Treatment and outcomes of dogs with hepatocutaneous syndrome or hepatocutaneous-associated hepatopathy

Abstract

Background: Superficial necrolytic dermatitis (SND) in dogs is a rare disorder most commonly associated with hepatocutaneous syndrome. Although often reported as fatal, sporadically reported long-term remissions might be more common than previously believed and linked to treatment regimens.

Hypothesis/objectives: Evaluate treatments and associated outcomes in dogs with hepatocutaneous-associated hepatopathy (HCH) with or without SND, designated collectively aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES).

Animals: Forty-one dogs of various breeds and ages diagnosed with ACHES.

Methods: Retrospective study. Electronic surveys, medical records (2014-2019), and communication with veterinarians provided data. Three treatment categories were each dichotomized: IV amino acid (IV-AA) infusions (≥2 vs <2), supplements including S-adenosylmethionine (SAMe), arginine with ornithine, glutathione, lysine, proline, omega-3 fatty acids, or zinc (≥3 vs <3), and diet type (home-cooked vs commercial). Optimal treatment was defined as receiving ≥2 IV-AA treatments, ≥3 nutritional supplements, and a home-cooked diet.

Results: Most dogs (29/41, 71%) received IV-AA infusions (23/29, ≥2 infusions). Twenty-one dogs (51%) were fed commercial diets; 17/41 (41%) were fed home-cooked diets. Most dogs received SAMe (32/41, 78%) and a median of 3 supplements. In 4 dogs, HCH remission occurred. Overall all-cause median survival time (MST) was 359 days, and disease-specific MST was 557 days (range, 1-1783 days). Optimally treated dogs (n = 9) lived significantly longer (MST, >1783 days, P = .02) than variably treated dogs (MST, 214 days).

Conclusions and clinical importance: Optimized ACHES management can resolve SND and HCH and confer long-term survival.

Keywords: hepatic disease; internal medicine-canine; metabolic disease.

FIGURE 1

Liver ultrasound images from 3 dogs before and during aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) treatment. Each row of panels represents an individual dog. Panels on the left are ultrasound images of livers obtained at diagnosis for 3 dogs (corresponding patient numbers in Table S1). The right panels are ultrasound images of the same dogs during treatment. Dates are the day of ultrasound examinations

FIGURE 2

Histologic resolution of hepatocutaneous hepatopathy (HCH) in a dog (#21) with ACHES. (A) Photomicrograph of liver section (H&E staining) at the time of definitive diagnoses, higher magnification inset illustrates the classic moth‐eaten interface between a region of degenerative vacuolar hepatopathy and proliferative nodule. (B) Photomicrograph of liver section (H&E staining) from the same dog after 4 years of ACHE management, documenting resolution of HCH. The higher magnification inset illustrates the interface between a region of mild to moderate vacuolar change and adjacent parenchyma

FIGURE 3

Survival of 41 dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) compared using the Kaplan‐Meier method. (A) Survival curves compare disease‐specific to all‐cause mortality. There was no significant difference between all‐cause or disease‐specific mortality (disease‐specific median survival, 557 days; all‐cause median survival, 359 days; P = .46). (B) Survival curves comparing ACHES cases by skin lesion status at diagnosis (none: median survival, 834 days; mild: median survival, 1191 days; fulminant: median survival, 203 days) disclosed no significant difference (P = .16). Legends indicate groups corresponding to survival curve lines. Tick marks indicate censored events

FIGURE 4

The relationship between infusion or diet treatments with disease‐specific survival of dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) using the Kaplan‐Meier method. (A) Survival curves comparing dogs receiving ≥2 (median survival, 667) days vs <2 (median survival, 168 days) amino acid infusions are significantly different (P = .05). (B) Survival curves of dogs fed home‐cooked (median survival, >1783 days) vs commercial diets (median survival, 214 days) are significantly different (P = .007). (C) Survival curves, excluding dogs surviving <30 days, comparing dogs fed home‐cooked (median survival, >1783) vs commercial (median survival, 359 days) diets are significantly different (P = .03). Legends indicate groups corresponding to survival curve lines. Tick marks indicate censored events

FIGURE 5

The relationship between treatment comprehensiveness and dogs' disease‐specific survival with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES). Survival curves comparing optimally‐treated dogs (receiving ≥2 IV‐AA treatments, ≥3 prioritized supplements, and home‐cooked diets) to all other, variably treated, dogs. Optimally‐treated dogs lived (median survival, >1783 days) significantly (P = .02) longer than variably treated dogs (median survival, 214 days). Legends indicate groups corresponding to survival curve lines. Tick marks indicate censored events

FIGURE 6

Author‐recommended treatment strategy for dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome ACHES. The typical sequence of treatment pillar implementation is not necessarily a recommended sequence and may be customized to each patient. ME = metabolizable energy. The PO supplemental zinc dose for HCS patients is 10 mg elemental zinc/10 lbs. body weight. Author supplement recommendations: S‐adenosylmethionine (SAMe, Denosyl or Denamarin, Nutramax Laboratories, Edgewood, Maryland), arginine/ornithine (PRO PERFORMANCE L‐ARGININE L‐ORNITHINE 2500, GNC, Pittsburg, Pennsylvania), glutathione (Glutathione 500 mg veg capsules preferred, NOW Foods, Bloomingdale, Illinois), lysine (L‐lysine, 500 mg veg capsules or Double Strength 1000 mg tablets, NOW Foods, Bloomingdale, Illinois), proline (L‐Proline 500 mg veg capsules, NOW Foods, Bloomingdale, Illinois)