Lack of blood may drive liver neoplasm: a case of an intrahepatic portosystemic venous shunt and liver focal nodular hyperplasia with elevation of serum PIVKA-II level

A 56-year-old male was admitted to the hospital as multiple liver masses and an intrahepatic portosystemic venous shunt (IPSVS) in the right liver lobe during a physical examination. The patient had no history of hepatitis but had a long-term history of alcohol intake. Protein induced by vitamin K absence-II (PIVKA-II 40.9 ng/mL, normal: ≤28.4 ng/mL) was positively elevated, while other tumor markers including alpha-fetoprotein (AFP 2.1 ng/mL, normal: ≤20.0 ng/mL), carcinoembryonic antigen (CEA 1.4 ng/mL, normal: ≤5.0 ng/mL) and carbohydrate antigen 19-9 (CA19-9 7.7 U/mL, normal: ≤34.0 U/mL) were negative. An abdominal magnetic resonance imaging (MRI) scan revealed masses in the left lobe were heterogeneous enhanced at arterial phase and washout at portal-venous phase (Figure 1), the right portal vein (RPV) and the right hepatic vein (RHV) were enlarged and there existed anastomoses between RPV and RHV, the left portal vein (LPV) and its sagittal part were unclear (Figure 2). Vascular ultrasound confirmed that blood flowed from the RPV to the RHV with flow velocity of 22 cm/s, while the LPV was doubtful and there was no obvious blood signal in its flowing area, for which thrombosis could not be ruled out. Based on the image features and elevated PIVKA-II, hepatocellular carcinoma (HCC) was suspected and laparoscopic partial hepatectomy was performed. The final pathological test (Figure 3) turned out to be focal nodular hyperplasia (FNH).

Figure 1 MRI in a 56-year-old male with multiple FNH and elevated PIVKA-II. (A) The mass in the left lateral segment was heterogeneous enhanced at arterial phase. (B) The mass in the left medial segment was heterogeneous enhanced at arterial phase. (C) The mass in the left lateral segment was washout at portal venous phase. (D) The mass in the left medial segment was washout at portal venous phase. The arrows indicate multiple FNH. FNH, focal nodular hyperplasia; MRI, magnetic resonance imaging; PIVKA-II, protein induced by vitamin K absence-II.

Figure 2 Images in 56-year-old male with intrahepatic portosystemic venous shunt. (A) MRI showing the RPV-RHV venous shunt in the right lobe. The arrow indicates the RPV-RHV venous shunt. (B) MRI showing the unclear LPV at portal venous phase. The arrow indicates the poorly visualized LPV. (C) Ultrasound showing the enlarged RPV (1.4 cm in width). (D) Ultrasound showing the blood flowing of venous shunt (from RPV to RHV, 22 cm/s in velocity). LPV, the left portal vein; MRI, magnetic resonance imaging; RHV, the right hepatic vein; RPV, the right portal vein.

Figure 3 Pathological image of the patient’s liver mass. Hematoxylin and eosin staining shows the typical histopathological features of focal nodular hyperplasia (magnification: 100×).

The interesting and noteworthy aspects of this case are as follows. First, the enhancement feature of the mass mimics the HCC and the unclear LPV was suspected as tumor thrombosis, which mislead the diagnosis. It is reasonable to think that due to LPV dysplasia, the mass is mainly supplied by hepatic artery, which is similar to the key reason and feature of enhanced scan of HCC. Thus, vascular malformation might change the enhancement feature of hepatic mass and more attention should be paid when making diagnostic and therapeutic decisions.

Second, it is a rare case of FNH with slightly elevated PIVKA-II, which has been extensively utilized as a reliable biomarker for HCC diagnosis. It is generally accepted that PIVKA-II is produced in HCC under conditions of vitamin K deficiency or impaired vitamin K utilization, where carboxylase activity is inhibited, resulting in the secretion of PIVKA-II into the bloodstream (1). Elevated PIVKA-II levels have been observed in hepatic hemangiomas, with studies showing a significant correlation with hemangiomas size and the attendant coagulation disorders (2). A series of case reports also show the phenomena of elevation of serum PIVKA-II levels in hepatocellular adenoma (HCA) patients, which PIVKA-II is described as useful for predicting the malignant transformation of HCA. In this case, although the serum level of PIVKA-II is slightly high, it is usually negative in patients of FNH and the underlining reasons of such elevation need further studies.

Third, there is an IPSVS (from RPV to RHV) in the right lobe. Enlarged RPV and unclear LPV means the left lobe is lack of blood supply from portal vein. It can be inferred that lack of blood supply from portal vein might be an inducement of neoplasm. FNH is the second most common of liver lesion and is most frequently found in young to middle-aged adults with a strong female predilection. It has been postulated that FNH is a regenerative response of hepatocytes to the presence of a preexisting vascular malformation. Wanless et al. have demonstrated that the development of FNH may be greater arterial blood flow to the liver region (3). In this case, the developmental anomaly of the LPV results in the left liver relying greater on blood supply from the left hepatic artery compensatorily. IPSVS is different from type II Abernethy malformation (extrahepatic venous shunt bypassing the liver), which is characterized by an intact but diverted portal vein through a side-to-side extrahepatic connection to the vena cava (4). Park et al. classified IPSVS into four types (5), and the case in the present study is an example of the second type: a localized peripheral shunt in which single or multiple communications are found between peripheral branches of portal and hepatic veins in one hepatic segment. Seyama et al. have reported a case of 27-year-old female with IPSVS between the branches of LPV and the left hepatic vein (LHV), while there were four masses in the right lobe and the final pathological diagnosis were HCA (6). Tyraskis et al. have quantitatively demonstrated that patients lack of intrahepatic portal venous flow were significantly more likely to develop benign and malignant hepatic tumors, including HCA, FNH, nodular regenerative hyperplasia, hepatoblastoma and HCC, with a relative risk 3.1 (7). IPSVS in the one side of liver lobe and liver neoplasms in the other side in this case also supported this hypothesis. Deprivation of portal venous supply means decrease in intestinal nutrients, gastrointestinal hormones and immune cells from the spleen and gut-associated lymphoid tissue. Compensatory increase of hepatic arterial flow means higher oxygen saturation and more hepatocytes being exposed to oxygen free-radicals. These factors might create a microenvironment conducive to the formation of FNH. However, this hypothesis requires further verification, as other potential factors (including genetic predisposition, hormonal influences, and chronic inflammatory stimuli) may also be involved in the pathogenesis of FNH. Therefore, the coexistence of vascular malformation and FNH in this case should not be interpreted as definitive evidence of a causal relationship, but rather as a potential association that warrants further investigation. These correlative findings are far from being the evidence of liver neoplasm in patients lack of portal venous supply and future researches are needed to elucidate the underlying mechanisms.

In conclusion, we report a rare case of FNH with elevated PIVKA-II coexisting with IPSVS. Notably, this presentation lends clinical support to the hypothesis that portal venous insufficiency may drive liver neoplasm. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article has undergone external peer review.

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Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2026-1-0048/coif). S.D. serves as an unpaid editorial board member of HepatoBiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

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