Elevated Serum Liver Enzyme Levels Research Articles

Mucinous cystic neoplasm of the liver with polypoid nodule prolapsing into the bile duct: a case report and review of literature

BackgroundMucinous cystic neoplasm of the liver (MCN-L) is a rare cystic tumor as defined by the 2010 World Health Organization classification. MCN-L usually does not communicate with or grow into the bile duct. Herein, we present a rare case of MCN-L with a polypoid nodule protruding into the bile duct.Case presentationA 69-year-old woman was referred to our hospital for elevated serum liver enzyme levels and obstructive jaundice. The patient also complained of abdominal pain in the right hypochondriac region. Abdominal ultrasonography showed a cystic lesion in segment 4 (S4) of the liver. Computed tomography revealed a 4-cm multilocular cystic lesion with a thick wall and multiple septal formations, showing a cyst-in-cyst appearance in S4. Endoscopic retrograde cholangiography showed a contrast defect between the left hepatic duct and the common bile duct, which was suspected to be a nodular lesion in the bile duct. Bile cytology and biopsy of the nodular lesion showed no malignant findings. Based on these findings, the differential diagnosis in this patient included intraductal papillary neoplasm of the bile duct and MCN-L, which had malignant potential. The patient underwent left hemihepatectomy, including caudate lobe excision with bile duct resection and right hepatocholangiojejunostomy. Macroscopic findings showed a 40 × 29 mm multilocular cystic lesion with a polypoid nodule that protruded into the left intrahepatic bile duct. As an ovarian-like stroma was observed in both cystic and polypoid lesions microscopically, the histopathological diagnosis was MCN-L. The postoperative course was uneventful, and the patient was discharged 24 days after surgery. The patient is currently alive without recurrence 22 months after the surgery.ConclusionAlthough MCN-L rarely communicates with the bile duct, it is necessary to consider that MCN-L could grow into the bile duct, occasionally causing obstructive jaundice.

Gut Commensal Fungi Protect Against Acetaminophen-Induced Hepatotoxicity by Reducing Cyp2a5 Expression in Mice.

Background and AimsDrug-induced liver injury (DILI) is a common cause of acute liver failure and represents a significant global public health problem. When discussing the gut-liver axis, although a great deal of research has focused on the role of gut microbiota in regulating the progression of DILI, the gut commensal fungal component has not yet been functionally identified.MethodsMice were pretreated with fluconazole (FC) to deplete the gut commensal fungi and were then subject to acetaminophen (APAP) gavage. In addition, transcriptome sequencing was performed to identify differentially expressed genes (DEGs) between control and fluconazole-pretreated groups of the mice challenged with APAP.ResultsGut commensal fungi ablation through fluconazole pretreatment predisposed mice to APAP-induced hepatotoxicity, characterized by elevated serum liver enzyme levels and more severe centrilobular necrosis, which appears to be caused by robust inflammation and oxidative stress. The 16S rDNA sequencing results indicated that Akkermansia muciniphila abundance had significantly decreased in gut fungi-depleted mice, whereas increased abundance of Helicobacter rodentium was observed. The gene interaction network between DEGs identified by the transcriptome sequencing highlighted a significant enrichment of Cyp2a5 in the liver of APAP-treated mice that were preadministrated with fluconazole. Pharmacological inhibition of Cyp2a5 by 8-methoxypsoralen (8-MOP) could significantly attenuate hepatic inflammation and oxidative stress in mice, thereby conferring resistance to acute liver injury caused by APAP administration.ConclusionOur data highlighted the significance of gut commensal fungi in hepatic inflammation and oxidative stress of APAP mice, shedding light on promising therapeutic strategies targeting Cyp2a5 for DILI treatment.

Macrophage activation syndrome: A fatal complication of systemic-onset juvenile idiopathic arthritis – A case report

Macrophage activation syndrome (MAS) is a life-threatening complication of systemic-onset juvenile idiopathic arthritis (sJIA) marked by the sudden onset of non-remitting high-grade fever, lymphadenopathy, hepatosplenomegaly, and profound depression in all three blood cell lines and elevated serum liver enzyme levels. Although MAS can occur in any systemic rheumatological disorder, it is most common in sJIA. In children with sJIA, the clinical picture may mimic sepsis or an exacerbation of the underlying disease. Early and aggressive immunosuppression is likely to benefit these patients. Hereby, we report a case of a 6-year-old male patient who presented with high-grade fever, joint pain, and rashes and was diagnosed as systemic-onset juvenile idiopathic arthritis with MAS.

Association of liver enzyme levels and alveolar bone loss: A cross-sectional clinical study in Sado Island.

BackgroundThe interaction of periodontopathic bacteria with host immune system induces the production of inflammatory mediators which leads to alveolar bone loss (ABL), the essential feature of periodontitis. Concurrently, periodontal diseases cause the elevation of blood cytokine levels, the alteration of gut microbiota and the dissemination of enterobacteria to the liver. Owing to these mechanisms, periodontal disease might be a risk for liver dysfunction. Several epidemiological studies have reported associations between periodontal diseases and liver dysfunction, although the association between ABL and liver dysfunction has not been investigated. This cross-sectional study determined if elevated serum liver enzyme levels were associated with ABL in Japanese adults.Material and MethodsJapanese adults living on Sado Island who visited Sado General Hospital were invited to participate in the study. Participants over 40 years of age who underwent dental panoramic radiography and blood tests were included. Drinking and smoking habits were self-administered. After excluding patients with edentulous jaw, diagnosed liver diseases, and those on dialysis, data from 44 men and 66 women with a mean age of 73 years were analyzed. The average percentage of ABL for each participant was calculated for mesial and distal sites of all remaining teeth. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were determined. Univariate analyses were performed to select covariates to be put in multivariate analyses. The association between elevated serum liver enzyme levels and the highest quartile of ABL were assessed by multiple logistic regression analysis.ResultsAfter adjusting for covariates, no significant association was found between elevated serum AST, ALT, or GGT levels as dependent variables and the highest quartile of ABL as an explanatory variable.ConclusionsThere was no significant association between the elevation of serum liver enzyme levels and ABL in Japanese adults. Key words:Liver enzymes, dental panoramic radiography, alveolar bone loss, Japanese adults.

Macrophage activation syndrome in a patient with systemic onset of the juvenile idiopathic arthritis.

Systemic onset juvenile idiopathic arthritis (sJIA) is defined as arthritis affecting one or more joint usually in the juvenile age group (< 16 years of age) with or preceded by fever of at least 2 weeks duration that is documented to be daily (“quotidian”) for at least 3 days which may be associated with evanescent (non-fixed) erythematous rash or generalized lymph node enlargement or hepatomegaly/splenomegaly/both or serositis. Macrophage activation syndrome (MAS) is a life-threatening complication of sJIA marked by sudden onset of non-remitting high fever, profound depression in all three blood cell lines (i.e. leukopenia, anemia, and thrombocytopenia), hepatosplenomegaly, lymphadenopathy, and elevated serum liver enzyme levels. In children with systemic juvenile idiopathic arthritis, the clinical picture may mimic sepsis or an exacerbation of the underlying disease.We report a case of a 16-year-old female patient presenting with high grade fever with joint pains and generalized weakness which proved to be systemic onset juvenile idiopathic arthritis with macrophage activation syndrome after ruling out all other differential diagnoses and responded well to intravenous steroids.

Candidate gene polymorphisms in patients with acetaminophen-induced acute liver failure.

Acetaminophen is a leading cause of acute liver failure (ALF). Genetic differences might predispose some individuals to develop ALF. In this exploratory study, we evaluated genotype frequency differences among patients enrolled by the ALF Study Group who had developed ALF either intentionally from a single-time-point overdose of acetaminophen (n = 78), unintentionally after chronic high doses of acetaminophen (n = 79), or from causes other than acetaminophen (n = 103). The polymorphisms evaluated included those in genes encoding putative acetaminophen-metabolizing enzymes (UGT1A1, UGT1A6, UGT1A9, UGT2B15, SULT1A1, CYP2E1, and CYP3A5) as well as CD44 and BHMT1. Individuals carrying the CYP3A5 rs776746 A allele were overrepresented among ALF patients who had intentionally overdosed with acetaminophen, with an odds ratio of 2.3 (95% confidence interval, 1.1-4.9; P = 0.034) compared with all other ALF patients. This finding is consistent with the enhanced bioactivation of acetaminophen by the CYP3A5 enzyme. Persons homozygous for the CD44 rs1467558 A allele were also overrepresented among patients who had unintentionally developed ALF from chronic acetaminophen use, with an odds ratio of 4.0 (1.0-17.2, P = 0.045) compared with all other ALF subjects. This finding confirms a prior study that found elevated serum liver enzyme levels in healthy volunteers with the CD44 rs1467558 AA genotype who had consumed high doses of acetaminophen for up to 2 weeks. However, both genetic associations were considered relatively weak, and they were not statistically significant after adjustment for multiple comparisons testing. Nevertheless, both CYP3A5 rs776746 and CD44 rs1467558 warrant further investigation as potential genomic markers of enhanced risk of acetaminophen-induced ALF.

Independent and supra-additive effects of alcohol consumption, cigarette smoking, and metabolic syndrome on the elevation of serum liver enzyme levels.

We investigated the independent and combined effects of alcohol consumption, cigarette smoking and metabolic syndrome on abnormal liver function, i.e., the elevation of serum liver enzyme levels. Participants of a Korean population-based prospective cohort aged ≥30 years without liver disease, diabetes, or cardiovascular diseases were included. Information on alcohol consumption, smoking status, and metabolic syndrome, defined as per the criteria of the Adult Treatment Panel III, were applied to evaluate their impact on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Alcohol consumption, cigarette smoking and metabolic syndrome were the significant individual factors that elevated serum liver enzyme levels. Supra-additive effects of metabolic syndrome and either alcohol consumption or cigarette smoking were also identified. The combination of heavy drinking (≥24 g/day) and metabolic syndrome conferred an effect that was higher than the sum of the two individual effects (Synergic Index (SI): AST, 2.37 [1.20–4.67]; GGT, 1.91 [1.17–3.13]). Only GGT level (odds ratio 6.04 [3.68–9.94], SI 2.33 [1.24–4.41]) was significantly elevated when the effect of moderate drinking (<24 g/day) and metabolic syndrome was combined. The combined effect of any level of alcohol consumption and cigarette smoking was also supra-additive on the elevation of GGT level with SIs of 5.57 for drinking <24 g/day and smoking ≤20 pack years, 5.12 for <24 g/day and >20 pack years, 1.80 for ≥24 g/day and ≤20 pack years, 2.03 for ≥24 g/day and >20 pack years, while only the combined effect of drinking ≥24 g/day and smoking >20 pack years elevated the AST level (SI 4.55 [3.12–6.61]). The combined effect of cigarette smoking and metabolic syndrome was not supra-additive. To prevent fatty liver disease and other related diseases, a multifactorial prevention strategy that includes limited alcohol consumption, smoking cessation and rectification of adverse metabolic profiles is required.

Systematic review and meta-analysis of the tolerability and hepatotoxicity of antifungals in empirical and definitive therapy for invasive fungal infection.

To evaluate the tolerability and liver safety profiles of the systemic antifungal agents commonly used for the treatment of invasive fungal infection, we conducted a systematic review and meta-analysis of randomized controlled trials published before 31 August 2009. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. We used the beta-binomial model to account for variation across studies and the maximum likelihood method to estimate the pooled risks. We identified 39 studies with more than 8,000 enrolled patients for planned comparisons. The incidence rates of treatment discontinuation due to adverse reactions and liver injury associated with antifungal therapy ranged widely. The pooled risks of treatment discontinuation due to adverse reactions were above 10% for amphotericin B formulations and itraconazole, whereas they were 2.5% to 3.8% for fluconazole, caspofungin, and micafungin. We found that 1.5% of the patients stopped itraconazole treatment due to hepatotoxicity. Furthermore, 19.7% of voriconazole users and 17.4% of itraconazole users had elevated serum liver enzyme levels, although they did not require treatment discontinuation, whereas 2.0% or 9.3% of fluconazole and echinocandin users had elevated serum liver enzyme levels but did not require treatment discontinuation. The results were similar when we stratified the data by empirical or definitive antifungal therapy. Possible explanations for antifungal agent-related hepatotoxicity were confounded by antifungal prescription to patients with a high risk of liver injury, the increased chance of detection of hepatotoxicity due to prolonged treatment, or the pharmacological entity.

Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis.

DNA-based HFE gene testing can confirm hereditary hemochromatosis in most people of Northern European descent. However, liver biopsy is important to detect cirrhosis. To develop noninvasive criteria to predict the presence or absence of advanced hepatic fibrosis or cirrhosis in Americans with hemochromatosis. Cross-sectional study. Six tertiary care referral clinics. 182 patients with phenotypically defined hemochromatosis. Liver histopathology and serum ferritin, aspartate aminotransferase, and alanine aminotransferase levels. Multivariate logistic regression analysis was used to examine factors associated with cirrhosis (defined as bridging fibrosis or unequivocal cirrhosis on biopsy). Cirrhosis was present in 40 of 182 (22%) patients in the overall group and in 35 of 147 (24%) of C282Y homozygotes. Only 1 of 93 patients with a serum ferritin level less than 1000 microg/L had cirrhosis compared with 39 of 89 patients with serum ferritin levels greater than 1000 microg/L (P < 0.001). No C282Y homozygotes or C282Y/H63D compound heterozygotes with serum ferritin levels less than 1000 microg/L had cirrhosis. Elevated serum aminotransferase levels (P = 0.001) and serum ferritin levels greater than 1000 microg/L (P = 0.001), but not age older than 40 years (P = 0.2), were independently associated with cirrhosis. In a multivariate model, the probability of cirrhosis was 7.4% among patients with serum ferritin levels less than 1000 microg/L compared with 72% among patients with serum ferritin levels greater than 1000 microg/L after adjustment for age and elevated serum liver enzyme levels. Patients with hemochromatosis and serum ferritin levels less than 1000 microg/L are unlikely to have cirrhosis. Liver biopsy to screen for cirrhosis may be unnecessary in such patients, regardless of age or serum liver enzyme levels.

Caspase-1-Independent, Fas/Fas Ligand–Mediated IL-18 Secretion from Macrophages Causes Acute Liver Injury in Mice

IL-18, produced as a biologically inactive precursor, is processed by caspase-1 in LPS-activated macrophages. Here, we investigated caspase-1-independent processing of IL-18 in Fas ligand (FasL)-stimulated macrophages and its involvement in liver injury. Administration of Propionibacterium acnes ( P. acnes) upregulated functional Fas expression on macrophages in an IFNγ-dependent manner, and these macrophages became competent to secrete mature IL-18 upon stimulation with FasL. This was also the case for caspase-1-deficient mice. Administration of recombinant soluble FasL (rFasL) after P. acnes priming induced comparable elevation of serum IL-18 in parallel with elevated serum liver enzyme levels. However, liver injury was not induced in IL-18-deficient mice after rFasL administration. These results indicate a caspase-1-independent pathway of IL-18 secretion from FasL-stimulated macrophages and its critical involvement in FasL-induced liver injury.

Abstracts of literature

Abstracts of literature

Ischemic liver dysfunction after elective repair of infrarenal aortic aneurysm: Incidence and outcome

Objective: To assess the frequency of early postoperative liver dysfunction in patients undergoing elective infrarenal aortic aneurysm repair, their hospital course, and outcome. Design: A retrospective case-control study. Setting: A single tertiary referral center. Participants: A review of medical records of 942 consecutive asymptomatic patients with normal preoperative liver function test results who had elective infrarenal aortic aneurysm repair with infrarenal aortic cross-clamping. The authors selected all patients who had an acute increase in serum hepatic enzyme levels (minimum fivefold increase in aspartate aminotransferase [AST] and twofold increase in lactate dehydrogenase [LDH] levels) within the first 7 perioperative days (study patients). The control group consisted of 42 patients with normal postoperative liver function test results, matched by age, sex, and year of surgery to study patients. Interventions: None. Measurements and Main Results: Aortic cross-clamping times, lowest intraoperative blood pressure, duration of hypotension (systolic blood pressure ≤95 mmHg), lowest intraoperative base deficit, and estimated blood loss were compared between control and study patients. The study also analyzed perioperative metabolic, hemostatic, hepatic, and renal function variables; the intraoperative course; postoperative complications; and inhospital outcome. Fourteen of 942 patients (1.5%) comprised a study group. In 11 patients (1.2%), AST and LDH levels moderately increased, and three patients (0.3%) developed changes consistent with a diagnosis of acute ischemic hepatitis (AIH). In all patients, the serum liver enzyme levels peaked between 24 and 72 postoperative hours. Three patients with AIH developed concomitant acute renal failure; one had associated disseminated intravascular coagulation (DIC) and died. Of 11 patients with moderate increases, one subsequently developed multisystem organ failure and died. The overall in-hospital mortality rate for patients with postoperative liver dysfunction was 14% ( 2 14 ) and for the control group it was 2.3% ( 1 42 ). The duration of hypotension and metabolic acidosis were more pronounced in patients who postoperatively developed liver dysfunction (both p < 0.001); however, study and control patients did not differ in the duration of aortic cross-clamping, lowest intraoperative blood pressure, or estimated blood loss. Conclusion: Liver enzyme levels acutely increased in 1.5% of patients after elective infrarenal aortic aneurysm repair with infrarenal cross-clamping. In patients with moderately elevated serum liver enzyme levels, postoperative recovery was relatively uncomplicated, whereas all three patients with AIH developed acute renal failure and had a more complicated postoperative course. Those with postoperative liver dysfunction had a longer duration of intraoperative hypotension and more pronounced metabolic acidosis.

Elevated liver enzymes after nontraumatic intracranial hemorrhages

Objective: To determine the prevalence and possible etiologies of liver enzyme abnormalities in patients with acquired brain injury and to assess the impact of these abnormalities on the rehabilitative process. Setting: University tertiary care rehabilitation center. Design: Retrospective study. Subjects: Fifty-six consecutive patients admitted to a brain injury unit in a 30-month period who had an intracranial hemorrhage without associated head or abdominal trauma. Main Outcome Measures: Liver function tests, Functional Independence Measure (FIM) scores, exposure to hepatotoxic drugs, antiepileptic medication serum levels, history of alcohol use, medical history, length of stay, and medical costs. Results: There was an increase (from acute hospital admission to inpatient rehabilitation admission) in gamma-glutamyltransferase (GGT) levels from 42 to 147U/L ( p = .0012). There was an increase in alkaline phosphatase from 83 to 125U/L ( p = .0079). There was a significant relationship between the GGT level on rehabilitation admission and exposure to hepatotoxic drugs, particularly phenytoin ( n = 55, p = .0007). Similar findings were noted between alkaline phosphatase and phenytoin ( n = 55, p = .0022) and systemic steroids ( n = 50, p = .0277). History of alcohol use was not predictive of changes in liver function tests ( p > .05). Correlation analysis revealed no detrimental effect of the elevated serum liver enzyme levels on the Rasch-converted FIM cognitive or motor admission or discharge scores or change in the scores while on rehabilitation ( p > .05). All radiologic testing and hepatitis profiles were negative, and 10 of the 16 patients with follow-up laboratory tests showed improvement in their serum liver enzyme levels. Conclusions: After nontraumatic brain injury there is a characteristic pattern of enzyme elevation that statistically relates to phenytoin exposure. No additional etiologic abnormalities were found on further workup, suggesting that further evaluation should be guided by the patient's clinical status, not laboratory value alone.

Effect of oestrogen/gestagen replacement therapy on liver enzymes in patients with Ullrich-Turner Syndrome

The absence of breast development and the prevention of osteoporosis in Ullrich-Turner syndrome (UTS) require oestrogen/gestagen substitution therapy. In 8 out of 35 (23%) patients with UTS treated with conjugated equine oestrogens and cyclically with norethisterone acetate, the serum liver enzymes increased to conspicuous levels (AST 35; 20-73 U/l, ALT 92; 37-141 U/l, GGT 77; 25-227 U/l, [median; min-max]). These findings were compared with those in 41 tall girls who received a six-fold larger dose of conjugated equine oestrogens for the reduction of final height. None of these 41 girls showed abnormal serum liver enzyme levels. The conspicuous rise in serum liver enzyme levels occurred in the majority of the UTS patients before norethistherone acetate was added to the oestrogen replacement therapy. No essential morphological equivalent was found in liver sonography and biopsy studies. During the follow up the elevated serum liver enzyme levels showed reversibility when medication was temporarily discontinued and either a slow decrease or a steady state after therapy was continued. CONCLUSION. Patients with UTS on oral oestrogen replacement therapy are more susceptible to develop increased serum liver enzyme levels as compared with eukaryotic females treated with the same oestrogen preparation for other disorders. As the underlying pathomechanism is unknown and adverse long-term effects cannot be ruled out, avoiding the portal vein and using the transdermal application of oestrogen may represent a viable solution to the problem.