Hepatic Hydrothorax Caused by Familial Inherited Cavernous Transformation of the Portal Veins: A Case Report

Hepatic Hydrothorax Caused by Familial Inherited Cavernous Transformation of the Portal Veins: A Case Report | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 27 October 2025 V1 Latest version Share on Hepatic Hydrothorax Caused by Familial Inherited Cavernous Transformation of the Portal Veins: A Case Report Authors : Qiurong Hu 0000-0002-4273-6986 [email protected] , Xuanyu Pan , Xinlu Wang , Feng Yang , and Zeguang Zheng Authors Info & Affiliations https://doi.org/10.22541/au.176154876.68163029/v1 133 views 93 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Hepatic hydrothorax (HH) is typically associated with cirrhotic portal hypertension (PH). However, its occurrence in non-cirrhotic PH due to cavernous transformation of the portal vein (CTPV) is exceedingly rare, especially in a familial context. Case presentation: We report a 43-year-old woman presenting with recurrent right-sided pleural effusion and clinical signs of portal hypertension but normal liver function and no typical cirrhosis risk factors. Imaging revealed CTPV with portosystemic collaterals. Other imaging, laboratory and thoracoscopic test excluded pleuropulmonary and cardiac causes. Notably, family screening identified CTPV in her mother and two children, suggesting a familial pattern. Whole-exome sequencing did not reveal pathogenic variants in known thrombophilia or liver disease genes. After exclusion of other causes of effusion, she was diagnosed with HH secondary to familial non-cirrhotic portal hypertension. No specific treatment was initiated. One year after discharge, the patient still has moderate right-sided pleural effusion but reports only mild symptoms that do not significantly impair her daily activities or quality of life. Conclusion: This case illustrates HH as an atypical manifestation of non-cirrhotic PH caused by familial CTPV, potentially indicating an inherited predisposition to portal vein thrombosis. Familial screening should be considered in patients with unexplained CTPV, even in the absence of identifiable genetic mutations. Hepatic Hydrothorax Caused by Familial Inherited Cavernous Transformation of the Portal Veins: A Case Report Qiurong Hu 1# , Xuanyu Pan 1# , Xinlu Wang 2# , Feng Yang 3* , Zeguang Zheng 3* 1 Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 2 Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 3 Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. #Qiurong Hu, Xuanyu Pan, Xinlu Wang should be regarded as co-first authors. * Corresponding author: Feng Yang, MD Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China. E-mail: [email protected] ; Tel: 13501535802 Zeguang Zheng Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China. E-mail: [email protected] ; Tel: 18928868242 Abstract Background: Hepatic hydrothorax (HH) is typically associated with cirrhotic portal hypertension (PH). However, its occurrence in non-cirrhotic PH due to cavernous transformation of the portal vein (CTPV) is exceedingly rare, especially in a familial context. Case presentation: We report a 43-year-old woman presenting with recurrent right-sided pleural effusion and clinical signs of portal hypertension but normal liver function and no typical cirrhosis risk factors. Imaging revealed CTPV with portosystemic collaterals. Other imaging, laboratory and thoracoscopic test excluded pleuropulmonary and cardiac causes. Notably, family screening identified CTPV in her mother and two children, suggesting a familial pattern. Whole-exome sequencing did not reveal pathogenic variants in known thrombophilia or liver disease genes. After exclusion of other causes of effusion, she was diagnosed with HH secondary to familial non-cirrhotic portal hypertension. No specific treatment was initiated. One year after discharge, the patient still has moderate right-sided pleural effusion but reports only mild symptoms that do not significantly impair her daily activities or quality of life. Conclusion: This case illustrates HH as an atypical manifestation of non-cirrhotic PH caused by familial CTPV, potentially indicating an inherited predisposition to portal vein thrombosis. Familial screening should be considered in patients with unexplained CTPV, even in the absence of identifiable genetic mutations. Key words: Hepatic hydrothorax; Cavernous transformation of the portal vein; Non-cirrhotic portal hypertension; Genetic predisposition Background Hepatic hydrothorax (HH) is defined as a transudative pleural effusion of ≥500 mL in patients with portal hypertension (PH), in the absence of primary cardiac, pulmonary, or renal disease [1]. It occurs almost exclusively in the setting of advanced liver cirrhosis and is associated with a poor prognosis, with a median survival of 8–12 months if left untreated [2]. In contrast, HH secondary to non-cirrhotic portal hypertension (NCPH) is exceedingly rare. Even more unusual is HH caused by cavernous transformation of the portal vein (CTPV)—a compensatory network of collateral vessels that develops following chronic portal vein thrombosis (PVT) [3-5]. Familial CTPV is exceptionally uncommon, with only isolated cases reported in the literature. Such familial clustering raises the possibility of an underlying genetic predisposition to portal vein maldevelopment or thrombotic diathesis. When HH presents in the absence of cirrhosis or conventional risk factors—particularly within a family context—it poses a significant diagnostic challenge and warrants thorough investigation. We report a rare case of HH in a patient with NCPH due to CTPV. Notably, imaging revealed similar CTPV findings in the patient’s mother and children, indicating familial aggregation and supporting the hypothesis of a heritable component. This case highlights the importance of considering familial CTPV in the differential diagnosis of unexplained pleural effusions, even in patients with preserved liver function and no identifiable mutations. Case Presentation A previous healthy 43-year-old female with no exposure history presented to our hospital due to exertional dyspnea and bilateral lower-extremity edema for 2 years and recurrent pleural effusion for 10 months. She had a slight cough with a little white sputum, without other symptoms. Her mother had CTPV, bilateral lower-extremity edema, and pleural effusion, but passed away due to renal pelvis cancer at 82. On arrival, the patient appeared alert and oriented. Respiratory rate was 23 breaths/min, with other vital signs normal. Hepatojugular reflux was positive. She had mild non-pitting edema in both lower limbs. Decreased breath sounds were noticed on the right side, with no dry nor moist rales or pleural friction rub heard. Routine blood tests revealed a decrease in white blood cell count (2.79×10 9 /L), lymphocyte count (0.6×10 9 /L), and mild anemia (hemoglobin 105g/L). The examination results of the pleural effusion are shown in Table 1. All other tests, including coagulation, tumor markers, rheumatic markers, sex hormones, thyroid function, bilirubin, pro-BNP, procalcitonin, erythrocyte sedimentation rate, autoimmune liver disease antibodies, hepatitis viruses, alpha-fetoprotein, cirrhosis markers, toxoplasma antibodies, and tuberculosis pathogens, were unremarkable. Abdominal ultrasound indicated cavernous transformation of the portal and splenic veins, heterogeneous liver parenchyma, and slight splenomegaly. Gastroscopy and colonoscopy revealed chronic superficial gastritis and internal hemorrhoids. No esophagogastric varices were seen. Lymphoscintigraphy and vessel ultrasound of both lower limbs showed no significant abnormalities. Chest CT (Figure 1) indicated a large right-sided pleural effusion, partial atelectasis, thickened interlobular septa. Thoracoscopy found smooth pleura with scattered congestion, and biopsies showed no tumors nor granulomas. Portal vein CT angiography (Figure 2) showed CTPV, PH, liver cirrhosis, splenomegaly, a small amount of ascites, and an enlarged pancreatic head. Laparoscopy didn’t see any ovarian tumor. There was approximately 100ml milky-white fluid (chylous test was positive) in the pelvic cavity, a slightly enlarged liver with white spots on its surface. No visible holes were seen in the diaphragm. Abdominal enhanced CT on the patient’s father, brother, son, and daughter revealed CTPV, liver cirrhosis and splenomegaly in the patient’s son and daughter (Figure 3), but they had no symptoms. Whole-exome sequencing found no variants explaining the patient’s condition. The patient still has a moderate amount of pleural effusion on the right side one year after discharge without any treatment. However, the patient reports that the shortness of breath is not severe and does not significantly affect her daily life and work. Discussion According to Light’s criteria, the patient’s pleural effusion should be classified as exudative [6]. However, both the protein ratio and lactate dehydrogenase ratio are close to the threshold between exudate and transudate, and the possibility of diuretic use cannot be ruled out. It’s also worth noting that Light’s criteria have a 30% misclassification rate of transudates as exudates [7]. Therefore, for this patient, we consider the pleural effusion to be transudative. According to the clinical studies, we ruled out causes such as infection, neoplasms, connective tissue diseases, pulmonary embolism, drug-related factors, heart failure, renal diseases, sarcoidosis, hypoalbuminemia, nephrotic syndrome, pulmonary arterial hypertension, superior vena cava obstruction, etc., narrowing down the potential etiologies to atypical Meigs syndrome and HH [8]. Laparoscopy didn’t see any ovarian tumor so that atypical Meigs syndrome was ruled out [9]. Hepatic hydrothorax is defined as more than 500 ml of pleural effusion in a patient with PH after excluding pulmonary, cardiac, renal, and other etiologies [1]. It has a median survival of 8 to 12 months [2]. Factors like diaphragmatic defects, PH, and low albumin are often implicated 5 . Hepatic hydrothorax often links to liver cirrhosis and PH. Portal hypertension can be classified into cirrhotic and non-cirrhotic. Non-cirrhotic PH has diverse causes and presentations and can be classified by the affected portal system segment (pre-hepatic, hepatic, or post-hepatic). Pre-hepatic PH includes portal vein developmental anomalies, portal vein thrombosis (PVT), congenital hepatic fibrosis, idiopathic non-cirrhotic PH (sinusoidal dilatation), and splenomegaly due to various blood or rheumatic immune diseases [3]. Imaging suggests the patient has some degree of cirrhosis and significant CTPV. However, unlike typical cirrhosis, she has normal liver function/fibrosis markers and no history of hepatitis, alcohol abuse, bleeding, spider nevi, etc. Excluding common cirrhosis causes, her atypical presentation, CTPV, made we consider the possible cause of pre-hepatic PH. CTPV mostly results from PVT [4, 5]. In this patient, imaging did not reveal any PVT, and coagulation function is normal, thereby PVT were ruled out. To explore genetic factors, whole-exome sequencing and family CT scans were performed. The patient’s mother and children showed similar CT findings, suggesting familial aggregation (Figure 4). While no specific mutations were found, the role of genetic factors cannot be entirely ruled out. The genetic pattern may be X-linked dominant inheritance, autosomal dominant inheritance, autosomal recessive inheritance, or mitochondrial inheritance. Further testing (whole genome sequencing, liver biopsy, etc.) was recommended but declined by the patient due to personal reasons. One year after discharge, the patient continues to have moderate right-sided pleural effusion despite receiving no specific treatment. However, she reports only mild dyspnea, which does not significantly impact her daily life or work. This clinical course stands in marked contrast to classic hepatic hydrothorax, which is typically associated with severe respiratory symptoms and a median survival of only 8–12 months without intervention. We reported a rare case of CTPV possibly caused by genetic factors, leading to non-cirrhotic PH and HH. Abbreviations list HH: Hepatic hydrothorax PH: Portal Hypertension CTPV: Cavernous Transformation of the Portal Vein PVT: Portal Vein Thrombosis NCPH：Non-cirrhotic Portal Hypertension Acknowledgements None. Authors’ contributions All authors have read, approved, and showed significant contribution toward this manuscript. Conception and design: Feng Yang and Zeguang Zheng. Clinical treatment and clinical follow-up: Qiurong Hu, Xuanyu Pan. Manuscript writing: Qiurong Hu, Xuanyu Pan, Xinlu Wang. Interpreting the clinical data: Xinlu Wang, Feng Yang, Zeguang Zheng. All authors approved the final version of the manuscript. Funding No funding. Data availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate Appropriate written informed consent was obtained for the publication of this case report and accompanying images. It was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. Consent for publication Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Competing interests The authors declare no competing interests. Clinical trial number Not applicable. References 1. Banini BA, Alwatari Y, Stovall M, et al. Multidisciplinary Management of Hepatic Hydrothorax in 2020: An Evidence-Based Review and Guidance. Hepatology 2020;72(5):1851–1863 2. Hou F, Qi X, Guo X. Effectiveness and Safety of Pleurodesis for Hepatic Hydrothorax: A Systematic Review and Meta-Analysis. Dig Dis Sci 2016;61(11):3321–3334. 3. Mo T-T, Li M, Wang X-Y. An Unusual Cause of Portal Hypertension. Gastroenterology 2023;165(3):e1–e3. 4. Layton BM, Lapsia SK. The Portal Vein: A Comprehensive Review. Radiographics 2023;43(11):e230058. 5. Wei B, Huang Z, Tang C. Optimal Treatment for Patients with Cavernous Transformation of the Portal Vein. Front Med (Lausanne) 2022;9:853138. 6.Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972;77(4):507–13. 7. Porcel JM, Light RW. Diagnostic approach to pleural effusion in adults. Am Fam Physician 2006;73(7):1211–20. 8. Sundaralingam A, Grabczak EM, Burra P, et al. ERS Statement on Benign Pleural Effusions in Adults. Eur Respir J 2024;2302307. 9. Handler CE, Fray RE, Snashall PD. Atypical Meigs’ syndrome. Thorax 1982;37(5):396–7. Table 1 Results of pleural effusion tests Appearance Yellow pleural effusion with clots Yellow pleural effusion with clots Yellow pleural effusion with clots Mononuclear cell ratio 90.9% 98.5% 98% Polynuclear cell ratio 9.1% 1.5% 2% Glucose (mmol/L) 5.99 6.28 - CEA (ug/L) ＜0.5 ＜0.5 ＜0.3 CA125(U/mL) - - 307 Pleural Fluid ADA (U/L) 7.7 5.4 7.5 Pleural Fluid LDH (U/L) 96 122 81.9 Serum LDH（U/L） 178 196 165 Pleural Fluid/Serum LDH Ratio 0.54 0.62 0.53 Pleural Fluid Protein (g/L) 39.2 24.5 33.8 Serum Protein (g/L) 59.8 65.3 52 Pleural Fluid/Serum Protein Ratio 0.66 0.38 0.65 Classification (Light’s criteria) Exudate Exudate Exudate Pleural fluid smear and culture No bacterial growth observed No bacterial growth observed - CEA：Carcinoembryonic Antigen; CA125: Cancer Antigen 125; LDH: Lactate Dehydrogenase. Figure 1-Chest CT showed a large right-sided pleural effusion with atelectasis of the right lower lung (red arrow), a small effusion on the left side (white arrow). No nodules, masses, nor inflammatory exudates were seen. Figure 2-The patient’s liver is reduced in size, indicating cirrhosis. The portal vein system has multiple, increased, and tortuous vessels, indicating cavernous transformation of the portal vein (red arrow), combined with portal hypertension. Figure 3- The patient’s son (A and B) and daughter (C and D) had cavernous transformation of the portal vein (red arrow), liver cirrhosis, and splenomegaly (white arrow), but without pleural or peritoneal effusion. Figure 4-A three-generation family pedigree chart indicate the possible role of genetic factors. Supplementary Material File (image4.emf) Download 56.07 KB Information & Authors Information Version history V1 Version 1 27 October 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords cavernous transformation of the portal vein genetic predisposition hepatic hydrothorax non-cirrhotic portal hypertension Authors Affiliations Qiurong Hu 0000-0002-4273-6986 [email protected] First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease View all articles by this author Xuanyu Pan First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease View all articles by this author Xinlu Wang First Affiliated Hospital of Guangzhou Medical University View all articles by this author Feng Yang First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease View all articles by this author Zeguang Zheng First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease View all articles by this author Metrics & Citations Metrics Article Usage 133 views 93 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Qiurong Hu, Xuanyu Pan, Xinlu Wang, et al. 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