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Liver cirrhosis in a patient with hepatic hereditary hemorrhagic telangiectasia and Budd–Chiari syndrome: a case report

Abstract

Background

Hereditary hemorrhagic telangiectasia (HHT) often involves the liver, and belongs to abnormal blood vessel disease. The etiology of Budd–Chiari syndrome (BCS) is not clear, but congenital vascular dysplasia is considered to be one of the causes. Liver cirrhosis due to hepatic hereditary hemorrhagic telangiectasia concomitant with BCS has not been reported. Here, we report a case of cirrhosis with hepatic hereditary hemorrhagic telangiectasia (HHHT) and BCS.

Case presentation

A 58-year-old woman with hepatic hereditary hemorrhagic telangiectasia showed decompensated liver cirrhosis, and abdominal imaging revealed Budd–Chiari syndrome. Disease has progressed considerably during 2.5 years after hospital discharge despite subsequent transjugular intrahepatic portosystemic shunting (TIPS). One hypothesis that might explain the coexistence of hepatic hereditary hemorrhagic telangiectasia and Budd–Chiari syndrome in this patient is ischemia and thrombosis of hepatic veins.

Conclusions

Further studies are required to evaluate the relationship between HHHT and BCS. Our observations already challenged the TIPS therapeutic strategy in BCS secondary to HHHT patients.

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Background

Hereditary hemorrhagic telangiectasia (HHT, previously Osler–Weber–Rendu syndrome) is an autosomal dominant disease characterized by telangiectasias in the skin and mucous membranes and arteriovenous malformations in the lungs, brain, gastrointestinal tract, and liver. If HHT involves the liver, Patients often have 3 types of intrahepatic shunts: hepatic artery–hepatic vein, hepatic artery–portal vein, and portal vein–hepatic vein, and may be accompanied by cirrhosis and related complications. The etiology of BCS is not clear, but congenital vascular dysplasia is considered to be one of the causes [1]. Both of the disease have the similar etiology. Liver cirrhosis due to hepatic hereditary hemorrhagic telangiectasia (HHHT) concomitant with BCS has not been reported, and the relationship between them is worth further clarification. Here, we report a case of cirrhosis with HHHT and BCS.

Case presentation

A 58-year-old woman was referred to hospital for abdominal distension of > 1-month duration. With a history anemia for > 10 years, she suffered intermittent bleeding of the nose and tongue which were diagnosed as HHT. Her mother, elder brother, and sister all suffered from HHT. They all had typical clinical symptoms and signs of HHT, such as repeated nasal bleeding and capillaries on face and lips. Her mother died of intracranial hemorrhage. The elder brother died of upper gastrointestinal bleeding with liver cirrhosis and refractory ascites. As far as we known her sister had not exact splanchnic vascular malformation but repeated nasal bleeding.

Physical examination showed her cheek (Fig. 1), fingers of both hands and tongue tip to have multiple stripes/reticulated capillaries. Shifting dullness was documented, Edema was negative in both lower limbs. Laboratory examination showed the hemoglobin level to be 86 g/L (normal range: 110–150 g/L). Levels of albumin, alanine aminotransferase, aspartate aminotransferase and bilirubin were in the normal range. The level of alkaline phosphatase was 227 U/L (normal range, 50–135 U/L). Serum levels of copper and iron were normal, as were blood levels of immune- globulin (Ig) G and IgM. Tests for hepatitis-B surface antigen, hepatitis-B e antigen, hepatitis-C antibody and immunologic tests were negative.

Fig. 1
figure1

Physical examination of her cheek: Cheek has a reticulated capillary that can fade under pressure

B-ultrasound of the abdomen revealed the caudate lobe to be enlarged (11.6 × 6.0 cm), the left hepatic vein and right hepatic vein to be narrow, and the middle hepatic vein to be occluded (Figs. 2, 3). This imaging modality also revealed liver cirrhosis, splenomegaly (thickness, 6.3 cm; longest diameter, 14.8 cm) and ascites (~ 1.0 cm in front of the liver, ~ 5.7 cm in the abdominal cavity).

Fig. 2
figure2

B-ultrasound of the abdomen: Ultrasound shows the left hepatic vein to be narrow (~ 0.5 cm in inner diameter). The right hepatic vein is narrow (the inner diameter is ~ 0.38 cm). The middle hepatic vein is occluded (inner diameter is ~ 0.38 cm; the distal end is dilated, with an inner diameter of ~ 0.8 cm)

Fig. 3
figure3

B-ultrasound of the abdomen: Ultrasound shows the left hepatic vein (blood-flow signal is narrow and disordered) and right hepatic vein (blood-flow signal was narrow) are narrow, and the middle hepatic vein is occluded (blood-flow signal is interrupted in the proximal vena cava; the distal end is dilated)

Contrast-enhanced spiral CT of the upper abdomen showed liver cirrhosis, ascites and formation of multiple arteriovenous fistulae (Fig. 4). Digital subtraction angiography revealed a hepatic arterioportal fistula to be the diffuse type. Angiography showed a narrow stenosis of the inferior vena cava (narrowest diameter, ~ 6 mm) (Figs. 5, 6). Gastroscopy demonstrated esophageal varices and portal hypertensive gastric mucosal lesions (Figs. 7, 8). The hepatic arterioportal fistula and slender hepatic vein meant that occlusion and dilatation, respectively, were unsuccessful.

Fig. 4
figure4

Contrast-enhanced spiral CT of the upper abdomen: This contrast-enhanced CT image shows the portal vein, enhanced liver parenchyma in the arterial phase, and multiple arteriovenous fistulae

Fig. 5
figure5

Angiography of liver: Digital subtraction angiography shows the main trunk and branches of the hepatic artery to be tortuous and thickened. The trunk and a branch of the portal vein in the arterial phase can also be seen

Fig. 6
figure6

Angiography of liver: Angiography shows a narrow stenosis of the inferior vena cava

Fig. 7
figure7

Gastroscopy results: Gastroscopy shows severe esophageal varices

Fig. 8
figure8

Gastroscopy results: Gastroscopy shows gastric mucosal lesions and mesh-like vascular changes

The patient was diagnosed with cirrhosis, HHT and BCS. We treated her with albumin, diuretics, intermittent peritoneocentesis and subsequent TIPS 1 month later. However, within 2.5 years after discharge from hospital, she still suffered increased ascites, primary peritonitis and epistaxis despite.

Unfortunately, because of the rapid deterioration of the patient’s condition (soon developed intractable ascites, severe hypersplenism and upper gastrointestinal hematorrhea), she didn’t perform the genetic tests and liver biopsy and died on January 2, 2020.

Discussion and conclusions

HHT is an autosomal-dominant disorder. Type-1 HHT is associated with mutations in the ENG gene that encodes endoglin [2]. Type-2 HHT is associated with mutations in the ACRLV1 gene that encodes activin receptor-like kinase-1 [3]. The lesions can affect the skin and mucous membranes of the nose, mouth, lips, tongue, limbs and internal organs (brain, gastrointestinal tract, liver) [4]. Hepatic involvement is much more common in type-2 HHT [5]. Unfortunately, the patient’s genetic testing and pathology were untouchable. According to her clinical characteristics and family history, the patient was considered to be type-2 HHT.

The pathologic changes wrought by HHT are that the capillaries, arterioles and venules of the affected area become thin. The vessel wall cannot respond to regulation of vascular wall-active substances, and lacks normal systolic and diastolic function [6].

HHHT is defined as all types of hepatic vascular malformations caused by HHT. The microvascular changes in the liver include sinus dilatation and parenchymal fistulae. The early clinical symptoms of HHHT are not obvious. Ianora and colleagues reported only 8.6% of HHHT patients with liver involvement to be symptomatic [7]. With disease development, the decompensation caused by cirrhosis leads to increased levels of transaminase, ascites, as well as esophageal and gastric varices.

According to the criteria revealed by Curacao and colleagues [8], our patient was diagnosed with HHT. DSA (the “gold standard” of BCS diagnosis [9] revealed her to have BCS. HHHT, cirrhosis and BCS coexisted in this patient. It is common to report on HHT complicated with hepatic arterioportal fistula-induced liver cirrhosis, but whether HHHT can lead to BCS has not been studied. We postulate that our patient with BCS had secondary changes in HHHT for two main reasons. First, HHT is characterized by abnormal development of the walls of capillaries, arteries and veins in various parts of the body. The theory of congenital vascular dysplasia is also associated with BCS [1]. BCS is also the least common manifestation of Splanchnic vein thrombosis. HHT is associated with hepatic-vein dysplasia, thin vascular walls, and the vessels cannot relax and contract appropriately. Hence, due to compressed hepatic veins, stenosis and atrophy will hamper the growth and development of the liver. Second, despite an overwhelming propensity for bleeding, HHT patients can also suffer from thrombotic complications [10]. Scholars have reported increased FVIII levels in the general HHT population and that 6–7% of HHT patients have pathologic thromboemboli [11]. Formation of intrahepatic arteriovenous fistulae can lead to hemodynamic changes, resulting in reduced blood flow from hepatic sinuses to the hepatic veins, and so ischemia and hypoxia occur in the hepatic veins. As the disease progresses, the hepatic veins become obstructed due to thrombi (and may even close).

Anticoagulants and/or antiplatelet agents are also recommended to prevent major ischemic or thromboembolic sequelae for HHT patients [10, 12]. In addition, HHHT combined with cirrhosis aggravates ischemia and hypoxia in the hepatic veins further, but the specific mechanism is not clear and further research is needed.

This patient advanced to portal hypertension with refractory ascites, which did not improve significantly after TIPS. We speculate that the reason is related to the long-term portal hypertension caused both by HHHT and BCS.

Liver transplantation (LT) may be considered to be the only cure for HHT [13,14,15] and hepatic arterioportal fistula [16], although the role and curative action of LT in patients with HHT is controversial [17].

We report a case of progressive cirrhosis with HHT and BCS. In our case, BCS may be secondary to HHT. Further studies are required to evaluate the relationship between HHHT and BCS but our observations already challenge the TIPS therapeutic strategy in BCS secondary to HHHT patients. In addition, it could result in a better understanding of the mechanisms of liver involvement by HHT.

Availability of data and materials

The datasets used and/or analyzed during the current study are available.

from the corresponding author on reasonable request.

Abbreviations

TIPS:

Transjugular intrahepatic portosystemic shunting

HHT:

Hereditary Hemorrhagic Telangiectasia

HHHT:

Hepatic Hereditary Hemorrhagic Telangiectasia

BCS:

Budd–Chiari syndrome

CT:

Computed tomography

LT:

Liver transplantation

References

  1. 1.

    Hirooka M, Kimura C. Membranous obstruction of the hepatic portion of the inferior vena cava. Surgical correction and etiological study. Arch Surg. 1970;100(6):656–63.

    CAS  Article  Google Scholar 

  2. 2.

    McAllister KA, Grogg KM, Johnson DW, et al. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet. 1994;8:345–51.

    CAS  Article  Google Scholar 

  3. 3.

    Johnson DW, Berg JN, Baldwin MA, et al. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet. 1996;13:189–95.

    CAS  Article  Google Scholar 

  4. 4.

    Khalid M, Malik N, Abbas S. A 33-year-old male with a chest lesion on a routine chest radiograph. Pulmonary arteriovenous malformation (PAVM). Ann Saudi Med. 2005;25:518–20.

    Article  Google Scholar 

  5. 5.

    Lesca G, Olivieri C, Burnichon N, et al. Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data from the French-Italian HHT network. Genet Med. 2007;9:14–22.

    Article  Google Scholar 

  6. 6.

    Tian JX, Zhou B, Wang T, et al. One case report of type IIhereditary hemorrhagic telangiectasia. Chin Arch Otolaryngol Head Neck Surg. 2006;13(5):308.

    Google Scholar 

  7. 7.

    Ianora AA, Memeo M, Sabba C, et al. Hereditary hemorrhagic telangiectasia: multi-detector row helical CT assessment of hepatic involvement. Radiology. 2004;230(1):250–9.

    Article  Google Scholar 

  8. 8.

    Shovlin CL, Guttmacher AE, Buscarini E, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu–Osler–weber syndrome). Am J Med Genet. 2000;91(1):66–7.

    CAS  Article  Google Scholar 

  9. 9.

    Bahar K, Karayalcin S, Kaya M, et al. Percutaneous transhepatic venoplasty: an alternative treatment for Budd–Chiari syndrome. Turk J Gastroenterol. 2002;13:83–8.

    PubMed  Google Scholar 

  10. 10.

    Dittus C, Streiff M, Ansell J. Bleeding and clotting in hereditary hemorrhagic telangiectasia. World J Clin Cases. 2015;3(4):330–7.

    Article  Google Scholar 

  11. 11.

    Shovlin CL, Sulaiman NL, Govani FS, Jackson JE, Begbie ME. Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism. Thromb Haemost. 2007;98:1031–9.

    CAS  Article  Google Scholar 

  12. 12.

    Faughnan M, Palda V, Garcia-Tsao G, et al. International guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia. J Med Genet. 2009;48(2):73–87.

    Article  Google Scholar 

  13. 13.

    Bauer T, Britton P, Lomas D, Wight DG, Friend PJ, Alexander GJ. Liver transplantation for hepatic arteriovenous malformation in hereditary haemorrhagic telangiectasia. J Hepatol. 1995;22:586–90.

    CAS  Article  Google Scholar 

  14. 14.

    Boillot O, Bianco F, Viale JP, et al. Liver transplantation resolves the hyperdynamic circulation in hereditary hemorrhagic telangiectasia with hepatic involvement. Gastroenterology. 1999;116:187–92.

    CAS  Article  Google Scholar 

  15. 15.

    Felli E, Addeo P, Faitot F, Nappo G, Oncioiu C, Bachellier P. Liver transplantation for hereditary hemorrhagic telangiectasia: a systematic review. HPB (Oxford). 2017;19:567–72.

    Article  Google Scholar 

  16. 16.

    Draghi F, Presazzi A, Danesino GM, et al. Hepatic sonography in patients with hereditary hemorrhagic telangiectasia hospitalized for epistaxis. J Ultrasound. 2012;15(3):164–70.

    CAS  Article  Google Scholar 

  17. 17.

    Sabba C. Hereditary haemorrhagic telangiectasia: to transplant or not to transplant? Liver Int. 2016;36:1745–7.

    Article  Google Scholar 

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The manuscript was prepared and revised according to the CARE Checklist (2013).

Funding

The funder is chief principal of the National 13th 5-year Plan for Hepatitis Reseach of China. The funder designed the report and afford the publishing fee.

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Contributions

TH designed the report. BGX and JL collected the patient’s clinical data, and wrote the paper. KFJ carried out the medical images collection and revised. BGX and JL contributed equally to this study. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Tao Han.

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Xu, B., Liang, J., Jia, K. et al. Liver cirrhosis in a patient with hepatic hereditary hemorrhagic telangiectasia and Budd–Chiari syndrome: a case report. BMC Gastroenterol 20, 169 (2020). https://doi.org/10.1186/s12876-020-01311-1

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Keywords

  • Hereditary hemorrhagic telangiectasia
  • Hepatic hereditary hemorrhagic telangiectasia (HHHT),Budd–Chiari syndrome
  • Cirrhosis
  • Case report