Introduction
Liver lobe torsion is an uncommon disease that has been reported in dogs,1 cats,2,3 horses,4 pigs,5 an otter,6 camels,7 a ferret,8 a guinea pig,9 and rabbits.10 Although the prevalence of liver lobe torsions has not been described, rabbits are one of the most commonly reported species in which this condition has been described in the veterinary literature.10–17
Currently, the recommended treatment for a liver lobe torsion is a liver lobectomy. However, this recommendation is based on results from a limited number of patients in retrospective studies.1,10 Surgical treatment of this condition in rabbits has been successful,10,12,14,17,18 with few reports of death or complications following surgery.11,18 Anecdotally, however, additional complications and deaths following liver lobectomy have been seen but not reported in the literature. Although survival rate was described for 16 rabbits with liver lobe torsion,10 specific prognostic factors associated with liver lobe torsion have yet to be investigated.
The objectives of the study reported here were to document clinicopathologic findings and outcomes for rabbits with liver lobe torsion examined between 2010 and 2020 at 4 referral veterinary hospitals and identify prognostic factors for affected rabbits.
Materials and Methods
Case selection
Electronic medical records at 4 referral veterinary hospitals were searched to identify rabbits with liver lobe torsion examined between January 1, 2010, and July 31, 2020. The following keywords were used: rabbit, lagomorph, Oryctolagus cuniculus, torsion, liver, liver lobe torsion, lobectomy, hepatectomy, and hepatopathy. Rabbits were included in the study if the diagnosis of liver lobe torsion had been made antemortem by means of diagnostic imaging (ie, abdominal ultrasonography or CT).
Medical records review
The complete medical record was reviewed for each rabbit that met the inclusion criteria and pertinent information was extracted. The duration of clinical signs prior to presentation was assigned to 4 categories (< 12 hours, 12 to 24 hours, 24 to 48 hours, and > 48 hours). Results of histopathologic examinations and gross necropsies performed by board-certified pathologists were recorded. Hematologic and serum biochemical results were evaluated for each rabbit, when available, from the time of diagnosis. Outcome data was collected for each case for which it was available. Short-term survival was defined as survival at least 7 days after presentation. Rabbits were classified as deceased if they died or were euthanized in that 7-day period. Additionally, overall survival time or time of last follow-up was recorded.
Statistical analysis
For continuous data, normality was assessed with the Kolmogorov-Smirnov test (Prism version 9.0; GraphPad Software Inc). Descriptive statistics were calculated for included variables.
Logistic regression modeling was used to identify variables associated with 7-day outcome (R version 4.0; R foundation for Statistical Computing). Predictors were selected by first-pass filtering of only those variables with a P value < 0.10 in univariate analyses, followed by removal of variables that were well-correlated with each other (r > 0.35) and ending with backward selection through use of the Akaike information criteria to arrive at a final model. Binary and categorical variables that were removed owing to correlation or separation or as part of the backward selection process were re-examined with the Fisher exact test
For determination of associations with overall survival times and final outcome, Cox proportional hazards models were used. Variable selection was done similarly to the logistic regression modeling, except with model selection done by means of ANOVA and testing variables with the highest P values one at a time.
Comparisons of survival times for surgery versus medical management alone were examined through Cox proportional hazards models. A Kaplan-Meier curve was generated. Overall survival time was calculated from admission date until the last available follow-up, with data collection ending in 2020. Examination of potential relationships between future anorexia or decreased defecation (ie, gastrointestinal stasis) and surgical or medical treatment, between short-term survival and caudate versus right liver lobe torsion, and between short-term survival and moderate or severe anemia versus no or mild anemia were examined with the Fisher exact test. A P value of < 0.05 was considered statistically significant.
Results
Overall, 82 rabbits fit the inclusion criteria and were included in the study. The total number of rabbits seen during the study period at all institutions combined was 11,402. Therefore, the prevalence of liver lobe torsion was 0.7% (82/11,402). In 26 of the 82 (31.7%) rabbits, the diagnosis was made between 2010 and 2015, and in 56 (68.3%), the diagnosis was made between 2016 and 2020
Signalment
Age was reported for 81 of the 82 rabbits. Median age was 3 years (range, 0.5 to 10 years). Forty-nine (59.8%) rabbits were male and 33 (40.2%) were female. Breed was listed for 60 rabbits. The most common breeds were Holland Lop (11/60 [18.3%]), miscellaneous lop (9 [15%]), French Lop (7 [11.7%]), New Zealand White (6 [10%]), Mini Lop (5 [8.3%]), Rex (4 [6.6%]), and Flemish Giant (4 [6.6%]).
Clinical history
Twenty-nine (35.4%) rabbits were referred from another veterinarian, with 33 (40.2%) rabbits receiving supportive care prior to arrival. The most common supportive care received included fluid therapy (n = 18), supplemental syringe feeding (17), meloxicam (17), prokinetics (15), antibiotics (12), and an opioid (10).
Information on duration of clinical signs prior to evaluation was available for 81 rabbits. Most rabbits were presented within 24 to 48 hours of the initial clinical signs (n = 28 [34.6%]) or within 12 to 24 hours of the initial clinical signs (24 [29.6%]). The remainder were presented < 12 hours (14 [17.3%]) or > 48 hours (15 [18.5%]) after the onset of clinical signs. The most common presenting complaint was hyporexia or anorexia (76/82 [92.7%]) followed by lethargy (46 [56%]) and decreased defecation (38 [46.3%]). Other commonly described clinical signs included urinating outside the litter box (n = 8), diarrhea (7), not drinking (7), and behavior changes (6). Overall, 25 (30%) rabbits had a historical episode of hyporexia or gastrointestinal stasis syndrome.
Physical examination findings
Rectal temperature at admission was reported for 79 rabbits, and mean rectal temperature was 38.3 °C (median, 38.4 °C; range, 36.0 to 40.6 °C; reference range,19,20 37.9 to 39.9 °C). Twenty-one (26.6%) rabbits were hypothermic19 (rectal temperature, < 37.9 °C), 56 (70.9%) were normothermic (37.9 to 39.9 °C), and 2 (2.5%) were hyperthermic (> 39.9 °C). Information on heart rate (HR) at admission was available for 77 rabbits, and mean HR was 247.4 beats/min (median, 240 beats/min; range, 160 to 390 beats/min; reference range,21 190 to 320 beats/min). Seven (9.1%) rabbits had bradycardia (HR < 190 beats/min20), 66 (85.7%) had a normal heart rate, and 4 (5.2%) had tachycardia (HR > 320 beats/min). Respiratory rate at admission was reported for 68 rabbits; mean respiratory rate was 120.6 breaths/min (median, 96 breaths/min; range, 30 to 300 breaths/min; reference range,20 30 to 60 breaths/min). Tachypnea (respiratory rate > 60 breaths/min) was present in 50 (73.5%) rabbits.
Most rabbits were described as having a quiet mentation (42/82 [51%]), whereas only 24 (29.2%) rabbits had a bright mentation. Dehydration was detected in 23 (28%) rabbits. Pale mucous membranes were described in 12 (14.6%) rabbits. Median body weight was 2.4 kg (range, 1.3 to 4.5 kg). Body condition scored on a scale from 1 to 9 was reported for 70 rabbits. Median body condition score was a 5 (range, 2 to 8). Abnormalities related to the gastrointestinal tract included a distended gastrointestinal tract (n = 22 [26.8%]), a firm stomach (11 [13.4%]), empty gastrointestinal tract (11 [13.4%]), decreased borborygmi (30 [36.6%]), and hypermotile gastrointestinal tract sounds (3 [3.7%]). There was a palpable mass in the cranial portion of the abdomen in 13 (15.9%) rabbits. Twenty-seven (32.9%) rabbits showed signs of pain on palpation of the abdomen. Uncommon findings potentially related to the presence of liver lobe torsion included a cardiac arrhythmia (2/82), a heart murmur (4/82), abdominal distension (4/82), an abdominal fluid wave (2/82), weak pulses (1/82), and petechia (1/82).
Diagnostic test results
Seventy-four rabbits had a CBC and an additional 5 had PCV and total solids concentration reported (Table 1). In total, 79 rabbits had either an Hct or PCV performed. Of those, 47 (59.5%) had anemia (PCV or Hct 32%22; Table 2). Severity of anemia was not significantly (P = 0.124) associated with 7-day outcome when categories were individually evaluated. However, when categories were grouped, rabbits with moderate or severe anemia were significantly less likely to survive for 7 days (P = 0.006; OR, 4.41; 95% CI, 1.55 to 12.51) than were rabbits with mild or no anemia.
Hematologic findings for 79 rabbits with liver lobe torsion examined at 4 referral veterinary hospitals between 2010 and 2020.
| Variable | No. of rabbits | Mean | Median (range) | Reference rangea |
|---|---|---|---|---|
| PCV or Hct (%) | 79 | 29.91 | 29.8 (6–48) | 32–50b |
| MCV (fL) | 71 | 66.29 | 66.3 (54.5–77.9) | 58–75 |
| MCHC (g/dL) | 71 | 32.63 | 33 (21.5–37) | 29–37 |
| WBC count (X 103 cells/μL) | 72 | 6.76 | 6.28 (0.36–14.18) | 5–12 |
| Heterophils (X 103 cells/μL) | 72 | 3.72 | 3.43 (0.18–9.34) | 1.75–6.6 |
| Lymphocytes (X 103 cells/μL) | 72 | 2.39 | 2.19 (0.11–7.33) | 1.25–7.2 |
| Monocytes (X 103 cells/μL) | 72 | 0.47 | 0.31 (0–2.67) | 0.1–1.2 |
| Eosinophils (X 103 cells/μL) | 72 | 0.08 | 0.06 (0–0.48) | 0–0.6 |
| Basophils (X 103 cells/μL) | 72 | 0.16 | 0.13 (0–0.53) | 0.1–0.96 |
| Platelets (X 103 platelets/μL) | 66 | 295.1 | 262 (230–807) | 290–650 |
| Fibrinogen (mg/dL) | 30 | 343.3 | 400 (100–600) | — |
Short-term (ie, 7 days after initial presentation) outcome as a function of severity of anemia for 79 rabbits with liver lobe torsion.
| Severity of anemiaa | Total No.of rabbits | Survived | Died or euthanized |
|---|---|---|---|
| Normal (> 32%) | 32 | 24 | 8 |
| Mild (26% to 32%) | 21 | 14 | 7 |
| Moderate (19% to 25.9%) | 18 | 7 | 11 |
| Severe (< 19%) | 8 | 2 | 6 |
As determined on the basis of PCV or Hct.
Reference range from Dettweiler et al.22
Five rabbits had a leukocytosis (WBC count > 12 X 103 WBCs/μL20) and 16 had a leukopenia (WBC count < 5 X 103 WBCs/μL20). Thirty-seven of 66 (56%) rabbits had thrombocytopenia (platelet count < 290 X 103 platelets/μL20). However, platelet clumping was present in 12 rabbits. In total, 44 of 74 (59.5%) rabbits had poikilocytosis. Fragmented RBCs, including schistocytes, microcytes, keratocytes, and spherocytes, were found in 9 (12.2%) rabbits.
Seventy-six rabbits had a serum biochemical panel performed (Table 3). Fifty-three of 76 (77.5%) rabbits had azotemia (BUN > 23.3 mg/dL24). Eight of 71 (11.3%) rabbits had a high serum creatinine concentration (reference range,20 0.5 to 2.6 mg/dL). Most rabbits had normoglycemia (48/70 [68.6%]; reference range,25 75 to 155 mg/dL), but 21 (30%) rabbits had hyperglycemia (> 155 mg/dL). Sixteen of 71 (22.5%) rabbits had hypoproteinemia (total protein < 5.4 g/dL20). Fifteen of those 16 rabbits also had anemia (PCV 32%22).
Serum biochemical values for 76 rabbits with liver lobe torsion.
| Variable | No. of rabbits | Mean | Median (range) | Reference rangea |
|---|---|---|---|---|
| Sodium (mmol/l) | 70 | 145.5 | 145 (139–160) | 136–147 |
| Potassium (mmol/L) | 70 | 3.8 | 3.9 (2.4–6.2) | 3.5–7 |
| Chloride (mmol/L) | 58 | 103.11 | 102.5 (90–115) | 92–112 |
| Bicarbonate (mmol/L) | 58 | 19.73 | 20 (2.1–33) | 16.2–38b |
| Phosphorous (mg/dL) | 67 | 3.98 | 3.6 (1.5–14.2) | 2.3–6.9 |
| Calcium (mg/dL) | 68 | 12.38 | 12.7 (8.6–15.4) | 11–14.8c |
| Urea nitrogen (mg/dL) | 76 | 37.13 | 31.5 (6–117) | 15–23.3d |
| Creatinine (mg/dL) | 71 | 1.75 | 1.3 (0.6–7.6) | 0.5–2.6 |
| Glucose (mg/dL) | 70 | 155.96 | 133.5 (79–352) | 75–155b |
| Total protein (g/dL) | 71 | 6.03 | 6 (4–7.5) | 5.4–8.3b |
| Alanine aminotransferase (U/L) | 73 | 666.62 | 577 (41–5141) | 14–80 |
| Aspartate aminotransferase (U/L) | 63 | 1491.53 | 1,131 (15–7,000) | 14–113 |
| Alkaline phosphatase (U/L) | 71 | 75.88 | 58 (11–328) | 4–70 |
| Creatinine kinase (U/L) | 39 | 4226.37 | 1,417 (253–26,485) | 150–1,000b |
| Glutamate dehydrogenase (U/L) | 59 | 14.89 | 11 (3–101) | 6.39b |
| Cholesterol (mg/dL) | 60 | 43.98 | 40 (15–170) | 12–116 |
| Bilirubin (mg/dL) | 45 | 0.2 | 0.2 (0.1–1) | 0–0.75 |
| Magnesium (mg/dL) | 56 | 2.66 | 2.6 (1.6–5.9) | 2–5.4b |
Hepatic enzyme activities were evaluated in most rabbits. Alanine aminotransferase activity was high (> 80 U/L20) in 69 of 73 (94.5%) rabbits, and aspartate aminotransferase activity was high (> 113 U/L20) in 59 of 63 (93.6%). Alkaline phosphatase activity was reported in 71 rabbits but was high (>70 U/L27) in only 29 cases (40.8%). Only 4 rabbits in which a serum biochemical panel was performed had no elevations in any hepatic enzyme activities. Total bilirubin concentration was high (> 0.75 mg/dL20) in only 2 of 45 (4.4% rabbits).
Diagnostic imaging was performed in all 82 rabbits. Radiography was performed in 67 (81.7%) rabbits, and abdominal ultrasonography was performed in all 82. Ultrasonography confirmed the diagnosis in all 82 rabbits. Peritoneal effusion was identified ultrasonographically in 63 of the 82 (76.8%) rabbits. The fluid was described as scant in 21 of the 63 (33.3%) rabbits, mild in 28 (44.4%), moderate in 10 (15.9%), and severe in 1 (1.6%); the amount of fluid was not described in the remaining 3 rabbits. Echogenicity of the fluid was described in 33 rabbits; the fluid was anechoic in 23 (69.7%) rabbits and mildly echogenic to echogenic in 10 (30.3%). Pleural effusion was diagnosed in 5 rabbits, and hepatic or portal vein thrombosis was found in 7 (5 survived at least 7 days and 2 died within 7 days after initial presentation).
Results of cytologic examination of hepatic aspirates from 2 rabbits were consistent with mixed inflammation, hemorrhage, and necrosis. Aerobic bacterial culture of a portion of the affected liver lobe obtained at surgery (n = 3) or necropsy (1) did not yield any growth.
In total, in 25 (30.5%) rabbits the diagnosis was made by means of ultrasonography alone. In 7 (8.5%) rabbits, the diagnosis was made by means of ultrasonography and confirmed at necropsy; in 42 (51.2%) rabbits, the diagnosis was made by means of ultrasonography and confirmed at surgery; and in 8 (9.8%) rabbits, the diagnosis was confirmed by means of ultrasonography, surgery, and necropsy.
Twelve rabbits had hemorrhagic abdominal effusion at the time of surgery or at necropsy. Of those 12 rabbits, 11 underwent surgery and 1 did not. In total, 7 of the 12 rabbits with hemorrhagic abdominal effusion died within 7 days. A formal fluid analysis was performed in only 5 rabbits. Two of these had a hemorrhagic effusion, 2 had a transudate, and 1 had a serosanguinous effusion.
Treatment
Overall, 50 (60.1%) rabbits underwent surgical treatment (ie, liver lobectomy), 23 (28%) received medical treatment only, and 9 (10.9%) were euthanized or died on presentation. Of those that underwent surgery, 36 (72%) survived at least 7 days, but only 14 of the 23 (60.9%) rabbits that received only medical treatment survived at least 7 days.
Surgery was most often performed the same day as presentation (23/50 [46%]). In 10 (20%) rabbits, surgery was performed 1 day after presentation; in 11 (22%) rabbits, surgery was performed 2 days after presentation; in 3 (6%) rabbits, surgery was performed 3 days after presentation; and in the remaining 3 (6%) rabbits, surgery was performed 4 days after presentation. Surgical technique was described in 44 rabbits, with suture ligation used in 26, instrument ligation (SurgiTie; Covidien) used in 15, a surgical looping device (Surg-I-Loop; Scanlan Int) used in 2, and a vessel sealing device (LigaSure; Covidien) used in 1. Surgical complications were uncommon but included hemorrhage (n = 5) and incomplete resection of the liver lobe (1). Two of the rabbits with hemorrhage died. In one of these rabbits, the liver lobe was adhered to the vasculature and the caudal vena cava ruptured during removal.
For rabbits that underwent surgery, median duration of anesthesia was 1.5 hours (range, 0.6 to 2.75 hours). Hypotension during anesthesia (blood pressure ≤ 60 mm Hg) was reported in 28 rabbits. Additional oncotic support or vasopressor administration was used in 12 rabbits, with 3 of those rabbits receiving > 1 drug. Hypothermia (rectal temperature < 37.9 °C) occurred in 46 rabbits during anesthesia. In total, 9 rabbits died during anesthesia (4 died during anesthetic induction and 5 died during general anesthesia). Additional anesthetic complications included difficult intubation (n = 7), arrhythmias (4), hyperthermia (3), slow recovery (2), and hypoventilation (1).
Supportive care was provided to rabbits that underwent liver lobectomy and to rabbits that received only medical treatment. In total, 69 rabbits received crystalloid fluid therapy. Of those, 28 (40.6%) received fluids SC, 17 (24.6%) received fluids IV, and 10 (14.5%) received fluids both IV and SC; in the remaining 14, route of administration was not reported. Three rabbits received hetastarch, 2 rabbits received dextrose, and 1 rabbit received hypertonic saline solution IV. Supportive care feedings in the form of a critical care feeding formulation were used in 55 (81.8%) rabbits. Additional supportive care medications included metoclopramide (n = 33), cholestyramine (9), simethicone (7), and maropitant (2).
Antimicrobials were prescribed in 61 (74.4%) rabbits, and in several of these rabbits, > 1 antimicrobial was used. The most common antimicrobial used was enrofloxacin or marbofloxacin (n = 53 [86.9%]), followed by metronidazole (13 [21.3%]) and penicillin procaine G (13 [21.3%]).
In total, 67 (81.7%) rabbits received an opioid, with 51 rabbits receiving buprenorphine and 41 rabbits receiving a full μ-opioid receptor agonist. Additional analgesic drugs included meloxicam (n = 37 [45.1%]), tramadol (23 [28%]), ketamine as a continuous rate infusion (13 [15.9%]), lidocaine as a continuous rate infusion (17 [20.7%]), and gabapentin (5 [6.1%]).
Nine (11%) rabbits received a blood transfusion. Of those, 6 died or were euthanized within 7 days after presentation and 3 survived. Days until defecation after initial presentation was reported for 68 rabbits. Fifteen (22.1%) rabbits did not defecate, and all those rabbits died. The remaining rabbits defecated < 1 day after presentation (n = 1 [1.5%]) or 1 (n = 25 [36.8%]), 2 (19 [27.9%]), 3 (6 [8.8%]), or 4 (2 [2.9%]) days after presentation.
Affected liver lobe
The affected liver lobe was described in 77 of the 82 rabbits. Most liver lobe torsions included the caudate lobe (n = 57 [74%]). The right liver lobe was affected in 16 (20.1%) rabbits, and the left lateral lobe was affected in 2 (2.6%). In 2 rabbits, > 1 liver lobe was affected (Table 4). Rabbits with a right liver lobe torsion were significantly less likely to survive 7 days, compared with rabbits in which the caudate lobe was affected (P = 0.046; OR, 3.27; 95% CI, 1.04 to 11.3). On the basis of histopathologic appearance, liver lobe torsion was described as acute in 19 of 22 (86.4%) rabbits and chronic in 3 (13.6%).
Short-term (ie, 7 days after initial presentation) outcome as a function of affected liver lobe for 77 rabbits with liver lobe torsion.
| Liver lobe | Total No. of rabbits | No. (%) alive | No. (%) died or euthanized |
|---|---|---|---|
| Caudate | 57 | 38 (67) | 19 (33) |
| Right | 16 | 6 (37) | 10 (63) |
| Left lateral | 2 | 1 (50) | 1 (50) |
| Two lobes | 2 | 1 (50) | 1 (50) |
Pathological findings
Fourteen rabbits underwent a full necropsy with histopathologic examination, 1 underwent a gross necropsy only, and 20 underwent histopathologic of a liver sample collected at surgery. Hepatic necrosis was found in 32 of 34 (94.1%) rabbits. Additional hepatic lesions included hepatic congestion (n = 21 [61.8%]), hepatitis (12 [35.3%]), serositis of the liver (9 [26.5%]), thrombosis (6 [17.6%]), hepatocellular degeneration (3), and hepatic lipidosis (2). There was a centrilobular distribution of hepatic lesions in 7 rabbits. Of those, 5 had centrilobular necrosis, 1 had lipidosis, and 1 had vacuolation. Thirteen rabbits had lesions in other areas of the liver, aside from the affected liver lobe. Hepatocellular degeneration or necrosis was found in additional liver lobes in 9 rabbits. In several rabbits, these changes were severe and encompassed all remaining liver lobes. Hepatitis or serositis of additional liver lobes was found in 6 rabbits.
Disease of a body cavity was described in 8 rabbits. Effusions included proteinaceous peritoneal effusion (n = 3), hemorrhagic abdominal effusion (2), serosanguinous effusion (1), and ascites (1). One rabbit had adhesions between the gastrointestinal tract and the liver. Disease of the gastrointestinal tract was noted in 7 rabbits, including gastroenteritis (n = 3), gastric distension or impaction (2), cecal rupture (1), and pancreatic atrophy (1). Two rabbits had evidence of vascular compromise to the intestines with thrombosis, edema, or vascular dilatation.
Cardiovascular system abnormalities were described in 5 rabbits, including myocarditis or endocarditis (n = 3), myocardial degeneration (1), and myocardial edema (1). Eight rabbits had abnormalities of the respiratory system, including pulmonary edema (n = 2), pneumonia (2), tracheal congestion (1), bronchiolar adenomas (1), circulating leukocytosis (1), and multifocal pulmonary thromboembolisms (1).
Renal lesions were described in 4 rabbits, including renal infarction (n = 2) and hemoglobinuria with tubular necrosis or nephritis (2). Another rabbit had hemosiderin pigment within the tubular epithelium of the kidney.
Six (42.9%) rabbits had evidence of a multisystemic inflammatory response with moderate to severe inflammation noted in ≥ 2 organ systems. All these rabbits died or were euthanized following liver lobectomy.
Additional complications
One rabbit developed anuric renal failure following partial liver lobectomy. One rabbit became hypotensive and anemic with a PCV of 11% on day 3 of hospitalization and was euthanized. A single rabbit was intermittently hyperthermic for 2 days following surgery.
Additional complications diagnosed at recheck examinations included distal vasculitis of the leg in which the catheter had been placed for surgery necessitating digit amputation. Two rabbits had slight dehiscence with ultimate healing of the midline abdominal skin incision.
Outcome and additional prognostic factors
Of the 82 rabbits included in the study, 32 (39%) died or were euthanized within 7 days after initial presentation and 50 (61%) survived for at least 7 days. The odds of surviving at least 7 days decreased with each additional day without defecating (P < 0.001; OR, 0.31 per additional day; 95% CI, 0.24 to 0.4). No other factors were associated with short-term outcome. For overall survival time, the final model included HR, days until defecation after initial presentation, tramadol usage, and monocyte count. A higher HR was associated with a worse outcome (P = 0.013; hazard ratio for each 10-beats/min increase in HR, 1.1; 95% CI, 1.02 to 1.19). For each additional day without defecating, patients had a significantly lower survival time (P < 0.001; hazard ratio, 1.77; 95% CI, 1.3 to 2.41,). Patients that received tramadol had longer survival time, compared with those that did not (P = 0.018; hazard ratio, 0.2; 95% CI, 0.06 to 0.7).
Overall, 8 animals went on to have episodes of hyporexia and decreased defecation following hospital discharge. Of those 8 rabbits, 5 had undergone liver lobectomy and 3 had received only medical treatment. Abdominal ultrasonography was performed 1.5 to 2 years after hospital discharge on 2 rabbits that had received only medical treatment. In both rabbits, a torsion was not apparent on repeated ultrasonography.
Patients that underwent surgery did not have a significantly different 7-day (P = 0.419) or overall (P = 0.257) outcome. Median overall survival time was 612 days when all patients were included and was 1,540 days when patients that survived < 7 days were excluded. Median survival time was 530 days for rabbits that received only medical treatment and was 1,452 days for rabbits that underwent surgery (Figure 1).
Kaplan-Meier survival curves for 73 rabbits with liver lobe torsion examined at 4 referral veterinary hospitals between 2010 and 2020 that underwent liver lobectomy (n = 50; black line) or received only medical treatment (23; gray line). Tick marks represent censored animals.
Citation: Journal of the American Veterinary Medical Association 260, 11; 10.2460/javma.22.03.0154
Discussion
The present study describes for the first time the prevalence of, clinicopathologic findings in, and prognostic factors for a large number of rabbits with liver lobe torsion examined at 4 institutions over a 10-year period. Although the prevalence of 0.7% suggests that the condition is uncommon, at least according to guidelines for human diseases,26 liver lobe torsion appears to be more common in rabbits than other veterinary species. For example, a 21-year retrospective study of liver lobe torsion at 4 institutions described only 6 horses with this condition.4 Additionally, most of the rabbits included in the present study were examined between 2016 and 2020. This may have been due to the increasing number of patients presented over the years, increased prevalence of disease, or increased awareness of the disease or most likely to a combination thereof.
The clinical signs and physical examination findings reported in the present study were similar to those described in previous reports.10,12,15 Unfortunately, the most common clinical signs, such as anorexia and decreased defecation, are not specific. Historically, rabbits with these findings have been said to have gastrointestinal stasis or ileus, but these are suggested to be inappropriate terms because they overshadow the underlying disease causing gastrointestinal tract dysfunction.27 The nonspecific clinical signs and examination findings of these rabbits also highlights the importance of further diagnostic testing and imaging that may help differentiate liver lobe torsion from other causes of inappetence.
The only physical examination finding that was statistically associated with a poor prognosis in the present study was a higher HR. To our knowledge, a high HR has not been previously described in rabbits as being associated with a negative outcome or death. However, tachycardia can occur secondary to pain, hypovolemia, sepsis, cardiac failure, stress, or various types of shock.28 In human children, tachycardia with abdominal pain increases the likelihood of life- or organ-threatening disease.29 Additionally, humans with systemic inflammatory syndrome or sepsis that were tachycardic had a higher mortality rate.30 Although increasing HR was statistically associated with prognosis in the present study, a minority of the rabbits had tachycardia. Therefore, the clinical utility of this finding is unknown.
Anemia was a common finding in the rabbits of the present study. Liver disease in other species results in anemia through alternative mechanisms other than hemorrhage. Humans with liver disease can develop erythrocyte surface changes that can cause hemolytic anemia as well as impaired coagulation.31 Several rabbits in this report had evidence of hemoglobinuria on necropsy, which can occur secondary to hemolysis. Additionally in humans, acute gastrointestinal hemorrhage can occur secondary to portal hypertension.32 Alternative etiologies of anemia in these rabbits may include hemorrhage or sequestration of RBCs in the affected liver lobe and erythrocyte fragmentation. Overall, rabbits with moderate to severe anemia were less likely to survive, compared with those with no or mild anemia. Rabbits with an Hct < 26% therefore may have a worse outcome, and monitoring of RBC parameters is warranted in rabbits with liver lobe torsion.
Thrombocytopenia was also a common finding in this study. This was also described in the previous retrospective study10 of liver lobe torsion in rabbits. Thrombocytopenia has been reported in other species as well with liver lobe torsion,8,33,34 and thrombocytopenia is also common in humans with chronic liver disease.32 Anemia was also a common finding in this study, present in approximately half of the rabbits. In rabbits with hyporexia and secondary dehydration, a normal to high PCV would be expected.29 Therefore, in a rabbit with these clinical signs and concurrent anemia, liver lobe torsion should be considered as a differential diagnosis.
Most rabbits in the present study had azotemia (77.5%), but only 11% had a high serum creatinine concentration. BUN concentration has been described as a poor prognostic indicator in rabbits in a previous study24. In rabbits at a single institution, a high BUN concentration (≥ 23.3 mg/dL) was a risk factor for nonsurvival. Whereas BUN concentration was not found to be a significant risk factor in the present study, azotemia may affect patient prognosis.
Most rabbits in our study had evidence of hepatocellular hepatopathy on serum biochemical testing. This has previously been found in rabbits as well as other species with liver lobe torsion and is likely due to hypoxemia and necrosis of the affected liver lobe.4,10,12,16,35 In the present study, only 4 rabbits had normal ALT and AST activities. Of those rabbits, 3 had histologic evidence of a chronic torsion and 1 had evidence of an acute torsion. In a study4 of liver lobe torsion in horses, hepatic enzyme activities were often within reference limits or only mildly high. Therefore, normal hepatic enzyme activities with other compatible clinical signs should not rule out liver lobe torsion.
An unexpected finding in our study was that even though peritoneal effusion was common (76.8%), hemorrhagic abdominal effusion was uncommon. Because fluid analysis was not performed in all rabbits, it was also not clear whether all rabbits in which hemoabdomen was diagnosed truly had a hemorrhagic effusion rather than a serosanguinous effusion. The relatively low occurrence of hemorrhagic effusion in this study supports alternative mechanisms other than hemorrhage from the liver lobe in the pathophysiology of anemia in these rabbits. Other causes of effusion in these rabbits may have included venous obstruction, portal hypertension, passive congestion, or increased hydrostatic pressure.8,36 Additionally, in the authors’ experience, scant or mild peritoneal effusion has been noted in clinically normal patients. To evaluate whether hemorrhage into the peritoneal cavity has occurred secondary to liver lobe torsion and help guide treatment, fluid analysis is recommended.
As described in a previous retrospective study,10 the most commonly affected liver lobe was the caudate lobe. There are 5 liver lobes in rabbits,37–39 but some descriptions in the literature have added confusion.40,41 Rabbits generally have right, left lateral, left medial, quadrate, and caudate liver lobes.37–39 The caudate lobe is further divided into the papillary process and the caudate process.37,39 It is suspected that the caudate lobe may be more predisposed to torsion because this lobe has a narrow stalk to the liver hilus, which may result in increased lobe mobility.40,41 Overall, rabbits with right liver lobe torsion had lower odds of survival, compared with rabbits with torsion of the caudate lobe. This may be because the smaller size of the caudate liver lobe results in less sequestration of RBCs or hemorrhage or because the narrow hilar attachment may make the surgical approach simpler.
On the basis of findings in previous studies,1,2,8,10,12,15,34 liver lobectomy has been considered the treatment of choice for rabbits with liver lobe torsion, as is the case for other species. In a previous retrospective study10 of liver lobe torsion in rabbits, all 9 rabbits that underwent liver lobectomy survived. In that study, supportive care alone was provided for 7 rabbits and only 3 of those rabbits survived. The prognosis following liver lobectomy is also good in other species. In 12 dogs that underwent a liver lobectomy for treatment of liver lobe torsion, 11 survived.1 The 7-day survival rate in the present study for rabbits that underwent liver lobectomy was 72%, versus 60.9% for those that only received medical treatment, which was lower than rates previously reported for dogs and rabbits.1,10 Statistically, there was no difference in 7-day survival rate for surgical versus medical treatment. However, the median survival time of patients that underwent surgery (1,452 days) was longer than that for rabbits that received only medical treatment (530 days). Perioperative complications described in this study included fatal hemorrhage, cardiopulmonary arrest, hypotension, hypothermia, and arrhythmias. Additionally, there was a perianesthetic mortality rate of approximately 17%. This perianesthetic mortality rate was higher than the previously described mortality rate of 7.37% in sick rabbits.42 Additionally, it is unknown whether those rabbits that died under anesthesia did so because of their underlying disease or as a result of anesthetic or surgical complications. Results of the present study should be interpreted with caution, and patient selection may have contributed to the lack of a significant difference between treatment modalities. For example, more stable patients may have been selected to receive only medical treatment. In fact, more rabbits with hemoabdomen and more rabbits that received blood transfusions underwent liver lobectomy. This may indicate more critical patients were selected for surgery, although no other variables were associated with outcome. In other species, liver lobectomy is the treatment of choice for liver lobe torsion and should likely still be the recommendation for rabbits. However, liver lobectomy may not be possible in every rabbit, owing to patient and client factors. The present report suggests rabbits may benefit from aggressive medical treatment if liver lobectomy cannot be performed.
Ultimately, the only medical treatment that was associated with greater odds of survival was tramadol usage. This was an unexpected finding, because studies43–45 evaluating tramadol in rabbits have produced conflicting results and its analgesic properties have yet to be proven. The increased chances of survival in those patients that received tramadol may have been due to patient selection; tramadol was prescribed to rabbits that could be managed on an outpatient basis and thus were potentially more stable.
One rabbit in the present study developed anuric renal failure following surgery, which has previously been described.10 In both rabbits, there was concern that disseminated intravascular coagulation may have been present. Thrombosis of the liver was found in 6 rabbits on necropsy and in 7 rabbits during abdominal ultrasonography. Additionally, pulmonary thromboembolism, intestinal thrombosis, and renal infarcts were diagnosed at necropsy. In total, 6 rabbits had evidence of a multisystemic inflammatory response on necropsy following liver lobectomy. All 6 of those rabbits died. Therefore, the prevalence may have been higher. It has been anecdotally postulated that rabbits with liver lobe torsion may develop a systemic inflammatory response syndrome or disseminated intravascular coagulation.10,16 A single case report46 describes a rabbit that developed pulmonary thromboembolism following liver lobectomy. Disseminated intravascular coagulation and multiorgan infarction have also been reported in dogs with liver lobe torsion.34,47 Coagulopathy of hepatic disease can mimic disseminated intravascular coagulation and differentiating between the two can be challenging.48 Coagulation testing should be considered in rabbits with liver lobe torsion and complications such as systemic inflammatory response syndrome and disseminated intravascular coagulation should be discussed when formulating individual therapeutic plans.
An unexpected finding of our study was the presence of disease in other liver lobes. Hepatocellular necrosis or degeneration was present in additional areas of the liver in 9 rabbits. In several rabbits, the entire liver was affected. Hepatic lesions in other lobes have not previously been discussed in rabbits with liver lobe torsion. The centrilobular distribution found in 7 rabbits suggested an ischemic injury or generalized hypoxia.49 In humans, centrilobular hepatic necrosis can occur following cardiogenic shock.50 It is unclear whether the additional hepatic lesions in this study were related to the development of the liver lobe torsion or were a consequence of the torsion, systemic disease, or therapeutic interventions.
Limitations of the present study include its retrospective nature. Although this study evaluated the largest number of rabbits with liver lobe torsion to date, a larger sample size may have revealed additional significant findings. Patient population, monitoring protocols, medical record protocols, and medical recommendations likely differed by institution. Additionally, long-term follow-up was not available for all rabbits. Future studies are needed to evaluate risk factors for the development of liver lobe torsion and the pathophysiology of this disease in rabbits.
The present retrospective study provides novel information regarding clinical findings and prognosis of rabbits with liver lobe torsion. The prognosis for rabbits with liver lobe torsion was less favorable than that described in previous studies, with 7-day survival rates of 72% (36/50) for rabbits that underwent liver lobectomy and 60.9% (14/23) for rabbits that only received medical treatment. Our findings suggest that medical management may be considered in rabbits with liver lobe torsion when surgery cannot be performed. Additionally, rabbits with higher HRs, an increasing number of days without defecation, right liver lobe torsion, or moderate to severe anemia were less likely to survive. Given the relatively high prevalence of thrombosis, systemic inflammation, and comorbidities, a thorough systemic evaluation should be performed for rabbits with liver lobe torsion. The complications, outcomes, and prognostic indicators identified in this study may help guide treatment decisions and educate owners on the prognosis of rabbits with liver lobe torsion.
Acknowledgments
No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.
The authors thank Dr. Kevin Keel for assistance with pathological interpretations.
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