Cholestatic Enzymes Research Articles

Liver disease in primary antibody deficiencies.

Liver disease has emerged as a major risk factor for increased mortality in patients with common variable immunodeficiency (CVID). This is mostly due to presinusoidal portal hypertension (PHTN) frequently secondary to nodular regenerative hyperplasia (NRH). Its pathogenesis is still poorly understood and treatment strategies for its various stages are often guided by trial and error. This review summarizes the most recent findings in the light of previous literature. In the last 2 years, different groups have addressed pathology, diagnostics, treatment, and liver transplantation. Histological examinations seem to support the pathogenetic sequence of T-cell mediated infiltration and damage of the sinusoidal space with secondary development of NRH, pericellular fibrosis, and the manifestation of PHTN. While markers of the early phase - beyond slight elevation of cholestatic enzymes - are still missing, elevated liver stiffness and splenomegaly above 16 cm longitudinal diameter have been suggested as warning signs for PHTN in CVID patients. Data on immunosuppressive treatment of this manifestation is still very heterogeneous, but a recent report on liver transplantation was encouraging for end stage liver disease. Liver disease deserves higher attention in the management of CVID. More studies are needed to understand its pathogenesis and optimal treatment.

Splenic spread and hepatic encephalopathy in metastatic malignant melanoma.

An older adult patient was admitted with epigastric pain and vomiting and found to have an abdominal mass, increased cholestatic liver enzymes and markedly elevated serum lactate dehydrogenase (LDH). Imaging revealed extensive liver metastases of unknown primary but also an unusual splenic metastasis diagnosed by liver biopsy as malignant melanoma. The patient became lethargic and developed mental status changes associated with asterixis, abnormal EEG, and increased serum ammonia levels. All reversed with high-dose lactulose and had no alternative explanation other than an unusual hepatic encephalopathy secondary to portosystemic shunts bypassing the extensively metastatic liver.

The new definition of dominant stricture in primary sclerosing cholangitis: Prevalence and clinical significance.

A new definition of dominant stricture (NDS) has recently been defined for patients with primary sclerosing cholangitis (PSC). Prevalence and clinical features of this, compared to traditional dominant stricture (TDS), have not been reported. In this single-centre longitudinal prospective cohort study, all PSC patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between October 2021 and 2022 were recruited. Symptoms of cholestasis, laboratory values (P-alkaline phosphatase, P-Bilirubin), Helsinki PSC-score, brush cytology findings and need for endoscopic therapy (i.e. dilation, stenting) were prospectively collected. Overall, 228 patients with PSC underwent 248 ERCPs. NDS was detected in 43 (17%; 36 patients) and TDS without NDS (TDS group) was detected in 62 (25%; 58 patients) ERCPs,respectively; in the remaining 143 ERCPs, neither TDS nor NDS was seen (no dominant stricture [NoDS] group). PSC duration (median 8 years) and patient's age did not differ between the three groups; males presented more often with NDS. Patients with NDS were more often symptomatic, had higher cholestatic liver enzymes, advanced bile duct disease and markers of biliary inflammation (p < .001). Patients with NDS needed dilation (81%) and stenting (21%) more often than the TDS group (60% and 5%, respectively). Dysplasia in brush cytology was more common in TDS (5%) and NDS (9%) than in NoDS (3%) groups (p = .04), but did not differ between TDS and NDS groups. Dominant stricture according to the new definition developed in 17% of PSC patients in our cohort and identifies patients with more advanced disease, biliary inflammation and need of endo-therapy.

Evaluation of patients with positive anti-mitochondiral antibody and normal alkaline phosphatase levels for primary biliary cholangitis.

Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease typically diagnosed by elevated cholestatic liver enzymes and a positive anti-mitochondrial antibody (AMA) test. The clinical importance of AMA positivity in patients with normal cholestatic liver enzymes is unclear. The aim of this study was to determine the relationship between PBC and AMA positivity detected in individuals with normal cholestatic enzyme levels. The files of patients with AMA and/or AMA-M2 positivity between 2009 and 2018 and whose alkaline phosphatase (ALP) levels were below upper limit of normal (ULN) at initial admission were retrospectively analyzed. The ALP levels were normal in all patients. All patients had AMA positivity demonstrated by indirect immunofluorescence (IIF) or AMA-M2 positivity demonstrated by ELISA. A total of 16 patients underwent liver biopsy and seven (43.75%) showed changes consistent with those with PBC. A total of 12 patients were diagnosed with PBC and were treated and followed up with this diagnosis. People with AMA positivity and normal cholestasis enzyme levels are closely associated with PBC. Some of these patients were diagnosed with PBC as a result of biopsy and some were diagnosed by clinical and laboratory findings during follow-up.. The patients with an AMA titration of 1/20 were not associated with PBC. In our study, results similar to the studies confirmed by biopsies were obtained. In this regard, there is a need for prospective and retrospective studies with longer follow-up periods.

#1814 Infection associated pancreatitis in peritoneal dialysis, a case report

Abstract Background and Aims Peritoneal dialysis (PD) patients seem to have a higher incidence of acute alithiasic pancreatitis. Though rare and with some suggested triggers described in the literature, this is still a poorly understood and potentially life-threatening complication. We present a 60 years old woman concluding antimicrobial therapy with an icodextrin night-dwell regimen for peritonitis presenting with epigastric pain. This work reviews our approach to cloudy effluent from non-infectious causes during an infection while managing acute pancreatitis in the PD setting. We report diagnostic difficulties and treatment considerations with a positive outcome. Method We present a 60 years old woman on PD for one year presenting to the emergency room in November of 2023 with severe epigastric pain, nausea and emesis. She suffered from stage 5 chronic kidney disease due to autosomal dominant polycystic kidney disease and had disease complications as anemia and secondary hyperthyroidism controlled within targets. She was on automated PD (APD) with glucose based solutions. She was on the 17th of 21 days antibiogram guided treatment (ceftazidime) for a Enterobacter ludwigii PD-related peritonitis with good clinical evolution and peritoneal effluent (PE) leukocyte count per μl from 1258 to 91 in 5 days. In the previous 3 months she had had 2 other infectious episodes. A bacteremic urinary tract infection to E. coli associated with peritonitis treated with antibiogram guided therapy (ceftazidime) followed by C. difficile colitis treated with oral vancomycin. During each infection period she transitioned from APD to continuous ambulatory peritoneal dialysis with an icodextrin night dwell. On admission she presented with normal vital signs, no fever, and abdominal distention with severe epigastric tenderness to palpation without muscular guarding. Her dwell exchange showed blood-tinged cloudy PE. She had hemoglobin of 11.3 g/dl, otherwise normal blood cell counts, and raised amylase (213 UI/l) and lipase (1467 UI/l). There was no elevation of transaminases, cholestatic enzymes, C-reactive protein or procalcitonin and lipidemia or hyperbilirubinemia were normal. PE cell count showed 213/μl leukocytes and 202/μl erythrocytes. Abdominal ultrasound showed no evidence of an obstructive cause. She was admitted in the surgical care unit for a conservative and watchful approach. Results On presentation we accounted for the peritonitis still under treatment, acute pancreatitis, drug therapy and recently introduced icodextrin solution. The acute alithiasic pancreatitis diagnosis was established but there was still a possible causative role of icodextrin or infection and refractory peritonitis could also not be promptly excluded. The literature suggests icodextrin and other drugs as causes for acute pancreatitis in some patients but also mentions the possibility of cloudy or hemorrhagic effluent due to abdominal inflammation processes. Considering the clinical stability, the multiple possible contributing causative agents and the differential diagnosis of refractory peritonitis we closely monitored PE cell count evolution keeping the icodextrin dwell and ceftazidime prescriptions and collected samples for bacterial and fungal culture. The cultures were negative and stability of leukocyte count and mononuclear cell predominance (Fig. 1) helped us exclude the peritonitis hypothesis and attribute the PE changes to the pancreatitis process. Conclusion Inpatient monitoring and identifying all possible causes are essential to ensure good outcomes in PD patients suffering from acute pancreatitis. Full anamnesis, physical examination and close attention to laboratory findings were key in allowing adequate antibiotic therapy and resolution of the abdominal inflammatory process at hand while maintaining an adequate PD prescription.

A294 CHOLESTASIS SECONDARY TO XANTHOGRANULOMATOUS CHOLANGITIS: A CASE REPORT

Abstract Background An 86-year-old female presented with four weeks of intermittent abdominal pain, postprandial nausea with an associated 10 lbs weight loss. Initial labs demonstrated a predominantly cholestatic liver enzyme elevation. Imaging revealed a thickened gallbladder with dilated CBD up to 15mm with no calculi, obstruction or pancreatic mass. EUS demonstrated a prominent ampulla with an area of hyperechogenicity, and ERCP was completed with sphincterotomy and biopsy of the ampulla. A cholangiogram showed a prominent common bile duct and a smooth distal taper without filling defects. Tumor markers, ampullary biopsy, and cytology of CBD brushings were negative for malignancy. Repeat ERCP for non-resolving symptoms with an extension of the sphincterotomy, brushings and insertion of a metal stent was completed without improvement in liver enzymes and a standard hepatitis workup returned negative. Her clinical course was further complicated by recurrent gram-negative bacteremia with CT findings of innumerable abscesses or metastasis in the liver. A US-guided targeted liver biopsy revealed large duct periductal tissue expansion by foamy macrophages with admixed neutrophils, eosinophils, plasma cells, and lymphocytes. These features were consistent with xanthogranulomatous cholangitis. We were planning to start ursodiol given the small duct disease however the patient succumbed to recurrent bacteremia and passed away. Aims Review of methods to attain diagnosis of xanthogranulomatous cholangitis. Methods Case Report. Results Diagnosis of xanthogranulomatous cholangitis can be attained from targetted US-guided biopsy, surgical excision, or EUS-guided CBD biopsy. Conclusions Xanthogranulomatous cholangitis is an extremely rare entity described in limited case reports, frequently mimicking neoplastic disease. Pathology is difficult to attain and historically case reports required surgical resections. One recent case reported diagnosis confirmed via EUS-guided FNA of the CBD. In our case, we attained the diagnosis through a targeted liver biopsy. Pathology of xanthogranulomatous cholangitis typically demonstrates foamy histiocytes, lipid-laden macrophages, eosinophils, lymphocytes, plasma cells, and fibrosis indicating xathogranulomas. The pathogenesis is thought to be an extension of xanthogranulomatous cholecystitis in which bile is extravasated into the gallbladder wall through Rokitansky-Aschoff sinuses or ulceration of the mucosa resulting in an inflammation caused by fibroblasts and macrophages as they phagocytose the lipids in bile, resulting in the formation of xanthoma cells. Given the rarity of the disease, there is no guideline on management and a majority of patients reported underwent surgical excision. This case demonstrates the utility of liver biopsy to establish this rare diagnosis, allowing for better detection and subsequently better-studied management. Funding Agencies None

Efficacy of a single-dose albendazole against lancet liver fluke Dicrocoelium dendriticum and liver enzymes activity in naturally infected sheep

Infections with D. dendriticum are distributed worldwide and mostly associated with ruminant livestock. Depending on the length and strength of the infection it can be manifested with losses in milk production, reductions in milk and wool quality, decreased weight gains, reproductive performance and poor carcass quality. The objective of this study was to determine the efficacy of albendazole (ABZ) against the lancet liver fluke Dicrocoelium dendriticum in naturally infected sheep using parasitological methods. Twenty-four sheep were divided into four groups: two untreated control groups (C1, C2) and two treated groups (T1, T2), with six animals in each group. The sheep in the treated groups were administered a single oral dose (15 mg/kg bwt) of ABZ suspension. After ABZ treatment the animals were slaughtered on Day 14 (groups C1, T1) and Day 30 (groups C2, T2) and were necropsied. Coprological therapeutic ABZ efficacy reached 92.4% on Day 14 (P < 0.001) and 88.5% on Day 30 (P < 0.001). On Day 30, the serum activities of hepatic and cholestatic enzymes including serological analysis of total protein concentration (TP) and protein fractions were evaluated. Significant decrease of aspartate aminotransferase (AST) (P < 0.01) and gamma-glutamyltransferase (GGT) (P < 0.05) activity by 36.9% and 34.6%, respectively, were detected for sheep in T2 group. These enzymes showed a strong positive correlation to fluke burden: AST (r = 0.654) and GGT (r = 0.768), respectively (P < 0.05). Additionally, the electrophoretic analysis of serum total protein and protein fraction concentrations revealed minimal hypoproteinemia and hyperalbuminemia after ABZ treatment. The decrease of liver enzyme activities and their correlation with fluke burden may indicate recovery of hepatocellular and biliary damage following the reduction of fluke burdens after ABZ therapy. A decline in AST and GGT activity could serve as a valuable adjunct bioindicator of liver damage and fluke reduction after treatment of dicrocoeliosis in naturally infected sheep.

Percutaneous Drainage and Alcohol-Retention Sclerotherapy for Two Adjacent Hepatic Cysts Causing Intra-Hepatic Bile Duct Dilatation

Simple hepatic cysts are usually asymptomatic and found incidentally. In most cases, no treatment is required, although various management techniques with different clinical features and advantage have been developed. As one of the nonsurgical treatments for hepatic cyst, percutaneous drainage and sclerotherapy are often applied. This study presents a case of a 67-year-old male with cholestatic liver enzyme abnormality. Two adjacent hepatic cysts were shown to be causing compression of the liver parenchyma and intra-hepatic bile duct. Ultrasonography and computed topography revealed two large hepatic cysts and intrahepatic duct dilatation. After ultrasonography-guided percutaneous drainage of one of two larger cysts, alcohol-retention sclerotherapy was performed twice on two consecutive days. At five days after the initial therapy, the larger hepatic cyst was decreased from 10 × 8.3 cm to 4.4 × 1.7 cm and the cholestatic liver enzyme abnormality was normalized.

A Rare Cause of Cholestatic Liver Enzyme Elevation From a Common Entity

A Rare Cause of Cholestatic Liver Enzyme Elevation From a Common Entity

Clinicopathological characteristics and key therapeutic options for liver involvement with vasculitis

Vasculitis, involving any levels of vessels throughout the body, has variable nonspecific clinical presentation and complicated classification, hence, the diagnose is difficult. The liver is not the major organ involved, so it is prone to overlook vasculitis-associated liver injuries. The main manifestations of vasculitis involving the liver include abnormal liver biochemistry test (mainly increase of cholestatic liver enzymes), portal hypertension, and hepatic occupying lesions. Treatment principles are primarily directed at systemic immunosuppressive therapy for vasculitis. This review summarized the classification of vasculitis, major presentations of liver involvement in vasculitis, and the principles of treatment, to improve the awareness of the rare vascular diseases.

Biochemical Markers of Liver Damage in Cattle Naturally Infected with Fasciola Hepatica

Abstract Fascioliasis is a worldwide spread parasitic disease with a high impact on the economy and public health in many countries. Therefore, it is important to apply prevention, effective treatment, and education campaigns, to prevent the disease. This work aimed to determine the biochemical markers of liver damage caused by Fasciola hepatica during 21 days (D0 – D21) post albendazole (ABZ) therapy in the blood sera. This study included 24 cows naturally infected with Fasciola hepatica, randomly divided into a control group (n = 12) and a group treated per os with ABZ (7.5 mg per kg body weight) (n = 12). The activity of hepatic enzymes – aspartate aminotransferase (AST), alanine aminotransferase (ALT) and cholestatic enzymes – gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP), were measured in both groups. The activity of AST has significantly increased in the course of the experiment (D0 – D21) in both groups (P &lt; 0.001). ALT activity during D0 – D21 was significantly decreased in both groups (P &lt; 0.001). Activity of GGT was not significantly changed in the control group in the course of the experiment (P &gt; 0.05). Contrarily, the activity of GGT in the treated group was significantly decreased (P &lt; 0.01) during D0 – D21. The activity of GGT in the blood sera of the treated group was significantly lower in comparison with the control group in D7 and D21 (P &lt; 0.01). This decreased GGT activity in the blood sera of the treated group may be caused by the effect of albendazole resulting in fasciola elimination and bile flow improvement. The results of ALP determination show no significant changes in ALP activity between groups. This can lead to the conclusion that the most useful marker of cholestasis caused by F. hepatica is the GGT activity and may help to evaluate the ABZ therapy effect in cattle.

An unusual cause of portal hypertension.

A 66-year-old male with a medical history of coronary artery disease presented with nonspecific symptoms of anorexia, lethargy and an increase in abdominal girth. He was diagnosed 3 months ago with chronic liver disease of undetermined aetiology. He did not smoke and was a social drinker till 4 months ago. He was taking tests showed progressive cholestatic liver enzymes (total bilirubin 1,09 mg/dL, AST 130 U/L, ALT 129 U/L, GGT 517 U/L and ALP 641 U/L) and a severe hypoalbuminemia. Laboratory workup made a metabolic, autoimmune, and viral aetiology of the suspected cirrhosis less probable. Urinalysis showed a rapidly progressive proteinuria in the nephrotic range accompanied by the presence of serum spike of monoclonal lambda light Furosemide, Aldactone, Pantoprazole, Acetylcysteine and Atorvastatin. He had no personal or familial history of liver diseases. Physical examination revealed a tender but distended abdomen and large ascites was present. The laboratory chain protein on electrophoresis with immunofixation. Doppler echocardiography revealed a hypertrophic cardiomyopathy based on diffuse left and right ventricular hypertrophy with relative apical sparing. A diagnostic paracentesis was undertaken and the results were consistent with portal hypertension (SAAG 1,6 g/ dL). Considering the concomitant presence of hypertrophic cardiomyopathy, nephrotic syndrome and a presentation of portal hypertension of undetermined aetiology in presence of a monoclonal IgG lambda light chain spike, a transjugular liver biopsy (figure 1 and 2) was performed with HVPG measurement consistent with significant portal hypertension (15 mmHg).

Prognostic value of right atrial strain in patients with isolated severe tricuspid regurgitation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Moderate or severe isolated Tricuspid regurgitation (TR) can lead to right ventricular (RV) dysfunction and adverse outcome. Only few patients with significant TR undergo intervention, and the optimal timing for intervention remains elusive. The right atrium (RA) is the receiving chamber of the tricuspid regurgitant volume. Changes in RA function has been described in chronic severe TR, specifically reduction in right atrial reservoir strain (RARS). The aim of this study was to evaluate the prognostic value of RA function in a cohort of patients with isolated severe TR. Materials and Methods Clinical, laboratory and echocardiographic data from 105 consecutive patients with isolated moderate-severe TR (grade≥+3) were analyzed. RARS was evaluated by two-dimensional speckle-tracking echocardiography using a semi-automated software (TOMTEC, Philips). The cohort was divided into two groups: RARS value above or below 10.9%, according to an optimal threshold obtained by a receiver operating characteristic (ROC) curve. Results and discussion A total of 105 patients (mean age 79Y, 59% female) were included. Compared with patients with higher RARS, patients with RARS≤10.9% had higher rate of atrial fibrillation and worse RV function. Lower RARS was also associated with larger inferior vena cava diameter, abnormal cholestatic liver enzymes and higher rate of diuretic use. During a median follow-up period of 19 months (IQR:8–25), 39 (37%) patients died. Patients with RARS ≤10.9% had significantly lower survival rates compared with patients with RARS&amp;gt;10.9 (60% vs. 20%; P&amp;lt;.001). A multivariable analysis (including age, RV longitudinal strain, systolic pulmonary artery pressure and atrial fibrillation) showed that lower RARS was independently associated with higher all-cause mortality (OR 2.47, 95%CI [1.07–6.06]; P=0.03). Conclusions Impaired RA function assessed by echocardiographic RA reservoir strain is independently associated with all-cause mortality in patients with isolated severe TR. Serial measurement of RARS can potentially aid in optimizing timing for intervention in patients with TR.

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Prognostic impact of cardiohepatic syndrome in patients with ST-segment elevation myocardial infarction.

Background: Cardiohepatic syndrome (CHS) indicates a bidirectional interaction between the heart and liver. This study was designed to evaluate the impact of CHS on in-hospital and long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention. Materials & methods: 1541 consecutive STEMI patientswere examined. CHS was defined as the elevation of at least two of three cholestatic liver enzymes: total bilirubin, alkaline phosphatase and gamma-glutamyl transferase. Results: CHS was present in 144 (9.34%) patients. Multivariate analyses revealed CHS as an independent predictor of in-hospital (odds ratio: 2.48; 95% CI: 1.42-4.34; p=0.001) and long-term mortality (hazard ratio: 2.4; 95% CI: 1.79-3.22; p<0.001). Conclusion: The presence of CHS is a predictor of poor prognosis in patients with STEMI and should be evaluated during the risk stratification of these patients.

Necrotizing hepatitis caused by Clostridium novyi type B in a dog with no predisposing liver lesions: a case report

BackgroundInfectious necrotic hepatitis (INH) is typically a disease of ruminants caused by Clostridium novyi type B. Growth of the causative agent is supported by development of an anaerobic environment within the liver. In dogs, C. novyi is rare and has only been previously reported as a post-mortem diagnosis. In one case, infection was secondary to metastatic pancreatic adenocarcinoma and the other was presumptively diagnosed on histopathology of a hepatic lesion in a dog initially presented for acute collapse.Case presentationAn 8-year-old spayed, female mixed breed dog was presented for acute onset of hyporexia and vomiting. Serum biochemistry revealed elevated hepatocellular injury and cholestatic liver enzymes. Ultrasound revealed peritoneal fluid accumulation and multiple hepatic masses. Cytologic examination of liver aspirates and peritoneal fluid revealed frequent 4 × 1 μm bacilli with a terminal endospore. Anaerobic bacterial growth isolated from the fluid sample could not be identified using typical laboratory identification techniques. Long-read, whole genome sequencing was performed, and the organism was identified as Clostridium novyi type B. Antimicrobial and hepatic support treatment were initiated. The patient re-presented 27 days later, and the follow up liver aspirate with cytology revealed no appreciable bacteria and anaerobic culture was negative. The patient was presented four months later and a large hepatic mass and peritoneal fluid were again identified on abdominal ultrasound. Cytologic examination of the peritoneal fluid revealed bacilli similar to those identified on initial presentation. The patient was euthanized. The most significant finding on necropsy was necrotizing hepatitis with intralesional endospore-forming bacilli compatible with recurrence of Clostridium novyi type B. There was no identifiable cause of an anaerobic insult to the liver.ConclusionsThis case demonstrates the diagnostic utility of using cytology as part of the initial diagnostic work up for infectious hepatitis. The cytologic findings coupled with whole genome sequencing and anaerobic culture were crucial for the identification and classification of the organism identified on fine needle aspirate. Clostridium novyi type B should be considered when bacilli organisms containing a terminal endospore are identified on liver aspirates collected from canine patients.

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT Study)

Abstract Background Liver dysfunction contributes to worse clinical outcome in heart failure (HF) patients, and cholestatic enzymes are associated with mortality in the setting of chronic HF (CHF). However, the temporal evolutions of liver function parameters in stable CHF patients, and their associations with clinical outcome, have not yet been investigated. Purpose We aimed to investigate in detail the temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB), and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction (HFrEF). Methods During 2.2 (1.4–2.5) years of follow-up, we collected 1984 tri-monthly plasma samples in 263 patients. We selected 749 samples in the 250 HFrEF patients included in the study - all baseline samples, the last two samples before censoring in event-free patients, and the last two samples preceding the primary endpoint (PEP; composite of cardiac death, heart transplantation, LVAD implantation, and hospitalization for the management of acute or worsened HF). In these samples ALP, GGTP, and ALB were measured using colorimetric assays, TBIL using diazomethod, all by Roche/Hitachi Cobas c analyser. The relationship between repeatedly measured biomarker levels and the PEP was evaluated by joint models. Results Mean age was 68±18 years; 74% were men, 25% in NYHA class III or IV. 66 patients (26%) reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP and ALB were associated with the PEP in a model adjusted for NT-proBNP and hs-TnT (hazard ratio (HR) [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p=0.002; 1.84 [1.09; 3.05], p=0.018, 1.33 [1.08; 1.63], p=0.006 and 1.14 [1.09; 1.20], p&amp;lt;0.001, respectively). Serially measured ALP and GGTP remained significantly associated with the PEP after adjustment for clinical covariates (HR [95% CI]: 1.13 [1.07; 1.19], p=0.018; 1.03 [1.01; 1.06], p=0.006, respectively). The levels of ALP and GGTP were higher in patients who experienced the PEP than in event-free patients long before the PEP occurred (&amp;gt;2 years), and as the PEP approached, levels diverged slightly between those with and without the PEP (Figure 1). Conversely, levels of ALB were higher in those with subsequent PEP, &amp;gt;2 years before the PEP, and subsequently fell; while TBIL levels rose less than 1 year before the PEP in those with subsequent PEP. The slopes of the temporal evolution of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP (HR [95% CI] per 20% decrease in the slope for albumin and increase in the slope of TBIL per year: 1.61 [1.43; 1.84], p&amp;lt;0.001 and 1.72 [1.28; 2.55], p&amp;lt;0.001, respectively). Conclusions Changes in serum levels of TBIL, ALP, GGTP and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in HFrEF patients in clinical practice. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Jaap Schouten Foundation (Rotterdam, the Netherlands)Noordwest Academie (Alkmaar, the Netherlands)

S2974 Common Variable Immune Deficiency With Atypical Hepatic Disease

Introduction: Common variable immunodeficiency (CVID) is a primary B-cell immunodeficiency disorder leading to hypogammaglobulinemia. Liver involvement may rely on immune dysregulation and includes abnormal liver biochemistries, primarily elevation of alkaline phosphatase (ALP), nodular regenerative hyperplasia (NRH) leading to chronic cholestasis, portal hypertension, and disruption of liver function. We present a case of CVID with atypical liver involvement on imaging and biopsy revealing focal nodular hyperplasia. Case Description/Methods: A 24-year-old female with a past medical history of CVID on Intravenous immunoglobulin (IVIG) present for follow-up with chronically elevated liver enzymes that is a cholestatic pattern (ALP 1050 U/L, AST 114 U/L, ALT 214 U/L, Total bilirubin 1.0 mg/dL) along with normal synthetic liver function. Previous comprehensive work up including autoimmune (Antinuclear, Anti-smooth muscle, anti-mitochondrial antibodies) were negative. Viral hepatitis including Hepatitis B, Hepatitis C, Herpes simplex, Varicella zoster, and Epstein Barr viruses polymerase chain reaction were all negative. other causes of elevated liver enzymes including genetic and metabolic work up all came back negative. The medications list included Ursodiol and Multivitamins. She reports no alcohol, recreational or herbal drugs use. She underwent liver protocol magnetic resonance imaging and magnetic resonance cholangiopancreatography that showed no biliary tree abnormalities, Innumerable hepatic lesions with characteristics suggestive of multiple focal nodular hyperplasias largest measures up to 3.8 cm, two benign hepatic hemangiomas with the larger measuring 1.9 cm and splenomegaly. Ultrasound-guided biopsy of the left hepatic lobe showed concern for focal nodular hyperplasia (confirmed by an outside pathologist at another liver transplant center) with unremarkable trichrome and PAS stains (Figure). Discussion: At least 10% of CVID patients present with liver involvement, including anicteric cholestatic liver enzymes (65%) and portal hypertension (50%). Histological analysis in recent studies revealed non-fibrosing architectural abnormalities consistent with nodular regenerative hyperplasia in 84% of CVID and less commonly, typical histologic features of primary biliary cholangitis. Our case liver imaging and biopsy read by 2 pathologists (2 institutions) revealed focal nodular hyperplasia, a new entity not described in previous studies.Figure 1.: Liver protocol MRI showing focal nodular hyperplasia.

Acute hepatitis and liver injury in hospitalized patients with COVID‑19 infection.

Coronavirus disease 2019 (COVID-19) is a systemic illness with an increased host inflammatory response that affects multiple extra-pulmonary organs, including the gastrointestinal tract. Abnormalities in liver biochemistry have been observed in a significant proportion of patients with COVID-19 upon admission, and this proportion increases with hospitalization. These abnormalities are typically manifested as elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, with less frequently detected elevations in the levels of cholestatic enzymes. Elevated aminotransaminase levels have been linked to an increased risk of mortality and complications, indicating the severity of COVID-19 infection. The present study evaluated the prevalence and the baseline factors associated with the development of acute hepatitis (ΑΗ), liver injury (LI) and associated patterns, as well as the presence of abnormalities in the levels of aminotransferases at discharge in the same cohort. For this purpose, 1,304 patients with confirmed COVID-19 infection were enrolled in the study. According to the results obtained, AST levels at baseline were the only independent factor for AH during hospital stay, while AST, alkaline phosphatase and ferritin levels were independent baseline factors for the development of LI. The patients with hepatocellular, compared to those with cholestatic LI, exhibited similar survival rates, as well as similarities in the development of acute kidney injury and the need for oxygen via high-flow nasal cannula and/or mechanical ventilation. In addition, age and ALT were independent risk factors for persistent abnormal values of AST and ALT at discharge.

Hepatosplenic T-Cell Lymphoma Mimicking Acute Onset of Cholestatic Hepatitis in a Young Immunocompetent Man: A Case Report

We herein report a case of hepatosplenic T-cell lymphoma (HSTCL) incidentally found in a 30-year-old man who came to the emergency department after an ankle trauma. At admission, laboratory tests revealed abnormal liver enzymes and pancytopenia, and imaging showed mild hepatosplenomegaly. During hospitalization, the patient’s clinical condition worsened rapidly, with a concomitant increase in cholestatic enzymes, severe jaundice, and the worsening of pancytopenia. Causes of liver injury, including many infectious diseases, were explored until the diagnosis of HSTCL was made by liver and bone marrow biopsies. Subsequently, the patient underwent six cycles of chemotherapy with a CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone or prednisolone) regimen and one with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) but, despite this aggressive treatment, died due to disease progression 2 months after diagnosis. This rare disease should be considered in the diagnostic workup of acute cholestatic hepatitis presenting with concomitant hepatosplenomegaly and cytopenia.