates the possible involvement of these viruses in the pathogenesis of AILD.

Evaluation of percutaneous blind liver needle biopsy results in chronic hepatitis B patients in a state hospital without interventional radiology

Evaluation of percutaneous blind liver needle biopsy results in chronic hepatitis B patients in a state hospital without interventional radiology

Evidence of Residual Ongoing Viral Replication in Chronic Hepatitis B Patients Successfully Treated With Nucleos(t)ide Analogues.

Chronic hepatitis B is usually treated with nucleos(t)ide analogues (NAs). However, a cure is rarely achieved, even with years of treatment. Here, we investigated whether viral replication is completely halted and how long covalently closed circular DNA (cccDNA) persists in patients successfully treated with NAs. A series of longitudinal serum samples and a collection of cross-sectional liver biopsies were obtained from patients successfully treated with NAs. Viral variants in serum HBV RNA were enumerated by deep sequencing. Viral replication intermediates in hepatocytes were directly visualized by in situ hybridization. The apparent half-life of each cccDNA was estimated. Three of 6 successfully treated patients demonstrated clear evidence of a small proportion of virus evolution, although the overwhelming proportion of variants were identical or possessed a similar degree of divergence through time. The apparent half-life of variants was estimated to be from approximately 7.42 weeks to infinite. Hepatocytes remained positive for cytoplasmic nucleocapsids-associated relaxed circular DNA in 4 of 7 liver needle biopsies. We conclude that even after prolonged treatment, a small proportion of the cccDNA reservoir is constantly replenished by continued low-level HBV replication, whereas a large proportion of the cccDNA reservoir persists over time.

Liver biopsy needle size and adequacy of sample: Review of practice at a children’s liver centre

Liver biopsy needle size and adequacy of sample: Review of practice at a children’s liver centre

Case Report On Cirrhosis Of Liver

Introduction: - The liver is irrevocably damaged and replaced with scar tissue as a result of the late-stage liver disease cirrhosis. Scar tissue prevents your liver from functioning properly. Cirrhosis typically develops decades after the onset of chronic liver disease. Men experience it twice as frequently as women. Clinical Findings:-Weakness, loss of appetite, easy bruising, skin yellowing (jaundice), itching, and weariness are all symptoms of cirrhosis. Diagnostic Evaluation: -Blood test: - HB % = 9.3gm%, total RBC count = 2. 99cu.mm, total WBC count = 11800cu.mm, total platelet count = 1.23 lac cu.mm, total protein = 6.5g/L, total bilirubin = 15.8g/L, lymphocytes = 10%, monocytes = 0.2%, albumin =2.2. Peripheral Smear: - RBCs - Normocytic mildly hypochromic Platelets - Reduced on smear APC - 38000 cells/mm³ as per cell counter no Haem parasite seen. Ultrasonography:- Options include liver needle biopsy, ultrasonography, and magnetic resonance imaging (MRI). an innovative imaging technique called electrography. Therapeutic Intervention: - Inj. Albumin 20% × OD, Inj. Vitamin K 10mg ×OD, Inj. Optineuron ×OD, Inj. Pan 40mg × OD, Inj. Emset 4mg × SOS, Inj. Levoflox 500mg × OD.&#x0D; Outcome: - After treatment the patient show&#x0D; Improvement. His appetite is improved and skin condition is also improved and his Weakness is reduced.&#x0D; Conclusion:- With a known case of liver cirrhosis, the patient was admitted to the hospital with complaints of weakness, loss of appetite, easy bruising, jaundice, itching, and weariness. His condition improved after receiving the proper care.

S3176 Tenofovir Disoproxil Fumarate-Related Metabolic Syndrome and Steatohepatitis in a Case of Chronic Hepatitis B

Introduction: Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used in the treatment of chronic hepatitis B virus infection (HBV). TDF is considered to have no direct hepatotoxicity. Herein we present a patient with HBV developing liver test abnormalities and biopsy-proven steatohepatitis (SH) after starting TDF, and the resolution of liver tests and SH after switching TDF to entecavir (ETV). Case Description/Methods: A 48-year-old female patient was admitted to our clinic with positive HBsAg and HBV-DNA level of 21600 copies/mL. Her Anti-HBe was positive and Anti-HDV was negative. Abdominal ultrasonography revealed 2 cm hepatomegaly; her AST was 74 U/L (5-40 U/L) and ALT 125 U/L (10-40 U/L). Her BMI was within normal limits, she had no comorbidities and was not on any medication. Her lipid panel was within the normal range. She was prescribed 245 mg/day TDF, and was scheduled for regular clinical follow-up. Six months later, her AST was 113 U/L, ALT 148 U/L, and her HBV-DNA was negative. The patient was advised to follow-up closely. Eighteen months after the initiation of TDF, her AST increased to 211 U/L and ALT to 216 U/L. Her HbA1c was 6.1% and HOMA-IR was 4.0. MRI showed fat accumulation in the liver, and a liver needle biopsy was performed. Histological evaluation revealed grade 2 steatosis with moderate ballooning degeneration and stage 3/4 fibrosis (Figure 1). Autoimmune serologies including antinuclear antibody and anti-smooth muscle antibody were negative, and ceruloplasmin phenotype was normal. The causation of TDF was hypothesized. TDF was stopped, and ETV 0.5 mg/day was initiated. Her follow-up at month 3 revealed a decreased trend in transaminase levels. The patient lost to follow-up for 2 years, but she used ETV regularly. Her control HbA1c was 5.5% at this last visit and a control abdominal ultrasonography showed no fat accumulation. Discussion: While it is known that TDF co-administration with other nucleoside analogs (e.g., didanosine, stavudine) can cause fatty infiltration of the liver, we present a rare case of metabolic syndrome and SH related with TDF monotherapy. Despite some reports suggesting tenofovir, specifically tenofovir alafenamide, might be associated with adverse metabolic changes in patients with HIV, our patient with HBV developed these changes while she was on TDF. We show that hepatic steatosis associated with TDF can be reversible with the medication change to ETV.Figure 1.: A: Hematoxylin-eosin staining shows 50% steatosis (grade 2), portal and lobular inflammation and moderate hepatocyte ballooning. B: Masson-trichrome staining shows portocentral and pericellular fibrosis (stage 3/4).

S1701 Bile Leak: A Rare Complication of Percutaneous Liver Biopsy

Introduction: Percutaneous liver biopsy is a cornerstone in diagnosing various hepatobiliary disorders. It is generally a safe procedure. Bile leak is a very rare complication, with rates less than 0.001%. Case Description/Methods: A 79-year-old woman presented to the emergency department with severe right upper quadrant abdominal pain along with nausea and vomiting after undergoing an ultrasound-guided percutaneous liver biopsy for elevated liver enzymes. On examination, right upper quadrant tenderness was appreciated. Computed tomography (CT) and Magnetic resonance imaging (MRI) of the abdomen were suggestive of blood products within the gallbladder. She underwent Endoscopic retrograde cholangiopancreatography (ERCP) for increased bilirubin (Table). On Fluoroscopy, she was found to have a bile leak at the level of the common hepatic duct (Figure). A temporary plastic biliary stent was placed into the common bile duct (CBD). Discussion: There are guidelines by the American Association for the Study of Liver and the Society of Interventional Radiology to prevent complications after percutaneous needle biopsies and liver biopsies. Utilizing ultrasound can help avoid injury to the gall bladder and large bile ducts. A biopsy of at least 2-3 cm length and 16-gauge caliber is considered sufficient. Patients should be closely observed for at least 2-4 hours after the procedure. Keeping a low threshold for prompt evaluation with appropriate imaging modalities and timely intervention can help overcome this challenge and reduce morbidity and mortality.Figure 1.: Fluoroscopy demonstrates extravasation of contrast at the level of the common hepatic duct, suggestive of bile leak Table 1. - Trend of total bilirubin through the hospital course. Notice the 50% decrease after biliary stent placement Total Bilirubin (mg/dL) 0.8 3.6 6.2 6.7 7.4 3.1 2.7 2.2 0.9

S3334 An Atypical Presentation of Propylthiouracil-Associated Fulminant Hepatitis in a Patient With Thyroid Storm

Introduction: Propylthiouracil (PTU) is an antithyroid agent used in thyrotoxicosis which is known to have hepatotoxic complications typically within weeks to months of administration. We present a case in which PTU liver injury was observed to occur within 48 hours of administration in a patient with underlying liver disease. Case Description/Methods: A 59 y.o. F with diet-controlled DM presented with palpitations and diarrhea. She was hypertensive and tachycardic in the ED; physical exam was unremarkable. Her laboratory workup was significant for TSH < 0.01 mcIU/mL with FT4 3.2 ng/dL, TSI positive at 353%. Liver function tests (LFTs) showed ALP 277, Tbili 2.4, DBili 1.5, ALT 76, and AST 98. An echocardiogram showed an EF of 35%. The patient was diagnosed with thyroid storm and started on PTU (received 800mg over 24hrs) and propranolol. On day 2, her LFTs showed ALT 450 and AST 890, and PTU was stopped. The next day, she became encephalopathic and developed acute liver failure with an INR of 4.1. General surgery was consulted for thyroidectomy. However, she was deemed unsuitable for surgery given her increased pre-operative risk. She was started on a NAC drip for DILI. Other etiologies for fulminant liver failure were ruled out including Hep A, B, and C, autoimmune hepatitis, and portal vein thrombosis. Liver biopsy showed acute steatohepatitis with necrosis, hepatocanalicular cholestasis, and periportal and pericellular fibrosis. After stopping PTU, patient’s LFTs normalized. On day 14, after potassium iodide preparation, the patient successfully underwent total thyroidectomy. Microscopic evaluation of thyroid tissue revealed multinodular hyperplasia. 6 weeks post-discharge she is asymptomatic with normal LFTs, TFTs and EF. Discussion: PTU is a thionamide used to manage hyperthyroidism. It causes DILI in approximately 1 in 10,000 people. Onset is often within 2-12 weeks of initiation. In our patient, fulminant hepatic failure developed within 48 hours of initiation. The findings of her core needle liver biopsy noted above indicated a DILI superimposed on baseline liver disease. This baseline liver disease may have been related to thyroid disease, NASH or congestive hepatopathy which may have predisposed her to an exaggerated response to PTU. Fortunately, our patient recovered and had a successful total thyroidectomy. This case illustrates that PTU-associated DILI may present atypically and with short latency. Close monitoring of LFTs and early surgical evaluation may prevent fulminant liver failure.

S3248 A Case of Drug-Induced Liver Injury Secondary to Clobenzorex Use

Introduction: Drug-induced liver injury (DILI) is a cause of both acute and chronic liver disease and is often a challenging condition for clinicians. It is a diagnosis of exclusion that requires a detailed history and workup to ensure other potential causes have been ruled out before affirming the diagnosis. There are numerous offending agents with varied presentations, often idiosyncratic in nature, with the additional challenge being a lack of specific testing or biomarkers to aid diagnosis. Case Description/Methods: We present a case of a 25-year-old male who immigrated from Mexico 4 months ago, with no reported past medical history, who presented to the emergency department for a two-day history of postprandial non-radiating right upper quadrant and epigastric pain. Associated symptoms include subjective fevers, chills, decreased appetite, nausea, one episode of blood-tinged emesis, night sweats and dyspnea. The patient worked as a driver in Mexico and was taking two different formulations of 30mg Clobenzorex, an amphetamine pro-drug, daily for two years to help him stay awake for work. These medications were available over the counter. He had not taken it since he moved to the US. He denies the use of illicit drugs, contact with any inmates or Tuberculosis patients. At the time of his presentation, he works in a wooden floor-making company. Labs revealed a markedly elevated total bilirubin of 4.4 mg/dL, INR 1.1, AST 1325 IU/L, ALT 3151 IU/L, LDH 745 IU/L and a mildly elevated ALP 220 IU/L. Acute hepatitis and autoimmune panels were not reactive. Serum acetaminophen level was also within normal limits. Ultrasound of the abdomen and MRCP noted gallbladder wall thickening but no biliary dilatation or pathology. The patient subsequently underwent a core-needle liver biopsy that displayed lobular infiltrates of inflammatory cells of predominantly lymphocytes (Figure 1). Given the absence of positive viral serology, a diagnosis of drug-induced hepatitis was concluded. Discussion: This case report documents a unique instance of drug-induced liver injury secondary to Clobenzorex use. This case highlights the importance of a detailed social history and should encourage clinicians not to neglect to ask about over-the-counter medications to help elucidate potential causes of liver injury. This is an important consideration, especially in the subset of patients from countries outside the United States who have access to a variety of OTC medications that are potentially hepatotoxic.Figure 1.: Core needle liver biopsy showing lobular infiltrates of inflammatory cells consisting of predominantly lymphocytes.