Pathophysiology of Hepatocellular Diseases

The liver is the largest solid organ and is involved in many critical metabolic functions of the body. It is important in metabolism, having a central role in synthesis, detoxification, excretion, and storage as well as host defensive mechanisms. The liver is also unique because of its dual blood supply derived from the portal vein and hepatic artery. The portal blood with its low oxygen tension provides approximately 70% to 75% of the hepatic blood flow to the liver. Disruption of liver function or circulation can have serious consequences to the patient. Lastly, the liver has the unique ability to regenerate. For example, following removal of one lobe, the liver will quickly regenerate to its original size. When dealing with the surgical patient, it is critical to understand basic liver function and to recognize conditions affecting the liver.

Identification of Liver Disease

The clinical history and physical examination may provide some insight to the presence of liver disease, but generally, the diagnosis of liver disease or circulatory disorders of the liver largely depends on combined information obtained from clinical findings, laboratory testing, ultrasonography, and histopathologic evaluation. Identification of abnormal liver enzymes or liver function tests such as bile acids, albumin, glucose, ammonia, and bilirubin indicate that the liver should be first investigated. It is important to point out, however, that the liver is also frequently a so-called "innocent by-stander", being affected by many non-hepatic metabolic or systemic disorders. Such hepatic changes are often referred to as reactive hepatopathies and rarely do they significantly alter hepatic function. Examples include certain drugs, endocrine disease, cardiovascular conditions, or intra-abdominal disorders such as pancreatitis or inflammatory bowel disease [1]. Consequently, non-hepatic conditions and drug-associated liver dysfunction should be excluded first in the diagnostic work up before a primary investigation of the liver begins.

Radiographs will reveal liver size and shape and may aid in detecting other intra-abdominal disorders. Ultrasonography is useful to detect parenchymal, biliary, and vascular abnormalities [2]. Hepatic cells for cytologic investigation are frequently obtained during ultrasonography using fine-needle aspiration; they may provide some useful information about the liver. Cytologic evaluation, however, is limited in the amount of information it can give. The best cytologic correlation with histopathologic findings is found with hepatic neoplasia and diffuse vacuolar disease [3].

The definitive diagnosis of biliary or parenchymal disorders generally requires histopathologic evaluation. Histopathologic samples are obtained by needle biopsy, laparoscopy, or surgery. Each technique has certain advantages but also inherent limitations. For example, a needle biopsy is the least invasive but a core needle biopsy sample only represents one fifty-thousandth of the entire liver. It is recommended that at least 3 core biopsies of 16 g each be obtained from the liver to get an adequate quantity of tissue for interpretation [4]. The diagnostic accuracy of a needle biopsy is highest with diffuse hepatic disease. Laparoscopic or surgical wedge biopsies can be visually directed and provide larger pieces of tissue for examination. Laparoscopy is considered to be minimally invasive, but it is limited in that it is difficult to view the entire liver surface. The advantage over needle biopsies is that larger and more diagnostic samples are obtained when compared with the smaller needle biopsies [5]. Surgery, although more invasive, allows one to evaluate all liver lobes and obtain large samples with good hemostasis. In the appropriate clinical situations, liver culture and or hepatic copper analysis should be obtained on a liver biopsy sample.

Metabolic Considerations

Response to Injury

The liver can respond to an injury in only a limited number of ways. Reversible hepatocyte injury includes hepatocellular swelling, steroid-induced hepatopathy (in dogs only), and steatosis or lipidosis [6]. Hepatocellular swelling (hydropic degeneration) is the first manifestation of almost all forms of injury to cells and occurs when the cells are incapable of maintaining ionic and fluid homeostasis and accumulate water. Excessive corticosteroids will induce hepatocyte vacuolar changes owing to abnormal hepatic glycogen accumulation in dogs, but not cats. Lipidosis with hepatocyte accumulation of triglycerides occurs from abnormalities in fat metabolism or mobilization.

Nonreversible hepatocyte death occurs by either apoptosis or necrosis [6]. Hepatocytes may be killed by various insults, including hypoxia, toxins, drugs, microorganisms, immunologic events, and severe metabolic disturbances. The response following destruction of hepatic parenchyma results in inflammation, regeneration of parenchyma, fibrosis, and ductular proliferation [6]. The degree of clinical liver disease is dependent on the extent of hepatic damage and the ability of the liver to maintain normal functions. The liver has a great reserve capacity, and liver disease must be much advanced before clinical signs occur. Because the liver is involved in so many functions, no one test will determine the liver's overall function. When approximately 60% of the liver function is lost, function tests start to become abnormal, and when approximately 80% of liver function is lost, clinical evidence of liver failure usually becomes apparent [7].

With persistent parenchymal damage (chronic hepatitis) or extensive loss of hepatocytes (massive hepatic necrosis) fibrosis can become extensive. In cirrhosis, collagen becomes deposited in the sinusoids, resulting in altered permeability, the formation of intrahepatic portovenous shunts, and regenerative parenchymal nodules. Impaired hepatic perfusion then results in portal hypertension [8].

The liver has the special ability to regenerate when a loss of hepatocyte numbers occurs and as long as the reticulin framework remains intact. Following partial hepatectomy, hyperplasia and hypertrophy of the remaining cells occurs. This process is known as "liver regeneration" [9-11]. However, regeneration may be a misnomer because the resected lobes never grow back. Potential stimuli for liver regeneration include cytokines and growth factors produced by the hepatocytes but also circulating substances (insulin, norepinephrin, or glucagon) [9-11]. These stimuli induce changes in gene expression in hepatocytes, leading to mitotic proliferation of all cells composing the intact organ, including hepatocytes, biliary epithelial cells, and endothelial cells [9,10].

In healthy dogs, 70% hepatectomy is well tolerated [12], whereas 84% hepatectomy is usually fatal [13]. The cause of death remains unclear with extensive hepatectomies. It has been postulated that portal hypertension may occur because the reduced portal vasculature is insufficient to accommodate a constant volume of portal blood [13]. Secondary bacterial translocation and death may then ensue [13]. The decreased number of hepatic Küpffer cells after extensive hepatectomy may reduce clearance of bacteria by the liver and possibly lead to sepsis [14]. Changes in laboratory values following extensive hepatectomy have been studied in dogs. Following 70 % hepatectomy in healthy dogs, a small, transient increase in serum alkaline phosphatase, total bilirubin, and transaminases occurs [12]. Monitoring of blood glucose and supplementation of intravenous fluids with dextrose is recommended following extensive hepatectomy [15]. A small transient decrease in serum albumin occurs concurrently [12]. The result of ammonia-tolerance testing is normal following 40% hepatectomy but abnormal after 60% hepatectomy [7]. In one study in healthy dogs, 91% of the liver mass returned 6 weeks following 70 % hepatectomy [12]. Finally, the potential for regeneration after repeated sublethal partial hepatectomies has been studied in rats [16]. Twelve sequential partial hepatectomies were performed and complete regeneration occurred each time [16] suggesting that the clonogenic potential of the liver may be endless.

Only when the normal hepatic stroma becomes disrupted from either collapse or from collagen deposition does hepatocyte regeneration become disorganized and regeneration result in nodular formation. Regenerative nodules in cirrhosis lose their ability to carry on normal hepatic function [8].

Risk of Sepsis

The liver of healthy dogs may normally harbor various bacteria [17]. The portal vein of normal dogs often carries gastrointestinal bacteria, which are then normally cleared by the liver. Bacteria are phagocyted by reticuloendothelial cells referred to as Kupffer cells and then either killed or excreted into the bile. Immunoglobulin A production in the liver and bile also contributes to the protection against infectious agents. Impairment of these protective mechanisms may predispose to sepsis or resident bacterial colonization. Acute portal hypertension from loss of normal parenchymal function may allow for translocation of gastrointestinal organisms. Congenital or acquired portosystemic shunts allows gastrointestinal endotoxins or bacteria to bypass the liver, often leading to systemic enterotoxemia or bacteriemia [18]. Animals with intrahepatic or extrahepatic cholestasis [19], hepatic ischemia, hepatic trauma, or portosystemic shunts may be at risk of sepsis and should be routinely treated with antibiotics perioperatively. The need for postoperative antibiotic is also based on the underlying disease and the condition of the animal [15]. Surgical resolution of biliary obstruction may result in release of bacteria into the biliary tract [20], and postoperative antibiotic therapy has been recommended in those cases [20]. Antibiotics used should be non-hepatotoxic, have wide distribution in the hepatic tissue and biliary tract, and be bactericidal and effective against the gastrointestinal flora. Ideally, the antibiotic selection should be based on the results of bile or liver culture and sensitivity testing. Recommended empiric perioperative antibiotics include the use of second-generation cephalosporins or possibly a combination of penicillin and fluoroquinolone. In some cases, when anaerobic infections are suspected, metronidazole (Flagyl, Pharmacia) or clindamycin (Antirobe, Pfizer) may also be used [21]. Because metronidazole requires hepatic metabolism, it is recommended that lower doses be used with hepatic disease.

Risk of Hemorrhage

The liver plays a central role in hemostasis. The liver produces all coagulation factors except factor VIII, von Willebrand's factor, calcium, and tissue thromboplastin [20]. It also regulates anticoagulant and fibrinolytic mechanisms [20]. Studies in animals having liver disease found laboratory evidence of abnormal coagulation in 93% dogs and 82% of cats evaluated [22,23]. Mechanisms involved in coagulopathies occur from decreased factor synthesis, vitamin K deficiency [24], excessive factor consumption, or inadequate clearance of activated factors. Thrombocytopenia and thrombocytopathies have also been reported in association with liver disease [20]. Disseminated intravascular coagulation (DIC) may also be initiated by liver disease because of release of thromboplastic substances by damaged hepatocytes, reduced clearance of intestinal bacterial endotoxins, decreased antithrombin III concentrations, stasis of mesenteric blood flow, and reduced clearance of activated clotting factors and fibrin degradation products [25]. As DIC progresses, fibrin degradation products (FDPs) accumulate, interfering with fibrin polymerization and platelet function [20]. Although mild coagulopathies are common in association with liver disease, clinical evidence of hemorrhage is uncommon [20,26]. In a large study in dogs, significant hemorrhage following ultrasound-guided liver biopsy occurred only when moderate thrombocytopenia was present [27]. Recommended testing in animals with liver disease should include a platelet count, prothrombin time (PT), and activated partial thromboplastin time (APTT). Buccal mucosal bleeding time should also be evaluated in animals with suspected platelet dysfunction. If DIC is suspected, fibrinogen, D-dimers, and FDP concentrations and antithrombin III activity are also measured. In cats with liver disease, measurement of protein invoked by vitamin K absence (PIVKA) is reported to be more sensitive than PT or APTT to detect coagulopathies [24].

Risk of Gastrointestinal Ulcerations

Liver disease has been associated with ulcerations in both animals and humans. Blood loss from gastrointestinal ulceration not only results in anemia and protein loss but also precipitates hepatic encephalopathy in advanced liver disease or portosystemic shunting [20]. In one study, dogs with liver disease made up 28% of animals with identified gastroduodenal ulcerations [28]. Gastroduodenal ulcerations occur if the normal mucosal protective mechanisms are disrupted. Factors that reduce epithelial cell turnover, affect quality or quantity of gastric mucus production, or decrease gastrointestinal blood flow may induce gastrointestinal ulcerations. The duodenum is the most common site of ulceration in dogs with liver disease [28]. With severe liver disease, negative nitrogen balance and hypoalbuminemia also occur, resulting in decreased turnover of epithelial cells [20]. Portal hypertension also reduces gastrointestinal blood flow [29-31]. The role of gastrin in the pathogenesis of gastroduodenal ulceration secondary to liver disease remains unclear [20]. Because the gastric pH may actually be high in humans with cirrhosis, the prophylactic use of H-2 receptor antagonists in those patients is controversial [20]. Sucralfate (Carafate, Aventis) may be useful prophylactically because it provides cytoprotection and may increase gastric blood flow in cirrhotic animals [32]. Anti-inflammatories (steroidal and nonsteroidal) should be used cautiously in animals with severe liver disease because they may further disrupt mucosal defense mechanisms [31]. Some H-2 receptor antagonist drugs (i.e., cimetidine, Tagamet, SK-Beecham) and the proton pump inhibitors (i.e., omeprazole, Prilosec, Astrazeneca) require hepatic metabolism and are contraindicated in animals with liver disease. Ranitidine is a safe antacid in animals with liver disease because of its minimal involvement in hepatic metabolism.

Hepatic Encephalopathy and Portal Hypertension

These important complications of liver disease will be discussed in detail in the vascular anomalies chapter (Portosystemic Vascular Anomalies).

Classification of Liver Disease

The basic classifications of liver disease in the dog and cat can be divided simply into one of four large categories: parenchymal, biliary, or circulatory disorders, and neoplasia.

Parenchymal Disorders

Damage involving hepatocytes is the hallmark of most of these disorders. The parenchymal disorders can be grouped into those causing reversible hepatocellular injury (cell swelling, steroid-induced hepatopathy, and steatosis), hepatic amyloidosis, hepatocellular death (apoptosis and necrosis), and acute and chronic hepatitis and cirrhosis. Hepatocellular death is a nonreversible injury most often associated with acute and chronic hepatitis, sometimes leading to cirrhosis.

Acute hepatitis is generally secondary to a hypoxic or toxic injury, infectious agents, or metabolic derangements [33]. Damage can be random, zonal, or diffuse throughout the liver. Diffuse or massive liver necrosis can lead to liver failure. Hepatic failure is complicated by the consequences of the loss of normal regulatory functions of synthesis, excretion, and metabolism. In these situations, recovery is possible if the patient can be maintained on life-support measures, if the reticulin framework remains intact, and if the liver retains it ability to regenerate. Metabolic consequences include hepatic encephalopathy, coagulopathies, cerebral edema, sepsis, and gastrointestinal ulceration [34].

Chronic hepatitis may result secondary to infections, toxins, drugs, and immune mechanisms [35-37]. Many breeds of dogs also have primary metabolic defects in copper metabolism with hepatic copper accumulation causing hepatocyte death. In most clinical situations, the etiology is never determined. Hepatocellular necrosis results in production of cytokines that recruit inflammatory cells locally. In most cases, the inflammatory changes originate in the portal areas but expand into the parenchyma. Inflammation also becomes a stimulus for collagen deposition. If the reticulin framework is destroyed, regeneration becomes disorganized, sinusoidal circulation becomes permanently altered, and the hepatocyte regeneration develops as nodules. Cirrhosis is the end-stage of chronic hepatitis and is defined as a diffuse process characterized by fibrosis of the liver, the conversion of normal liver architecture into structurally abnormal nodules, and the presence of altered vascular circulation with portal-central vein anastomoses [8].

In addition to the consequences listed with acute liver failure, portal hypertension results from the failure of the portal blood to adequately perfuse the sinusoids. The result of portal hypertension is the development of acquired portosystemic shunting and ascites. Portal collaterals become visible as multiple, tortuous vessels, particularly in the mediastinum along the esophagus, originating from the cardia of the stomach (cardioesophageal anastomoses), in the omentum between the spleen and the left dorsal abdominal wall cranial to the kidney (splenorenal anastomoses), and in the mesocolon and mesorectum (mesenteric anastomoses) [38,39].

Hepatic Biliary Disorders

The biliary disorders can be grouped into cystic disorders and cholangitis. Biliary cysts result from congenital defects in the development of the biliary tree [40,41]. They may be solitary or multiple, of variable size, and are characterized by dilatation of segments of the bile ducts. They are frequently associated with polycystic kidney disease especially in Persian cats. Cysts rarely have connection with the remaining biliary system and are often incidental findings on ultrasound, through palpation, or at surgery. Large cysts may be drained. Occasionally, they require surgical removal.

Cholangitis results from inflammation centered on the bile ducts within the liver. This condition is most commonly observed in cats. An acute neutrophilic (suppurative) cholangitis is thought to result secondary to enteric bacteria ascending the biliary system [42]. The extrahepatic biliary system can also be involved. Cholangitis can become chronic associated with mixed inflammatory infiltrates, bile duct proliferation, and variable fibrosis [43]. Chronic cholangitis is also reported to have an association with chronic pancreatitis and inflammatory bowel disease in cats. Liver flukes also produce bile ductal dilation and chronic cholangitis.

Hepatic Neoplasia

Liver tumors are divided into primary, metastatic, and hemolymphatic neoplasia [44]. In cats, hemolymphatic tumors are most common; whereas metastatic neoplasms are the most common form of liver tumors in dogs [45]. Primary liver tumors comprise less than 1% of findings in all canine and feline necropsies [46,47]. Malignant primary tumors are more common in dogs than in cats [46,48]. Primary liver neoplasms are categorized according to their histologic origin into hepatocellular, biliary, mesenchymal, and neuroectodermal [46]. They may also be divided into massive, nodular, and diffuse forms according to their distribution within the liver [46]. Biliary tumors are discussed in the biliary diseases chapter.

Most dogs and cats with primary liver tumors are 10-years old or older. The exception is in animals with carcinoids, which affect dogs at an average age of 8 years [46,48]. Clinical signs include anorexia, lethargy, vomiting, weight loss, polyuro-polydypsia, diarrhea, jaundice, and abdominal distension [46,49]. An abdominal mass may be palpated in 50% to 80% of cases [44,49]. Other reported findings include seizures associated with hypoglycemia or hepatic encephalopathy and, rarely, exercise-induced weakness owing to myasthenia gravis [46,50]. At the time of diagnosis of primary liver tumor, 28% of animals are asymptomatic [49].

Laboratory findings are nonspecific and may include thrombocytosis, elevation of liver enzymes, and less commonly, hyperbilirubinemia or hypoglycemia [45,46,48,51,52]. In one study in cats, azotemia was the most common laboratory finding [53]. Thoracic radiographs should be performed to rule out lung metastasis, reported to occur in 14% of cases [54,55]. Abdominal ultrasonography allows confirmation of the hepatic origin of an abdominal mass and evaluation of other abdominal organs for metastasis (peritoneum, lymph nodes), and may help define the relation of the lesion to other abdominal structures such as the caudal vena cava and the gallbladder [56,57], but it cannot differentiate neoplasia from benign nodular hyperplasia [58]. Fine-needle aspirate or core biopsies can be obtained with ultrasonographic guidance. Prior evaluation of hemostasis is advised as many large hepatic masses may be highly vascular and hemorrhage is a possible complication. MRI has also been proposed as a means to differentiate benign from malignant hepatic nodules in dogs [59].

Hepatocellular tumors include hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma. Hepatocellular adenoma is the most common hepatocellular tumor in cats and rarely has any clinical significance [48]; however, significant hemorrhage and hypoglycemia have been reported [51]. Prognosis is then based on tumor resectability. Hepatocellular carcinoma is the most common primary liver neoplasm in dogs [44,46]. The left liver lobes are most commonly involved [46,56,60]. Massive form is the most common HCC observed in dogs [44,46,60]. They are often resectable, rarely metastasize, and carry a good long-term prognosis after successful surgery [56]. Massive right-sided tumors may have a worse prognosis because of higher intraoperative mortality rate [56]. Nodular or diffuse forms of HCC are less common and carry a poor prognosis because they are rarely resectable and often metastasize [56,60]. Metastases to the lungs, peritoneum, and peritoneal lymph nodes are most common, but metastases to the kidneys, spleen, adrenal glands, gastrointestinal tract, and bone marrow have also been reported [60]. Prognosis is related to resectability and the presence of metastasis [56]. Adjuvant therapies such as radiation or chemotherapy are uncommonly used because of poor efficacy [56].

Carcinoid neoplasms are rare primary liver tumors in dogs and cats [46,60,61]. Carcinoids originate from neuroectodermal hepatic cells. These cells are also classified as enterochromaffin or APUD cells (they are capable of amine precursor uptake and decarboxylation). Prognosis is poor because of diffuse liver involvement and high rate of metastasis [60].

Mesenchymal tumors or sarcomas are rare primary hepatic tumors in dogs and cats [44,46,48,56,62]. A poor prognosis has been suggested because of early metastasis [44,46]. A combination of surgical resection and adjuvant chemotherapy is recommended [54,63].

Hepatic nodular hyperplasia (ENH) is a common necropsy finding in dogs [64,65]. It has been reported to occur in 70% of dogs older than 6 and 100% of dogs over 14 years [64]. The etiology of ENH is unknown. In dogs, ENH is not thought to be a preneoplastic lesion [65]. Macroscopically, superficial, multifocal, well-circumscribed, pinkish to pinkish-tan nodules may be seen [64,65]; however, deeper nodules, within the parenchyma are not visible [64]. In a post-mortem study, nodule sizes ranged from 0.1 to 5 cm in diameter [65]. Microscopically, well differentiated hyperplastic hepatocytes with increased mitotic activity may be seen [64,65]. The lobular architecture is maintained [64,65]. In affected animals, clinical signs are often lacking [66]. Laboratory findings may include mild to severe increase in serum alkaline phosphatase (up to 14 times normal) and, less commonly, increase in serum alanine aminotransferase [66]. Ultrasonographic findings are nonspecific [58,67]. Hyperplastic nodules may be hyperechoic, isoechoic, or hypoechoic to the surrounding parenchyma [58]. ENH is clinically significant because it may easily be confused with primary or metastatic hepatic neoplasia on abdominal ultrasound or at surgery. Histopathologic study is required to differentiate ENH from neoplasia. However, even microscopically, it may be impossible to differentiate ENH from hepatocellular adenoma [65]; and large samples (wedge rather that needle biopsies) may be required to differentiate ENH from hepatocellular adenocarcinoma [66].

Other Hepatic Conditions

Liver Torsion

Liver lobe torsion is a rare condition that has been reported in man, rabbits, pigs, horses, dogs, and in one cat [68-80]. The affected lobe rotates around its vascular pedicle causing congestion, cholestasis, and ischemic necrosis [75-77]. Clostridial proliferation may then occur [73,77,81] occasionally leading to abscessation of the affected lobe [69]. As clostridial toxins and inflammatory mediators are liberated, septic shock and death may follow [73,77]. The left lateral liver lobe is most commonly affected in small animals, but torsion of the quadrate, caudate, and right medial lobes has also been reported [69,73,75-77,80,82]. Factors that cause stretching or rupture of the supporting ligaments of the liver may predispose to liver lobe torsion [73,77]. Congenital absence of the triangular ligaments, chronic gastric dilatation, traumatic diaphragmatic hernia, and tear of the hepatogastric ligament of the lesser omentum have been reported as possible causes [73,76-78]. Hepatic masses may also predispose to lobe torsion [76]. Liver lobe torsion has also been reported following routine ovariohysterectomy [80]. Clinical signs range from low-grade abdominal pain, anorexia, lethargy, vomiting, and ascites to acute abdominal crisis and death [76]. Occasionally a cranial abdominal mass can be palpated [75]. Intermittent clinical signs with intermittent lobe torsion have been described in a child [83]. Diagnostic findings may include an inflammatory leukogram, increased ALT, alkaline phosphatase (ALP), and total bilirubin [69,76]. Abdominal radiographs and ultrasound may reveal a cranial abdominal mass, but definitive diagnosis is often made at surgery or necropsy [69,76]. Preoperative management should include intravenous fluids and antibiotics directed against Clostridium sp. (e.g., ampicillin, Fort Dodge) [81]. Immediate surgical intervention with liver lobectomy is indicated [76]. Derotation of the affected lobe is generally avoided because it may lead to systemic release of clostridial exotoxins [69]. The resected lobe should be submitted for cytologic and histopathologic studies and both anaerobic and aerobic bacterial cultures. Antibiotic therapy is continued postoperatively based on results of bacteriologic culture. Prognosis appears to be good if prompt surgical intervention is performed [68,75,76].

Hepatic Abscesses

Hepatic abscesses are uncommonly reported in humans, dogs, and cats [69,75,82,84-91]. Abscesses may be single or multiple and are associated with high mortality rates in both humans and animals [82,85 Underlying pathologies in humans include liver trauma, ascending infection from the biliary tract, malignant obstruction of the biliary tract, extension from an adjacent abdominal abscess, and hematogenous spread.85 Hematogenous spread may be divided into systemic hematogenous (secondary for example to pneumonia, endocarditis, or otitis media) and portal spread from abdominal septic focus (e.g., inflammatory bowel disease, or pancreatitis) [85,88,89]. Immunocompromised individuals are also predisposed [85]. In newborn puppies it may occur secondary to ascending omphalophlebitis [87]. In adult dogs and cats, hepatic abscess formation has been associated with diabetes mellitus [86,90], liver lobe torsion [69], ascending biliary tract infection [91], and hepatic neoplasia [90]. In most cases, however, the underlying cause remains unknown [82,90,91]. Clinical signs often are nonspecific and include lethargy, anorexia, and fever [82,85,90,91]. Abdominal pain, jaundice, vomiting, and diarrhea are reported less frequently [82,90,91]. Laboratory findings may include an inflammatory leukogram, mild non-regenerative anemia, and increase in liver enzyme activities [82,90,91]. Hyperbilirubinemia may indicate sepsis or hepatic dysfunction. Hyperbilirubinemia may also be associated with primary biliary obstruction. Disseminated intravascular coagulation has been suspected in both dogs and cats [82,91]. Imaging modalities include abdominal radiographs, ultrasound, computed tomography, and scintigraphy [85]. In humans, the use of WBC-labeled scintigraphy may help differentiate an abscess from a metastatic lesion [85]. Ultrasound-guided or intraoperative aspiration and cytologic evaluation confirm the diagnosis [82,85,90,91]. If ultrasound-guided aspirate is chosen, a surgeon should be available if hemorrhage or contamination of the abdominal cavity occurs [85]. E. coli is the most common bacteria isolated but multiorganism infections are common and anaerobic infections have been reported [82,85,90,91]. Treatment consists of appropriate antibiotic therapy combined with drainage techniques or abscess resection [85]. However, antibiotic therapy alone may be adequate in selected cases, especially when multiple small abscesses are present [92]. Bactericidal antibiotics that are distributed in the liver should be used based on bacteriologic sensitivity results. While awaiting sensitivity results, a four-quadrant antibiotic therapy is recommended. Quinolones in combination with clindamycin have been recommended [85]. Drainage procedures may be surgical or ultrasound-guided. In humans, ultrasound-guided drainage for 11 to 19 days with an in situ catheter is the modality of choice and has a high success rate (70 - 90%) [85]. This technique fails in 10% to 30% of cases, and surgical intervention is then required [85]. Repeated ultrasound-guided drainage has also been successful in 10 of 14 dogs [90]. Resolution after ultrasound-guided drainage and alcohol injection has also been reported [93]. Surgical intervention may consist of drainage or abscess resection with partial or complete lobectomy [82,90,91]. Intraoperative identification of parenchymal abscesses may be difficult; however, the use of intraoperative ultrasound may help localize the abscess. Laparotomy allows thorough inspection of abdominal viscera and treatment of the primary disease. If the animal is stable, biopsies of the liver and intestinal tract are indicated to identify an underlying cause. Laparoscopic drainage has also been reported in humans [94]. Regardless of the modality of treatment, frequent ultrasonographic monitoring is indicated [85]. Antibiotic therapy should be continued for at least 2 weeks after ultrasonographic imaging indicates resolution of the abscess [82]. Prognosis is guarded, especially in debilitated animals with septic shock [82,85,90,91]. However, with early diagnosis and treatment, long-term successful outcomes are common in patients who survive the perioperative period [82,85,90,91].

Hepatic Trauma

Following blunt or penetrating injury, disruption of hepatobiliary structures may occur. Isolated hepatic injuries are uncommonly recognized in small animals. In humans, capsular lacerations, parenchymal fractures, and subscapular hematomas are most common [95,96]. Trauma to the major vascular structures is uncommon [95,96]. In humans, peritoneal lavage, ultrasound, and computed tomography are used to identify and classify hepatic injuries and their severity [95,96]. Conservative management, with intravenous fluids and blood products is advocated in hemodynamically stable patients [54,96]. Heart rate, blood pressure, and packed cell volume (PCV) should be monitored to evaluate the need for surgical intervention. PCV should not be used as sole monitor during acute hemorrhage [97]. Indeed, acute hemorrhage results in splenic contraction and loss of both plasma and red cells [97]. Thus, PCV may remain normal in an animal that is bleeding heavily [97]. Abdominal exploration may be necessary to control severe hemorrhage.