Elevated Liver Enzyme Activities Research Articles

Outcome following liver lobectomy using thoracoabdominal staplers in cats

To present outcomes and complications following liver lobectomy using thoracoabdominal staplers in cats, to identify factors associated with survival time and to confirm safety and feasibility. Retrospective analysis of case records (n=18) of cats that underwent liver lobectomy with a thoracoabdominal stapler. Fourteen of the 18 cats (78%) survived to discharge. Median survival time was 136·5 days. On log-rank univariate analysis, preoperative abdominal fluid (P=0·002), preoperative anaemia (P=0·03) and perioperative transfusion (P=0·01) were associated with decreased survival time. Perioperative anaemia was common (89%), and rate of transfusion during hospitalisation was 61%. Clinical signs of illness, azotaemia, elevated liver enzyme activities and malignant neoplasia did not appear to impact survival; however, anaemia, abdominal fluid and transfusion may be associated with decreased survival time. Liver lobectomy using thoracoabdominal staplers was effective in removal of hepatic lesions and all cats survived surgery. Outcome was negatively associated with preoperative abdominal fluid (haemorrhagic and non-haemorrhagic), preoperative anaemia or perioperative transfusion. Surgeons should be prepared to employ ancillary methods of haemostasis to augment the staple line, and need for blood transfusion should be anticipated.

Carbimazole‐associated hypersensitivity vasculitis in a cat

Feline hyperthyroidism can be treated medically, surgically or with radioactive iodine. Carbimazole inhibits both triiodothyronine and thyroxine synthesis in the thyroid gland and reported side effects include mild eosinophilia, leucopenia and lymphocytosis, thrombocytopenia, elevated liver enzyme activities, gastrointestinal signs and skin abnormalities. This case report describes a cat with carbimazole-associated apparent hypersensitivity vasculitis causing digital and tail necrosis, with multiple renal infarcts. Withdrawal of carbimazole resulted in stable disease.

Steatohepatitis Secondary to Long-Term Glucocorticoid Treatment for Congenital Adrenal Hyperplasia: A Potential Diagnostic Pitfall

A 24-year-old woman with congenital adrenal hyperplasia (CAH) was referred for evaluation of elevated liver enzyme activities over the preceding 6 months. The patient was diagnosed with CAH at the age 12 when she presented with irregular menses and hirsutism. Since then, she had been on dexamethasone to maintain a normal menstrual cycle and prevent hirsutism and acne. She had no history of chronic liver disease and drank alcohol socially. An extensive workup for other treatable causes of liver disease was unrevealing. Therefore, a liver biopsy was performed, which revealed extensive ballooned degenerative hepatocytes containing Mallory-Denk hyalines. The ballooned hepatocytes were located predominantly in centrilobular areas and without any accompanying steatosis. Even though the histopathologic features are most compatible with alcoholic and/or nonalcoholic steatohepatitis, it was not supported by the patient's medical history and clinical presentation. The patient had a normal body mass index and only occasional alcohol use. Based on the biopsy finding and clinical presentation, we postulated that the abnormal liver enzyme and pathological features seen on the liver biopsy were secondary to CAH and long-term use of glucocorticoid. A few studies have shown that patients with CAH often develop metabolic abnormalities and insulin resistance, particularly women treated with glucocorticoid for several years. To our knowledge, this is the first report describing steatohepatitis secondary to CAH and prolonged glucocorticoid treatment. It is important to be aware that steatohepatitis can develop in these patients due to long-term glucocorticoid use and potentially lead to progressive liver damage. Furthermore, in patients with CAH who develop abnormal liver enzyme activities a liver biopsy is warranted to assess for steatohepatitis and any associated fibrosis. If indeed fibrosis is already present, a consultation with the endocrinologist should be undertaken in an effort to lower the dose of the glucocorticoids as much as possible while still controlling the symptoms of the disease.

Transition between Acute and Chronic Hepatotoxicity in Mice Is Associated with Impaired Energy Metabolism and Induction of Mitochondrial Heme Oxygenase-1

The formation of protein inclusions is frequently associated with chronic metabolic diseases. In mice, short-term intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) leads to hepatocellular damage indicated by elevated serum liver enzyme activities, whereas only minor morphological changes are observed. Conversely, chronic administration of DDC for several weeks results in severe morphological damage, characterized by hepatocellular ballooning, disruption of the intermediate filament cytoskeleton, and formation of Mallory-Denk bodies consisting predominantly of misfolded keratins, Sqstm1/p62, and heat shock proteins. To evaluate the mechanistic underpinnings for this dichotomy we dissected the time-course of DDC intoxication for up to 10 weeks. We determined body weight change, serum liver enzyme activities, morphologic alterations, induction of antioxidant response (heme oxygenase-1, HO-1), oxidative damage and ATP content in livers as well as respiration, oxidative damage and the presence and activity of HO-1 in endoplasmic reticulum and mitochondria (mtHO-1). Elevated serum liver enzyme activity and oxidative liver damage were already present at early intoxication stages without further subsequent increase. After 2 weeks of intoxication, mice had transiently lost 9% of their body weight, liver ATP-content was reduced to 58% of controls, succinate-driven respiration was uncoupled from ATP-production and antioxidant response was associated with the appearance of catalytically active mtHO-1. Oxidative damage was associated with both acute and chronic DDC toxicity whereas the onset of chronic intoxication was specifically associated with mitochondrial dysfunction which was maximal after 2 weeks of intoxication. At this transition stage, adaptive responses involving mtHO-1 were induced, indirectly leading to improved respiration and preventing further drop of ATP levels. Our observations clearly demonstrate principally different mechanisms for acute and chronic toxic damage.

Hepatocellular Carcinoma in a Noncirrhotic Patient with HIV: A Case Report and Review of the Literature

A 59-year-old man with human immunodeficiency virus (HIV) was referred for persistently elevated liver enzyme activities. His HIV was well controlled on antiretroviral therapy and his viral load was undetectable. He had no history of chronic liver disease and had minimal alcohol intake. He was asymptomatic and his physical exam was unremarkable without any stigmata of liver disease. Beyond the elevations in alkaline phosphatase and gamma-glutamyl transferase, the rest of his laboratory work, including viral hepatitis serologies and serum α-fetoprotein, was within normal limits. A computed tomography (CT) scan revealed a mildly nodular liver but hepatic mass or ascites was not seen. He was subsequently followed every 3 to 6 months without any change in his clinical symptoms, laboratory values, or imaging tests. Two years after the original visit, the patient presented with acute onset of abdominal pain, an AFP of 15.8 ng/mL, and a 9-cm hepatic mass on imaging. Given his preserved liver function, he underwent right hepatic lobectomy. Histologic examination of the resected tissue was consistent with hepatocellular carcinoma (HCC). The uninvolved liver was noncirrhotic and unremarkable except for mild portal inflammation. As the vast majority of HIV patients who develop HCC have established chronic liver diseases such as hepatitis B and/or C along with cirrhosis, this case of HCC in an HIV patient without cirrhosis or viral hepatitis is rare. Although current screening guidelines recommend imaging only for patients with HIV and hepatitis B/C cirrhosis, closer monitoring may be important in HIV patients with even subtle liver dysfunction.

Lipid-Lowering Agents in Nonalcoholic Fatty Liver Disease and Steatohepatitis: Human Studies

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease which refers to the presence of hepatic steatosis without significant intake of alcohol. NAFLD is an asymptomatic disease that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is currently the most common cause of incidental abnormal liver tests and elevated serum liver enzyme activities in the developed world. Obesity, diabetes, and other components of the metabolic syndrome are frequently associated with the NAFLD. The treatment of NAFLD focuses on life-style modifications. Statins, fibrates, and other lipid-lowering agents have been proposed as effective lipid-lowering treatments in patients with NAFLD/NASH. However, clinicians are concerned that hyperlipidemic patients with NAFLD/NASH who are treated with statins could develop transaminitis. We assessed the efficacy and safety of lipid-lowering agents for NAFLD/NASH by reviewing reports of human studies including pilot, prospective, preliminary, and post hoc analysis studies on online databases during the period of 1980 to December 2012. The results of studies provide compelling evidence that lipid-lowering agents are safe and efficacious in patients with NAFLD/NASH and that some of these agents can induce a reduction in the extent of the hepatic steatosis. Well-designed randomized controlled studies of adequate size and duration with histological endpoints are needed in order to establish a suitable lipid-lowering treatment for hyperlipidemic patients with NAFLD/NASH, and for nonhyperlipidemic patients with NAFLD/NASH with a high risk for cardiovascular disease.

Photosensitisation, crystal-associated cholangiohepatopathy, and acute renal tubular necrosis in calves following ingestion of Phytolacca octandra (inkweed)

CASE HISTORY: In March 2006, an outbreak of photosensitivity affecting 6–8-month-old Friesian heifer calves on a farm in the Rangitikei district of New Zealand was investigated. The calves were grazing wheat stubble paddocks that also had a variety of weeds, especially Phytolacca octandra (inkweed). They also had access to pond water that contained potentially toxic concentrations of the cyanobacteria (blue–green algae) Microcystis and Planktothrix spp. CLINICAL FINDINGS: Initially, affected animals showed acute irritation, agitation, reluctance to walk, recumbency in some animals, hyperaemia of unpigmented skin and jaundice. Serum chemistry revealed elevated liver enzyme activities and azotaemia. Later in the outbreak, exudative dermatitis with formation of crusts on unpigmented skin, dehydration and inappetence were notable signs, as well as occasional diarrhoea. PATHOLOGICAL AND TOXICOLOGICAL FINDINGS: Post-mortem examinations following euthanasia of four severely affected calves and a fifth animal that died naturally revealed livers that were grossly orange brown and mildly enlarged, and kidneys that were enlarged and pale brown. Microscopic lesions in the liver were mild; however, small birefringent crystals in the bile ducts were noted in the first two cases. In contrast, renal lesions were moderate to severe, and included prominent segmental tubular necrosis, granular and cellular casts, and mild interstitial non-suppurative inflammation. In the kidneys of animals examined later in the outbreak, there was early interstitial fibrosis as well as tubular regeneration, with numerous hyaline casts in the renal medulla. Inkweed plants had been heavily browsed, and recognisable portions of the plant were found in the gastrointestinal tracts of affected calves. Chemical analysis of inkweed material revealed triterpene saponins. No known hepatotoxic or nephrotoxic plants were identified in the paddocks. The hepatic lesions were not consistent with published descriptions of cyanobacterial toxicity. Sporidesmin toxicity was ruled out. DIAGNOSIS: Hepatogenous photosensitivity, crystal-associated cholangiohepatopathy, toxic acute renal tubular necrosis, associated with the ingestion of P. octandra, and possibly complicated by cyanobacteria in the water. CLINICAL RELEVANCE: Crystal-associated cholangiohepatopathy with photosensitivity in cattle is rare, and has only been reported in steroidal saponin-containing Brachiaria decumbens poisoning, in Brazil. The consistent pattern of toxic acute renal tubular necrosis was similar to that caused by the ingestion of Quercus, Amaranthus or Lantana spp. A combination of toxicities was conceivable but circumstantial evidence strongly implicated P. octandra. Further toxicological investigation of this plant is warranted before it can be listed as a known nephrotoxin of cattle.

Vaginal rupture and evisceration in a dog

A 1.5-year-old German Shepherd mixed breed dog was admitted with mild haemorrhage from the vulva and a perineal mass of 24-hour duration, which had been first observed immediately after parturition. Parturition had occurred at low ambient temperature, and only one puppy survived out of the seven oversized fetuses. The dog was in poor body condition, dehydrated, hypothermic, depressed, non-ambulatory and in a state of shock. Intestinal loops, the urinary bladder and the uterine horns and body were protruding from the vulva. A true vaginal prolapse was also observed. The abdominal viscera were flushed with warm sterile saline solution, protected and maintained wet. The laboratory findings included moderate anaemia, leukocytosis, hypoalbuminaemia, azotaemia and elevated liver enzyme activities. Stabilisation of the dog's general condition was attempted before surgery. Antimicrobial and analgesic drugs were also administered. After exploratory laparotomy the protruding organs, which were in good condition, were reduced. A recent rupture in the vaginal wall, approximately 6 cm long, was observed. Ovariohysterectomy and partial vaginectomy were performed. The preoperative course of therapy was continued, but the bitch died 12 hours later. The probable cause of vaginal rupture and evisceration in this bitch was tenesmus and/or trauma due to the oversized fetuses.

Elevated Liver Enzymes in Metabolic Syndrome Are Associated with Coronary Stenosis in a Tunisian Population

Recently, elevated liver enzymes have attracted great interest as potential novel markers of cardiovascular risk. The aim of this study was to investigate if there is a relationship between elevated liver enzymes and coronary stenosis associated with metabolic syndrome in a Tunisian population. We enrolled 192 patients who underwent coronary angiography. Significant coronary stenosis (SCS) was diagnosed in the presence of coronary stenosis with lumenal narrowing >or=50%. Metabolic syndrome was defined according to the International Diabetes Federation criteria. Frequencies of subjects with liver enzyme activities belonging to quartile 4 were higher in the group with metabolic syndrome. Association of SCS with metabolic syndrome was more significant in the quartile 4 of gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT). Odds ratios of SCS associated with metabolic syndrome were: [1.40 (0.66-2.9) for quartile 1 versus 4.20 (1.3-9.9) for quartile 4 of GGT; 1.52 (0.29-3.7) for quartile 1 vs. 5.30 (1.39-18.9) for quartile 4 of ALT]. Elevated liver enzyme activity was associated with metabolic syndrome and only GGT and ALT seem to be associated with an increase of the coronary stenosis in the studied population with metabolic syndrome.

Bilirubin cholelithiasis and haemosiderosis in an anaemic pyruvate kinase‐deficient Somali cat

A Somali cat was presented with recurrent anorexia, lethargy, vomiting and icterus. A macrocytic-hypochromic, regenerative haemolytic anaemia was identified and hereditary pyruvate kinase deficiency was confirmed by means of breed-specific DNA mutation analysis. The case was complicated by the presence of markedly elevated serum liver enzyme activities, hyperbilirubinaemia, coagulopathy and ultrasonographic evidence of gall bladder choleliths and extrahepatic bile duct obstruction. The choleliths consisted of 100 per cent bilirubin, likely because of chronic haemolysis and haeme degradation. In conclusion, haemosiderosis and bilirubin cholelithiasis can be a consequence of chronic haemolysis in pyruvate kinase-deficient cats, as seen in human beings with a variety of chronic haemolytic disorders.

Cholangiectasis and Duodenal Diverticulosis in a Farm-Raised Elk (Cervus Elaphus)

A 6-year-old male elk presented in August with a 4-month history of weight loss and a 1-day history of being recumbent and unable to rise. The elk's body condition score was 1.5/5. Hematology and blood chemistry showed an inflammatory leukogram, mild electrolyte abnormalities, and elevated liver enzyme activities. Because of poor prognosis, the owner elected euthanasia. On necropsy, 8 diverticula were in the duodenum distal to the common bile duct, which was dilated and filled with feed material. Many intrahepatic bile ducts were dilated up to 5 cm, were filled with ingesta and gritty material, and had walls thickened up to 1.5 mm. On histologic examination, mural thickening of dilated bile ducts was because of increased fibrous connective tissue with inflammatory cell infiltration and hyperplastic and hypertrophic epithelial lining. Portal tracts diffusely contained hyperplastic bile ducts and had increased amounts of fibrous connective tissue. Abscesses that contained bacteria were scattered throughout the liver. Duodenal diverticula lacked the tunica muscularis, and the muscularis mucosa was hypertrophied. Caudal to some diverticula, the duodenal lumen was narrowed. An additional finding was embolic pneumonia with fungi morphologically and immunohistochemically consistent with Aspergillus spp.

Epidemiology and Molecular Virus Characterization of Reemerging Rabies, South Africa

The incidence of dog rabies in Limpopo Province, South Africa, increased from 5 cases in 2004 to 100 in 2006. Human rabies had last been confirmed in 1981, but investigations instituted after an index case was recognized in February 2006 identified 21 confirmed, 4 probable, and 5 possible human cases between August 5, 2005, and December 31, 2006. Twelve of these case-patients were identified retrospectively because the diagnosis of rabies was not considered: 6 of these patients consulted a traditional healer, 6 had atypical manifestations with prominent abdominal symptoms, and 6 of 7 patients tested had elevated liver enzyme activity. Molecular genetic analysis indicated that outbreak virus strains were most closely related to recent canine strains from southern Zimbabwe. Delayed recognition of the human cases may have resulted from decreased clinical suspicion after many years of effective control of the disease and the occurrence of atypical clinical presentations.

Cortical liquefaction in severe human herpesvirus 6 encephalopathy

Human herpesvirus 6 (HHV6) is the causative agent of the common childhood infectious disease exanthema subitum. Primary infection of CNS by HHV6 can cause seizures and encephalitis/encephalopathy.1 We report a 9-month-old girl with severe HHV6 encephalopathy, in whom a subacute MRI showed an unusual appearance of the cerebral cortex suggesting cortical liquefaction. A previously healthy 9-month-old Japanese girl was admitted because of status epilepticus for 1 hour following a 1-day prodromal illness consisting of fever (around 38.5 °C for 3 days) and vomiting. After her seizure was controlled, she was in a comatose state and required intubation. Laboratory examination revealed elevated serum liver enzyme activities. CSF showed normal cell count (1/mm3), protein level (18 mg/dL), and glucose level (122 mg/dL). EEG showed polyspikes in bilateral centroparietal regions. HHV6 was later isolated from her throat swab and serum, and a diagnosis of HHV6 encephalopathy was established. Clinical symptoms or laboratory data suggesting hemorrhagic shock and encephalopathy syndrome (shock, diarrhea, disseminated intravascular …

Autoimmune Liver Disease in Three Children with Sickle Cell Disease

Autoimmune Liver Disease in Three Children with Sickle Cell Disease

Hepatocellular Toxicosis Associated with the Alternate Administration of Carprofen and Meloxicam in a Siberian Husky

A 4-year-old female Siberian Husky was diagnosed with pyogranulomatous steatitis at the site of a recurrence of left anal sac rupture (day 1). Carprofen and orbifloxacin were given for 13 days without improvement. A single dose of meloxicam was administered prior to surgical resection of the anal sac, and based on elevated liver enzyme activity, liver supportive therapy was initiated. The dog received carprofen and orbifloxacin orally on the evening of day 14. The dog became anorectic the following morning, and began vomiting. Despite supportive therapy, the dog was unresponsive to treatment and died on day 16. Postmortem examination revealed severe vacuolar change and acute necrosis of hepatocytes consistent with carprofen and meloxicam induced-toxicosis.

Acute exacerbation of autoimmune hepatitis induced by Twinrix

We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix. In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid, and led to complete normalization of the pathological liver function tests. We believe that Twinrix led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.

High levels of HDL-cholesterol do not protect against CAD* in men with elevated liver enzyme activity,

High levels of HDL-cholesterol do not protect against CAD* in men with elevated liver enzyme activity,

Eicosanoid production by adult Fasciola hepatica and plasma eicosanoid patterns during fasciolosis in sheep

Fasciola hepatica infection in sheep is known to cause anaemia, fever and elevated levels of liver enzymes. It was hypothesised that eicosanoids play a role in these pathophysiological changes, so the pattern of plasma eicosanoids during the course of acute and chronic fasciolosis was studied in sheep infected with a single dose of 800 F. hepatica metacercariae. Blood plasma was collected weekly until week 17 p.i. from infected sheep, and from uninfected controls. Adult F. hepatica were then recovered from bile ducts and incubated for production of ES products. Eicosanoids were determined by enzyme immuno-assay in blood plasma, fluke homogenates and ES products after chromatographic purification of the samples. Fever and anaemia were seen from 3 to 12 weeks p.i. and from 8 to 17 weeks p.i., respectively. Onset of fever was accompanied by elevated liver enzyme activities (aspartate amino transferase and gamma glutamyl transferase) in the plasma. In general, the plasma levels of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and leukotriene B4 (LTB4) were reduced during the acute and chronic stages of the infection, whereas thromboxane B2 (TXB2) was reduced only at 8 weeks p.i. The TXB2/PGI2 ratio was increased in favour of TXB2 at 3 and 11 weeks p.i. Additionally, TXB2, PGI2, PGE2 and LTB4 were detected both in ES products and in homogenates of F. hepatica. It was concluded that eicosanoid depletion in the plasma is caused by parasite-induced liver damage. The changes in eicosanoid levels are highly correlated to the clinical signs of the disease. Changes in the pattern of host plasma eicosanoids during fasciolosis, as well as parasite-derived eicosanoids, may reflect or contribute to the pathology of the disease.

Elevated liver enzyme activity in construction workers: prevalence and impact on early retirement and all-cause mortality.

Gamma-glutamyl transferase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST) are widely used as markers of hepatobiliary disorders in occupational health surveillance. Little is known, however, about the prevalence and occupational and non-occupational determinants of elevated levels of these enzymes in specific occupational groups or about the prognostic value of elevated levels with respect to long-term outcomes such as all-cause mortality and vocational disability. A cohort study was conducted among 8,043 male construction workers aged 25-64 years who had undergone occupational health examinations in 6 centers in southern Germany from 1986 to 1988 and had been followed until 1994. The prevalence of elevated levels of GGT, ALT, and AST, depending on the sociodemographic and medical characteristics determined at the baseline examination and the risk of vocational disability and all-cause mortality in relation to elevated liver enzyme activity at baseline were assessed. Covariates considered in multivariate analysis included age, nationality, occupation, body mass index (BMI), smoking, and alcohol consumption. The baseline prevalence of elevated activity levels of GGT (>28 U/1 at 25 degrees C), ALT (>22 U/1), and AST (>18 U/1) was 32%, 22%, and 12%, respectively. Factors most strongly related to elevated serum activity levels for all three enzymes were self-reported alcohol consumption, diabetes, and hypertension. BMI was strongly associated with elevations in GGT and ALT but not in AST. Elevated levels of AST and GGT were strongly related to early retirement and all-cause mortality. Men with AST levels exceeding 18 U/1 had a 2-fold risk of early retirement and a 3 times higher risk of all-cause mortality as compared with men with lower AST levels. No significant association was observed between ALT and either of the long-term outcomes. Our findings suggest that screening for elevated GGT and AST levels, which are a common finding among construction workers, may be a powerful tool for the identification of individuals at increased risk of early retirement and preterm mortality and may be helpful in targeting of prevention efforts.

Human ehrlichioses: newly recognized infections transmitted by ticks.

Human ehrlichioses are tick-borne infections caused by bacteria in the genus Ehrlichia. Human monocytic ehrlichiosis is caused by Ehrlichia chaffeensis and human granulocytic ehrlichiosis is caused by an agent similar to Ehrlichia equi. E. chaffeensis infects mononuclear phagocytes and is transmitted by Lone Star ticks (Amblyomma americanum) found in the south central and eastern United States. The agent of human granulocytic ehrlichiosis infects mostly neutrophils, it transmitted by Ixodes species ticks, and occurs mostly in the upper midwest and northeast United States. Despite the undifferentiated presentation of both ehrlichioses with fever, headache, myalgias, leukopenia, thrombocytopenia, and elevated liver enzyme activities, the diagnostic methods are distinct. Occasional severe complications include meningoencephalitis, adult respiratory distress syndrome, shock, and opportunistic infections. Immunocompromised patients are at high risk for death. An adverse outcome is associated with delayed diagnosis and therapy; thus, empirical treatment is advocated. Treatment with doxycycline usually results in prompt defervescence and cure.