Small enhancing hepatic nodules are problematic, indeterminate lesions that are commonly encountered during interpretation of contrast-enhanced CT and MR imaging studies of cirrhotic liver [17]. Most of these findings are benign pseudo-lesions due to underlying diseases that severely alter perfusion, such as Budd-Chiari syndrome and, less commonly, chronic portal venous occlusion and large arterio-portal fistula [12].
Given their enhancement pattern, these nodules may be difficult to differentiate from HCC. Many therefore are categorized as LI-RADS 3 or 4. If a well-defined homogeneously hyper-enhancing nodule without a capsule appearance remains stable for longer than 1 year, particularly in a patient with the underlying conditions described, a diagnosis of benign hyperplastic nodule becomes increasingly likely [18].
When the hyper-enhancing observation is subcapsular and shows a triangular shape, it can be confidently labeled as definitely benign (LI-RADS 1) or probably benign (LI-RADS 2). In contrast, the more central lesions with a round or oval shape, in the absence of comparison studies, are more likely to be labeled as indeterminate (LI-RADS 3) [19].
The LI-RADS category may, therefore, evolve from 4 to 3, or occasionally to 2. Conversely, if the patient presents with a history of viral hepatitis, alcoholism, non-alcoholic steatohepatitis, or other chronic liver diseases, NAPH should be followed to ensure it does not represent HCC or its precursors [20].
In the current study, 25 lesions initially showed NRAP with neither washout nor delayed capsular enhancement and were described as LI-RADS 3 category, from which 2 lesions (8%) were evolved in the follow-up to LI-RADS 5 category (using version 17 of the LI-RADS), while using LI-RADS version 18, 3 lesions evolved (12%).
The current study results match with the findings described by Holland et al. [18] who found that the majority (93%) of NRAP-only lesions are non-neoplastic, even in patients with pathologically proved HCC.
Matching results were also described by Choi et al. [21], who reported that 94% of LI-RADS 3 identified at gadoxetic acid-enhanced MR imaging remained stable or decreased during imaging follow-up.
There is partial discrepancy between the current study results and the results described by Quaia et al. [22] who found in their study on 151 NRAP hepatic nodules a percentage of 24% HCC.
Using LI-RADS version 17 and older versions, 5 lesions in the current study were described as LI-RADS 4 category, and all the lesions showed progression in size, 2 of which progressed to LI-RADS 5.
In the literature, similar results were encountered by Tanabe et al. [19] who found that 38% of LI-RADS 4 lesions progressed to a malignant category (LI-RADS 5 or LI-RADS M) within 6 months to 3 years, and 43% remained stable in category, while the remainder decreased in category, only 4% of LI-RADS 3 observations progressed to LI-RADS 5, and most remained stable or decreased in category.
Partial validation also is provided by Darnell and colleagues [23], who showed that 96% of LR-4 with a histologic reference standard were HCC. The LI-RADS 4 (“probably HCC”) category is intended to convey high probability of HCC, and this was confirmed by these investigators.
In the current study, all the lesions (five lesions ) between 1 and 2 cm in diameter with NRAP and delayed washout progressed in size compared with 36% of the other less than 2 cm lesions; from these five lesions, two of them had growth exceeding 50% of their size. These findings are matching with the recent update of the LI-RADS system version 18 [16] which upstaged these lesions from probable HCC to definite HCC.
We acknowledge the limitation in the current study; first, there were relatively a limited number of cases, and this is attributed to the exclusion of some cases, either due to loss of contact with the patients of the study population or interventional management that was done in some cases with lesions less than 2 cm with NRAP and delayed washout out of our institution. The second limitation was the interval follow-up duration which was in the current study between 4 and 6 months; we think that if the time interval was above 6 months, there would be more progression of the lesions with delayed washout. Further studies using larger study population and longer follow-up interval are recommended to confirm the results of the current study.