Submitted by: Patricia Shea, DVM
J Vet Intern Med. 2022; 36:1648-1659. doi:10.1111/jvim.16525
Domestic cat hepadnavirus associated with hepatopathy in cats: A retrospective study.
Piewbang C, Dankaona W, et al.
Domestic cat hepadnavirus (DCH) is a novel hepadnavirus first discovered in an Australian cat with FIV and hepatic large cell lymphoma. Hepadnaviruses are blood-borne, enveloped hepatotropic viruses of the family Hepadnaviridae. They have very small genomes of partially double-stranded and partially single-stranded DNA and encode their own polymerase rather than using host cell machinery like some other viruses.
Similar to the Retroviridae family, which includes feline leukemia (FeLV) and feline immunodeficiency (FIV) viruses, Hepadnaviridae produce a polymerase with reverse transcriptase activity, allowing the conversion of RNA into DNA to replicate the genome. A well-known member of the Hepadnaviridae is the human hepatitis B virus, which is associated with hepatic cirrhosis and hepatocellular carcinoma in people. Hepadnaviruses are also found in vertebrate species other than humans and are similarly associated with hepatobiliary diseases in nonhuman animals.
Since its discovery in Australia, DCH has emerged as a possible new feline infectious disease in the USA, United Kingdom, Italy, Malaysia, Thailand, and New Zealand, and not just in cats with concurrent retroviral infection. Using molecular detection techniques, DCH has been found in archived samples of feline liver tissues with chronic hepatitis or hepatocellular carcinoma, but not in cases with cholangitis or cholangiocarcinoma only, and not in normal feline liver tissue samples. Moreover, in previous studies of cats with abnormal hepatic biochemical profiles, DCH was found to be more prevalent, but most of the DCH-positive cats thus identified had concomitant infections, which could also have an impact on biochemical parameters associated with liver function.
In the present retrospective cross-sectional study of 1,022 cats in Thailand without concurrent diseases or treatments adversely affecting the liver, the authors aimed to determine whether DCH has a definitive role in feline liver disease. They investigated the prevalence of DCH in domestic cats which tested negative for other feline viruses associated with hepatopathy and also sought information about the presence of DCH in cats with and without a histologically diagnosed hepatic parenchymal disorder, as well as any association between the presence of DCH and liver damage based on a histologic determination of proliferative and apoptotic indices.
Based on the information provided through history taking or evaluation of medical records, cats included in the study had no evidence of concurrent diseases such as hyperthyroidism, pancreatitis, or cardiovascular disorders. They also had no history of treatment with corticosteroids, antifungal drugs, or anticonvulsants within 3 months prior to sample collection, or any history of surgery within a month before sample collection. EDTA blood samples (n=898) and liver tissue samples (from deceased cats; n=124), totaling 1,022 samples, were collected from individual cats that met the previous inclusion criteria. After the blood samples were screened for feline calicivirus, feline coronavirus, FeLV, and FIV, and the liver tissue samples were checked for evidence of portosystemic shunts, portal hypertension, outflow disturbances, and suppurative cholangitis, 341 blood samples, and five liver tissue samples were eliminated from the investigation, leaving 557 EDTA blood samples and 119 liver tissue samples to be subjected to DCH detection and further analysis.
The 557 blood samples ultimately used in the study came from 274 (49.19%) male and 229 (41.11%) female cats, with 54 (9.69%) not identified as to sex; cats providing blood samples had a mean age of 5.05 years (range 22 days-20 years). Most of the cats (415/557; 74.51%) were domestic shorthair, 37 were Persian (6.64%), and 20 were Scottish Fold (3.59%); the rest of the samples came from cats of other breeds or unidentified breeds. Liver samples came from 70 males (58.82%), and 49 females (41.18%); the mean age of the cats providing liver samples was 4.25 years (range, 2 months-17 years); domestic shorthair (n=101; 84.87%) was also the most prevalent breed in this group.
Almost 20% (n=103; 18.49%) of the 557 blood samples tested positive for DCH using a quantitative polymerase chain reaction (qPCR). Older cats (5.0-9.9 years) were more likely to test positive for DCH than those less than a year old. Sex and breed were not shown to be correlated with the presence of DCH. DCH-positive cats had significant elevation of two liver enzymes: AST and ALT, which could point to hepatocyte damage, but not ALP and GGT. Total serum protein, albumin, cholesterol, triglyceride, and total bilirubin were not associated with the presence of DCH.
11 of the 119 (9.24%) liver tissue samples tested positive for DCH using qPCR; of these, the majority (9/11; 81.81%) also demonstrated histologic evidence of parenchymal disease. DCH was found within the cytoplasm of the hepatocytes, particularly in the areas most adjacent to inflammatory lesions. Tissue sections of these nine diseased livers revealed both lymphoplasmacytic periportal and parenchymal infiltrations in varying degrees. The number of DCH viral copies present in the samples was positively correlated with the degree of portal hepatitis and parenchymal hepatitis, as well as with the intensity of DCH hybridization signals in the tissue samples. The two cats with DCH-positive liver tissue samples that had a histologically normal liver had only small amounts of fatty degeneration in their hepatic parenchyma with no inflammation and were considered to be possibly in the acute stages of DCH infection.No immunohistochemical or hybridization signals were identified within the hepatocytes in the DCH-negative liver tissue sections.
DCH was found to be more prevalent in chronic hepatitis. Interface hepatitis, which is characterized by the death of hepatocytes at the interface of parenchyma and the connective tissue of the portal zone, accompanied by a variable degree of inflammation and fibrosis, was the most common pathological feature in DCH-positive liver tissue samples. Hepatic parenchymal proliferation, not apoptosis, was associated with DCH infection.
The investigators concluded that DCH infection was associated with high serum activity of AST and ALT, two enzymes that originate from within hepatocytes and therefore directly reflect hepatocyte damage, and chronic lymphoplasmacytic hepatitis, but not pyogranulomatous hepatitis.
J Am Vet Med Assoc 2022;260:1471-1474.
Conservative nonsurgical treatment for cranial cruciate ligament disease can be an effective management strategy in cats based on validated owner-based subjective assessment in some cases
Stoneburner RM, Howard J, et al.
Cranial cruciate ligament disease (CCLD) is one of the most common and well-investigated orthopedic problems in dogs. Despite the prevalence of CCLD in dogs, its exact pathogenesis is unclear; however, risk factors such as obesity, abnormal conformation, age, and breed, have been identified. Likewise, the pathogenesis of CCLD in cats is also unclear. Particularly in dogs over 15 kg, surgical stabilization results in the best outcome for the patient. Small dogs (<15 kg) are thought to fare better than their larger conspecifics with conservative management only, but no recent studies have been done to document this. A recent study of cats with CCLD in Norway and Sweden with a long follow-up period (41 months) determined that those animals treated conservatively had less chronic pain over the long term than those who had surgical intervention.
In this retrospective study of medical records of cats with CCLD treated conservatively at two university veterinary teaching hospitals, owner follow-up was obtained via telephone or email interview. Ultimately, 18 cats presented between 2000 and 2021 presented to the two facilities involved in the study were included. CCLD was diagnosed in these patients based on the presence of a cranial drawer sign, cranial tibial thrust, or both. The presence of meniscal tears in these patients was unknown because they did not undergo surgery.
Owners of the study cats were interviewed by the investigators and answered a two-part questionnaire. The first part of the questionnaire focused on short-term (< six months) outcomes following the start of medical management for CCLD; a normal/successful outcome was defined as the cat returning to its level of mobility prior to the cruciate ligament injury. The validated Feline Musculoskeletal Pain Index (FMPI) clinical metrology instrument was used to evaluate long-term (>six months) outcomes. The mean follow-up time for the group was 66.5 ±46.7 months (range, seven to 154 months).
The body weight mean at presentation was 5.8 ± 2.7 kg (range, 2.5-15.5 kg), and the mean age at presentation was 8.8 ± 5.0 years (range, 0.5-19 years). Nine spayed females, eight castrated males, and one intact male were in the study; breeds included were Domestic Shorthair (n=13), Maine Coon (n=3), Ragdoll (n=1), and American Shorthair (n=1). CCLD was found in the right stifle in eight cats, in the left stifle in eight cats, and two had bilateral disease. Body condition scoring demonstrated that one cat was underweight, eight were in ideal body condition, four cats were overweight, and 2two were obese. Three cats did not have a body condition score recorded at the presentation.
Other musculoskeletal comorbidities in the patients included a capital physeal fracture in the contralateral limb (treated with a femoral head and neck ostectomy; n=1), obesity (n=2), and bilateral grade 2/4 medial patellar luxations (n=1). One patient had placing defects in the pelvic limbs which were thought to be associated with suspected myelopathy. Only nine of the 18 cats were confirmed alive at the time of follow-up.
The cats received a number of treatments. 17 of the patients were prescribed oral analgesics including robenacoxib, buprenorphine, gabapentin, meloxicam, tramadol, or prednisolone. The most commonly administered oral analgesics used in the patient group were NSAIDs, particularly meloxicam and robenacoxib. Other disease-modifying treatments included exercise restriction (mean 6.7 weeks; range 2-8 weeks) in 14 patients, treatment with injectable polysulfated glycosaminoglycans (n=3), or glucosamine hydrochloride and sodium chondroitin sulfate products (n=3), and weight loss (n=2).
No additional veterinary care for CCLD beyond their initial visit to the veterinary teaching hospital was necessary for 16 of the 18 cats. One of the two cats who did require additional care had worsening lameness two days after the first presentation, for which they received additional oral analgesia, and the other received cold laser therapy with their primary care veterinarian.
Outcomes for the 18 cats were as follows: 13 either were always weight-bearing on the affected limb or resumed weight-bearing within a week of beginning medical therapy; an additional four became weight-bearing on the affected leg within 2-4 weeks, and one took over a month to become weight-bearing. A significant majority of the patients (15/18; 83%) were perceived by their owners as having clinically normal mobility and no obvious lameness within three months after starting medical therapy. Two cats never became clinically normal, and one took over 3 months to become clinically normal. Caregivers of 17/18 cats (94%) stated that their cat had a good to excellent outcome with the medical therapy they received.
Limitations of this study were many: its retrospective nature; a small number of subjects; variability in management strategies; unavailability of patients for long-term veterinary follow-up evaluation of stifle joint stability, stifle range of motion, subtle lameness and/or pain; lack of advanced imaging studies to determine the presence of meniscal tears or degree of cruciate ligament rupture; and long duration of follow-up, with half of the patients being deceased by the time of the survey. However, the findings of this study do illustrate the potential for excellent long-term outcomes in cats with CCLD with medical management only. Prospective studies of larger patient populations in which advanced imaging studies are performed and outcomes compared for surgery versus medical management, as well as investigations of risk factors for the development of feline CCLD, are needed to determine which treatment strategy is optimal in different situations. The authors’ recommendation is that cats with CCLD treated with medical management be re-evaluated within 2-3 months of initial presentation; if they are not responding well, surgical intervention should be seriously considered.