Abnormal Liver Enzyme Tests Research Articles

S2394 The Truth Behind the Transaminitis

INTRODUCTION: Abnormal liver enzyme tests are a common finding in the clinical setting but the differential is broad and requires critical thinking. Often, the etiology is unclear in medically complex patients as the cause may be multifactorial. Sarcoidosis is a systemic autoimmune condition and many clinicians are familiar with its pulmonary involvement but about 30% of affected patients have extrapulmonary manifestations. Clinically significant gastrointestinal disease occurs in less than 1% of sarcoidosis patients but the liver can be involved in up to 65% of affected individuals. Accurate assessment and diagnosis can be difficult and requires one to always be open to a broad differential. CASE DESCRIPTION/METHODS: Our case involved a 47-year-old female with history of hashimoto’s disease, multiple sclerosis on tecfidera, and pulmonary sarcoidosis in remission. Incidental elevation of AST, ALT, and alkaline phosphatase were noted on labs when she was admitted after a car accident. Initial liver biopsy was nondiagnostic and lab work revealed normal ferratin, negative ASMA, AMA, A1AT, hepatitis C antibody and acute hepatitis panel but ANA was positive. Due to report of right upper quadrant abdominal pain at that time, she underwent MRI of the abdomen/pelvis and the common bile duct was noted to be 7 mm. She had an ERCP at that time with a sphincterotomy and though the pain resolved, her labs persisted. Tecfidera was another confounder as it also causes transaminitis. However, a medication interruption showed no improvement. Since a clear diagnosis was not found, her team trialed her on steroids for presumed autoimmune hepatitis and her labs improved. When her taper ended, she was readmitted for transaminitis and repeat liver biopsy at that time showed portal and periportal granuloma with associated lymphohistiocytic lobular necroinflammatory activity, which was more consistent with hepatic sarcoidosis. She was started on budesonide with imuran and her labs normalized. DISCUSSION: Though the patient had a remote history of sarcoidosis, she also had a number of other possible causes for her transaminitis and prior to the second biopsy, the working diagnosis of autoimmune hepatitis was supported by a positive ANA and improvement following steroids. This case highlights the importance of keeping a broad, evolving differential while merging clinical assessment with critical interpretation of laboratory data.

Lead poisoning; a neglected potential diagnosis in abdominal pain

BackgroundAbdominal pain may be a presenting symptom of lead poisoning and is often difficult to diagnose. This study aimed to determine the prevalence of abdominal pain in patients seen in the Laghman Hakim Hospital ED and GI clinic who were lead-intoxicated, with or without opiate use disorder.MethodsBetween July 2017 and January 2018, patients seen in the ED and GI clinic of Loghman Hakim Hospital with unexplained abdominal pain or abdominal pain resistant to treatment were enrolled. Informed consent was obtained from potential enrollees. For standardization, a pre-designed data collection tool was developed for uniform data acquisition. Opiate use was determined historically. For this study, lead poisoning was defined as a blood lead level (BLL) greater than or equal to 30 μg/dL (1.45 μmol/L) with concomitant GI symptoms.ResultsOf 125 patients admitted, 28 (22.4%) had BLLs higher than 30 μg/dL. None of the patients had signs and symptoms of opioid withdrawal syndrome during evaluation. Elevated BLLs were significantly correlated with oral opium use/abuse, history of addiction for over the preceding 12 years. The daily opium use was more than 2.75 g. There was a statistical correlation between lead toxicity and abdominal pain consistency and intensity, constipation, and paresthesias. Anemia, leukocytosis, and abnormal liver enzyme tests were laboratory findings associated with lead toxicity. Four patients died, one of whom was diagnosed with lead toxicity.ConclusionLead toxicity should be considered in the potential differential diagnosis of severe and resistant abdominal pain in patients referring to general EDs or GI clinics if a positive history of opium abuse exists.

Predictors of persistent common bile duct stones in mild acute biliary pancreatitis; the role of liver enzyme and dilated CBD on ultrasound

Background: Abnormal liver enzyme tests (LET) are frequent in acute biliary pancreatitis (ABP), and not always related to persistent common bile duct stones (CBDS). The aim of our study was to determine whether LET on admission, value variations at 24 h and dilated common bile duct (CBD) on ultrasound (US) are appropriate predictors of CBDS in mild ABP. Methods: Data were analysed from our prospective database of 56 consecutive patients diagnosed of mild ABP; of whom 14(25%) had persistent CBDS confirmed by endoscopic retrograde cholangio-pancreatography. LET; alanin aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TB) on admission and at 24 h were evaluated. Higher LET values were considered: TB>1.2mg/dl, AST>75U/l, ALT>75U/l. Abdominal US was performed. Predictive accuracy of the variables was measured using area-under-the-receiver-operating characteristic curve (AUC) analysis. Results: Neither abnormal LET on admission or its raised values at 24h showed accuracy in predicting CBDS (AUC values under 0.5), nor did the association of the 3 abnormal LET (AUC=0.66; 0.51-0.82). However, dilated CBD on US showed good accuracy for predicting CBDS (AUC=0.75; 0.58-0.91). Conclusion: A dilated CBD on US seems to be superior than abnormal LET in predicting CBDS in mild ABP, it could help to guide decisions making in the emergency setting of mild ABP, on selection of patients who will benefit from other specific imaging techniques.

Predictors of persistent common bile duct stones in mild acute biliary pancreatitis; the role of liver enzyme and dilated CBD on ultrasound

Background: Abnormal liver enzyme tests (LET) are frequent in acute biliary pancreatitis (ABP), and not always related to persistent common bile duct stones (CBDS). The aim of our study was to determine whether LET on admission, value variations at 24 h and dilated common bile duct (CBD) on ultrasound (US) are appropriate predictors of CBDS in mild ABP. Methods: Data were analysed from our prospective database of 56 consecutive patients diagnosed of mild ABP; of whom 14(25%) had persistent CBDS confirmed by endoscopic retrograde cholangio-pancreatography. LET; alanin aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TB) on admission and at 24 h were evaluated. Higher LET values were considered: TB>1.2mg/dl, AST>75U/l, ALT>75U/l. Abdominal US was performed. Predictive accuracy of the variables was measured using area-under-the-receiver-operating characteristic curve (AUC) analysis. Results: Neither abnormal LET on admission or its raised values at 24h showed accuracy in predicting CBDS (AUC values under 0.5), nor did the association of the 3 abnormal LET (AUC=0.66; 0.51-0.82). However, dilated CBD on US showed good accuracy for predicting CBDS (AUC=0.75; 0.58-0.91). Conclusion: A dilated CBD on US seems to be superior than abnormal LET in predicting CBDS in mild ABP, it could help to guide decisions making in the emergency setting of mild ABP, on selection of patients who will benefit from other specific imaging techniques.

Human herpes virus 6 infection in pediatric organ transplant patients.

Transplant patients need lifelong immunosuppressive medication, but this reduces their defense mechanisms, making them prone to viral infections and reactivations. We aimed to clarify the prevalence and clinical manifestations of the human herpes virus 6 (HHV-6) infection in children after pediatric solid organ transplants. Clinical findings and viral loads were compared between primary HHV-6 infections and reactivations. The study comprised 47 kidney, 25 liver, and 12 heart transplant patients who underwent surgery from 2009 to 2014. HHV-6 antibodies were analyzed before surgery, and HHV-6 DNAemia tests were regularly carried out after the transplant using a real-time quantitative polymerase chain reaction method. We found the primary HHV-6 infection in 19 of 22 (86%) seronegative patients, and it was more common in patients under 3years of age (79%) than over 3 (38%, P=.0002). Post-transplant HHV-6 DNAemia affected 48 of 84 (57%) patients and was significantly higher in primary infections than reactivations (P=.001), and 17 of 48 (35%) patients had symptoms when it was detected at a median of 2weeks post-transplant. The HHV-6 infection was common after solid organ transplants, especially under 3years of age, and it typically started 2weeks after surgery. Testing for HHV-6 DNAemia is recommended shortly after transplantation, especially in patients with fever, diarrhea, rash, seizures, or abnormal liver enzyme tests.

Population exposure-response modeling of oral Nepadutant administration in Colicky infants

August 2015 e115 mild to moderate AEs were mild to moderate infections (upper and lower respiratory tract most commonly), abnormal liver enzyme tests and infusion reaction or local reaction at the injection site. Of severe AEs, two cases of reactivation of tuberculosis, one case of colon carcinoma and one hospitalization due to the febrile state was observed. Conclusion: Our data confirm that anti-TNF therapy can be considered safe, as most of the AEs were mild to moderate in severity. However, vigilant follow-up of patients during and after the therapy is needed for early recognition and treatment of severe AEs.

Prognostic factors for mortality with febrile neutropenia in hospitalized patients

Background: Febrile neutropenia is a life-threatening complication of cancer treatment that results in hospitalization and delays cancer therapy. The aim of this study is to identify prognostic factors of patients admitted with febrile neutropenia. Methods: A retrospective study via chart review without direct patient contact was conducted. All adults above 18 years with the diagnosis of febrile neutropenia hospitalized in University Medical Center in Lubbock, Texas, between January 2010 and December 2013 were reviewed. The data were analyzed with IBM SPSS statistics. Results: One hundred twenty-seven patients were included in this study. The hospital mortality rate was 17.3%, and the 30-day mortality rate was 20.5%. The median length of stay (LOS) was eight days. Hematologic malignancies accounted for 66.1% of the patients. On multivariate analysis, the in-hospital mortality rate was associated with fever duration (adjusted odds ratio [OR] 7.19; 95% CI 1.06-50.00; p <0.04), abnormal liver function tests (adjusted OR 63.72; 95% CI 5.95-682.07; p <0.001), ICU admission (OR 45.78; 95% CI 4.97-420.99; p <0.001) and positive culture (adjusted OR 12.71; 95% CI 1.14-142; p <0.039). The independent risk factors for a 30-day mortality rate were abnormal liver enzymes (OR 48.38; 95% CI 5.27-444.29; p <0.001), ICU admission (OR 63.66; 95% CI 5.96-680.30; p <0.001) and fever duration more than four days (OR 8.26; 95% CI 1.11-62.50; p=0.039). The data indicated that diagnosis of hematologic malignancies (OR 4.06; 95% CI 1.34-12.31 p=0.013), fever duration (adjusted OR 6.29; 95% CI 1.81-21.92; p 0.004) and neutropenic duration more than five days (OR 3.68; 95% CI 1.44-9.40 p=0.007) were associated with LOS more than eight days. Conclusions: Febrile neutropenia in hospitalized patients results in a significant mortality rate. Factors associated with increased mortality include ICU admission and abnormal liver enzyme tests.

Plasma cell hepatitis (de-novo autoimmune hepatitis) developing post liver transplantation

Cases of de-novo autoimmune hepatitis/plasma cell hepatitis (PCH) are increasingly being diagnosed by liver transplant centers. Its pathogenesis is poorly understood but this entity appears to be a variant of rejection. Herein, we review recent clinical reports of patients developing PCH. Histologically, PCH is a challenging diagnosis, especially in the setting of recurrent hepatitis C and, in some cases, can be mistaken for acute cellular rejection. Recent case reports and case-control studies have shown that interferon appears to trigger PCH in hepatitis C posttransplant patients. Optimization of the immunosuppression regimen was found to prevent the development of PCH. In the nonhepatitis C posttransplant patient, tacrolimus-based immunosuppression appears to have some protective effect from PCH development. A combination therapy of cyclosporine and everolimus has also been shown to be effective in treating PCH. PCH is a variant of rejection and is a cause of late graft loss post liver transplantation, especially in patients with hepatitis C. It should be part of the differential diagnosis of abnormal liver enzyme tests occurring in the post-liver transplant setting.

International Criteria for the Diagnosis of Ocular Sarcoidosis: Results of the First International Workshop on Ocular Sarcoidosis (IWOS)

Aim: To report criteria for the diagnosis of intraocular sarcoidosis, taking into account suggestive clinical signs and appropriate laboratory investigations and biopsy results. Design: Concensus workshop of an international committee on nomenclature. Methods: An international group of uveitis specialists from Asia, Africa, Europe, and America met in a concensus conference in Shinagawa, Tokyo on October 28–29, 2006. Based on questionnaires that had been sent out prior to the conference, the participants discussed potential intraocular clinical signs eligible for a diagnosis of ocular sarcoidosis. A refined definition of clinical signs, which received two-thirds majority of votes, was included in the list of signs consistent with ocular sarcoidosis. Laboratory investigations were similarly discussed and those tests reaching a two-thirds majority were retained for the diagnosis of ocular sarcoidosis. Finally diagnostic criteria were proposed based on ocular signs, laboratory investigations, and biopsy results. Results: The concensus conference identified seven signs in the diagnosis of intraocular sarcoidosis: (1) mutton-fat keratic precipitates (KPs)/small granulomatous KPs and/or iris nodules (Koeppe/Busacca), (2) trabecular meshwork (TM) nodules and/or tent-shaped peripheral anterior synechiae (PAS), (3) vitreous opacities displaying snowballs/strings of pearls, (4) multiple chorioretinal peripheral lesions (active and/or atrophic), (5) nodular and/or segmental peri-phlebitis (± candlewax drippings) and/or retinal macroaneurism in an inflamed eye, 6) optic disc nodule(s)/granuloma(s) and/or solitary choroidal nodule, and (7) bilaterality. The laboratory investigations or investigational procedures that were judged to provide value in the diagnosis of ocular sarcoidosis in patients having the above intraocular signs included (1) negative tuberculin skin test in a BCG-vaccinated patient or in a patient having had a positive tuberculin skin test previously, (2) elevated serum angiotensin converting enzyme (ACE) levels and/or elevated serum lysozyme, (3) chest x-ray revealing bilateral hilar lymphadenopathy (BHL), (4) abnormal liver enzyme tests, and (5) chest CT scan in patients with a negative chest x-ray result. Four levels of certainty for the diagnosis of ocular sarcoidosis (diagnostic criteria) were recommended in patients in whom other possible causes of uveitis had been excluded: (1) biopsy-supported diagnosis with a compatible uveitis was labeled as definite ocular sarcoidosis; (2) if biopsy was not done but chest x-ray was positive showing BHL associated with a compatible uveitis, the condition was labeled as presumed ocular sarcoidosis; (3) if biopsy was not done and the chest x-ray did not show BHL but there were 3 of the above intraocular signs and 2 positive laboratory tests, the condition was labeled as probable ocular sarcoidosis; and (4) if lung biopsy was done and the result was negative but at least 4 of the above signs and 2 positive laboratory investigations were present, the condition was labeled as possible ocular sarcoidosis. Conclusion: Various clinical signs, laboratory investigations, and biopsy results provided four diagnostic categories of sarcoid uveitis. The categorization allows prospective multinational clinical trials to be conducted using a standardized nomenclature, which serves as a platform for comparison of visual outcomes with various therapeutic modalities.

Hypothyroidism presenting as liver test abnormalities

It is unusual to find abnormal liver enzyme tests due to hypothyroidism. In contrast, it is well known that hypothyroidism may develop in patients with liver disease, especially in those treated for Hepatitis C. We present 2 cases referred for abnormal liver enzymes who were discovered to be hypothyroid and who's liver tests normalized following hormone replacement therapy.

A comparison between previous and present histo-logic assessments of chronic hepatitis C viral infec-tions in humans

AIM:To compare the previously employed classification of liver histology (minimal,chronic persistent hepatitis, chronic active hepatitis and cirrhosis) with a new classification recently described by sheuer et al (activity grade and fibrosis stage) in percutaneous liver biopsies from patients with chronic hepatitis C viral infections.METHODS:Liver biopsies from 79 untreated patients were reviewed. Anti-HCV testing had been performed by ELISA and confirmed by a recombinant immunoblot assay.With respect to the new classification, all the specimens were evaluated using the Knodell score for activity.RESULTS:A good correlation was revealed between the previous and more recent histologic classifica-tions in patients with abnormal liver enzyme tests. However, in 13/15 (87%) of patients with normal aminotransferase values, changes were consistent with chronic persistent hepatitis whereas normal activity and no fibrosis were demonstrated by the Sheuer classifica-tion.CONCLUSION:The old classification is more often mislead-ing but correlates well with the new classification and thereby permits comparisons between historically clinical studies.

Canadian Association of Gastroenterology Practice Guidelines: Evaluation of Abnormal Liver Enzyme Tests

Approximately one in 10 Canadians has at least one abnormal liver biochemical test on routine screening. Although in the majority of these individuals the abnormality reflects a benign liver condition such as Gilbert’s syndrome or enzyme induction from recent alcohol consumption, a subgroup will have progressive and potentially life-threatening liver disease for which therapeutic interventions are often available (1). The objectives of these guidelines are to, first, outline when screening for liver disease would be appropriate; second, determine which biochemical tests should be used in screening for liver disease; third, review second-line tests for when screening tests are positive; fourth, outline when referrals to specialists would be appropriate; and, fifth, review additional testing that specialists might undertake in their evaluation of the patient. Because sanctioned guidelines for investigating asymptomatic patients with liver biochemical abnormalities have not been developed, the options, outcomes and evidence considered in formulating the present guidelines largely reflect the experience of individuals with expertise in the area and a limited number of clinical studies in which liver biochemical abnormalities were described in the healthy blood donor population as well as in patients with various forms of acute and chronic liver disease. BENEFITS, HARMS AND COSTS The benefits, harms and costs of screening for liver disease can only be estimated on the basis of efficiently arriving at a correct diagnosis (or at least appreciation) of the general form of liver disease (hepatocellular versus cholestatic), avoidance of unnecessary, interventional procedures and efficient use of laboratory testing.

New developments in drug hepatotoxicity

The spectrum of drug-related hepatotoxicity can range from sub-clinical liver disease with mildly abnormal liver enzyme tests to subfulminant and fulminant hepatic failure requiring liver transplantation. Many commonly used prescription and nonprescription drugs are known to have hepatotoxic side effects. In this review, only those medications that have received the most attention in the recent literature are discussed. Additionally, a number of the many herbal medicines and other alternative health agents commonly used in the United States that are now recognized as having unappreciated hepatotoxic potential are reviewed along with another over-the-counter medication, sustained-release niacin. The recently recognized hepatotoxicity of some of the newer antimicrobials is described as well as the newly identified hepatotoxic effects of other older antibiotics. Updated recommendations regarding methotrexate treatment of rheumatoid arthritis and the potential for liver disease are presented. Other commonly used drugs with possible hepatotoxic side effects are also discussed.

Recommendations for the investigation of abnormal hepatic function in asymptomatic workers.

Occupational medicine programs use medical surveillance tests to measure physiologic parameters that may be affected by workplace exposures. Surveillance tests can detect early detrimental changes before workers manifest recognizable symptoms. Hepatic function testing is one type of surveillance test used to monitor workers exposed to hepatotoxins. However, a significant proportion of these test reports return showing abnormal hepatic function without a readily apparent etiology. Follow-up investigation of abnormal liver enzyme tests is a commonly encountered problem in occupational medicine clinics. The algorithm proposed in this paper will outline a systematic approach for investigating abnormal hepatic function tests from asymptomatic workers.

Evaluating Liver Enzyme Abnormalities in Clinical Trials Involving Diabetic Patients

The frequent occurrence of elevated liver enzymes in otherwise healthy diabetics confounds evaluation of drug-induced hepatotoxicity in clinical trials involving diabetic patients. In a recent single-dose tolerance study of an aldose-reductase inhibitor, we found abnormal liver enzyme tests occurring in 19 of 34 (56%) “healthy” diabetic patients. Alkaline phosphatase (AP) deviations occurred in 35%, and serum gluatamic-oxaloacetic transminase (SGOT) elevations occurred in 32%. Of these elevations, 91% were less than 30% above the upper limit of normal in the nondiabetic population. The enzyme elevation patterns varied both between and within patients and were not typical of a specific liver abnormality. We recommend guidelines to perform valid clinical trials in diabetics without either inappropriately excluding potential participants who are healthy or unnecessarily dropping them from the study. The guidelines also allow for maintenance of good safety monitoring practices. We recommend (1) increasing the...

Genital herpes and hepatitis in healthy young adults.

Although case reports of herpes simplex virus (HSV) causing acute hepatitis in otherwise healthy adults have appeared recently in the literature, a prospective study of the incidence of HSV-hepatitis in the general population hitherto has not been reported. In the present study, serum samples from 124 young adults attending a sexually transmitted disease clinic with either genital herpes infections (n = 86) or non-herpes sexually transmitted diseases (n = 38) (controls) were analyzed for liver enzyme abnormalities (including aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). Twelve of eighty-six (14%) herpes-infected patients had mildly abnormal liver enzyme tests (less than or equal to twice the upper limit of normal) as opposed to only 1 of 38 controls (2.6%), (P less than .05). All individuals in the herpes-hepatitis group were anicteric, and only two complained of constitutional symptoms (malaise and fatigue). Liver enzyme tests were repeated in nine herpes-hepatitis patients 1 week after their genital lesions had resolved, and in six of nine patients the results had returned to within normal limits. Four patients subsequently returned at the onset of a recurrence of their genital herpes. In all four, serum ALT levels were elevated from the previous occasion, and in three of the four levels just exceeded the upper limit of normal. One patient was followed through three recurrences of his genital herpes. In that individual, the extent of liver enzyme abnormalities appeared to correlate with the presence or absence of his genital lesions.(ABSTRACT TRUNCATED AT 250 WORDS)