Spontaneous Hepatic Hemorrhage Caused by Emphysematous Cholecystitis: A Case Report and Literature Review

Case Report

This study was reviewed by the Institutional Review Board of Zhuji People's Hospital, the Affiliated Hospital, Wenzhou Medical University, Zhejiang, China. Informed consent was obtained from the patient for the publication of this case report.

A 49-year-old male presented to the emergency department with fever, chills, right upper quadrant pain, vomiting, and diarrhea of four days' duration. Fifteen days prior, an examination indicated gas in the gallbladder on abdominal computed tomography (CT; Fig. 1A and 1B); blood tests were normal except for hyperglycemia. He had a history of poorly controlled diabetes mellitus, hypertension, and uarthritis with the dexamethasone abuse. On physical examination, he was febrile with a temperature of 39.9°C. Blood pressure was 87/55 mm Hg; heart rate, 110 beats per minute; and respiratory rate, 25 breaths per minute. No jaundice was noted. There was moderate tenderness in the right hypochondrial area. Laboratory tests revealed an increased white blood cell count (12,700 per milliliter); hemoglobin (8.7 g/dL); platelet count (12,000 per microliter); elevated liver enzymes (aspartate aminotransferase, 75 U/L; alanine aminotransferase, 180 U/L); total bilirubin (18.8 mcmol/L); elevated blood glucose (25.4 mmol/L) with high glycated hemoglobin (HbA_1c; 9%); and albumin (28.3g/L). Tumor markers of carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA-125, and α-fetoprotein (AFP) were normal. The results of coagulation tests showed prothrombin time (PT; 13.3 sec) and fibrinogen (5.55 g/L). An abdominal CT scan (Fig. 1C, 1D, and 1E) was performed immediately and showed an enlarged gallbladder with intra-luminal, intra-mural, and peri-cholecystic air, subcapsular high-density fluid collection, and an intra-hepatic mass with gas and liquid. After aggressive resuscitation, the patient was stable and then admitted to the telemetry unit for observation. He was treated with imipenem, and underwent two drainages (Fig. 1F) of the gallbladder and the hepatic mass under ultrasonographic guidance. The bloody fluid with gas was released from the tube after drainage of the hepatic mass. The drainage of the gallbladder contained gas and bile mixed with blood. The two initial blood cultures yielded Klebsiella pneumoniae that was consistent with the drainage cultures. The patient was discharged 21 days later. Six months after discharge, a laparoscopic cholecystectomy was performed; the patient was doing well at six-month follow-up.

OPEN IN VIEWER

FIG. 1.

Non-contrast CT in healthy examination demonstrated severe fatty liver whose density is lower than veins (A, B) and spleen (A, B). Also, it showed gas in gallbladder (arrow, A) and stone (arrow, B). Contrast enhanced CT in hospital illustrated perforation of the gallbladder with gas (white triangle, D), a hepatic cavity with gas (arrow, D) and a subcapsular high density fluid collection (arrow, E) as well as stone without gas (arrow, C). There were two drainages: one is blood with gas from the intrahepatic cavity (arrow, F), and the other was bile (black triangle, F) mixed with blood (white triangle, F) from the gallbladder.

Discussion

Emphysematous cholecystitis is a rare variant of acute cholecystitis that is caused by gas-producing bacteria, including Escherichia coli, Klebsiella pneumoniae, and Clostridium perfringens [3]. It progresses rapidly and is life-threatening, with higher incidence in acalculous diseases. Most patients are between 50 and 70 years of age, with a male to female ratio of 2:1 [4]. Approximately 50% of patients have diabetes mellitus, frequently complicated with other types of pathology such as neuropathy [5]. The pathophysiologic mechanism is ischemic necrosis of the gallbladder wall caused by occlusion or thrombosis of the cystic artery [6] and an acute infection caused by gas-forming organisms.

Given its characteristics, prompt diagnosis and appropriate management are crucial. Imaging studies can play a vital role. The effervescent gallbladder sign [7], reported previously as a radiologic feature of emphysematous cholecystitis, manifests on ultrasound as a stream of tiny echogenic foci, arising from the dependent portion of the gallbladder to the top, similar to bubbles rising in a glass of champagne. However, Niederhauser et al. [8] concluded that the effervescent gallbladder sign could be caused by other etiologies such as the benign release of gas from gallstones and is not a pathognomonic finding for emphysematous cholecystitis, which should be confirmed based on findings of inflammation of the gallbladder. In our case, gas in the gallbladder stones disappeared on the abdominal CT, which is consistent with this theory. A CT scan is considered to be the standard of diagnosis because ultrasound is not as sensitive [9].

Perforation and gangrene are the most common complications of emphysematous cholecystitis. Because of complications that require immediate surgical intervention upon diagnosis, emphysematous cholecystitis has a higher mortality compared with that of acute uncomplicated cholecystitis (1.4%) [10]. However, this is the first reported case of spontaneous hepatic hemorrhage caused by perforation of emphysematous cholecystitis.

Spontaneous hepatic hemorrhage is an uncommon but potentially fatal event, often labeled hepatic rupture and associated with a high morbidity [11]. It is probably best described as the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome in pre-eclamptic or eclamptic pregnant females [12]. Risk factors in the general population include benign and malignant lesions in the absence of trauma, anti-coagulant therapy, and iatrogenic factors [13]. Hepatocellular carcinoma is the most frequently encountered underlying malignancy [2], followed by angiosarcoma, hemangioendothelioma, and metastases from other organs. The relatively common benign lesions are adenoma [14], but with a malignant tendency. Other rare conditions include connective tissue disease, peliosis hepatis, hemodialysis, and amyloidosis.

The pathogenesis is uncertain. The prevalent mechanism is often associated with hepatic necrosis [15] and vascular endothelial damage [16], leading to hemorrhage, regardless of cause. Extravasation of blood from hepatic parenchyma forms a subcapsular hematoma, subsequently increasing the pressure within the Glisson capsule. In our case, we speculated that the severe emphysematous cholecystitis caused by occlusion or thrombosis of the cystic artery resulted in perforation of the gallbladder wall into the contiguous liver parenchyma, causing hepatic infection and necrosis. The long-term abuse of anabolic steroids [17] and diffuse fatty deposition of liver caused hepatic fragility and reduced vascular elasticity. Gas rupturing into hepatic parenchyma resulted in a parenchymal tear and hemorrhage of fragile vessels. Thrombocytopenia caused by sepsis and hypertension aggravated the situation. Spontaneous hemorrhage led to a final common pathway of capsular distension, hematoma exacerbation, and even the rupture of the hematoma, manifesting as signs of hemodynamic collapse. Jain et al. [18] indicated that the mortality of rupture into the peritoneum was high, ranging from 60% to 75% and remained 36.5% through surgical intervention afterwards.

Because most patients usually present with non-specific symptoms such as right upper quadrant pain, vomiting, anorexia, shock, and peritonitis the diagnosis may be delayed, resulting in a poor treatment outcome. Radiologic adjuncts such as ultrasound, CT, or magnetic resonance imaging (MRI) are useful to achieve an earlier diagnosis. Ultrasound could be the initial choice as a simple and reliable method to confirm the diagnosis of spontaneous hepatic hemorrhage. Magnetic resonance imaging can specify the etiologic diagnosis of the hemorrhage, but it is hindered by unstable hemodynamics and the patient's breathing [19]. A CT scan is preferred in an acute setting to assess the extent and the gravity of the hematoma [20].

Once the diagnosis has been made, resuscitation with intravenous fluids and transfusion of blood and fresh frozen plasma and platelets is crucial as initial management, especially in hemodynamically unstable patients. Therapeutic approaches for obtaining hemostasis include conservative treatment, arterial embolization, and surgery, most likely relying on the patients' hemodynamic state. To our knowledge, when the patient is stable, the majority of non-ruptured spontaneous hematomas can be cured conservatively [21]. For patients with active hemorrhage demonstrated on CT scan or unstable hemodynamics, hepatic angiography and embolization of any identifiable bleeding sites are the favored modality [22]. However, infection control is equally essential for patients with emphysematous cholecystitis that fails to respond to conservative treatment and embolization, even more so than hemostasis without obvious evidence of active bleeding. The more gas formed by infection, the higher the pressure in hematoma, leading to the greater possibility of rupture. Moreover, the embolization procedure was likely not feasible in up to 20% of patients [23]. The history of dexamethasone abuse is another factor in spontaneous rupture of the liver hematoma [24].

Theoretically, surgical intervention is the standard of treatment. Operative therapies include evacuation of hematoma, resection of lesion, over-sewing of lacerations, ligation of arteries, tamponade with materials, and even orthotopic liver transplantation [25]. However, because of massive or diffuse lesions, proximity to vascular structures, and pre-existing comorbidities, it may lead to massive hemorrhage, with the potential for extensive resection and a high rate of morbidity and mortality. Thus, percutaneous cholecystostomy and drainage of hepatic hematoma as minimally invasive techniques combined with appropriate antibiotic agents are more effective in controlling the infection and decompression of hepatic hematoma. Should these be effective, alternative surgery is performed afterwards and has been confirmed as the best treatment.

Spontaneous hepatic hemorrhage is a rare condition caused by emphysematous cholecystitis. Both are emergent and potentially fatal disorders, associated with severe complications. Early diagnosis is critical in improving the prognosis, based not only on the radiologic features but also the inflammatory presentation. Therapy should include hemostasis, infection control, and decompression of hepatic hematoma. However, the choice of treatment modality should be individualized, according to the patient as well as etiology and characteristics of lesions.