Feline Liver Failure

Sonopath Forum

Feline Liver Failure

– 1.5 yr old female breeding Savannah cat presented for pyrexia, anorexia

– she was treated with ronidazole about 1 week previous due to positive tritrichomonas test on PCR although she was not symptomatic at the time (the breeder tries to be proactive)

– after a few days, the cat was showing ataxia (a known side effect) so the ronidazole was stopped; neuro signs ceased but  she then became sick

– 1.5 yr old female breeding Savannah cat presented for pyrexia, anorexia

– she was treated with ronidazole about 1 week previous due to positive tritrichomonas test on PCR although she was not symptomatic at the time (the breeder tries to be proactive)

– after a few days, the cat was showing ataxia (a known side effect) so the ronidazole was stopped; neuro signs ceased but  she then became sick

– bloodwork shows neutrophilia with toxic neuts and left shift, mild anemia, elevated bilirubin, low alb, low Ca, low ALP and a low normal ALT. TP and Globulins wnl. fPLI wnl. FeLeuk Neg.  She is not clinically jaundiced

– the breeder was concerend about pyometra

– u/s showed midly hypoechoic liver, enlarged portal, gastric, jejunal and ileocecal LN’s with peri-nodal inflammation

– no evidence of biliary obstruciton, pancreas uterus appeared normal; no peritoneal effusion

– there is a persisting fever despite antibiotics and fluids (very FIP like symptom)

My differentials are acute hepatitis/cholangiohepatitis (toxic, infectious), FIP, neoplasia (less likely but possible). We are tentatively performing FNA’s on the liver and lymph nodes on Monday as breeder wants to see how she does over the weekend first. Vit K was also started. I have two questions regarding FNA in this case:

1. Will pyogranulomatous inflammtion show up in a liver FNA or is core biopsy required?

2. Any experience with the IDEXX PCR testing using FNA samples? I  don’t even bother running this test on blood as it is useless but I attended an IDEXX talk recently where they recommended sending in FNA samples of tissue to screen for FIP – I am skeptical but they were quite persistent that this is a good test.

Comments

randyhermandvm

Here is an overview and

Here is an overview and summary from a good article on VIN:

 

Polymerase chain reaction (PCR) testing

a.  Body fluids, feces (to document an FECV infection), and tissues.

b.  It was developed to detect virus particles in whole blood based on the assumption that FIP virus spreads via the bloodstream whereas FECV remains in the intestinal epithelium. Unfortunately, virus particles can still be detected in the blood of healthy cats with FECV, suggesting that small numbers of FECV particles do circulate but are unable to replicate or cause problems outside of the intestinal tract. Moreover, this test has not been shown to be capable of differentiating between FECV and FIPV.

c.  mRNA PCR: It is a NEW PCR test. It detects and quantifies the replicating virus as opposed to only detecting the presence of viral genomic RNA that may or may not be associated with active viral replication. It recognizes messenger RNA (mRNA) of the highly conserved M gene of all known coronavirus strains in ANY sample. mRNA is produced during viral replication in mononuclear cells. It seems to better differentiate FIP from FECV infection. It takes advantage of the fact that the pathogenic feline coronavirus is able to replicate within mononuclear cells, whereas FECV may be able to enter the bloodstream but is not able to replicate outside of the intestinal tract (thus no mRNA is produced). Therefore, for diagnosis of FIP, only the detection of mRNA outside of the intestinal tract is indicative since active replication of the virus in circulating mononuclear cells is typical for FIP. In contrast, non-FIP feline coronavirus strains replicate in the intestinal tract, but not in blood mononuclear cells.

i.  Based on initial results there is still a lot of work to be done–Simons, F.A.; Vennema, H.; Rofina, J.E.; Pol, J.M.; Horzinek, M.C.; Rottier, P.J.M.; Egberink, H.F. A mRNA PCR for the diagnosis of feline infectious peritonitis. Journal of Virological Methods 124 (2005), 111-116.

ii.  It has not been widely used clinically to determine its ease of use, cost effectiveness, and reliability.

iii.  Currently, FIP mRNA Triple Test is being recommended in order to maximize the predictive value for confirmation as well as exclusion of FIP (near 100% positive and negative predictive value). Three independent samples from the same cat are examined: blood, effusion fluid (ascites, pleural), biopsy or aspirate of the tissue of an affected organ (e.g., kidney, enlarged lymph node). The addition of a fecal sample will not increase the positive predictive value of the extra-intestinal samples, but negativity in this test will rule out concurrent intestinal feline coronavirus infection. This will increase the negative predictive value of the FIP mRNA Triple Test if all extra-intestinal samples are also negative.

iv.  It is available from the College of Veterinary Medicine at Auburn University (Molecular Diagnostics, College of Veterinary Medicine, Auburn University; http://www.vetmed.auburn.edu/index.pl/feline_infectious_peritonitis_virus).

v.  Disadvantages of PCR testing: risk of contamination and adequate controls not used. In addition, the number of virus strains and the rate of mutation of the viral genes can result in an inaccurate outcome. The other major drawback of PCR is the potential consequence (euthanasia) of a false positive result. Therefore, the results of any PCR test should be carefully interpreted in the context of clinical suspicion and not relied on as a stand-alone diagnostic test.

11.  Histological diagnosis: It is necessary to confirm a diagnosis either at post-mortem or following biopsy of an affected organ. Owners (particularly of catteries and multiple-cat households) should be strongly encouraged to have a diagnosis of FIP confirmed.

a.  It typically shows pyogranulomatous lesions.

b.  To diagnose FIP definitely, vasculitis must be confirmed.

c.  Immunohistochemistry or direct fluorescent antibody testing may be necessary to confirm a diagnosis in samples with atypical histological appearance. Viral detection can be applied to effusion, cytologic, or biopsy specimens. Immunohistochemistry is the absolute gold standard!

Overview of the Issue

Currently the presumptive diagnosis of FIP is based on clinical data and characteristic changes in some blood parameters. No single laboratory test is reliable for the diagnosis. It must be made by a preponderance of evidence from history, clinical signs, fluid analysis, and the new PCR test. Routine serum biochemistry and hematology may give some clues of FIP (e.g., hyperglobulinemia, hyperbilirubinemia, mild non-regenerative anemia, lymphopenia, mature neutrophilia). In a practical manner a young cat with persistent fever, pleural effusion, purple background over the slide (effusion), low PCV (< 20%), hyperproteinemia, A:G ratio < 0.6 and leukocytosis, there is a 98% of chance of having a FIP cat. Cytology and biochemistry of the effusion should be done since tests on effusions are more reliable than on blood or serum. Because of that, the most important step is to identify any effusion that might be present. In cases with no effusion, consider systemic (e.g., fever, depression, icterus, renal failure, diarrhea), neurologic and ocular signs as well. A through clinical examination including complete neurological and ophthalmological examination is important in order to look for evidence of inflammatory disease which can be associated with non-effusive FIP. CSF analysis may be indicated in those cats with neurological disease. The new PCR test must be requested as a very important parameter, although a definitive diagnosis can still only be made on the basis of histological examination of biopsy material or post-mortem.

Summary

Feline Infectious Peritonitis (FIP) is a disseminated disease caused by a highly pathogenic feline coronavirus. This virus is a mutation of the Feline Enteric Coronavirus (FECV) that is either non-pathogenic or causes only mild intestinal disease. Those two strains can not be distinguished from one another morphologically or antigenically. This is what makes FIP diagnosis so challenging. The diagnosis of feline infectious peritonitis in most patients is complicated. It should never be based solely on one diagnostic test. Clinical signs, laboratory findings, serologic testing and organism-specific identification are essential parameters that need to be considered.

randyhermandvm

Here is an overview and

Here is an overview and summary from a good article on VIN:

 

Polymerase chain reaction (PCR) testing

a.  Body fluids, feces (to document an FECV infection), and tissues.

b.  It was developed to detect virus particles in whole blood based on the assumption that FIP virus spreads via the bloodstream whereas FECV remains in the intestinal epithelium. Unfortunately, virus particles can still be detected in the blood of healthy cats with FECV, suggesting that small numbers of FECV particles do circulate but are unable to replicate or cause problems outside of the intestinal tract. Moreover, this test has not been shown to be capable of differentiating between FECV and FIPV.

c.  mRNA PCR: It is a NEW PCR test. It detects and quantifies the replicating virus as opposed to only detecting the presence of viral genomic RNA that may or may not be associated with active viral replication. It recognizes messenger RNA (mRNA) of the highly conserved M gene of all known coronavirus strains in ANY sample. mRNA is produced during viral replication in mononuclear cells. It seems to better differentiate FIP from FECV infection. It takes advantage of the fact that the pathogenic feline coronavirus is able to replicate within mononuclear cells, whereas FECV may be able to enter the bloodstream but is not able to replicate outside of the intestinal tract (thus no mRNA is produced). Therefore, for diagnosis of FIP, only the detection of mRNA outside of the intestinal tract is indicative since active replication of the virus in circulating mononuclear cells is typical for FIP. In contrast, non-FIP feline coronavirus strains replicate in the intestinal tract, but not in blood mononuclear cells.

i.  Based on initial results there is still a lot of work to be done–Simons, F.A.; Vennema, H.; Rofina, J.E.; Pol, J.M.; Horzinek, M.C.; Rottier, P.J.M.; Egberink, H.F. A mRNA PCR for the diagnosis of feline infectious peritonitis. Journal of Virological Methods 124 (2005), 111-116.

ii.  It has not been widely used clinically to determine its ease of use, cost effectiveness, and reliability.

iii.  Currently, FIP mRNA Triple Test is being recommended in order to maximize the predictive value for confirmation as well as exclusion of FIP (near 100% positive and negative predictive value). Three independent samples from the same cat are examined: blood, effusion fluid (ascites, pleural), biopsy or aspirate of the tissue of an affected organ (e.g., kidney, enlarged lymph node). The addition of a fecal sample will not increase the positive predictive value of the extra-intestinal samples, but negativity in this test will rule out concurrent intestinal feline coronavirus infection. This will increase the negative predictive value of the FIP mRNA Triple Test if all extra-intestinal samples are also negative.

iv.  It is available from the College of Veterinary Medicine at Auburn University (Molecular Diagnostics, College of Veterinary Medicine, Auburn University; http://www.vetmed.auburn.edu/index.pl/feline_infectious_peritonitis_virus).

v.  Disadvantages of PCR testing: risk of contamination and adequate controls not used. In addition, the number of virus strains and the rate of mutation of the viral genes can result in an inaccurate outcome. The other major drawback of PCR is the potential consequence (euthanasia) of a false positive result. Therefore, the results of any PCR test should be carefully interpreted in the context of clinical suspicion and not relied on as a stand-alone diagnostic test.

11.  Histological diagnosis: It is necessary to confirm a diagnosis either at post-mortem or following biopsy of an affected organ. Owners (particularly of catteries and multiple-cat households) should be strongly encouraged to have a diagnosis of FIP confirmed.

a.  It typically shows pyogranulomatous lesions.

b.  To diagnose FIP definitely, vasculitis must be confirmed.

c.  Immunohistochemistry or direct fluorescent antibody testing may be necessary to confirm a diagnosis in samples with atypical histological appearance. Viral detection can be applied to effusion, cytologic, or biopsy specimens. Immunohistochemistry is the absolute gold standard!

Overview of the Issue

Currently the presumptive diagnosis of FIP is based on clinical data and characteristic changes in some blood parameters. No single laboratory test is reliable for the diagnosis. It must be made by a preponderance of evidence from history, clinical signs, fluid analysis, and the new PCR test. Routine serum biochemistry and hematology may give some clues of FIP (e.g., hyperglobulinemia, hyperbilirubinemia, mild non-regenerative anemia, lymphopenia, mature neutrophilia). In a practical manner a young cat with persistent fever, pleural effusion, purple background over the slide (effusion), low PCV (< 20%), hyperproteinemia, A:G ratio < 0.6 and leukocytosis, there is a 98% of chance of having a FIP cat. Cytology and biochemistry of the effusion should be done since tests on effusions are more reliable than on blood or serum. Because of that, the most important step is to identify any effusion that might be present. In cases with no effusion, consider systemic (e.g., fever, depression, icterus, renal failure, diarrhea), neurologic and ocular signs as well. A through clinical examination including complete neurological and ophthalmological examination is important in order to look for evidence of inflammatory disease which can be associated with non-effusive FIP. CSF analysis may be indicated in those cats with neurological disease. The new PCR test must be requested as a very important parameter, although a definitive diagnosis can still only be made on the basis of histological examination of biopsy material or post-mortem.

Summary

Feline Infectious Peritonitis (FIP) is a disseminated disease caused by a highly pathogenic feline coronavirus. This virus is a mutation of the Feline Enteric Coronavirus (FECV) that is either non-pathogenic or causes only mild intestinal disease. Those two strains can not be distinguished from one another morphologically or antigenically. This is what makes FIP diagnosis so challenging. The diagnosis of feline infectious peritonitis in most patients is complicated. It should never be based solely on one diagnostic test. Clinical signs, laboratory findings, serologic testing and organism-specific identification are essential parameters that need to be considered.

Pankatz

Thanks Randy – you’re the

Thanks Randy – you’re the king of research!  It might be interesting to send an FNA sample of the liver and LN’s to see what happens. I believe the IDEXX test is just the straight-forward PCR test.

Pankatz

Thanks Randy – you’re the

Thanks Randy – you’re the king of research!  It might be interesting to send an FNA sample of the liver and LN’s to see what happens. I believe the IDEXX test is just the straight-forward PCR test.

randyhermandvm

It just seems to me, if this

It just seems to me, if this is a valuable breeding animal, it would make sense to open this cat up and get full thickness biopsies. FIP could devestate her cattery. I think that is the only way to know for sure.

randyhermandvm

It just seems to me, if this

It just seems to me, if this is a valuable breeding animal, it would make sense to open this cat up and get full thickness biopsies. FIP could devestate her cattery. I think that is the only way to know for sure.

Pankatz

Randy, corona is

Randy, corona is transmissible but FIP itself is not. It is a mutation of the non-pathologic corona virus that decides to mutate in an individual.  Many cats are corona positive but never develop FIP.  But I agree we should get a firm diagnosis.

Pankatz

Randy, corona is

Randy, corona is transmissible but FIP itself is not. It is a mutation of the non-pathologic corona virus that decides to mutate in an individual.  Many cats are corona positive but never develop FIP.  But I agree we should get a firm diagnosis.

EL

Nice thx Randy

Nice thx Randy

EL

Nice thx Randy

Nice thx Randy

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