Cholestatic Enzymes Research Articles

Hepatic Enzyme Profile in Horses.

Simple SummaryThis review aims to highlight the importance of using enzyme profiles for the diagnosis of common liver disorders in the horse. This review also highlights the limitations and alternative explanations for isolated or collective abnormalities of the different liver enzymes. This review also provides information on the screening test(s) of choice, their interpretation, and the results to confirm the diagnosis. Similarly, documented liver cases in the equine clinic are reviewed, with emphasis on abnormal enzyme activity.For diagnostic purposes, liver enzymes are usually classified into hepatocellular and cholestatic. These two groups of equine liver-specific enzymes include sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), γ-glutamyl transferase (GGT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP). SDH and GLDH mostly reflect hepatocellular injury and cholestasis, while GGT expresses high values in biliary necrosis or hyperplasia. Likewise, AST, LDH, and ALP also reflect hepatocellular and biliary disease, but these enzymes are not liver specific. From the clinical point of view of the course of liver or biliary disease, AST and ALP are indicative of chronic disease, whereas SDH, GGT, and GLDH indicate an acute course. The patterns of enzymatic changes at the blood level are associated with different types of liver pathologies (infectious, inflammatory, metabolic, toxic, etc.). Increases in hepatocellular versus biliary enzyme activities are indicative of a particular process. There are different ways to diagnose alterations at the hepatic level. These include the evaluation of abnormalities in the predominant pattern of hepatocellular versus cholestatic enzyme abnormalities, the mild, moderate, or marked (5–10-fold or >10-fold) increase in enzyme abnormality concerning the upper limit of the reference range, the evolution over time (increase or decrease) and the course of the abnormality (acute or chronic).

Panpancreatic Infiltration and Painless Jaundice in HIV/AIDS

A 41-year-old man with a history of poorly controlled HIV/AIDS and persistent Kaposi sarcoma (KS) despite paclitaxel treatment was admitted with jaundice. Laboratory studies revealed cholestatic liver enzymes with CA19-9 elevation. Positron emission tomography/computed tomography scan showed diffuse enhancement of the pancreas (Figure A). Endoscopic ultrasound demonstrated a panpancreatic infiltration with marked vascularity on Doppler analysis (Figure B) and biliary obstruction. Histopathology of endoscopic ultrasound–guided aspiration was diagnostic of panpancreatic KS revealing spindle/epithelioid cells separated by slitlike vascular spaces (Figure C) staining positive for CD31 and human herpesvirus-8.

Cardiohepatic Syndrome Is Associated With Poor Prognosis in Patients Undergoing Tricuspid Transcatheter Edge-to-Edge Valve Repair.

The aim of this study was to evaluate the prevalence and prognostic implications of cardiohepatic syndrome (CHS) in patients with tricuspid regurgitation (TR) treated with tricuspid transcatheter edge-to-edge valve repair (T-TEER). The role of CHS in patients undergoing T-TEER for severe TR has not been studied. This study included patients who underwent T-TEER for TR between 2016 and 2020 at 2 high-volume academic centers. CHS was defined as elevation of at least 2 of 3 cholestatic hepatic enzymes. The impact of CHS on 1-year all-cause mortality and clinical outcomes after T-TEER was investigated. T-TEER reduced TR severity to≤2+ in 257 of 305 included patients (86.2%). CHS was present in 45.2% of patients and was associated with a higher rate of mortality and of first hospitalization for heart failure (HHF) (CHS vs no CHS: estimated 1-year mortality, 34.0% vs 15.9% [P< 0.01]; HHF, 23.0% vs 12.2% [P=0.01]). CHS was identified as an independent predictor of 1-year all-cause mortality (HR: 1.86; 95% CI: 1.10-3.14; P< 0.05). Irrespective of CHS, T-TEER improved New York Heart Association functional class and 6-minute walk distance in the majority of patients. Inpatients with impaired baseline hepatic function, laboratory liver parameters improved after T-TEER. CHS is a strong predictor of mortality and HHF after T-TEER and should be evaluated in the process of procedural decision making for T-TEER. Nevertheless, T-TEER is associated with relevant symptomatic alleviation irrespective of CHS.

Defining the Patterns of Liver Enzyme Derangement in Acute Cholangitis - Is It Enough to Be "Cholestatic"?

Intrdouction: Diagnosis of acute cholangitis using Tokyo Guidelines 2018 (TG18) requires evidence of cholestasis. This is defined as hyperbilirubinemia or any liver enzyme derangement above 1.5 times the upper limit of normal - a rather broad inclusion criteria given that a cholestatic enzyme pattern is considered typical of biliary obstruction. The ratio of ALT and ALP elevation (R-value) characterizes cholestatic, hepatocellular, and mixed liver enzyme derangements. The pattern of liver enzyme derangement in acute cholangitis has not previously been defined.

The impact of late liver allograft dysfunction on physical activity of liver transplant recipients

Introduction. Liver transplantation restores patients' physical and social life, and its quality. The prevalence of low physical activity in liver recipients is unknown as well as the impact of late liver allograft dysfunction on it. Liver transplantation enhances patient's return to the usual physical and social activity and improves the quality of life. However, the prevalence of low physical activity among liver recipients and the impact of the late allograft dysfunction on it, which is a risk factor for obesity and cardiovascular diseases, require studying.The aim of the study was to identify whether the late liver allograft dysfunction influences the physical activity of recipients.Material and methods. The study included 87 liver recipients. We measured anthropometric parameters, physical performance (SPPB, LFI, 6-min walk test), mean step count per day. Late liver allograft dysfunction was determined if elevated transaminases and/or cholestatic enzymes or hepatic failure have been diagnosed later than 3 months posttransplant. Activity trackers were provided to assess physical activity.Results. Median age was 54 years [45;61], 33% were men. The median follow-up period was 36 months [16;64]. The median of the average steps count was 5.9 [4.1;8.7] thousand per day. 60.5% of recipients were sedentary and low active, 24.4% were somewhat active, 15.1% were active. In cases of liver allograft dysfunction, the mean step count was significantly lower than in patients with normal liver function: 4.1 thousand [2.6;5.3] versus 6.8 thousand [4.2;9.4], p=0.003, despite no differences in the physical activity test results.Conclusion. In case of a late liver allograft dysfunction, the physical activity can decrease; 60.5% of liver recipients, in the absence of pathological restriction of movement, have a sedentary and low active lifestyle. Activity trackers may allow identifying patients who need additional check-up or physical training.

Liver injury associated with acute respiratory distress syndrome and the prospects of mesenchymal stem cells therapy for liver failure

The pathogenesis of acute respiratory distress syndrome (ARDS) includes neutrophilic alveolitis, alteration of alveolar epithelium and endothelium, formation of hyaline membranes and microvascular thrombosis, which results in an acute hypoxemic respiratory failure. ARDS results in major structural and cellular changes in organs and organ systems. It causes liver dysfunction in critical patients through paracrine action of cytokines and other pro-inflammatory mediators as well as hypoxemia, oxidative stress, toxins and hypoperfusion. Coronavirus disease 2019 (COVID-19)-associated ARDS affects liver through the development of systemic inflammatory response syndrome and hypoxia as well as cytokine storm. Liver injury manifests itself as increased plasma levels of hepatic transaminases and cholestatic liver enzymes. Stem cell therapy is one of the promising modern methods for treating ARDS-induced liver failure. Many studies showed the ability of multipotent mesenchymal stem cells (MMSCs) to differentiate into functional hepatocyte-like cells, which were then successfully used for liver regeneration. MMSCs were proven to be able to prevent the apoptosis of hepatocytes, as well as have anti-fibrotic and anti-inflammatory activity which allows their successful use in the treatment of ARDS-induced liver injury.

Liver dysfunction in idiopathic pulmonary arterial hypertension: prevalence, characteristics and prognostic significance, a retrospective cohort study in China

ObjectivesThe aim was to elucidate the relationship between liver function and idiopathic pulmonary arterial hypertension (IPAH).Design and settingRetrospective, longitudinal study in urban tertiary care centre in Shanghai, China.Participants407 IPAH consecutive...

Acute pancreatitis and low ascites-serum albumin gradient ascites caused by Brucellosis

Objective: Brucellosis is a zoonotic disease seen widely around the world. Although many aspects and treatment of this disease is well known, peritoneal involvement and ascites is not well established so far.&#x0D; Material and Methods: This study retrospectively enrolled 346 adult patients (aged &gt;17 years) with acute Brucellosis attending Hepatology Clinic, Van Yuzuncu Yil University, between April 2013 and May 2016. Characteristics of those with and without ascites were analyzed using Pearson correlation coefficients and Chi-Square test in SPSS software system.&#x0D; Results: Of the 346 cases, 20 (5, 7%) had ascites. Those with ascites had significantly higher transaminase, cholestatic enzyme and amylase levels compared to those without ascites.&#x0D; Conclusions: We conclude that acute Brucella infection can lead to a unique low gradient ascites probably resulting from pancreatic leakage followed by peritoneal accumulation of serum proteins.

Pauci-symptomatic widespread nodal extra-pulmonary tuberculosis in end-stage kidney disease.

An elderly Ethiopian-born patients developed end-stage kidney disease and haemodialysis was started. Shortly after, she developed some weight loss, lassitude, and diffuse body pain attributed to the ESKD, but also brief febrile episodes with non-contributory examination and work-up except for acute-phase response and mild cholestatic liver enzyme disturbance. Imaging revealed enlarged necrotic lymph nodes above and below the diaphragm. Needle biopsy was consistent with mycobacterium tuberculosis (TB) infection by pathology, PCR, and culture. TB is endemic in Africa and our patient had latent TB with reactivation due to her advanced age and especially, ESKD. The relatively subtle symptoms easily ascribed to ESKD are notable, as is the value of imaging, tissue diagnosis and PCR in establishing her widespread nodal extra-pulmonary tuberculosis. Current guidelines support screening foreign-born individuals who have recently immigrated. We suggest that when risk factors accumulate as in our patient (e.g. origin in an endemic area, ageing, hemodialysis), a routine interferon gamma release assay test is prudent, and positive patients may well benefit from chemoprophylaxis.

Autoimmune liver disease-associated serologic profiling in Chinese patients with acute hepatitis E virus infection

The association between hepatitis E virus (HEV) and autoimmune liver diseases has been well-researched; however, the focus has been on autoimmune hepatitis (AIH) and not primary biliary cholangitis (PBC). Therefore, we aimed to investigate the prevalence and evolution of AIH- and PBC-related autoantibodies in Chinese patients with HEV infection. In this retrospective study, 164 patients with acute HEV were included, specifically those whose liver autoantibody results were available and who had no pre-existing liver disease at the time of HEV diagnosis. Positive liver autoimmune serology was present in 69 (42.1%) patients and 21 (12.8%) had at least two autoantibodies at diagnosis. Greater age and alkaline phosphatase levels were independent risk factors for autoantibody positivity. Follow-up serologic tests, which were available for 27 of the 69 autoantibody-positive patients, showed that although antinuclear antibodies disappeared in 11/20 (55.0%) and antimitochondrial antibodies disappeared in 4/5 (80%) patients, 16 still remained positive for autoantibodies and two of them even developed new PBC-related antibodies, as described below. One patient developed a rim-like ANA pattern, accompanied by an enhancement of anti-gp210 positivity; and the other was diagnosed as PBC, based on chronic elevation of cholestatic enzymes and presentation with de novo AMA-M2, 18 months after HEV clearance. In conclusion, AIH- and PBC-related autoantibodies are frequently present during acute HEV infection, indicating that HEV should be excluded before diagnosing AIH and/or PBC. Importantly, some cases maintained or developed autoantibodies after viral clearance, and one patient subsequently developed PBC, highlighting that these individuals warrant long-term follow-up.

Syphilitic hepatitis; a rare manifestation of a common disease.

Syphilis is a sexual transmitted disease caused by Treponema pallidum and an underdiagnosed and underreported cause of acute hepatitis. In recent years, reported cases of primary and secondary syphilis have been increasing, mostly in men who have sex with men. Clinical manifestations of syphilis are diverse, earning the name of "the great imitator" which can affect virtually any organ. Nonetheless, hepatic involvement is rare, but it can occur at any stage of the disease. We present the case of a 41-year-old immunocompetent male, that presents to us with a cholestatic hepatitis and a diffuse erythematous rash with palmo-plantar affection. The patient had no history of primary syphilis. After throughout aetiologic study, he was diagnosed with syphilitic hepatitis and treated with intramuscular Benzathine benzylpenicillin, with the disappearance of the rash and normalization of liver enzymes after 3 months. We would like to highlight that this aetiology should be considered in patients with unexplained elevation of liver enzymes (mainly cholestatic enzymes) and an epidemiologic context of unsafe sexual exposure.

Takayasu arteritis and primary sclerosing cholangitis: A casual association or different phenotypes of the same disease?

Takayasu arteritis and primary sclerosing cholangitis are two rare disorders. The pathogenesis of Takayasu arteritis involves immune-mediated mechanisms, and corticosteroids represent the mainstay for treatment. Conversely, the aetiology of primary sclerosing cholangitis remains elusive, even if dysimmunity seems to be one of the contributors to bile duct damage. Despite this, immunosuppressants do not alter disease course. In this paper we describe the association of these two rare disorders, with an unexpected normalization of cholestatic enzymes following steroid treatment. This might hint a novel subtype of sclerosing cholangitis with a prevalent immunebackground, or a local manifestation of Takayasu arteritis.

Chronic cholangitis: Differential diagnosis and role of MRI

The idiopathic chronic cholangitides comprise a group of hepatobiliary diseases of probable autoimmune origin that are usually asymptomatic in the initial stages and can lead to cirrhosis of the liver. Elevated cholestatic enzymes on blood tests raise suspicion of these entities. Among the idiopathic cholangitides, the most common is primary sclerosing cholangitis, which is associated with inflammatory bowel disease and with an increased incidence of hepatobiliary and digestive tract tumours. It is important to establish the differential diagnosis with IgG4-associated cholangitis, primary biliary cholangitis, and secondary cholangitides, because the therapeutic management is different. Magnetic resonance cholangiopancreatography (MRCP) is the best test to evaluate the intrahepatic and extrahepatic biliary tract, and MRI also provides information about the liver and other abdominal organs. An appropriate MRCP protocol and knowledge of the different findings that are characteristic of each entity are essential to reach the correct diagnosis.

Colangitis crónicas: diagnóstico diferencial y papel de la resonancia magnética

The idiopathic chronic cholangitides comprise a group of hepatobiliary diseases of probable autoimmune origin that are usually asymptomatic in the initial stages and can lead to cirrhosis of the liver. Elevated cholestatic enzymes on blood tests raise suspicion of these entities. Among the idiopathic cholangitides, the most common is primary sclerosing cholangitis, which is associated with inflammatory bowel disease and with an increased incidence of hepatobiliary and digestive tract tumors. It is important to establish the differential diagnosis with IgG4-associated cholangitis, primary biliary cholangitis, and secondary cholangitides, because the therapeutic management is different. Magnetic resonance cholangiopancreatography (MRCP) is the best test to evaluate the intrahepatic and extrahepatic biliary tract, and MRI also provides information about the liver and other abdominal organs. An appropriate MRCP protocol and knowledge of the different findings that are characteristic of each entity are essential to reach the correct diagnosis.

Liver involvement in rheumatic diseases.

Liver involvement in rheumatic diseases may occur as a primary liver disease, primary rheumatic disease with hepatic manifestations or antirheumatic drug-induced liver disease. The aim of our article is to underline the importance of monitoring and control of the level of aminotransferases and cholestatic enzymes in rheumatic disorders. Some of the rheumatic diseases with constantly elevated liver enzymes need to be investigated in consideration of concomitant primary autoimmune liver disease (such as autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis) or drug hepatotoxicity. Also, we should be aware of hepatitis B reactivation or hepatitis C flare when immunosuppressants are used.

Prevalence of antimitochondrial antibodies in subacute cutaneous lupus erythematosus.

In approximately 13% of systemic lupus erythematosus (SLE) patients, a hallmark of primary biliary cirrhosis (PBC) can be detected: antimitochondrial M2 antibodies (AMA-M2). It has not been determined if the presence of AMA-M2 in SLE patients results in a higher risk of PBC in comparison to those with AMA but no SLE. Until now, there have been no such analyses among individuals with subacute cutaneous lupus erythematosus (SCLE). To assess the seropositivity rates for AMA-M2 and autoantibodies associated with autoimmune hepatitis in patients with newly diagnosed SCLE and to determine the coexistence and risk of development of autoimmune liver disease in these patients within 1year of follow-up, data from 33 patients with newly diagnosed SCLE were analyzed. AMA-M2 was found in 20% of SCLE patients. Patients from the AMA-M2-positive group were characterized by significantly higher levels of cholestatic liver enzymes when compared to those without AMA-M2 (P<0.05). After introducing therapy with hydroxychloroquine and prednisone, the levels of hepatocellular enzymes increased significantly only in AMA-M2 positive patients (P<0.05). A high prevalence of AMA-M2 was found in patients with SCLE. Patients with SCLE and AMA-M2 had significantly higher values of cholestatic enzymes than patients without AMA. Newly diagnosed patients with SCLE should be screened for the presence of AMA and should be clinically followed up. Avoiding drugs with potential liver toxicity should be recommended in patients with SCLE and AMA.

Risk of Renal Function Decline in Patients with Ketamine-Associated Uropathy.

Ketamine-associated diseases have been increasing with the rise in ketamine abuse. Ketamine-associated uropathy is one of the most common complications. We investigated the effects of ketamine-associated uropathy on renal health and determined predictors of renal function decline in chronic ketamine abusers. This retrospective cohort study analyzed 51 patients (22 with ketamine-associated hydronephrosis and 29 with ketamine cystitis) from Kaohsiung Veterans General Hospital in Taiwan. Primary renal outcome was end-stage renal disease or estimated glomerular filtration rate decline >30% from baseline. Compared with the ketamine cystitis group, the hydronephrosis group had lower initial and final estimated glomerular filtration rates and higher alkaline phosphatase and gamma-glutamyl transferase levels (p < 0.05). Elevated cholestatic liver enzyme levels correlated with renal dysfunction in ketamine-associated uropathy. The hydronephrosis group had a higher proportion of patients reaching endpoints than the ketamine cystitis group (50% and 7%, respectively, p < 0.001). After adjusting for age, sex, and initial serum creatinine level, hydronephrosis remained an independent risk factor for renal function deterioration. Ketamine-associated hydronephrosis was a poor renal outcome and strong predictor of renal function decline in chronic ketamine abusers. Elevated cholestatic liver enzyme levels correlated with the severity of ketamine-associated uropathy. Ultrasonography screening of these high-risk groups and regular renal function follow-ups are necessary.

Hepatic involvement by T-cell neoplasms: a clinicopathologic study of 40 cases

Hepatic involvement by a T-cell neoplasm is rare and often challenging to diagnose in liver biopsies. We collected 40 cases of T-cell neoplasms diagnosed in the liver from five large academic institutions to assess the clinicopathologic features. The patients included 11 women and 29 men, with a median age of 54 (range: 2-75) years and a high mortality rate (31/37, 83.8%). Fourteen (35%) patients were diagnosed with hepatosplenic T-cell lymphoma (HSTCL), 13 (32.5%) peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and 13 (32.5%) other types of T-cell neoplasms. Patients with HSTCL were much younger and had worse survival than PTCL-NOS and other T-cell neoplasms (P<0.05). On imaging studies, 20 cases (50%) showed abnormalities, including 10 with mass lesions that correlated with normal or cholestatic pattern enzyme elevation. Histomorphological analysis revealed four main patterns; with the exception of mass forming lesions (pattern 4; n=8), cases with sinusoidal predominant (pattern 1; n=12), portal predominant with sinusoidal infiltrates (pattern 2; n=13) or lobular aggregates (pattern 3; n=5) demonstrated small to medium lymphocytes resembling a reactive/inflammatory process. In addition, we described two cases of T-cell large granular lymphocytic leukemia that mimicked HSTCL, and a case of aggressive post-transplant lymphoproliferative disorder that developed after chronic Epstein-barr virus (EBV) infection, suggesting the importance of EBV testing in some lymphoma cases. As the largest cohort of T-cell neoplasms in liver, our study provides critical data on disease frequency, distribution, and clinicopathologic features that are essential for accurate diagnosis.

The effect of liver test abnormalities on the prognosis of COVID-19

IntroductionCOVID-19 caused by the SARS-CoV-2 continues to spread rapidly across the world. In our study, we aim to investigate the relationship between the liver enzymes on admission (AST, ALT, ALP, GGT) and severity of COVID-19. We evaluated course of disease, hospital stay, liver damage and mortality. Materials and methodsOur study included 614 patients who were hospitalized with the diagnosis of COVID-19 between 03.16.20 and 05.12.20. Patients with liver disease, hematological and solid organ malignancy with liver metastases were excluded, resulting in 554 patients who met our inclusion criteria. We retrospectively evaluated liver transaminase levels, AST/ALT ratio, cholestatic enzyme levels and R ratio during hospital admission and these were compared in terms of morbidity, mortality and clinical course. ResultsMean age of 554 subjects were 66.21±15.45 years, 328 (59.2%) were men. The mean values of liver enzymes on admission were AST (36.2±33.6U/L), ALT (34.01±49.34U/L), ALP (78.8±46.86U/L), GGT (46.25±60.05U/L). Mortality rate and need for intensive care unit were statistically significant in subjects that had high ALT–AST levels during their admission to the hospital (p=0.001). According to the ROC analysis AST/ALT ratio was a good marker of mortality risk (AUC=0.713: p=0.001) and expected probability of intensive care unit admission (AUC=0.636: p=0.001). R ratio, which was used to evaluate prognosis, showed a poor prognosis rate of 26.5% in the cholestatic injury group, 36.1% in the mixed pattern group and 30% in the hepato-cellular injury group (p 0.001). ConclusionsALT–AST elevation and AST/ALT ratio >1 was associated with more severe course and increased mortality in COVID-19.

Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients.

Background Systemic sclerosis (SSc) and primary biliary cholangitis (PBC) are autoimmune diseases that may occur concomitantly and are both strongly associated with disease-specific autoantibodies. This study investigated the prevalence and fine specificity of PBC-specific serology (PBC-Ab) and associations with the SSc-subtypes and SSc-specific antibodies as well as the association with cholestatic liver enzymes. Furthermore, three different techniques for the detection of PBC-Ab were compared. Methods Serum of 184 Belgian SSc patients with a known SSc-antibody profile, was analyzed for PBC-Ab (antimitochondrial antibodies [AMA], anti-Gp210, anti-Sp100 and anti-PML) using indirect immunofluorescence (IIF) analysis on human epithelioma-2000 (HEp-2000) cells (ANA-IIF, Immunoconcepts) and liver-kidney-stomach tissue sections (IIF-LKS) (Menarini), and a line immunoblot (LB) (EuroImmun). Alkaline phosphatase/γ-glutamyl transferase (ALP/GGT) were evaluated at time of first sampling (t0) and after 3 years of follow-up (t3). Results PBC-Ab were present in 13% of patients and significantly correlated with centromere antibodies (anti-CENP-B), but not correlated with the limited cutaneous SSc subgroup (lcSSc). The most frequent reactivities were AMA (11%, with 9% AMA-M2) and Sp-100 antibodies (5%), showing a major overlap. There was no relevant association between the presence of PBC-Ab and ALP or GGT elevation at t0 nor at t3. Detection of AMA with IIF-LKS is comparable to LB. ANA-IIF screening was less sensitive compared to LB. Conclusions A wide range of PBC-Ab is detectable in SSc in the absence of cholestatic liver enzyme elevations, even after 3 years of follow-up. However, as these antibodies may precede PBC-disease up to 10 years further prospective follow-up of our cohort will be necessary.