Liver Flashcards
Case control exercise challenge study on the pathogenesis of high serum GGT in Thoroughbred racehorses
•High GGT activity may reflect increased glutathione recycling and mild cholestasis, rather than uncompensated oxidative stress or significant liver dysfunction.
•Oxidative Stress and Antioxidant Status:No significant differences in baseline or post-exercise levels of oxidative stress markers. High GGT horses showed higher baseline glutathione levels, suggesting increased recycling to counter oxidative stress.
•Bile Acid Profiles: taurocholic acid + glycochenodeoxycholic acid were elevated in high GGT horses, pointing to mild cholestasis. Differences in taurine-conjugated bile acids observed consistently across studies.
•Lipid and Metabolic Responses: No significant alterations in overall lipid metabolism or glucose handling were observed.
•Hormonal Responses: High GGT horses had higher cortisol levels at all time points, possibly reflecting heightened adrenal responsiveness. Cortisol differences were not significant enough for diagnostic use.
Pathophysiology:
• Enhanced glutathione recycling likely reflects an adaptive response rather than a pathological process.
•Mild cholestasis suggested by bile acid changes could contribute to elevated GGT levels, though clinical relevance is uncertain.
Investigation of circulating concentrations of microRNA-122 as a potential biomarker for liver disease in horses
miR-122 concentrations were significantly higher in horses with liver disease compared to controls. ROC analysis showed good diagnostic accuracy.
Active equine parvovirus-hepatitis infection is most frequently detected in cases of idiopathic or suspected Theiler’s disease
EqPV-H detected in 62% of idiopathic hepatitis cases but only 10% of other liver diseases. Antibody prevalence was high across populations.
Successful management of an outbreak of Tyzzer’s disease on a Thoroughbred breeding farm in central Kentucky; use of sorbitol dehydrogenase to identify sub-clinical cases
•Caused by Clostridium piliforme, an intracellular, spore-forming bacterium -Acute necrotizing hepatitis in foals, often fatal within 2–48 hours.Refractory hypoglycemia is a hallmark symptom of the disease.
• plasma SDH concentration >20 IU/L was identified as the cut-off for detecting subclinical or early disease cases -> prophylactic penicillin
•Faecal PCR testing of affected foals, their dams, and a control group yielded no detection of C. piliforme.
•SDH had reduced sensitivity in very early cases and lacked specificity in foals older than 40 days.
Epidemiology:
•The disease primarily affected younger foals (17–56 days old), consistent with prior reports.
•Subclinical or mild hepatic damage may precede acute disease onset in outbreaks.
•Despite the high fatality of Tyzzer’s disease, early intervention significantly improved survival chances.
•No clear source of C. piliforme was identified. Previous associations with muskrats or contaminated feed were not evident in this case.
•Spore persistence and environmental contamination are potential factors in recurrent outbreaks.
First report of equine parvovirus-hepatitis-associated Theiler’s disease in Europe
•EqPV-H nucleic acid was detected in the liver tissues of all affected horses via PCR and in situ hybridization (ISH).
•Consistent with Theiler’s disease:
-Centrilobular hepatic necrosis.
-Cytoplasmic vacuolation in periportal hepatocytes.
-Sinusoidal congestion.
-Mixed inflammatory cells in hepatic lobules and portal areas.
-ISH confirmed the presence of EqPV-H nucleic acid within hepatocytes, primarily in periportal regions.
•Four horses on a single stud farm, three of which received tetanus antitoxin. The fourth horse, while not directly exposed to equine biological products, was housed with an exposed horse, suggesting contagious transmission.
•Clinical signs ranged from depression, ataxia, and anorexia to severe liver dysfunction and neurological symptoms.
•Sequence analysis revealed a close genetic relationship between the virus in the biological products and the affected horses.
•Case of indirect transmission (horse without antitoxin exposure) highlights potential horizontal transmission via contact or vectors.
Investigating the pathogenesis of high-serum gamma-glutamyl transferase activity in Thoroughbred racehorses: A series of case-control studies
Core Hypothesis: Oxidative stress and mild cholestasis appear to be primary contributors to high GGT syndrome rather than a single pathological cause.
Key Study Outcomes
•No Viral Link
•Metabolic Indicators: Increased levels of pyroglutamic acid and glutamate suggest glutathione cycle involvement, indicating oxidative stress. Decreased levels of Vitamin B6 (pilot study) and selenium (both studies) further point to oxidative stress mechanisms.
•Mild increases in certain bile acids (e.g., taurocholic acid) and biomarkers of cholestasis (e.g., ALP, total bile acids) support a cholestatic contribution to high GGT activity.
•Liver and Metabolic Function: Subclinical liver injury may play a role, with slightly elevated GLDH and bilirubin levels observed in affected horses.
•Evidence of altered lipid metabolism includes increased abundance of fatty acids (e.g., palmitic acid) and decreased carnitine derivatives, suggesting impaired energy metabolism.
Oxidative Stress Hypothesis:
•Oxidative stress, indicated by glutathione depletion and associated metabolic changes, is a likely driver of the syndrome.
•Mild cholestasis could explain increased GGT activity through biliary epithelial damage or hyperplasia.
Association between forage mycotoxins and liver disease in horses
•Over 80% of hay samples analyzed contained mycotoxins, regardless of being sourced from premises with or without outbreaks of liver disease.
•10 mycotoxins were exclusively identified on premises with liver disease outbreaks, including fumonisin B1, aflatoxins, zearalenone, and deoxynivalenol, which are known hepatotoxins.
-Fumonisin B1 was the most prevalent hepatotoxic mycotoxin, with significantly higher levels on case premises than controls.
-Other exclusive hepatotoxic mycotoxins in cases included: Aflatoxins B1 and G1, 15-acetyldeoxynivalenol, Deoxynivalenol, Nivalenol, Zearalenone, Wortmannin
•Fumonisin B1 Mechanism: Acts as a ceramide synthase inhibitor, disrupting sphingolipid biosynthesis. Associated with neurotoxicity (leukoencephalomalacia) and hepatotoxicity in horses. Chronic low-dose exposure is less understood but may cause subtle hepatocyte apoptosis and necrosis. Histo was consistent
•Evidence suggests synergistic effects among hepatotoxins (e.g., aflatoxins, trichothecenes, fumonisins), potentially exacerbating liver damage in outbreaks.
•Improved storage conditions could minimize fungal contamination and mycotoxin production. Regular screening of hay for known hepatotoxic mycotoxins is recommended, especially during liver disease outbreaks.
•Mycotoxin binders and other feed additives could help mitigate exposure in horses at risk. Identifying and excluding affected forage from equine diets is critical during disease outbreaks.
Nasal transmission of equine parvovirus hepatitis
• confirms nasal transmission of EqPV-H, expanding the understanding of natural transmission modes.
•No evidence supports oral transmission of EqPV-H in this experimental setting, contradicting earlier findings.
•A prolonged eclipse phase (up to 12 weeks) was observed before detectable viremia after nasal inoculation.
•Horizontal transmission between horses was inferred during the study period, emphasizing the efficiency of spread within herds.
Challenges in Containment:
•Horses shed EqPV-H for at least 10 weeks during acute infections, complicating efforts to isolate infected animals.
•Chronic infections may persist for years, with the potential for shedding, though this remains unstudied.
•The prolonged incubation phase means monitoring for infection requires extended observation periods.
•A vaccine inducing strong IgA-mediated mucosal immunity in the nasal passages is suggested as a promising approach.
•The study supports the hypothesis that concurrent hepatic or systemic stress could promote EqPV-H replication in hepatocytes, as described by the “two-hit” theory of viral replication.
Subclinical infection and potential shedding routes of equine parvovirus-hepatitis among hospitalized horses in Austria
•EqPV-H viremia was detected in 12.9% of hospitalized horses, while 10.3% of horses were seropositive for anti-EqPV-H antibodies.
•The viral load was generally low, with quantifiable levels in only a small subset of samples.
•EqPV-H DNA was identified in nasal secretions (2 horses) and fecal samples (1 horse), suggesting potential routes for horizontal transmission.
•Viral shedding in nasal and fecal samples aligns with previous studies but occurred at lower levels than experimental inoculation studies.
•EqPV-H is a non-enveloped virus, making it highly stable under environmental conditions. This increases the risk of environmental and nosocomial transmission in hospital settings.
Detection Limitations:
•Many samples were close to the detection limit of qPCR, resulting in inconclusive results that could not be validated by nested PCR (nPCR).
•The low viral loads in some samples raise questions about the relevance of these findings, particularly whether the detected DNA represents infectious particles.
•Horses with viremia but no antibodies could represent acute infections, immune evasion by the virus, or insufficient immune responses.
•Persistent low-level viremia, as seen in humans with parvovirus B19, may also occur with EqPV-H, complicating diagnosis and management.
Risk Factors
•No significant associations were found between EqPV-H infection and age, sex, or seasonality in this cohort.
•This contrasts with some studies reporting higher viremia in older horses or seasonal patterns of infection.
Nosocomial Risk:
•Hospitalized horses may be at higher risk for EqPV-H due to immunosuppression or stress, which could increase susceptibility to infection or viral shedding.
•Screening of horses, especially before plasma or blood transfusions, is critical to mitigate the risk of iatrogenic transmission.
Detection of Hepatitis E Virus Genotypes 3 and 4 in Donkeys in Northern China
•12.22% of donkeys were seropositive for anti-HEV antibodies, and 4.24% were RNA-positive, indicating active infection.
• The HEV RNA isolated belonged to genotypes 3b, 4b, and 4h, which are prevalent in domestic pigs in China. These findings support the hypothesis of cross-species transmission from pigs to donkeys.
•Younger donkeys (0.5–1 year) had higher RNA positivity rates (8.02%) compared to older age groups (declined to 0% by 1.5–2 years).
•Older donkeys (1.5–2 years) exhibited higher antibody levels, suggesting successful immune responses after prior exposure.
•HEV is zoonotic, and donkeys may pose a risk of transmission through meat products or direct contact, especially as intensive farming practices expand in China.
•While primarily transmitted via the fecal-oral route, other routes (e.g., vertical transmission, contaminated dairy products, blood transfusion) are documented in other species and may apply to donkeys.
First Report of Equine Parvovirus-Hepatitis (EqPV-H) in Argentina
EqPV-H DNA was detected in:
•15.7% of equine serum pools (8/51 pools).
•60% of commercial horse serum batches (3/5 batches).
•1.71% of individual serum samples (3/175 donor horses).
•The viral load in commercial serum (940 copies/ml) and donor horse samples (1100–8885 copies/ml) was consistent with levels reported in other countries, indicating similar infection dynamics.
•Sensitivity Issues in qPCR: Some samples were classified as indeterminate due to low viral DNA levels near the limit of detection -> nested-PCR
•Pooling Effect: Serum pools showed a lower detection rate due to the dilution effect when mixing sera from multiple horses
•Local EqPV-H strains exhibited low genetic variability and high similarity to strains from Germany and China.
•Phylogenetic clustering of Argentine strains with German and Chinese strains suggests potential shared origins or transmission pathways.
A seasonal idiopathic hepatitis syndrome in horses presented to a Midwestern veterinary teaching hospital
-seasonal idiopathic hepatitis syndrome in horses, observed during two 4-month periods across two years (2021-2022)-biphasic fevers, systemic inflammation, and histologically confirmed multifocal hepatitis.
-No single etiologic agent (bacterial, viral, or toxic) was conclusively identified despite extensive diagnostic testing.
Potential Etiologies and Differential Diagnoses
Infectious Pathogens:
-Hepatotropic viruses such as EqPV-H and NPHV were considered but deemed unlikely due to lack of liver failure and incidental molecular findings. Novel?
-Bacterial Causes: Unlikely as cultures and PCR tests for common pathogens were negative
-Not typical of toxin-induced liver injuries which generally show zonal necrosis and mild inflammation.
-Piecemeal necrosis raises suspicion of autoimmune mechanisms; however, recovery without corticosteroids makes this less likely.
-All affected horses showed clinical recovery without liver failure or recurrence by the time of publication.
-Normalization of liver enzyme activity (GGT) took up to 162 days in some cases.
-No long-term sequelae were reported among horses that completed follow-up.
Active equine parvovirus-hepatitis infection is most frequently detected in Austrian horses of advanced age
-sero+ 30.1% of horses, DNA in 8.9%, Evidence of infection found in 17 of 21 properties, highlighting its widespread presence.
-Donkeys (n=3) showed no antibodies or DNA
-69% negative for both, 22% sero+ PCR-, 21% sero+ PCR +, 0.8% sero- PCR +. PCR + horses tended to have higher titres.
-1 co-infected with EqHV = 4.3%
Age-related Risk:
-Older horses (16–31 years) had higher odds of active infection: 8.19x higher than horses aged 1–8 years. 2.96x higher than those aged 9–15 years.
-Risk increases with age (1.1x per additional year).
-Most active infections were subclinical.
Genetic Stability:
-Austrian strains highly similar to those in Germany, Italy, China, and the USA. Low genetic diversity suggests a globally stable virus.
-Austrian variants closely clustered with strains worldwide, reinforcing shared origins.
Liver Parameters:
-Mild GGT elevations in two infected horses; all other markers (GLDH, bile acids, albumin) within normal ranges. Most are subclinical
-Variability in antibody response hints at differences in infection clearance.
-Older horses may show increased susceptibility due to accumulated exposure or weaker immunity.
Fasciola hepatica in UK horses
F. hepatica excretory-secretory (ES) ELISA:
• 71% sensitivity and 97% specificity.
•Seroprevalence in the UK horses sampled at abattoirs was 8.7%, with 10% overall prevalence across all study horses.
•Horses with liver disease had 6.4 times higher odds of testing positive for F. hepatica than controls.
Epidemiology and Risk Factors
•Horses frequently graze with sheep and cattle, which are significant reservoirs for F. hepatica.
•New Forest ponies had higher fluke exposure (15%), likely due to unmanaged grazing on wet, fluke-prone pastures.
•Geographic origin was significant, with liver fluke more prevalent in wetter regions like Wales and western England.
Clinical Implications
•Clinical signs in seropositive horses were vague and variable, including lethargy, weight loss, jaundice, and colic, with many cases showing no clinical abnormalities.
•Elevated gamma-glutamyl transferase (GGT) and glutamate dehydrogenase (GLDH) were common biochemical indicators.
•The stage and intensity of infection influenced clinical presentation, with some fluke infections being asymptomatic.
Genetic Analysis
•Low genetic differentiation (FST = 0.0236) between flukes from horses, sheep, and cattle indicates significant gene flow among species.
•Shared grazing environments facilitate this genetic exchange, emphasizing the interconnectedness of parasite populations in different hosts.
Management and Treatment
•Treatments reported in literature include triclabendazole (15 mg/kg p/o), closantel (10 mg/kg p/o), oxyclosanide (10 mg/kg p/o), and nitroxynil (7 mg/kg s/c).
