Hepatic Artery Variations Analyzed in 1141 Patients Undergoing Digital Subtraction Angiography

Background: The hepatic artery has several variations that can be observed by digital subtraction angiography (DSA). In recent years, clinical studies have continued to explore its diversity, leading to the discovery of rare variations and the development of new classications. Methods: Institutional Review Board approval was attained. This retrospective study was based on analysis of DSA images in 1141 patients who were pathologically or clinically diagnosed with liver tumor from May 2015 to December 2019. All patients involved in this study had undergone hepatic arteriography at our hospital. The study aimed to complete angiographic assessments of the left gastric artery (LGA), superior mesenteric artery (SMA) and HA, which supply the liver parenchyma. Results: It was worth mentioning that we found ve new cases of hepatic artery variations. The four major types of hepatic artery anatomy were identi ﬁ ed. Normal hepatic artery anatomy was pointed in 871 (76.3%) of 1141 patients, and the incidence of hepatic artery variation was 270 (23.7%) cases. Variation in hepatic artery origin was identi ﬁ ed in 240 (21.1%) cases. Variation in bifurcation was identi ﬁ ed in 18 (1.6%) cases. Three (0.5%) cases had synchronized bifurcate and variation of origin, which has not been reported previously. Conclusion: Hepatic artery variation have diversity and complexity. The known and newly is covered variations were thoroughly analyzed in detail, which has important clinical signicance for hepatobiliary surgeries and interventional operations.


Introduction
The anatomical variations of the hepatic artery are highly variable, and their incidence is generally from 19.7-49% [1][2][3][4]. Michels [3] proposed an internationally recognized classi cation of hepatic artery abnormalities in 1966, which was based on the results of 200 autopsies to describe the anatomical variations in the hepatic artery blood supply. In 1994, Hiatt [5] analyzed the hepatic arteries of 1000 patients accepted liver transplantation and modi ed the Michels classi cation. Nowadays, DSA characterized by accurate imaging and evaluation of the blood supply of hepatic arteries is playing a crucial role in the treatment of liver tumor [6]. For liver tumor resection, liver transplantation, and even pancreatoduodenal surgery [7][8][9], angiography is a critical part of preoperative assessment in order to reduce or even avoid unnecessary intraoperative vascular damage. Full familiarity with these variations can also help us to avoid complications. Interventional radiologists who perform hepatic artery embolization operation must be acquainted with common and rare hepatic artery variations; If radiologist failure to recognize the presence of abnormal blood vessels can lead to incomplete hepatic tumor embolization [10].
The aim of this study was to describe and evaluate the incidence and types of hepatic artery variations using DSA method in patients with liver tumor. The procedure paid much attention to rare variations Page 3/19 which were previously unreported.

Patients
From May 2015 to December 2019, a retrospective analysis was conducted in 1141 liver tumor patients who were clinically or pathologically diagnosed. Besides, all of them had at least accepted one DSA examination. The only inclusion criteria were DSA images, including angiography of all normal branches of the celiac axis (CA) and the superior mesenteric artery (SMA).
During the study period, we eliminated 15 patients due to incomplete data format and inability to provide images, and excluded 29 patients with surgical resection of the liver or gastroduodenal arteries. Duplicate data for individual patients, such as those receiving repeated interventional embolization, were not included. The study included 928 men and 213 women patients, aging from 28 to 86 years. The diagnosis included 1073 cases of primary liver cancer, 38 of metastatic liver cancer (from stomach cancer, colorectal cancer, pancreatic cancer) and 10 of hepatic hemangioma.

DSA examination
All patients were examined by DSA (Artis Zee Floor, Siemens, Germany). Patients accepted successful puncture using the Seldinger technique under local anesthesia. Then, through a 5F catheter (Cobra or Simmons, Boston Scienti c, Natick, MA, USA), primary angiography was performed on the CA and SMA using a nonionic contrast agent (iodoxanol; Jiangsu Hengrui Medicine Co. Ltd., Jiangsu, China). The location and distribution of the main blood vessels and hepatic artery were revealed. If necessary, a microcatheter (Progreat, 2.7/2.8F, Terumo, Tokyo, Japan) was inserted into the speci c vessels which supply the liver. DSA was performed by three interventional radiologists who had 5-20 years of experience in the angiography eld. Regardless of their origin, we always attempted a complete angiographic evaluation of the left gastric artery (LGA), SMA, and all hepatic artery that supply the liver parenchyma.

Assessment of outcomes
All data were recorded in standard form immediately after angiography, and the procedure was recorded by one of the operators. The origin, shape and distribution of the hepatic arteries were recorded. Hepatic artery variations were recorded and a CD-ROM was made. The CD-ROM was reread and systematic analysis of the hepatic artery variations was done by us.

Results
In the study of 1141 patients with DSA images, 871 (76.3%) were proved to have normal hepatic artery anatomy ( Fig. 1), however 270 (23.7%) had hepatic artery variation, including 62 cases could not t into the Michels classi cation. The new classi cation (Table 1) revealed all 10 types of hepatic artery variation in the Michels classi cation, unclassi ed variations, as well as 5 new variations which were unreported before. c DHA belongs to the special type of variation in HA origin, which was analyzed separately.
Variation in the origin of left hepatic artery (LHA) was con rmed in 73 patients (6.4%); the most common being a replaced or accessory LHA originating from the LGA in 71 patients. In one patient, the rare replaced LHA arose from the gastroduodenal artery (GDA) (Fig. 2a), and in another rare case, a replaced LHA arose from the SMA (Fig. 2b, c). There were 108 patients (9.5%) with variation in the origin of right hepatic artery (RHA). Replaced RHA stemming from the SMA was the most common variation in 81 patients, followed by accessory RHA stemming from the SMA in 16 patients. In an unusual case, an accessory RHA arose from the CA (Fig. 3a). In three patients, accessory RHA originated from the GDA (Fig. 3b, c). In one rare case, a replaced RHA originated from the SMA and an accessory RHA originated from the GDA (Fig. 3d, e). Simultaneous variations in the origin of the RHA and LHA were pointed in 15 patients (1.3%), and the most common was LHA arising from the LGA, with the RHA originated from the SMA concurrently in ve cases. There was an uncommon case in which the accessory LHA originated from the LGA and the accessory RHA originated from the SMA (Fig. 4), which belongs to the Michels type VII. It is worth mentioning that two cases of hepatic artery variation have not reported in the literature. In a very rare case, the LHA arose from the rst branch of the GDA and the RHA arose from the SMA (Fig. 5ac). In another case, the LHA and RHA respectively originated from the SMA (Fig. 5d-f).
Variations in the origin of the common hepatic artery (CHA) were identi ed in 27 cases (2.4%), and the most common was CHA originating from the SMA in 24 cases. There was one case of CHA arising from the abdominal aorta (AA) and one case of Michels type X in which the CHA originated from the LGA ( Fig. 6), which is the rst case reported by DSA. In another case, the CHA arose from the SMA, and simultaneously, an accessory LHA originated from the LGA (Fig. 7). The PHA arose from the rst branch of the SMA or AA in two cases (0.2%), which was considered as a scarce variation. Double hepatic artery (DHA) was proved in 15 cases (1.3%), which referred to the situation where one or both hepatic arteies originated directly from the CA or AA (Fig. 8). These were considered to be a special type of variation in hepatic artery origin, and were analyzed separately.
Bifurcation variation of the CHA were observed in 18 cases (1.6%) without proper hepatic artery (PHA), including 15 cases of trifurcation (1.3%) and three of quadrifurcation (0.3%) (Fig. 9a, b). Bifurcation and variation in origin occurred simultaneously in three cases (0.3%), which has not been reported in the literature previously. In one case, the rst branch of SMA was the CHA, which trifurcated into the LHA, RHA and GDA (Fig. 10a, d). The second case that the trifurcation of CHA and the accessory LHA originated from the LGA (Fig. 10b, e). The third case that the CHA forked into RHA, GDA and RGA, while LHA originated from the LGA (Fig. 10c, f).
We observed stenosis or occlusion of the CHA, even at the root of the CA. Tortuous arterial perfusion in the CHA formed by collateral branches of the SMA was found in eight cases (0.7%). A persistent anastomotic channel was formed between the CHA and SMA (Fig. 11), which resulted from stenosis or occlusion at the root of the CA and was di cult to classify into any type. The primary liver cancer with situs inversus totalis (SIT) was found in only one case (0.1%) (Fig. 12).

Discussion
In the normal anatomy of the hepatic artery, the CA divides into three branches [10]. The rst branch is the LGA, followed by the SA and the CHA, which divides into the GDA and PHA, while the PHA divides into the LHA and RHA. According to autopsy and early DSA report [2,[10][11][12], some papers even reported the sensitivity of computed tomography (CT) and magnetic resonance (MRI) angiography to describe hepatic artery variation [13][14][15][16][17]. Hepatic artery variation has been found to be diverse and complex. In general, the description of hepatic artery variation has been enriched and the classi cation has been improved [11][12][13]15]. Although DSA is an invasive examination, it is an important method for vascular examination and a means of treatment. Moreover, in this study, we reported some rare variations and de ciency of the complement type. Through retrospective analysis of the origin, shape and branches of the hepatic artery by DSA, we concluded that the incidence of hepatic artery variation rate in 1141 patients with hepatic tumor was 23.7%, which was lower compared with previous reports [1][2][3]. First of all, our study was performed retrospectively and was based on analysis of DSA images. Moreover, regional differences, ethnic differences, and differences in selected investigation populations who all had liver tumor were considered.
The most common variation is the RHA originating from the SMA, then LHA from LGA, and CHA from SMA. Extensive MEDLINE search showed that the presence or absence of middle hepatic artery which is considered normal is independent from this [10]. It has been reported that both the LHA and RHA can originate from the CA, AA, LGA, GDA, SMA, SA and even right renal artery [18][19][20][21]. The CHA may arise from the CA, AA, SMA and LGA [11]. The PHA can arise from the CA, AA and SMA [10]. Compared with the Michels [3] and Hiatt [5] classi cations, which were con ned to origin of the hepatic artery from the LGA and SMA. We found ve new variations and proposed a new classi cation. The rst type is normal hepatic artery anatomy.
The second type is variation in origin which is considered to be the primary type of variation, including variation in origin of the LHA, RHA, PHA and CHA. DHA belongs to a special type of variation in origin, which was analyzed separately. Fasel et al [22] proposed that DHA refers to the situation in which one or two hepatic arteries directly originate from the CA or AA. It is an uncommon but important variant, in which there is no CHA and the GDA may originate from either hepatic artery. As far as we know, many case reports have been made about rare variations in the literature [23][24][25][26][27][28]. In our study, we discovered uncommon cases arising from the SMA, such as LHA originating from the SMA [23], PHA from SMA [10], LHA and RHA both originating from SMA, which has not been reported before. There are rare cases of the hepatic artery originating from the LGA, including CHA originating from the LGA [3,11]. In addition to replaced or accessory LHA and RHA from vessels other than the SMA or LGA, there are infrequent cases of GDA origin. In this study, we observed that rarely, the LHA arose from the GDA [24,25], and the accessory RHA arose from the GDA [26]. In rare cases of AA origin, including the CHA originated from the AA alone [11], and the PHA originated from the AA [10]. Some of the original variants even have double replaced or accessory systems, including: RHA arising from the SMA and accessory RHA arising from the GDA [26]; accessory LHA derived from the LGA and accessory RHA derived from the SMA [3,27]; CHA arising from the SMA and accessory LHA arising from the LGA [28]; and LHA arising from the GDA and RHA from the SMA, which has never been reported before. Thus, variation in origin is variable, while rare variations also play an important role in understanding tumor blood supply.
The third type is variation in bifurcation [11], including trifurcation, quadrifurcation and pentafurcation of the CHA. Németh et al [25] referred to one case of pentafurcation that underwent 3D volumetric CT reconstruction. However, it was not observed in this study, and trifurcations accounted for 1.4%, which was less than the 2.0% of patients in the study by Vandamme et al [29]. Quadrifurcation is a peculiar variation, and we only discovered three cases (0.3%). Covey et al 10 also described this category.
The fourth type is bifurcation and variation of origin, which has not been reported by DSA examination. We refer to the situation where the CHA bifurcated directly as having any variation of hepatic artery origin. We found 3 new cases that the incidence rate of this speci c situation was only 0.3%. Although only a few authors detect and consider bifurcation to be a variant condition [11,29], it does have critical surgical implications. Especially for transcatheter arterial chemoembolization (TACE), the catheter should be superselected into the liver parenchyma for injection. Obviously, practice has proved that this variation proposed was reasonable, feasible as well as necessary.
Besides, we discovered eight cases of stenosis or occlusion in the CHA, even at the root of the CA [11,30], with multiple tortuous collateral vessels, forming a continuous anastomotic channel between the CHA and SMA, which only accounted for 0.7%. This variation was not common, and could not be classi ed as a speci c type. Song et al. [11] reported the ambiguous CA anatomy and the prevalence of this persistent anastomotic channel was 0.2%. It can be seen that in the treatment of such patients with TACE, and it needs to be performed by SMA uplink superselection. The more tortuous the anastomotic channel is, the more di cult the operation.
Moreover, we found one case of liver cancer with SIT. SIT is a rare congenital disease with an incidence rate of 1:500-1:20 000 [31], in which the abdominal and thoracic viscera are all mirror image shifted. The etiology of visceral transposition is unknown and does not affect normal health or life expectancy, but has important surgical signi cance. To our knowledge, hepatocellular carcinoma (HCC) with SIT is extremely rare, and only 10 cases have been reported in Pubmed [31][32][33][34][35]. The condition was rst described by Kanematsu et al [32] in 1983. Later Tao Li et al [35] reported a case of HCC with SIT by writing to the editor in 2007, which was treated by TACE. We also successfully treated such a patient who is still alive, and it was the second report by DSA.
We know that CHA can be divided into four types, arising from the CA, AA, SMA and LGA, and has been analyzed by CT and DSA. All forms were found in our study, including rare CHA separately originating from the AA or LGA. In previous studies the incidence of the latter was 0.4-0.5% [11,36,37], with a total of 15 cases. Michels [3] and Uva [36] respectively reported a case, which was found at autopsy. Two cases were found by Gruttadauria [38] during hepatic surgery and Waki [37] during pancreatic surgery.
The remaining 11 cases, which were detected by CT angiography and 3D reconstruction, were reported by Okada [39] and Song [11]. However, it is the rst case of the CHA arising from the LGA with liver tumor treatment reported by DSA image in the world.

Conclusions
We systematically classi ed complex hepatic artery variations, including several rare and unreported variations, enriching the data for hepatic artery variation. For many hepatobiliary and interventional surgeries, hepatic angiography is a central part of preoperative evaluation. Surgeons should be familiar with common and rare hepatic artery variations, because knowledge of the patients' vascular conditions can save operation time, achieve ideal effects of embolization, and reduce or avoid unnecessary vascular injury.