Clinical experience of liver transplantation in the treatment of peliosis hepatis

Yang Zhao , Yu Liu , Lin Zhou, Xin-Xue Zhang, Ping Li, Qiang He

Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, No.8, Gongtinan Road, Chaoyang District, Beijing 10 0 020, China

TotheEditor:

Peliosis hepatis (PH) is an uncommon benign vascular disorder characterized by widespread blood-filled cysts in the liver. This disease was first described by Wagner in 1861, and because the liver lesions were generally red or blue-purple, it was first named PH by Schoenlack in 1916 [1] . The etiology of PH is not completely clear now, which is mainly related to drug factors, immune factors, and infections. The diagnosis of PH is difficult because of the lack of specific clinical manifestations and imaging features. Pathological biopsy represents the gold standard in diagnosis of PH [2] .The treatment of PH varies from person to person and no consensus has been reached, including the removal of pathogenic factors,hepatic artery embolization, hepatectomy, etc. [3 , 4] . Liver transplantation (LT) may be the best treatment for PH with fatal complications [5 , 6] . This study described a rare case of recurrence of PH after LT.

A 28-year-old female patient was admitted for whole-body edema. She denied any fevers, chills, abdominal pain, abdominal distension, nausea, vomiting, yellow staining of skin and sclera,tea-colored urine, clay-colored stool, or alterations in bowel habits.The patient underwent LT in another hospital 13 years ago because of PH and received long-term immunosuppressive therapy(tacrolimus, 1 mg/tab twice a day). She also denied regular use of alcohol, tobacco, illicit drug, or other drugs. Personal history and family history were not unusual. The physical examination revealed hepatomegaly without other positive signs. The laboratory test results were as follows: the blood count showed anemia with hemoglobin (Hb) 109 g/L (reference 130-175 g/L); and white blood cells (WBC) 2.3 × 109/L (reference 3.5-9.5 × 109/L), red blood cells (RBC) 3.6 × 1012/L (reference 4.3-5.8 × 1012/L), and platelets(PLT) 77 × 109/L (reference 125-350 × 109/L) were all lower than normal which indicated hypersplenism. Decreased albumin (ALB)27.1 g/L (reference 40.0-55.0 g/L), elevated alkaline phosphatase(ALP) 173 U/L (reference 45-125 U/L) and total bilirubin (TBIL) 80.8 μmol/L (reference 5.0-21.0 μmol/L) were noted. There was no evidence of hepatitis B and C infection. Tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9),and alpha-fetoprotein (AFP) were all in the normal range. On noncontrast abdominal CT, the images showed hepatomegaly with irregular shape ( Fig. 1 A). Contrast-enhanced CT images revealed numerous nodular enhancement lesions in the early arterial phase( Fig. 1 B), and abnormal patchy enhancement areas can be seen in the arterial phase ( Fig. 1 C) and venous phase ( Fig. 1 D). The patient was also subjected to positron emission tomography/computed tomography (PET-CT) and the result suggested that the enlargement of the liver had no abnormal metabolic activity.

According to the examination results of the patient, no evidence of malignancies was found. We tried to delay the disease through conservative treatment, but failed and the patient’s liver dysfunction progressed. LT was the only life-saving choice for this patient.Finally, she underwent successful orthotopic piggy-back LT from a donor after brain death. Cold ischemic time was 6.17 h, and warm ischemic time was 30 min. Intraoperative estimated blood loss was 2500 mL and the patient received 12 units of packed red blood cells and 800 mL of plasma. On macroscopic examination, the surface of the liver randomly distributed irregular multiple bloodfilled cystic processes, and no obvious tumor-like tissue was seen( Fig. 2 A). The volume of the liver atrophied after the blood flows out of the capsule ( Fig. 2 B). Postoperative pathology showed that cystic blood cavities of different sizes could be seen in the hepatic parenchyma, partially lined by endothelial cells and/or fibrosis( Fig. 2 C). It confirmed the diagnosis of PH.

PH is a rare benign disease. Except for liver, the lesions may occur in the spleen, pancreas, bone marrow, lymph nodes, pituitary gland, and kidney [7] . The etiology of PH remains unclear, which may be related to the following factors: (1) drug-related factors,such as steroids, diethylstilbestrol, immunosuppressants, oral contraceptive, and iron chelating agents [2 , 8] ; (2) certain toxins, such as arsenic, thorium [9] ; (3) infectious diseases or immune deficiencies, such as tuberculosis, acquired immunodeficiency syndrome(AIDS), and immunodeficiency after organ transplantation [2 , 8] ; (4)chronic consumptive diseases or malignant tumors, such as hepatocellular carcinoma, myeloproliferative diseases [2] . We considered that the main causes of recurrence of PH, in this case, may have been related to her post-LT status and long-term immunosuppressive therapy. But it is difficult to explain the relationship between the etiology of PH in the first and the second time.

Fig. 1. Abdominal computed tomography (CT). A : Plain scan of noncontrast CT; B - D : early arterial phase ( B ), arterial phase ( C ) and venous phase ( D ) of contrast-enhanced CT.

Fig. 2. Gross appearance ( A and B ) and pathologic examination ( C) (HE staining, original magnification × 200) of the PH liver. HE: hematoxylin-eosin; PH: peliosis hepatis.

Clinical classification of PH is mainly divided into the focal type and diffuse type based on the size and extent of the lesion, and even though more often it is diffuse [4] . For asymptomatic clinical manifestations, most of the patients with focal type are found in physical examination or encountered an acute event such as hemorrhage. Besides, some patients could have atypical gastrointestinal symptoms such as abdominal distension, loss of appetite, and weight loss. Patients with diffuse PH could be complicated with liver cirrhosis, liver failure, and portal hypertension [9] . Our patient presented with hepatomegaly and body edema. The imaging findings of PH depend on lesion size and the degree of thrombosis or hemorrhage inside the cavity, as they can appear with variable imaging performances [9] . Ultrasonography often shows a pseudocyst of hepatic parenchyma or hypervascular nodules. It appears hyperechoic in steatosis, and hypoechoic in the normal liver parenchyma [9] . CT images of PH often showed low-density lesions, low-density or centripetal enhancement in the arterial phase, centrifugal enhancement in the venous phase, and diffuse uniform enhancement in the delayed phase. Compared with neoplastic lesions, lesions of PH generally have no mass-like edge, lack of space-occupying effect, and still have an enhancement in the delayed phase [2 , 9] . MRI examination shows a high value in radiologic diagnosis for this disease. Different enhancement patterns can be shown in contrastenhanced imaging that is attributable to hemorrhagic necrosis, and the most common enhancement patterns are central enhancement in the arterial phase and marginal enhancement in the venous phase [9] .

At present, histopathological examination is the gold standard for the diagnosis of PH [7] . Small blue-purple or blue-black nodules can be seen at the gross inspection. Hyperemia of hepatic parenchyma and dilatation of hepatic sinusoids can be seen under a microscope, which could be divided into two subtypes:parenchyma type and venous dilatation type. For the parenchyma type, there are no endothelial cells in the cavity, and the formation may be related to hemorrhagic necrosis; The venous dilatation type is characterized by fibrous tissue or endothelium lined with the dilated lumen. The percutaneous transhepatic biopsy can be used for a definite diagnosis, but the risk of hemorrhage is high and should be used with caution [2] .

PH is recognized as a benign disease, but it can cause serious fatal complications such as hemorrhage and liver failure. Currently, there is still no specific treatment for PH [4 , 8] . Removal of pathogenic factors could delay or even reverse the progression of the disease [10] . We claim that whether PH could be reversed are associated with different stages of disease progression and pathogenic factors, but more clinical data are needed to verify it. For this patient, we considered that hepatic lesions may regress upon the withdrawal of immunosuppressants, but this approach was accompanied by an increase in the risk of transplant rejection.Therefore, the patient continued to use immunosuppressants while waiting for a donor’s liver. Besides, surgical resection or embolization of hepatic artery is feasible for focal PH to reduce the risk of hemorrhage, but there is the possibility of embolization failure and inability to remove all PH lesions [3 , 4] . LT can be considered when other treatments are ineffective for PH patients complicated with serious complications. Several cases of LT for PH have been reported previously [5 , 6] . There are great advantages for LT in the radical cure of PH, especially in the case of PH with uncontrollable liver hemorrhage and liver failure.

Through the review of previous literature, no related reports of PH recurrence after LT were found. Combined with the medical history of this patient, we propose that PH can be completely cured by LT, but there is still a risk of recurrence. The cause of recurrence may be related to the post-organ transplantation status and the long-term use of immunosuppressants, but it can not be ruled out that it is caused by the same etiology of the patient’s first attack of PH, or as a result of the joint action of the two. Unfortunately, we did not find the pathogenic factors of PH in the patient’s medical history 13 years ago, which made it impossible for us to conduct a more in-depth study of the etiology of PH. We hope to obtain more valuable information about the prognosis of PH patients after LT through a long-term follow-up of this patient.

In conclusion, PH is a rare benign liver disease and is difficult to be diagnosed because of the nonspecific clinical symptoms and variable imaging findings. The histopathological examination is the gold standard for a definite diagnosis. LT is the only life-saving choice for PH patients with serious complications.

Acknowledgments

We thank the patient for her great help in this report.

CRediT authorship contribution statement

Yang Zhao : Data curation, Formal analysis, Writing - original draft, Writing - review & editing. Yu Liu : Data curation, Formal analysis, Writing - original draft, Writing - review & editing. Lin Zhou : Investigation, Software. Xin-Xue Zhang : Investigation, Software. Ping Li : Investigation, Software. Qiang He : Project administration, Resources, Writing - review & editing.

Funding

None.

Ethical approval

Written informed consent was obtained from the patient, as required by the Institutional Review Board of Beijing Chaoyang Hospital. The consent was obtained from the patient for publication of this report.

Competing interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.