Therapeutic management of diabetes mellitus with focal hepatic necrosis in dog.
Diabetes mellitus is a common condition in dogs with many concurrent complications such as cataract, urinary tract infection, metabolic acidosis, nephropathy, neuropathy, hepatic lipidosis and liver failure (Munana, 1995). Many times the treatment is directed towards maintaining euoglycemia and ignoring other important conditions resulting from diabetes mellitus. Clinical signs are typically polyuria, polydipsia and polyphagia. In the present study, proper diagnosis and management of a dog suffering from focal hepatic necrosis associated with diabetes mellitus was made using synergy of appropriate complementary examinations (including imaging and clinical pathology) and proper treatment.
History and Diagnosis
A 7 year old, intact female, Labrador retriever was presented with 5 day history of anorexia, weakness, polyuria and polydipsia. The report of the referring Veterinarian revealed normal body temperature (102[degrees]F), progressive weight loss and dullness at physical examination. Hematology and biochemistry profiles is presented in Table 1 and 2, respectively. Remarkable results included subtle elevation of liver enzymes (subtle increased alanine aminotransferase and aspartate aminotransferase activities), decreased hepatic function (moderately increased fasting serum bile acids, mild hypoalbuminemia and slightly perbilirubinemia) and cholestasis (markedly increased alkaline phosphatase and gamma-glutamyltransferas activities). Leukogram revealed inflammatory response (absolute neutrophilia with moderate left shift and marked toxic changes in many neutrophils). Urine analysis revealed bilirubinuria (+ ++), glucosuria (++), proteinuria (++), ketonuria (++++), isosthenuria and acidic urine pH. Coagulation profiles were within reference ranges. Microscopic examination of urine sediment revealed many coarsely to finely granular casts along with large number of intact RBCs and occasional pus cells (1-2 cells per HPF). Lateral abdominal radiograph revealed hepatomegaly with rounded liver margins. Abdominal ultrasound was conducted to investigate suspected liver damage and showed grossly enlarged liver with hyperechoic echotexture and had multiple hypoechoic nodules measuring 0.81-2.2 cm in liver lobes suggestive of liver abscess/neoplasia or large focal hepatic necrosis (Fig. 1). There was splenomegaly with normal echotexture. An ultrasound guided, fine needle aspiration of nodules revealed hepatocellular degeneration, severe fatty changes and necrosis with loss of nuclei and in some places mild mononuclear cells infiltration, RBCs and neutrophils were also seen (Fig. 2).
The 18.5 kg dog was treated for 6 weeks with NPH Insulin (Mixact (a)) 9 Units BID and Ampicillin (Roscillin (a)) 250 mg, IM, twice daily for 2 weeks, liver extract (Belamyl (b)), silymarin syrup 10 mg, BID, ursodeoxycholic acid (Udiliv (c)) tablets, 300 mg, PO, SID and N- Acetylcysteine (Mucinac (d) 600) tablets 300 mg, PO, SID. In addition, owner was advised to give low carbohydrate, high fiber and high protein diet. A careful glucose monitoring and frequent dose adjustment of insulin was carried out for next 2 weeks. Hematologic and serum biochemical results obtained 2 months after diagnosis showed rapid and satisfactory improvement (Table 1).
Ultrasonographic scanning of liver after 60 days showed hyperechoic echotexture of liver which could be attributed to chronicity of disease/ secondary hepatic lipidosis but large focal areas of hepatic necrosis had disappeared.
Diabetes mellitus is commonly seen in dogs presented for treatment, but thorough investigation of other organ systems involved is rarely done, treatment is always directed toward maintaining blood glucose and ignoring the other complications which could be life threatening as well. Many hepatic lesions are frequently associated with diabetes mellitus and ultrasonographic-guided FNAB for pathological examination of hepatocytes help to determine the diagnosis of hepatic lesions (Vignoli and Saunders, 2011). Microscopic examination of FNAB confirmed focal hepatic necrosis. Patients with diabetes have a high prevalence of liver disease and patients with liver disease have a high prevalence of diabetes (Tolman et al., 2007). The mechanism of hepatic necrosis in this case is unclear. Many factors such as shock, sepsis, anaesthesia, biliary disease and diabetic ketoacidosis may result in hepatic necrosis. Deng et al (2006) reported diabetes mellitus in a man who developed multiple hepatic infarctions. However, hepatic disease is often treatable and has a predictable prognosis when a definitive diagnosis is made. The treatment is often nonspecific, empirical and symptomatic (Watson, 2004; Bexfield and Watson, 2006).
The management of diabetes in patients with liver disease is theoretically complicated by liver related alterations in drug metabolism, potential interactions between drugs and a low, albeit real, incidence of hepatotoxicity. There are few clinical trials that specifically target patients with coexistent diabetes and liver disease. In this report, we share our experience in management of patients with concurrent diabetes and liver disease. The massive hepatic necrosis was managed by administration of N-acetylcysteine and Silymarin along with ursodeoxycholic acid and liver extract. Following treatment, focal hepatic lesion were found to decrease significantly and totally disappeared after 3 months based on ultrasonographic examination, though liver remained hyperechoic in echotexture due to hepatic lipidosis. It seems that N-acetylcysteine and silymarin were able to counteract lipid peroxidation and enzyme leakage. Effectiveness of N-acetylcysteine was attributed to its membrane stabilizing ability, antioxidant, anti-inflammatory and hepatoprotective properties (De Flora et al., 2001, Kerksick and Willoughby, 2005). Silymarin possesses an antioxidant activity (Bexfield and Watson, 2009). Ursodeoxycholic acid was also included in the treatment regimen as it reduces cell damage and oxidative stress resulting from retention of bile acids in liver (Meyer et al., 1997) as well as is potentially indicated in most cases of liver disease, particularly those associated with biliary stasis (Bexfield and Watson, 2009). In summary, we suggest that dogs with diabetes mellitus should be investigated for liver functions and other conditions. This will allow early detection of occult complications and successful medical treatment. This study also suggests that antioxidants such as N-acetylcysteine administration should be considered in patients with hepatic insufficiency.
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M.A. Hiblu, K. Dua (1), C.S. Randhawa, J. Mohindroo (2) and N.K. Sood (3)
Department of Veterinary Medicine College of Veterinay Science Guru Angad Dev Veterinary and Animal Sciences University (GADVASU) Ludhiana--141004 (Punjab)
(1.) Corresponding author. E-mail : email@example.com
(2.) Department of Veterinary Surgery and Radiology
(3.) Department of Teaching Veterinary Clinical Complex
(a)--Brand of Ranbaxy India Ltd., Delhi
(b)--Brand of Zydus Animal Health, Ahmedabad
(c)--Brand of Solvay Pharma India, Mumbai
(d)--Brand of Cipla Ltd., Mumbai
Table 1: Serum hemato-biochemical profile Parameter On presentation Post treatment Hematocrit (%) 22.5 35.7 Hemoglobin (g/dL) 8.0 10.9 WBC (x [10.sup.3]/[micro]L) 15.6 9.56 Neutrophils (%) 86 82 Lymphocytes (%) 14 18 Total protein (g/dL) 4.9 6.1 Albumin (g/L) 2.0 2.7 Globulin (g/L) 2.9 6.3 ALT (U/L) 90 62 AST (U/L) 90 83 ALP (U/L) >1500 349 GGT (U/L) 40 13 Preprandial serum bile 22.7 ND acids ([micro]mol/L) Total bilirubin (mg/dL) 3.0 0.4 Cholesterol (mg/L) 160 278 Parameter Reference range Hematocrit (%) 37-55 Hemoglobin (g/dL) 12-18 WBC (x [10.sup.3]/[micro]L) 6-17 Neutrophils (%) 60-70 Lymphocytes (%) 12-30 Total protein (g/dL) 5.5-7.5 Albumin (g/L) 2.6-4 Globulin (g/L) 2.1-3.7 ALT (U/L) 8.2-57 AST (U/L) 8.9-49 ALP (U/L) 10.6-101 GGT (U/L) 1-9.7 Preprandial serum bile 0-15 acids ([micro]mol/L) Total bilirubin (mg/dL) 0.1-0.6 Cholesterol (mg/L) 116-254 WBC--white blood cell count, N--neutrophils, L--lymphocytes, ALT--alanine aminotransferase, AST-aspartate aminotransferase, ALP--alkaline phosphatase, GGT--gamma-glutamyl transferase
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|Title Annotation:||Short Communication|
|Author:||Hiblu, M.A.; Dua, K.; Randhawa, C.S.; Mohindroo, J.; Sood, N.K.|
|Date:||Jan 1, 2015|
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