Continuing Education Activity

Peliosis hepatis is a rare vascular condition that often goes unrecognized. Generally seen in adults of any age, it can also present in children with certain genetic disorders. This activity reviews the evaluation, pathophysiology, and management of patients with suspected peliosis hepatis and the role of an interprofessional team in the care of patients with this condition.

Objectives:

• Review the etiologies of peliosis hepatis.

• Describe the pathophysiology of peliosis hepatis.

• Identify imaging modalities to evaluate patients with suspected peliosis hepatis.

• Summarize the importance of communication amongst the interprofessional team to enhance the care of patients with peliosis hepatis and improve outcomes.

Introduction

Peliosis hepatis is a vascular condition in which the sinusoids of the liver proliferate, resulting in engorgement of the capillary bed and cavities within the liver. The condition often goes undiagnosed and is typically seen incidentally on abdominal studies and autopsy.

Etiology

First described by E. Wagner in the late 18th century and later seen in patients with known tuberculous infections, peliosis hepatis is now associated with a wide range of conditions from medications, infections, hematologic conditions, transplants, malignancy, and autoimmune conditions. Of the medications, many toxic therapies, including immunosuppressants such as 6-mercaptopurine, azathioprine, methotrexate, and tamoxifen, have demonstrated an association with the condition. Infectious causes include tuberculosis (TB), human immunodeficiency virus (HIV), and bacillus infections. The prevalence of the disease in patients with known associated conditions ranges from 0.2% to 22%. Although rarely documented, patients with known X-linked myotubular myopathy seem to have a genetic predisposition to the condition, demonstrating that there is likely a genetic component as well.[1][2][3]

Epidemiology

The number of reported cases of peliosis hepatis is rising with advances in imaging modalities and medicine, as well as the number of autopsies performed. Peliosis hepatis is most commonly idiopathic; however, it seems to have developed an association with patients with recent renal transplants. There is no documented difference in incidence between males and females. Although it is more often a condition observed in adults, it can be seen in the pediatric population as well.

Pathophysiology

Though the pathogenesis of the condition is still unknown, a variety of hypotheses exist stating that there is often a triggering event, such as epithelial damage or post-sinusoidal obstruction, which may lead to the eventual dilatation of the hepatic sinusoids and cavities. 

The anatomy of the sinusoidal capillaries is different than other capillary beds within the body. The fenestrations which are present within the liver allow for passes and filtration of larger molecules such as albumin. Epithelial damage can result from smoking, which can disrupt the architecture through the formation of free radicals. This damage, in turn, impairs vasodilation by inhibiting nitric oxide formation, which allows for normal physiologic relaxation of the arteries. Additionally, inflammation, whether it be autoimmune, direct trauma through surgical instrumentation, medication-induced, or invasion by malignancy, can result in the recruitment of inflammatory cytokines and cells, sometimes resulting in further epithelial damage. An alternate mechanism may be the depletion of glutathione, a critical regulatory molecule that assists in many biochemical detoxification reactions, which may disrupt the integrity of the epithelial wall and allow toxic metabolites to build up. However, through signal proteins such as vascular endothelial growth factor and others, re-endothelization can occur; thus, that is why using the absence of epithelial lining on imaging studies is not adequate to diagnose patients with peliosis hepatis, though it can raise the concern for it.[4][5]

Lastly, post-sinusoidal obstruction from several conditions such as malignant invasion, autoimmune inflammation, and drug injury is also hypothesized to be an alternate mechanism in the formation of peliosis hepatis.

History and Physical

Often an incidental finding, many patients present without symptoms, and a peliosis hepatis diagnosis may become included within the differential once a patient has notable derangements in their liver function tests. However, some patients may demonstrate no changes within their hepatic panel with pristine synthetic function, often making this diagnosis a challenging one. Less frequently, patients may present with signs more consistent with hepatobiliary pathologies such as abdominal pain, especially right upper quadrant pain, jaundice, and signs of portal hypertension.

To date, the symptoms associated with peliosis hepatis have not demonstrated a temporal relationship with the extent of disease burden. However, depending on the trigger and specific pathophysiology related to the development of the disease, patients may present in their unique way. Often the patients do not appear acutely ill and may be turned away by providers given their vague abdominal symptoms together with their benign laboratory findings. There have been some case reports in the literature that demonstrates patients presenting with severe abdominal pain found to have an intra-abdominal hemorrhage. Occasionally patients may also present with signs and symptoms of infection, including fever and abdominal pain, at which time prompt imaging is necessary to rule out intra-abdominal biliary sepsis. However, in those presenting with the symptoms above as well as weight loss, lymphadenopathy, and loose stools, Bartonella peliosis should be considered, especially in the setting in which patients may have exposure to household pets.[6][7]

Evaluation

If a diagnosis of peliosis hepatis is suspected, the evaluation often starts with laboratory studies, mainly a hepatic panel, which may or may not demonstrate changes. Following this, further abdominal imaging studies can be obtained, most frequently ultrasonography of the liver. Additional testing, including computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen, or angiography are also options; however, they are not necessary for the workup. Rather if ultrasound can demonstrate findings raising concern for peliosis hepatis, a biopsy is typically the next best step to make the diagnosis.

Treatment / Management

Given that the peliosis hepatis diagnosis is often made on autopsy or is an incidental finding due to an idiopathic cause, interventions are not always necessary. If the condition appears to be secondary to a medical therapy, the medication can be stopped, or if immunosuppression is the likely culprit, the immunosuppression therapy can be switched to an alternate agent. For those individuals who have findings consistent with peliosis hepatis due to other treatable medical conditions, the thinking is that the management of those individual conditions may lead to the regression of the condition. Patients with bacillary peliosis have demonstrated a response to antibiotic therapy in the appropriate setting. There is no current consensus on whether patients with asymptomatic peliosis hepatis warrant routine imaging studies to monitor disease burden or progression. However, some experts believe annual or more frequent evaluation with ultrasound is adequate.[8]

Differential Diagnosis

Due to peliosis hepatis being difficult to diagnose, the differentials are different for both microscopic findings and radiographic findings. Under the microscope, peliosis hepatis can appear similar to other causes of sinusoidal obstruction and volume overload states such as portal vein thrombosis as well as heart failure and nephrotic syndrome.

Radiographically the lesion can appear similar to many other hepatic lesions. Ranging from 1 to 2 millimeters to centimeters in size and occupying any portion of the liver, it is often mistaken for malignant lesions. To further evaluate, a variety of imaging modalities exist and can be of utmost utility. Angiography often demonstrates contrast accumulating within the parenchyma itself or the sinusoids, depending on when the image is captured. Depending on the degree of involvement and severity of the condition, these findings may or may not be present and often need further advanced imaging with either a triple-phase CT, which can reveal alternating regions of low then high foci, or MRI findings of hypo or hyperintensity based of which weighted image is utilized to observe that there is likely a pooling of blood in these regions.[9] The radiographic differential includes:

• Polycystic liver disease
• Congenital hepatic fibrosis
• Solitary congenital cysts
• Hydatid cyst
• Von Meyenburg complexes
• Caroli disease (type V choledochal cyst)
• Type IV choledochal cysts

Prognosis

The progression of peliosis hepatis is still largely uncertain. Researchers have not observed any apparent patterns of disease progression. However, often patients found to have the condition will remain asymptomatic for the remainder of their life, whereas others may develop complications known to be associated with portal hypertension. Very seldom, patients can develop life-threatening complications related to high rates of mortality, including intraperitoneal hemorrhage.[10]

Complications

Though the incidence of intraperitoneal and intrahepatic hemorrhage do not seem to be common complications, the risk does exist. Thus surgical resection appears to assist in the avoidance of such complications, especially if imaging studies have demonstrated worsening of the cavitary lesions.[6]

Deterrence and Patient Education

Patients who receive a diagnosis of peliosis hepatis should receive adequate counseling from medical providers regarding the disease condition as well as their prognosis. Those with incidental lesions found on abdominal imaging with subsequent biopsies demonstrating this condition should receive a referral to a gastroenterologist with expertise for annual monitoring of disease progression. Given the limited research, a specialist should provide the patients, families, and friends with both early and anticipatory counseling to best understand this disease process.

Enhancing Healthcare Team Outcomes

Although a rare condition, peliosis hepatis has known, well-documented associations with other disease states. In a patient with a confirmed diagnosis of peliosis hepatis, steps should take place to identify and remove the cause. The management of a patient with peliosis hepatis often involves an interprofessional team of providers, including a hepatologist, general surgeon, interventional radiologist, and gastroenterologist. The condition, which can present itself at any point in life, can result in liver, kidney, intestinal, or pulmonary issues. Given the rarity of the condition and the fact that clinicians so seldom uncover it, it is hard to gauge the natural history and course of the disease truly. However, current thought is that the majority of the patients continue living their lives without ever knowing of their condition.