Recurrent hepatobiliary sepsis in a patient with von Meyenburg complexes: a case report and review of the literature

Abstract

The von Meyenburg complex (VMC) is a rare, congenital malformation of the ductal plate. It is typically asymptomatic and usually discovered incidentally. We report a unique case of recurrent life-threatening hepatobiliary sepsis caused by VMC and a review of the literature. A 62-year-old man presented with recurrent episodes of life-threatening hepatobiliary sepsis. Extensive investigations only showed that he has VMCs without any other source of sepsis or underlying immunodeficiency states. Despite prolonged courses of antibiotics which resolved each episode of sepsis, he suffers repeated recurrences of hepatobiliary sepsis. Liver transplantation is now being considered in view of his refractoriness to medical therapy. As VMC can present with severe hepatobiliary sepsis, it is therefore essential to recognise its presence. This case adds to the literature the atypical but life-threatening clinical presentation of VMC.

Introduction

Von Meyenburg complexes (VMC) or biliary hamartomas are hepatic tumour-like lesions, first described by von Meyenburg in 1918. VMCs are related to congenital malformation of the ductal plate and are part of the ciliopathy spectrum of disorders. ¹ They are rare incidental pre-mortem findings, but are found relatively frequently at laparotomy and autopsy. ² Its incidence based on autopsy studies is approximately 5.6% in adults and 0.9% in children. ³

VMCs consist of multiple, small (<1 cm), well-defined nodular cystic lesions which can be easily confused with metastatic disease of the liver on imaging, leading to the occasional need for liver biopsy for definite diagnosis.^4,5 Magnetic resonance imaging (MRI), including magnetic resonance cholangiopancreatography (MRCP), is a valuable diagnostic tool for identifying multiple small hyperintense cystic lesions on T2-weighted images, the characteristic ‘starry sky’ phenomenon, without communication with the normal biliary tree.^6,7 Histologically, the lesion consists of cystic dilatation of the bile ducts surrounded by abundant fibrous stroma. ⁸

Patients with VMCs are usually asymptomatic. However, there have been case reports on VMCs on its variety of clinical manifestations, from benign non-specific symptoms, to infections and malignancies resulting in deaths.^9–12

We present a unique case of recurrent life-threatening hepatobiliary sepsis caused by VMC and a review of the literature.

Case presentation

A 62-year-old man presented with fever, jaundice and right hypochondrial pain in May 2009. Physical examination revealed mild tenderness in the right hypochondrium with a positive Murphy’s sign. A contrasted computed tomography (CT) scan of the abdomen and pelvis was performed, which showed evidence of cholecystitis, as well as mild periportal oedema and multiple small sub-centimetre non-enhancing hypodensities in both lobes of the liver which could not be characterised further. The patient subsequently underwent cholecystectomy. Intraoperatively, in addition to the inflamed gall-bladder, multiple liver abscesses and perihepatic adhesions were seen, resulting in a wedge liver resection being performed. Liver histology showed multiple VMCs composed of aggregates of angulated bile ducts within a fibrous stroma, and portal fibrosis. The bile ducts within the VMCs were involved by acute inflammation with microabscess formation (Figure 1). Features of large duct obstruction, portal–portal bridging necrosis and ductular proliferation were also present. He fully recovered and was discharged on post-operative Day 6.

Figure 1.

Micrograph of von Meyenburg complex (VMC) composed of angulated bile ducts within a fibrous stroma (H&E, original magnification ×100). Inset shows bile ducts of VMC involved by acute inflammation with microabscess formation (H&E, original magnification ×200).

He remained well the following two and a half years, but subsequently had recurrent admissions for fever with no other accompanying symptoms. Each episode of fever was associated with raised inflammatory markers and evidence of sepsis but normal biochemical liver function tests. Blood cultures were often positive with Klebsiella pneumoniae and Escherichia coli and occasionally positive with extended-spectrum beta-lactamase (ESBL)-producing organisms. Urinary and respiratory cultures were repeatedly negative. Multiple CT scans of the abdomen and pelvis and MRI of the abdomen were performed during these episodes of sepsis; the CT scan showed only multiple sub-centimetre liver and renal hypodensities (Figure 2), while the MRI scan showed multiple small hyperintense cystic nodules on T2-weighted imaging, not communicating with the biliary tree (Figure 3). On a few occasions, there was evidence of oedema in the peripheral portal triads, differing areas of focal hepatitis at areas of pre-existing biliary hamartoma and subcapsular liver abscess on the abdominal imaging. He was treated as for hepatobiliary sepsis secondary to VMC, and responded well to prolonged 3–4 weeks courses of intravenous and oral antibiotics, including ceftriaxone, co-amoxiclav, cefuroxime and ciprofloxacin.

Figure 2.

Abdominal computed tomography (CT) with contrast showing multiple sub-centimetre liver hypodensities.

Figure 3.

Liver magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) showing multiple hyperintense cystic lesions scattered in both lobes (arrowed).

Extensive investigations were performed to rule out other sources of sepsis. These included positron emission tomography (PET) scan, CT of the thorax, two-dimensional echocardiogram, colonoscopy, endoscopic ultrasound of the hepatobiliary tree and tuberculosis (TB) serology, all of which were normal. Technitium-99m-labelled white blood cell (WBC) scan showed focal increased tagged WBC activity in the liver. Autoimmune markers were negative, and serum immunoglobulin performed to rule out possible immunodeficiency states were within normal limits. Retroviral disease screen was also negative. A repeated liver biopsy, which was performed percutaneously, showed only multiple VMCs, similar to findings from the initial wedge liver biopsy.

As his episodes of sepsis became more frequent, more severe and life-threatening, he was started on oral cyclical antibiotics for prophylaxis. This consisted of cycles of ciprofloxacin, cefuroxime or co-amoxiclav. Trial of ursodeoxycholic acid and probiotics in addition to the antibiotics were unsuccessful. Subsequently bacteraemias switched from sensitive organisms, K. pneumoniae and E. coli, to occasionally more resistant ESBL-producing organisms. He has had at least 20 admissions over the last 3 years, and in view of his refractoriness to medical therapy, we are considering liver transplantation as an alternative for the management of his recurrent life-threatening hepatobiliary sepsis from VMCs.

Discussion

VMCs are rarely diagnosed clinically, since the vast majority of patients are asymptomatic and the VMCs are an incidental finding at imaging. However, to date, there are multiple case reports on the different clinical manifestations of VMCs, including non-specific abdominal pain, progressive abdominal distension, obstructive jaundice, portal hypertension, infectious complications and malignant transformation to cholangiocarcinoma and hepatocellular carcinoma.^9–13

This is the first case report of a VMC patient presenting with recurrent life-threatening hepatobiliary sepsis, refractory to medical therapy. To the best of our knowledge, there are only six cases of VMCs presenting with infectious complications reported in the English literature.^9,13–16 These included presentations with cholangitis, microabcesses and unexplained prolonged fever with abnormal liver function test and Gram negative bacteraemia from hepatobiliary source. Only one of these patients had recurrent sepsis, while the others presented with a single episode of infection, all of which responded well to antibiotics. Table 1 summarises the published cases of these group of patients.

Table 1.

Summary of published cases.

Reference	Year	Sex	Age	Clinical presentation	Diagnosis	Imaging findings	Treatment, duration and response	Histopathology
Hashimoto et al. 14	2011	Male	75	Fever, confusion	E. coli bacteraemia from hepatobiliary source	MRI: multiple hepatic nodule, hypointense on T1 and hyperintense on T2-weighted images	Ceftriaxone 2 g/day, duration not specified, good response after 3 days of antibiotics	No biopsy performed
Chen et al. 13	2000	Male	63	Fever, jaundice, right upper quadrant pain	Hepatic microabscesses	MRI: numerous tiny cystic lesions with peripheral enhancement	Parenteral antibiotics, duration not specified, good response	Bile duct hamartomas with microabscess formation
Van Vlerken et al. 15	2011	Male	77	Recurrent fever, chills, abdominal discomfort, vomiting	Cholangitis	MRCP: multiple sub-centimetre hyperintense liver nodules without communication with biliary tree	Ciprofloxacin, duration not specified, good response	Presence of VMC on previous liver biopsy specimen
Wei et al. 16	1997	Male	64	Fever, diarrhoea, abdominal pain	E. coli bacteraemia from hepatobiliary source	MRI: many tiny lesions with low signal in T1 and high signal in T2-weighted images	Ceftriaxone and netilmicin sulfate, duration not specified, good response	Bile duct hamartomas, no abscesses
Sinakos et al. 9	2011	Female	60	Fever, jaundice, right upper quadrant pain	Hepatobiliary infection	MRI: multiple cystic lesions <1.5 cm	Parenteral antibiotics for 10 days, good response	No biopsy performed
Sinakos et al. 9	2011	Male	25	Prolonged fever, epigastric discomfort	Hepatobiliary infection	MRI: multiple liver cystic lesions	4 weeks of antibiotics, recurrence of fever after withdrawal of antibiotics, then a 3 month course of cyclical antibiotics including cephalosporin, ciprofloxacin and doxycycline	No biopsy performed

The presumptive pathogenesis for the recurring sepsis is likely from biliary stasis, leading to superinfection of the cystic contents which makes sterilisation hard to achieve, followed by subsequent formation of microabscesses. This is supported by the change in MRCP findings, where there were signal abnormalities indicating inflamed liver segments at areas of small hyperintense foci on T2-weighted sequence of VMCs, as well as oedema of the peripheral portal triads. These findings resolved and recurred again in different liver segments on separate occasions. Another potential explanation could be excess mucous secretion resulting in biliary obstruction and ascending infection. Percutaneous needle aspiration and biopsy of the cyst can confirm the presence of cystic bacterial infection, but was not performed for our patient due to concerns of disseminating the underlying infection.

Treatment with antibiotics should have resulted in sterilisation of the cyst content and resolution of the sepsis. Unfortunately for our patient, his sepsis was recurrent and life threatening despite adequate antibiotic treatment of each septic episode as well as oral cyclical antibiotics. The exact triggers to the recurrence of his hepatobiliary sepsis have not been established. A liver biopsy performed during the convalescence period, were consistent with only VMCs, with no evidence of bacterial infection, no cholestasis, lobular inflammation, or malignancy. There were also no acid-fast bacilli seen on ZN stain, no granulomas or viral inclusion bodies seen. K-RAS mutational analysis was negative, side viewing duodenoscopy as well as ampullary biopsy was also normal, excluding the possibility of an underlying malignant process.

For our patient, since the interval between the septic episodes are getting shorter, more resistant organisms are being implicated and treatment options becoming limited, we feel that liver transplantation which removes the underlying source of infection will be of benefit. Recurrent biliary sepsis is an accepted indication for liver transplantation as in the case for primary sclerosing cholangitis (PSC) and Caroli disease. ¹⁷

Conclusion

Hepatobiliary sepsis is an unusual but can be a clinically significant mode of presentation in patients with VMCs. It is therefore essential to recognise its presence. This case adds to the literature the atypical but life threatening clinical presentation of VMCs.