Formation and rupture of liver hematomas caused by intrahepatic gallbladder perforation: A case report and review of literature

Abstract

BACKGROUND

Gallbladder perforation is a serious complication of acute cholecystitis. Such perforation is a rare but life-threatening situation that can lead to the formation and rupture of liver hematomas. Here, we report a case of a ruptured intrahepatic hematoma caused by intrahepatic gallbladder perforation, and we present a literature review.

CASE SUMMARY

A 70-year-old male was admitted to the hospital with a complaint of right upper quadrant abdominal pain, flustering and dizziness. The preoperative diagnosis was a ruptured malignant liver tumor, and the patient’s medical images and increased level of carbohydrate antigen-199 suggested that the gallbladder had been invaded. However, the tumor was proven to be a liver hematoma secondary to gallbladder perforation after surgery. The patient was discharged uneventfully on the fifteenth postoperative day.

CONCLUSION

Intrahepatic gallbladder perforation is difficult to diagnose preoperatively. Radiological examinations play a crucial role in the diagnosis but only for partial cases. Early diagnosis and appropriate surgery are key to managing this rare condition.

Key Words: Intrahepatic gallbladder perforation; Cholecystitis; Liver rupture; Intraperitoneal hemorrhage; Case report

Core Tip: In this work, we present a rare clinical case in which a ruptured malignant liver tumor with invasion of the gallbladder was suspected but was proven to be a liver hematoma secondary to gallbladder perforation after surgery. Moreover, we conducted a literature review on intrahepatic gallbladder perforation. Here, the symptoms, examinations, diagnosis and treatments of intrahepatic gallbladder perforation are summarized. Additionally, we propose a new classification system for gallbladder perforation, which provides a valuable reference for the diagnosis and treatment of this condition.

INTRODUCTION

Gallbladder perforation (GBP) is a rare but life-threatening complication of acute cholecystitis, occurring in 2%-11% of patients with cholecystitis[1,2]. GBP remains an important problem for surgeons because many cases fail to be diagnosed before surgery, and the mortality rate is as high as 12%-16%[3]. In 1934, Niemeier firstly classified GBP into three types: (1) Type I chronic perforation with fistula formation between the gallbladder and another viscus; (2) Type II subacute perforation where the perforated gallbladder is surrounded by an abscess that is walled off by adhesions from the general peritoneal cavity; and (3) Type III acute perforation into the free peritoneal cavity without protective adhesions[1]. Intrahepatic GBP is a rare type that has only been reported in a few studies. Cases of GBP leading to the formation and rupture of liver hematomas have seldom been reported.

Herein, we report a case of a ruptured liver hematoma caused by GBP. Moreover, we conducted a literature review about intrahepatic GBP to characterize the common clinical manifestations, diagnosis and treatments.

CASE PRESENTATION

Chief complaints

Right upper quadrant abdominal pain.

History of present illness

A 70-year-old man with a past history of chronic constipation presented to the Emergency Department of a local hospital complaining of worsening colicky pain in the right upper quadrant of the abdomen, as well as for flustering and dizziness. He had repeatedly experienced right upper quadrant abdominal pain for one week with nausea, vomiting and referred pain in the right shoulder. On September 11, 2022, the patient was taken to the local hospital because his symptoms had worsened dramatically. At the same time, he also exhibited an insufficient blood volume, which caused him to be flustered and to experience dizziness.

After admission, emergency abdominal computed tomography (CT) revealed a mixed density shadow in the right lobe of the liver combined with abdominopelvic effusion and an enlarged gallbladder adjoining the mass, suggesting that the liver tumor had ruptured, bled and invaded the gallbladder (Figure 1). The laboratory results showed that the hemoglobin (Hb) level had decreased to 9.4 g/dL and the serum carbohydrate antigen-199 (CA-199) level had increased to 1972 U/mL. Then, he planned to receive hepatic artery embolization, but angiography revealed no active bleeding artery. This might suggest that the bleeding vessel was a vein or that the hemorrhage had stopped. The patient was transferred to our hospital for further treatment on the evening of September 12, 2022, after his general condition had stabilized.

Figure 1 Abdominal computed tomography revealing a mixed density shadow in the right lobe of the liver combined with abdominopelvic effusion and an enlarged gallbladder adjoining the mass.

History of past illness

The patient denied a history of trauma or falls, chronic hepatitis, alcoholic liver disease, cirrhosis, hemangioma, other liver tumors, or cholecystolithiasis.

Physical examination

On admission, the patient’s hemodynamics were stable, with a heart rate of 99 beats per minute, a blood pressure of 18.5/10.4 kPa, and an oxygen saturation of 95%. Physical examination revealed abdominal distension and marked tenderness in the right upper quadrant of the abdomen.

Laboratory examinations

The laboratory results (Table 1) revealed low Hb levels (8.7 g/dL), elevated white blood cell (WBC) counts (14.56 × 10⁹/L), elevated alanine aminotransferase (ALT) levels (2509 U/L) and total bilirubin levels (37.8 μmol/L). Additionally, the levels of serum CA-199 and protein induced by vitamin K absence or antagonist-II (PIVKA-II) had elevated to 106.5 U/mL and 59.02 mAu/mL, respectively. The serum alpha fetoprotein level was 2.76 ng/mL. After admission, the patient underwent a blood transfusion and intravenous infusion of analgesics, hemostatic agents and antibiotics. After treatment, his condition stabilized, and the laboratory parameters gradually improved.

Table 1 Laboratory results.

Parameters	On admission	Postoperative
White blood cell (109/L)	14.56	5.20
Hemoglobin (g/L)	87	105
Platelet (109/L)	72	158
Alanine aminotransferase (U/L)	2509	80
Aspartate aminotransferase (U/L)	2403	44
Total bilirubin (µmol/L)	37.8	13.5
γ-glutamyl transferase (U/L)	89	123
Prothrombin time (second)	15.7	12.8
Alpha fetoprotein (ng/mL)	2.76	NA
Carcinoembryonic antigen (ng/mL)	3.74	NA
Carbohydrate antigen-199 (U/mL)	106.5	NA
Protein induced by vitamin K absence or antagonist-II (mAu/mL)	59.02	NA

Imaging examinations

Magnetic resonance imaging (MRI) of the abdomen performed on September 16, 2023, revealed a mass with mixed signals in the right lobe of the liver, with a large cross-sectional area of 114 mm × 131 mm. There were several rounded long T1 signals in the mixed-signal mass. The parenchymal region showed hyperintensity on diffusion-weighted imaging (b = 1000), and no obvious enhancement was found on dynamic contrast-enhanced MRI (DCE-MRI). The gallbladder was distended, with a thickened wall, and was poorly demarcated from the mass (Figure 2).

Figure 2 Magnetic resonance imaging of the abdomen showing a mass of mixed signal in the right lobe of the liver. White arrow: Several rounded long T1 signals in the mixed-signal mass; Blue star: The “hole sign”.

FINAL DIAGNOSIS

Based on the results of MRI and the elevated tumor markers (CA-199, PIVKA-II), we initially determined that the patient had a ruptured malignant liver tumor with invasion of the gallbladder.

TREATMENT

The patient underwent surgery on September 26, 2022, after other examinations were completed and contraindications were excluded.

OUTCOME AND FOLLOW-UP

Laparotomy revealed the following findings: bloody ascites in the abdominal cavity and a 14 cm × 10 cm dark-red mass located in the segments V and VI of the liver (Couinaud segment). The mass was adherent to the transverse colon, omentum and gallbladder which was enlarged to 12 cm × 4 cm. During the surgery, the Calot triangle was first dissected to ligate the cystic duct and the cystic artery. Second, we prepositioned the blocking bands at the first hepatic portal and the inferior vena cava to control bleeding during partial liver resection. Third, we planned to remove the mass and gallbladder completely. However, during the resection, we found that there was no capsule or boundary between the mass and the liver parenchyma. Unexpectedly, there was no solid tissue but many blood clots as well as several hard yellow stones inside the mass, indicating that the lumen of the mass was connected to the gallbladder cavity. The gallbladder seemed to be the root of the disease. At this point, we suspected that the hemorrhage was caused by gallbladder cancer invading the liver. However, upon exploration of the resected specimen, we found that there was no obvious malignant tumor in the liver. Instead, the mass appeared to be a simple hematoma that was connected to the gallbladder. The gallbladder body was perforated, and the area around the perforation felt firm upon palpation. Surprisingly, the histopathologic examination revealed that the liver mass was a hematoma and that there was no cancer but an ulcer of the gallbladder with fibrosis and inflammatory cell infiltration (Figure 3).

Figure 3 Ulceration of the gallbladder with fibrosis and inflammatory cell infiltration.

The patient was discharged on the fifteenth postoperative day without any complications. During the 1-year follow-up, neither cholelithiasis recurrence nor death occurred.

DISCUSSION

A systematic review of the literature was conducted to identify published cases of intrahepatic GBP. The terms ‘gallbladder’, ‘perforation’, ‘liver’, ‘intrahepatic’ and ‘transhepatic’ were searched in various combinations with the Boolean operators AND and OR via the OVID databases and PubMed databases. The abstracts of all the full-text English articles were scrutinized. The reference lists of the articles obtained were also searched to identify further relevant citations. Six publications were excluded because they were not available for online access owing to their publication in an older era. Ultimately, 30 publications containing 40 patients were included (Table 2)[4-33]. The majority of these publications (n = 24) were single patient case studies. A summary of the clinical cases of intrahepatic GBP is presented in Table 2. Among all patients, the mean age was 59.6 years ± 18.1 years (range 13-95 years) old. Males accounted for the majority of cases (n = 33, 82.5%). In total, 22.5% of patients (n = 9) had a past history of confirmed cholelithiasis, 17.5% (n = 7) had hypertension, 15% (n = 6) had diabetes mellitus (DM), 5% (n = 2) had coronary arterial disease (CAD), 5% (n = 2) had chronic obstructive pulmonary disease and 5% (n = 2) consumed alcohol. Interestingly, there was one particular patient with a ruptured liver hemangioma caused by GBP[10].

Table 2 Review of the literature on intrahepatic gallbladder perforation.

Ref.	Year	Age	Sex	Classification1	Past history	Abdominal pain	Fever	Neusa or vomiting	Shock	Jaundice	Abnormal laboratory tests	Examinations	Treatment
Paramythiotis et al[4]	2022	69	Female	B	DM, hypertension	1				1	CRP, ALT, AST, TBIL	US, MRCP	S2
Paramythiotis et al[4]	2022	79	Male	B	Chronic abdominal pain	1	1	1		1	WBC, CRP, TBIL, GGT	CT, MRI	S1
Paramythiotis et al[4]	2022	54	Male	B	Chronic alcohol consumption	1	1				WBC, CRP, ALP	CT	D1+S1
Mach et al[5]	2022	55	Male	A	Ccholelithiasis	1			1		HB	CT	S1
Nikumbh et al[6]	2020	55	Male	B	Rheumatoid arthritis	1	1				N/A	US, CT, MRCP	D3+S2
Nikumbh et al[6]	2020	28	Female	B	Cholelithiasis	1					N/A	CT, MRCP	D3+S2
Chikamori et al[7]	2020	87	Male	A, B	Cholelithiasis, CAD	1	1		1		WBC, CRP, ALT, AST, ALP	CT, cholangiography	D1
Lan et al[8]	2019	53	Male	A	N/A	1			1		WBC, ALT, AST, TBIL, carbohydrate antigen-199	CT	S1
Parekh et al[9]	2019	68	Female	B	N/A	1		1			N/A	CT	D3
Ke et al[10]	2017	44	Male	A	Hepatic hemangiomas, cholelithiasis				1		HB	CT	S1
Williams et al[11]	2017	61	Male	B	N/A	1	1	1			CRP, ALP	CT	D3+S2
Hussain et al[12]	2016	72	Male	B	Cholelithiasis	1	1			1	WBC, CRP	CT	D1+S2
Hussain et al[12]	2016	62	Male	B	Cholelithiasis	1	1				WBC, CRP	US, CT	D1+S2
Cristian et al[13]	2014	76	Male	B	Hypertension, a repaired inguinal hernia	1	1	1			WBC, CRP	X-ray, US, CT	S2
Donati et al[14]	2014	62	Male	B	Inguinal hernia		1				WBC	US, CT, MRI	S3
Alessiani et al[15]	2014	77	Male	B	Alzheimer's disease, hypertension, atrial fibrillation	1	1				WBC, ALT, AST	US, CT	D1
Agarwal et al[16]	2013	18	Male	B	N/A	1					N/A	US, CT	S3
Agarwal et al[16]	2013	40	Male	B	N/A	1					N/A	US	D1+S2
Agarwal et al[16]	2013	42	Male	B	N/A	1					N/A	US, MRCP	S2
Singh et al[17]	2013	50	Male	B	Chronic abdominal pain	1					N/A	US, CT	S1
Hollanda et al[18]	2013	50	Male	C	N/A	1	1	1		1	WBC, ALT, AST, TBIL	US, CT	S1
Coulier et al[19]	2012	68	Male	A	Epigastric pain	1			1		HB, CRP, ALT, AST	CT, MRI	S1
Taneja et al[20]	2012	62	Male	C	N/A	1	1				WBC, ALT, AST, ALP	US, CT	D1+S1
Kalfadis et al[21]	2011	95	Male	C	Cholelithiasis, hypertension	1	1				WBC, GGT	US, CT	D1
Göbel et al[22]	2011	30	Female	B	Hypertension, nephrectomy, hypernephroma, cholelithiasis	1	1				WBC, CRP	US, CT	S1
Shakya et al[23]	2010	60	Male	N/A	Epigastric pain	1		1		1	WBC, ALT, AST, TBIL, ALP	X-ray, US	S1
Tsai et al[24]	2010	66	Male	C	COPD, chronic kidney disease	1	1	1			WBC, ALP	US, CT	D2
Kochar et al[25]	2008	67	Male	B	DM, diverticular disease, stroke	1	1				WBC, CRP, ALP	US, CT, abscessogram,MRCP	D1+S1
Łebkowski et al[26]	2008	80	Male	A	Hypertension	1			1		N/A	US	S1
Nural et al[27]	2007	73	Male	A	COPD, CAD, DM, hypertension	1		1			WBC, ALT	CT	S1
Kang et al[28]	2007	70	Male	B	Stroke	1	1				N/A	CT	D1+D3
Ceylan et al[29]	2003	13	Male	N/A	N/A	1	1	1			WBC, ALT, AST, TBIL, ALP	US	conservative drug treatment
Peer et al[30]	1994	69-81	2 males, 2 females	B	DM	1	1				WBC, ALP	CT	D1+S1
Chen et al[31]	1990	60	Male	B	Alcohol consumption	1	1	1			WBC, AST, ALP	US	S1
Syme et al[32]	1989	74	Female	A	Cholelithiasis	1			1		N/A	N/A	S1
Teefey et al[33]	1987	69	Male	B	DM		1				WBC, AST, TBIL, ALP	US, CT	S1
Teefey et al[33]	1987	55	Male	B	N/A	1	1				WBC, ALP	US, CT	D1+S1

¹Classification: A: Hemorrhage; B: Liver abscess; C: Liver biloma.

DM: Diabetes mellitus; CAD: Coronary arterial disease; COPD: Chronic obstructive pulmonary disease; N/A: Not applicable; CRP: C-reactive protein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; HB: Hemoglobin; WBC: White blood cell; GGT: γ-glutamyl transferase; ALP: Alkaline phosphatase; US: Ultrasound; CT: Computed tomography; MRCP: Magnetic resonance cholangiopancreatography; MRI: Magnetic resonance imaging; S1: Open surgery; S2: Laparoscopic surgery; S3: Laparoscopic conversion to open surgery; D1: Percutaneous drainage; D2: Endoscopic nasal bile drainage; D3: Endoscopic drainage by the placement of a stent.

In these cases, except for two cases in which GBP occurred in the hospital and no further complications developed, intrahepatic GBP could be divided into three categories: (1) Type A, GBP leading to the formation and rupture of a liver hematoma manifesting as hemorrhage and shock; (2) Type B, GBP leading to a liver abscess; and (3) Type C, GBP manifesting as a liver biloma. The most common form of intrahepatic GBP was type B (n = 27, 67.5%), followed by type A (n = 8, 20%) and type C (n = 4, 10%). Specifically, there was one case in which an intrahepatic GBP led to hemoperitoneum and abscess formation at the same time[7]. The majority of the patients presented with right upper quadrant abdominal pain (n = 34, 91.9%). The remaining symptoms were fever (n = 22, 59.5%), nausea or vomiting (n = 10, 27%), shock (n = 7, 18.9%), and jaundice (n = 5, 13.5%). The common abnormal laboratory tests included WBC, c-reactive protein (CRP), ALT, aspartate aminotransferase (AST) and alkaline phosphatase (ALP). The remaining abnormal results included Hb, total bilirubin, γ-glutamyl transferase (GGT) and CA-199. Ultrasound (US) and abdominal CT were the common approaches for identifying cholecystitis and intrahepatic GBP. Most of the patients (n = 32, 80%) eventually underwent surgery, including open surgery (n = 22, 68.75%), laparoscopic surgery (n = 8, 25%) and laparoscopic conversion to open surgery (n = 2, 6.25%). Because of severe comorbidities, 8 patients underwent conservative treatment, including percutaneous drainage or endoscopic nasal bile drainage (ENBD). All patients were discharged successfully.

GBP is usually associated with the presence of gallbladder stones but can also be encountered in acute acalculous cholecystitis, although this occurs rarely[2]. Occlusion of the cystic duct (most frequently by stones), which leads to biliary stasis and gallbladder distension with consequential increased pressure and impaired circulation in the gallbladder, combined with bacterial colonization and infection, causes necrosis and perforation of the gallbladder[21,34]. The gallbladder fundus is the most common position of GBP owing to the poor blood supply[2,35]. Generally, perforation in the fundus leads to bile drainage into the peritoneal space without protective adhesions. In our patient, the perforation was located in the gallbladder body, which contacts the liver. The occurrence of GBP is more common in males over 60 years old, whereas acute uncomplicated cholecystitis is more common among females[2]. The literature review revealed similar results. Other risk factors related to GBP include previous cholecystitis, hypertension, DM, CAD and long-term use of steroids. As our study showed, many patients had a past history of cholecystitis, hypertension or DM. GBP was based on cholecystitis. Hypertension and DM could lead to poor microcirculation in the gallbladder because of changes in arterioles.

There are considerable debates in the literature regarding the modification of Niemeier’s classification. Anderson and Nazem[36] and Ibrarullah et al[37] recommended labeling the cholecystobiliary fistula as type IV GBP, considering the unique operative approach needed in such cases. However, Kochar et al[25] argued that GBP with fistula formation or a demonstrable communication, including cholecystobiliary and cholecystohepatic connections, should be divided into Niemeier type III perforations, to maintain uniformity in reporting. However, uniformity cannot be achieved, as intrahepatic GBP with liver abscess formation is usually considered as a Niemeier type II perforation[22,38]. In addition, intrahepatic GBP with hemorrhage is an urgent and life-threatening condition that is not suitable for Niemeier’s classification. Therefore, a new classification of GBP must be formulated. Here, we propose the following conceptions: (1) Type I, perforation into the peritoneal cavity with (IA, acute perforation) or without (IB, subacute or chronic perforation) adhesions; (2) Type II, intrahepatic perforation including three subcategories (IIA, acute perforation with the formation and rupture of a liver hematoma; IIB, subacute or chronic perforation leading to a liver abscess; IIC, chronic perforation leading to a liver biloma); and (3) Type III, chronic perforation with the formation of a fistula that can communicate with the outside, including cholecystobiliary, cholecystoenteric and cholecystocutaneous fistulas. This classification is simple and unlikely to cause confusion in the diagnosis.

There are no classical symptoms or signs related to intrahepatic GBP. Patients usually present right upper quadrant abdominal pain, fever and nausea. In our case, the patient also exhibited insufficient blood volume, with symptoms that included feeling flustered and experiencing dizziness. Increased levels of inflammation indicators, such as WBC and CRP, and elevated liver enzymes, including ALT, AST, ALP and GGT, are commonly observed. However, it is difficult to clinically distinguish GBP from an uncomplicated acute cholecystitis, as the majority of the above features are present in both of them. There were two characteristics in our case. One was extremely elevated ALT and AST levels due to the formation and rupture of a huge liver hematoma. Considering the high risk of post-hepatectomy liver failure, emergency surgery was excluded. The other was increased CA-199, which was most commonly used as a tumor marker to help diagnose hepatobiliary and pancreatic malignancies[39]. A ruptured mass on medical imaging combined with increased CA-199 caused us to misdiagnose this case, which was similar to the findings of Lan et al[8]. Previous studies have shown that high CA-199 levels can be detected in patients with calculous cholecystitis and are associated with the degree of gallbladder inflammation[40]. This phenomenon deserves more attention from clinicians to avoid a misdiagnosis.

The preoperative diagnosis of GBP depends on radiological examinations, including US, CT, and MRI. The findings of acute cholecystitis, such as gallbladder stones, distention and wall thickening, can also be presented in GBP. The reliable sign of GBP is a defect in the gallbladder wall (the “hole sign”)[25,35,41]. CT is superior to US in depicting the hole sign[41]. However, both US and CT may not be useful for diagnosing some cases with perforation[2,27,42]. Kim et al[43] reported that defects could not be visualized via CT in 54% of patients. In our case, the hole sign could be identified via MRI (Figure 2) but failed to be detected on CT. Several rounded long T1 signals in the mass were confirmed to be gallbladder stones after the operation. No obvious enhancement was found on DCE-MRI, which also indicated that the mass was not a malignancy. Intrahepatic perforations with the formation of a liver abscess or biloma could be diagnosed more easily than perforations with ruptured liver hematomas. According to our review, all cases were accurately diagnosed except for two cases of GBP with liver rupture[5,8]. The diagnosis rate was much higher than that in previous reports. This might be due to a publication bias.

Regarding treatments for type A intrahepatic GBP, emergency laparotomy is the first consideration for patients who are in good general condition[19,26]. For patients in poor condition, transarterial embolization combined with secondary hepatectomy and cholecystectomy is an ideal treatment strategy. According to the literature review, percutaneous transhepatic drainage combined with secondary cholecystectomy is the most common treatment for intrahepatic GBP of types B and C. Laparoscopic cholecystectomy is challenging because of severe inflammation and adhesions in the abdominal cavity. Among the 10 patients who chose laparoscopic cholecystectomy, two cases were eventually converted to open surgery[14,16]. Additionally, ENBD is a safe and effective treatment for patients who are not suitable for surgery[9,24].

CONCLUSION

In summary, intrahepatic GBP is difficult to diagnose preoperatively. Radiological examinations play a crucial role in diagnosis only for partial cases. How to improve the diagnostic rate needs further investigation. Early diagnosis and appropriate surgery are key to managing this rare condition.

ACKNOWLEDGEMENTS

The authors thank the patient for his collaboration.