Prevalence of Hepatic Space-Occupying Lesions Based on Sonographic Findings in Patients Referred to Guilan Cohort Center, Iran

authors:

avatar Ahmad Alizadeh 1 , avatar Farahnaz Joukar ORCID 2 , avatar Najmeh Ghorani 2 , avatar Alireza Mansour-Ghanaei 2 , avatar Mohammadjavad Tabatabaii 2 , avatar Niloofar Faraji ORCID 2 , avatar Tahereh Zeinali 2 , avatar Mohammadreza Naghipour 2 , avatar Fariborz Mansour-Ghanaei ORCID 2 , *

Department of Radiology, School of Medicine Caspian Digestive Diseases Research Center, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran
Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran

How To Cite Alizadeh A, Joukar F, Ghorani N, Mansour-Ghanaei A, Tabatabaii M, et al. Prevalence of Hepatic Space-Occupying Lesions Based on Sonographic Findings in Patients Referred to Guilan Cohort Center, Iran. Hepat Mon. 2022;22(1):e127545. https://doi.org/10.5812/hepatmon-127545.

Abstract

Background:

Early diagnosis of hepatic lesions can result in more successful treatment.

Objectives:

The present study aimed to diagnose hepatic space-occupying lesions by sonography in Guilan Cohort Center participants.

Methods:

In this cross-sectional prospective epidemiological research studies of Iranian adults (PERSIAN) Guilan cohort study (Sowme'eh Sara, Guilan, Iran) conducted in 2014 - 2017, the sample included 960 individuals of both genders, aged 35 - 60 years. A radiologist examined all individuals with sonography to determine hepatic space-occupying lesions. Demographical and clinical characteristics were recorded via a questionnaire. Data analysis was performed using SPSS software (version 16).

Results:

Only 2.3% of the patients were diagnosed with hepatic lesions such as hemangioma, hepatic cysts, and other lesions with frequencies of 1.1%, 0.8%, and 0.4%, respectively. Also, there was a significant relationship between gender and the presence of hepatic lesions (P < 0.05). The frequencies of hepatic lesions were 1.7% and 3.6% in men and women and 1.6%, 2.5%, and 4.4% in the age groups of 35 - 45, 45 - 55, and over 55 years, respectively.

Conclusions:

Hemangioma was the most common hepatic lesion diagnosed in ultrasonography examinations. Moreover, the only factor influencing the frequency of hepatic lesions was gender, which was found twice more in women than in men.

1. Background

The liver is considered an essential organ for body metabolism. Diseases that can create masses or cysts in the liver include primary hepatic malignancies and benign lesions like hemangioma, hepatocellular nodules, hepatic adenoma, hepatic cysts, and abscess (1). Hepatic space-occupying lesions are among liver disorders due to growth and development, neoplasm, inflammation, and other complications. Although the diagnosis of hepatic lesions based on imaging alone is difficult in some cases, focal hepatic lesions can be diagnosed with ultrasonography, computed tomography (CT), and magnetic resonance (MR) (2). Ultrasonography is a non-invasive technique, usually welcomed by patients for its relatively low cost and ability to determine focal liver lesions, which uses probes with 2.5 to 7.5 megahertz (MHz) frequencies (3, 4).

Space-occupying liver lesions result from various diseases with or without clinical symptoms (5), which are divided into two sets, benign and malignant (6). Benign hepatic lesions usually represent pain in the upper quarter of the right side of the abdomen and/or a mass touchable in examination or are discovered by chance during imaging and laparotomy for other problems. In addition, malignant hepatic lesions can also be diagnosed by jaundice, blood ascites, hepatic bruit, loss of appetite, and unjustifiable weight loss (3). The most frequent liver lesions are hemangiomas, hepatic cysts, focal nodular hyperplasia (FNH), and hepatocellular adenomas as benign lesions (7-9). Sometimes, atypical hemangiomas are difficult to distinguish from other more worrying hepatic lesions such as metastases and hepatocellular carcinoma. Furthermore, some malignant lesions can display features that simulate hemangiomas (10). Also, the epidemiology of hepatic hemangioma has not been evaluated well.

The prevalence of hepatic hemangioma ranges from 0.4% to 20% (11). A retrospective study on patients referred for transabdominal ultrasonography to the Ultrasound Unit of Firoozgar hospital, Tehran, Iran, reported that the prevalence of hemangioma was 2.04% in the study population, with women predominance (12).

2. Objectives

As no comprehensive study has been performed in the northern population of Iran, we aimed to evaluate the prevalence of hepatic space-occupying lesions by sonography in Guilan Cohort Center participants.

3. Methods

3.1. Participants

This cross-sectional study was conducted within the prospective epidemiological research studies of Iranian adults (PERSIAN) cohort study (13), started in September 2014 in Sowme'eh Sara (GPS coordinator latitude: 37.308003 and longitude: 49.315022), Guilan, northern Iran, engaging both genders aged 35 - 60 years, being followed for 10 years to determine new diseases and underlying genetic factors for chronic diseases. We selected 960 out of 10,520 individuals based on a non-randomized simple sampling method. Guilan cohort profile was published in detail previously (14). Written consent was taken after informing each participant of the purpose and importance of the study. To ensure the confidentiality of participants’ information, we used codes to omit the participants' names and identifiers in the questionnaires. This study was approved by the Ethics Committees of the Ministry of Health and Medical Education and the Guilan University of Medical Sciences (P/3/132/215). Informed consent was obtained from all participants.

3.2. Data Collecting

Demographic data and clinical characteristics of all individuals were recorded in questionnaires, including age, sex, marital status, education level, occupation, body mass index (BMI; as low weight < 18.5 kg/m2, normal weight 18.5 - 24.99 kg/m2, overweight 25 - 29.9 kg/m2, and obese ≥ 30 kg/m2), history of smoking, alcohol consumption, and diabetes. Ultrasonography was carried out by a radiologist after at least 12 hours of fasting, using an Ultrasonic Device of Sonix SP type with 3.5 MHz to 5 MHz probes to determine the hepatic space-occupying lesions. The exclusion criteria were acute and chronic hepatic diseases like B and C viral hepatitis, known hepatic and biliary diseases, cancer, and pregnancy.

3.3. Statistical Analysis

Continuous variables were expressed as percentage and frequency. The normality was evaluated using the Shapiro-Wilk normality test. Absolute and relative frequency, mean, and standard deviation were used to describe the data, and the chi-Square test was used to determine the relationship between variables. Statistical analysis was undertaken using SPSS for Windows (version 16.0) at the significance level of 0.05.

4. Results

From 2017 to 2018, the presence of liver lesions was examined by ultrasound in 950 individuals, of whom 37.7% (n = 361) were female, and 62.3% (n = 596) were male. About 83.2% (n = 797) of the individuals were aged 35-55 years and 16.8% (n = 160) were over 55 years. Most participants were married (95.3%, n = 912), had a diploma degree (56.7%, n = 543), with no history of smoking (69.3%, n = 663) or alcohol consumption (95.6%, n = 915), without diabetes (90.3%, n = 864) (Table 1).

Table 1.

Demographic Characteristics of the Studied Individuals

Demographic CharacteristicsFrequency (%)
Age
35 - 45435 (45.4)
45 - 55362 (37.8)
Over 55160 (16.8)
BMI
Below 25237 (24.8)
25 to 30432 (45.1)
Over 30288 (30.1)
Gender
Female361 (37.7)
Male596 (62.3)
Marital status
Single29 (3)
Married912 (95.3)
Divorced6 (0.6)
Widower or widowed10 (1)
Education level
Illiterate64 (6.4)
Primary school207 (21.6)
Diploma543 (56.7)
University degrees143 (15.3)
Occupation
Farmer109 (11.4)
Employee164 (17.1)
Worker133 (13.9)
University student6 (0.6)
Housewife308 (32.2)
Self-employed237 (24.8)
Smoking
Nonsmoker 663 (69.3)
Smoker 294 (30.7)
Alcohol use
Nonalcoholic915 (95.6)
Alcoholic42 (4.4)
Diabetes
Nondiabetic 864 (90.3)
Diabetic 93 (9.7)

The total frequency of liver lesions was 2.3%; the most frequent was hemangioma with 1.1% (n = 11) while liver cyst was 0.4% (n = 4) and others (not defined) were 0.8% (n = 8) (Table 2).

Table 2.

Frequency of Hepatic Lesions in the Studied Individuals

LesionFrequency (%)
Hemangioma11 (1.1)
Cyst4 (0.4)
Others8 (0.8)
No lesion934 (97.6)

Females had a higher frequency of hemangioma (63.3%, n = 7) than males (36.4%, n = 4). Compared to females, males had a higher frequency of liver cysts (25%, n = 1 vs. 75% n = 3). Statistical analysis revealed that the presence of liver lesions was slightly higher in females than in males (3.6%, n = 13 vs. 1.7%, n = 17; P = 0.05) (Table 3). Other variables had no statistically significant relationship with the presence of liver lesions (Table 3).

Table 3.

Hepatic Lesions by Demographic Characteristics of the Studied Individuals

Demographic CharacteristicsHepatic LesionP Value
NegativePositive
Age0.421
35 - 44428 (98.4)7 (1.6)
45 - 54353 (97.5)9 (2.5)
Over 55 153 (95.6)7 (4.4)
BMI0.117
Below 25231 (97.5)6 (2.5)
25 to 30418 (96.8)14 (3.2)
Over 30285 (99)3 (1)
Gender0.050
Female348 (96.4)13 (3.6)
Male586 (98.3)10 (1.7)
Marital status0.711
Single28 (100)1 (0)
Married890 (97.5)22 (2.5)
Divorced6 (100)0 (0)
Widowed or widower10 (100)0 (0)
Education level0.613
Illiterate59 (96.7)5 (3.4)
Primary school200 (96.6)7 (3.4)
Diploma532 (98)11 (2)
Academic degree143 (97.9)3 (2.1)
Occupation0.251
Farmer107 (98.2)2 (1.8)
Employee157 (95.7)7 (4.3)
Worker131 (98.5)2 (1.5)
University student 6 (100)0 (0)
Housewife298 (96.8)10 (3.2)
Self-employed235 (99.2)2 (0.8)
Smoking0.110
Smoker 290 (98.6)4 (1.4)
Nonsmoker644 (97.1)19 (2.9)
Alcohol use0.711
Alcoholic41 (97.6)1 (2.4)
Nonalcoholic893 (97.6)22 (2.4)
Diabetes0.623
Diabetic91 (97.8)2 (2.2)
Nondiabetic843 (97.6)21 (2.4)

5. Discussion

Recently, there has been a significant increase in incidentally detected focal liver lesions. These lesions are found in up to one-third of individuals screened with cross-sectional imaging without any liver-related diseases or symptoms (15, 16).

Focal hepatic lesions have various benign and malignant causes, and many are not readily characterizable in imaging studies, particularly when smaller than 1 cm. These lesions can usually be evaluated with serial follow-up imaging tests in patients without known cancer because nearly all will be benign (17). In cancer patients, however, prompt determination of the cause (or likely cause) of such lesions may be pivotal for defining prognosis and therapy (18). Despite extensive complete diagnostics, the precise diagnosis of focal hepatic lesions remains unclear in up to 50% of cases (19-21). Semaan et al. report a rate of merely 64% of correctly diagnosed lesions by CT and MRI. Studies concerning the prevalence of benign focal liver lesions present a quite heterogeneous picture due to population size, and investigation method. It is, therefore, difficult to compare different study results and apply them to routine ultrasound primary diagnostics (22). The prevalence of liver lesions in our study was 2.3%. In the same way, Kaltenbach et al. studied the sonographic prevalence of benign focal liver lesions in hospital patients in Germany. They indicated about 15.1% of the individuals with at least one hepatic lesion (23). The prevalence of hepatic hemangioma in various studies ranges from 0.1% to 20.0% (24-27). Our prevalence of 1.1% for hemangioma lies in the mid-range compared to the results of ultrasound-based studies (26-29). Compared to CT, MRI, and autopsy studies, which show a far higher prevalence range, our figure is in the lower third (24, 25, 30, 31).

Concerning hemangioma, there are a comparatively large number of prevalence studies for hepatic cysts, but they also differ in study size, patient population, and diagnostic techniques. Retrospective and prospective studies based on ultrasound have reported the prevalence of hepatic cysts between 0.1% and 11.3% (27, 29, 32, 33). We are also in the mid-range with our determined prevalence of 0.8%.

In our collective, hemangioma was the highest diagnostic hepatic lesion in ultrasonography examinations, with a higher frequency in females. Similarly Rungsinaporn and Phaisakamas reported a higher prevalence of hepatic hemangioma in women, while some other studies reported a higher prevalence of hemangioma in middle-aged or elderly patients, which was contrary to our results (32-34). On the contrary, Jacob et al. reported no statistically significant relationship between gender and liver lesions, which is inconsistent with the present study (35). Studies reported an increasing prevalence of hepatic cysts with age (7, 36-38). Most studies have also found a gender-dependent relationship, with a higher prevalence of hepatic cysts in women (32, 36-38). On the contrary, the presence of liver lesions was not significantly related to age in our results. In line with our results, some studies in France and Japan indicated no statistically significant relationship between age and the presence of liver lesions (39, 40).

In the present study, there was no statistically significant relationship between BMI and the presence of liver lesions. Hussain and Semelka in the Netherlands and Jacob et al. in England obtained similar results consistent with the present study (2, 35). CT, MRI, or autopsy studies report much broader prevalence rates than ultrasound-based studies for liver lesions (24, 41-43). Our prevalence is in the mid to lower third of the range compared to CT, MRI, and autopsy studies. CT studies have reported the highest prevalence rates (43). Ultrasound is a high-resolution, non-invasive imaging technique with high accuracy, low cost, and without side effects, which is well accepted by patients in many diagnostic situations (3). Benign masses, on the other hand, are relatively common in the general population. Most of these lesions are cystic, and some are hemangiomas. Focal nodular hyperplasia and adenomas are rare but can produce an appearance quite similar to malignant masses, requiring careful ultrasound examination (44).

This virtual epidemic of hepatic incidentalomas is mainly based on the constant improvement and widespread availability of radiologic technologies and their inflationary use in routine clinical work. This progress holds both opportunities and risks. On the one hand, it may result in the detection of a life-threatening lesion at an early, curable stage. On the other hand, detecting focal liver lesions may result in a harmful over-treatment of patients for whom merely follow-up or no treatment is adequate (45).

Despite recent technical advances in modern radiology settings, a correct preoperative diagnosis of asymptomatic focal liver lesions remains challenging. This was a cross-sectional study; hence, further research is suggested, including the group and prospective studies characterized by long follow-up periods and long-term intervals that can be instrumental in identifying more variables influencing hepatic lesions. Hence, along with the determination of accuracy and justification of ultrasound efficiency, more comprehensive research concerning some variables, such as the history of oral contraceptive pills (OCP), is warranted. It is also suggested that other diagnostic tools be used along with ultrasonography to confirm diagnostic findings. As our study was conducted on outpatients with no acute or chronic hepatic diseases, like B and C viral hepatitis, biliary diseases, and cancer, the results can be powerfully generalized to the general population.

5.1. Conclusions

Hemangioma was the most common liver lesion diagnosed by ultrasound, which was reported marginally higher in females. Also, sonography is not recommended for the general population but is advisable in risk groups.

Acknowledgements

References

  • 1.

    Thyagarajan MS, Sharif K. Space Occupying Lesions in the Liver. Indian J Pediatr. 2016;83(11):1291-302. [PubMed ID: 27783314]. https://doi.org/10.1007/s12098-016-2240-x.

  • 2.

    Hussain SM, Semelka RC. Hepatic imaging: comparison of modalities. Radiol Clin North Am. 2005;43(5):929-47. ix. [PubMed ID: 16098348]. https://doi.org/10.1016/j.rcl.2005.05.006.

  • 3.

    van Rosmalen BV, Bieze M, Besselink MG, Tanis P, Verheij J, Phoa SS, et al. Long-term outcomes of resection in patients with symptomatic benign liver tumours. HPB (Oxford). 2016;18(11):908-14. [PubMed ID: 27553837]. [PubMed Central ID: PMC5094485]. https://doi.org/10.1016/j.hpb.2016.07.013.

  • 4.

    Davies NH, Yu D. Space-Occupying Lesions: The Diagnostic Approach. In: Dooley JS, Lok ASF, Burroughs AK, Jenny Heathcote E, editors. Sherlock's Diseases of the Liver and Biliary System. 12th ed. Chichester, England: Wiley-Blackwell; 2011. p. 660-70. https://doi.org/10.1002/9781444341294.ch33.

  • 5.

    Mallick SI, Sarkar PB, Dasgupta S, Kar A, Mukherjee S, Bothra SJ, et al. Evaluation of Liver Space Occupying Lesion with Special Reference To Etiology and Co-Morbid Condition. Int J Curr Res Rev. 2015;7(1):28-33.

  • 6.

    de Rave S, Hussain SM. A liver tumour as an incidental finding: differential diagnosis and treatment. Scand J Gastroenterol Suppl. 2002;(236):81-6. [PubMed ID: 12408510]. https://doi.org/10.1080/003655202320621517.

  • 7.

    Oldhafer KJ, Habbel V, Horling K, Makridis G, Wagner KC. Benign Liver Tumors. Visc Med. 2020;36(4):292-303. [PubMed ID: 33005655]. [PubMed Central ID: PMC7506257]. https://doi.org/10.1159/000509145.

  • 8.

    Thomeer MG, Broker M, Verheij J, Doukas M, Terkivatan T, Bijdevaate D, et al. Hepatocellular adenoma: when and how to treat? Update of current evidence. Therap Adv Gastroenterol. 2016;9(6):898-912. [PubMed ID: 27803743]. [PubMed Central ID: PMC5076773]. https://doi.org/10.1177/1756283X16663882.

  • 9.

    Venturi A, Piscaglia F, Vidili G, Flori S, Righini R, Golfieri R, et al. Diagnosis and management of hepatic focal nodular hyperplasia. J Ultrasound. 2007;10(3):116-27. [PubMed ID: 23396642]. [PubMed Central ID: PMC3478711]. https://doi.org/10.1016/j.jus.2007.06.001.

  • 10.

    Dane B, Shanbhogue K, Menias CO, Taffel MT. The humbling hemangioma: uncommon CT and MRI imaging features and mimickers of hepatic hemangiomas. Clin Imaging. 2021;74:55-63. [PubMed ID: 33434867]. https://doi.org/10.1016/j.clinimag.2020.12.028.

  • 11.

    Mocchegiani F, Vincenzi P, Coletta M, Agostini A, Marzioni M, Baroni GS, et al. Prevalence and clinical outcome of hepatic haemangioma with specific reference to the risk of rupture: A large retrospective cross-sectional study. Dig Liver Dis. 2016;48(3):309-14. [PubMed ID: 26514738]. https://doi.org/10.1016/j.dld.2015.09.016.

  • 12.

    Kamyab AA, Rezaei-Kalantari K. Hepatic Hemangioma in a Cluster of Iranian Population. J Med Ultrasound. 2019;27(2):97-100. [PubMed ID: 31316220]. [PubMed Central ID: PMC6607875]. https://doi.org/10.4103/JMU.JMU_98_18.

  • 13.

    Poustchi H, Eghtesad S, Kamangar F, Etemadi A, Keshtkar AA, Hekmatdoost A, et al. Prospective Epidemiological Research Studies in Iran (the PERSIAN Cohort Study): Rationale, Objectives, and Design. Am J Epidemiol. 2018;187(4):647-55. [PubMed ID: 29145581]. [PubMed Central ID: PMC6279089]. https://doi.org/10.1093/aje/kwx314.

  • 14.

    Mansour-Ghanaei F, Joukar F, Naghipour MR, Sepanlou SG, Poustchi H, Mojtahedi K, et al. The PERSIAN Guilan Cohort Study (PGCS). Arch Iran Med. 2019;22(1):39-45. [PubMed ID: 30821159].

  • 15.

    Schwartz LH, Gandras EJ, Colangelo SM, Ercolani MC, Panicek DM. Prevalence and importance of small hepatic lesions found at CT in patients with cancer. Radiology. 1999;210(1):71-4. [PubMed ID: 9885589]. https://doi.org/10.1148/radiology.210.1.r99ja0371.

  • 16.

    Devine AS, Jackson CS, Lyons L, Mason JD. Frequency of incidental findings on computed tomography of trauma patients. West J Emerg Med. 2010;11(1):24-7. [PubMed ID: 20411070]. [PubMed Central ID: PMC2850848].

  • 17.

    Assy N, Nasser G, Djibre A, Beniashvili Z, Elias S, Zidan J. Characteristics of common solid liver lesions and recommendations for diagnostic workup. World J Gastroenterol. 2009;15(26):3217-27. [PubMed ID: 19598296]. [PubMed Central ID: PMC2710776]. https://doi.org/10.3748/wjg.15.3217.

  • 18.

    Karhunen PJ. Benign hepatic tumours and tumour like conditions in men. J Clin Pathol. 1986;39(2):183-8. [PubMed ID: 3950039]. [PubMed Central ID: PMC499674]. https://doi.org/10.1136/jcp.39.2.183.

  • 19.

    Skalicky T, Treska V, Sutnar A, Liska V, Molacek J, Mirka H, et al. [Surgical treatment of benign liver tumours--indications and results]. Zentralbl Chir. 2009;134(2):141-4. German. [PubMed ID: 19382044]. https://doi.org/10.1055/s-2008-1076871.

  • 20.

    Grimm J, Muller-Hulsbeck S, Blume J, Biederer J, Heller M. [Comparison of biphasic spiral CT and MnDPDP-enhanced MRI in the detection and characterization of liver lesions]. Rofo. 2001;173(3):266-72. German. [PubMed ID: 11293872]. https://doi.org/10.1055/s-2001-11596.

  • 21.

    Strobel D, Seitz K, Blank W, Schuler A, Dietrich CF, von Herbay A, et al. Tumor-specific vascularization pattern of liver metastasis, hepatocellular carcinoma, hemangioma and focal nodular hyperplasia in the differential diagnosis of 1,349 liver lesions in contrast-enhanced ultrasound (CEUS). Ultraschall Med. 2009;30(4):376-82. [PubMed ID: 19688669]. https://doi.org/10.1055/s-0028-1109672.

  • 22.

    Semaan A, Branchi V, Marowsky AL, Von Websky M, Kupczyk P, Enkirch SJ, et al. Incidentally Detected Focal Liver Lesions - A Common Clinical Management Dilemma Revisited. Anticancer Res. 2016;36(6):2923-32. [PubMed ID: 27272806].

  • 23.

    Kaltenbach TE, Engler P, Kratzer W, Oeztuerk S, Seufferlein T, Haenle MM, et al. Prevalence of benign focal liver lesions: ultrasound investigation of 45,319 hospital patients. Abdom Radiol (NY). 2016;41(1):25-32. [PubMed ID: 26830608]. [PubMed Central ID: PMC4735268]. https://doi.org/10.1007/s00261-015-0605-7.

  • 24.

    Moschetta M, Telegrafo M, Rella L, Stabile Ianora AA, Angelelli G. Let's go out of the breast: prevalence of extra-mammary findings and their characterization on breast MRI. Eur J Radiol. 2014;83(6):930-4. [PubMed ID: 24656879]. https://doi.org/10.1016/j.ejrad.2014.02.022.

  • 25.

    Marin D, Galluzzo A, Plessier A, Brancatelli G, Valla D, Vilgrain V. Focal nodular hyperplasia-like lesions in patients with cavernous transformation of the portal vein: prevalence, MR findings and natural history. Eur Radiol. 2011;21(10):2074-82. [PubMed ID: 21710271]. https://doi.org/10.1007/s00330-011-2161-z.

  • 26.

    Khosa F, Warraich H, Khan A, Mahmood F, Markson L, Clouse ME, et al. Prevalence of non-cardiac pathology on clinical transthoracic echocardiography. J Am Soc Echocardiogr. 2012;25(5):553-7. [PubMed ID: 22406164]. https://doi.org/10.1016/j.echo.2012.01.022.

  • 27.

    Massironi S, Branchi F, Rossi RE, Fraquelli M, Elli L, Bardella MT, et al. Hepatic hemangioma in celiac patients: data from a large consecutive series. Gastroenterol Res Pract. 2015;2015:749235. [PubMed ID: 25649925]. [PubMed Central ID: PMC4306374]. https://doi.org/10.1155/2015/749235.

  • 28.

    Jansen MJA, Kuijf HJ, Veldhuis WB, Wessels FJ, Viergever MA, Pluim JPW. Automatic classification of focal liver lesions based on MRI and risk factors. PLoS One. 2019;14(5). e0217053. [PubMed ID: 31095624]. [PubMed Central ID: PMC6522218]. https://doi.org/10.1371/journal.pone.0217053.

  • 29.

    Varbobitis IC, Pappas G, Karageorgopoulos DE, Anagnostopoulos I, Falagas ME. Decreasing trends of ultrasonographic prevalence of cystic echinococcosis in a rural Greek area. Eur J Clin Microbiol Infect Dis. 2010;29(3):307-9. [PubMed ID: 20091330]. https://doi.org/10.1007/s10096-009-0858-6.

  • 30.

    Lam K. Autopsy Findings in Diabetic Patients: A 27-Yr Clinicopathologic Study with Emphasis on Opportunistic Infections and Cancers. Endocr Pathol. 2002;13(1):39-46. https://doi.org/10.1385/ep:13:1:39.

  • 31.

    Hu HT, Wang W, Chen LD, Ruan SM, Chen SL, Li X, et al. Artificial intelligence assists identifying malignant versus benign liver lesions using contrast-enhanced ultrasound. J Gastroenterol Hepatol. 2021;36(10):2875-83. [PubMed ID: 33880797]. [PubMed Central ID: PMC8518504]. https://doi.org/10.1111/jgh.15522.

  • 32.

    Rungsinaporn K, Phaisakamas T. Frequency of abnormalities detected by upper abdominal ultrasound. J Med Assoc Thai. 2008;91(7):1072-5. [PubMed ID: 18839847].

  • 33.

    Tsuruya K, Nishizaki Y, Tatemichi M, Mishima Y, Shimma Y, Arase Y, et al. The Prevalence and Natural History of Hepatic Cysts Examined by Ultrasound: A Health Checkup Population Retrospective Cohort Study. Sci Rep. 2022;12(1):12797. [PubMed ID: 35896780]. [PubMed Central ID: PMC9329350]. https://doi.org/10.1038/s41598-022-16875-z.

  • 34.

    Bajenaru N, Balaban V, Savulescu F, Campeanu I, Patrascu T. Hepatic hemangioma -review. J Med Life. 2015;8 Spec Issue:4-11. [PubMed ID: 26361504]. [PubMed Central ID: PMC4564031].

  • 35.

    Jacob J, Deganello A, Sellars ME, Hadzic N, Sidhu PS. Contrast enhanced ultrasound (CEUS) characterization of grey-scale sonographic indeterminate focal liver lesions in pediatric practice. Ultraschall Med. 2013;34(6):529-40. [PubMed ID: 24132647]. https://doi.org/10.1055/s-0033-1355785.

  • 36.

    Engler A, Shi R, Beer M, Schmidberger J, Kratzer W, Barth TFE, et al. Simple liver cysts and cystoid lesions in hepatic alveolar echinococcosis: a retrospective cohort study with Hounsfield analysis. Parasite. 2019;26:54. [PubMed ID: 31469072]. [PubMed Central ID: PMC6716343]. https://doi.org/10.1051/parasite/2019057.

  • 37.

    Tocchi A, Mazzoni G, Costa G, Cassini D, Bettelli E, Agostini N, et al. Symptomatic nonparasitic hepatic cysts: options for and results of surgical management. Arch Surg. 2002;137(2):154-8. [PubMed ID: 11822951]. https://doi.org/10.1001/archsurg.137.2.154.

  • 38.

    Marrero JA, Ahn J, Rajender Reddy K; Americal College of Gastroenterology. ACG clinical guideline: the diagnosis and management of focal liver lesions. Am J Gastroenterol. 2014;109(9):1328-47. [PubMed ID: 25135008]. https://doi.org/10.1038/ajg.2014.213.

  • 39.

    Vilgrain V, Boulos L, Vullierme MP, Denys A, Terris B, Menu Y. Imaging of atypical hemangiomas of the liver with pathologic correlation. Radiographics. 2000;20(2):379-97. [PubMed ID: 10715338]. https://doi.org/10.1148/radiographics.20.2.g00mc01379.

  • 40.

    Luo W, Numata K, Morimoto M, Nozaki A, Ueda M, Kondo M, et al. Differentiation of focal liver lesions using three-dimensional ultrasonography: retrospective and prospective studies. World J Gastroenterol. 2010;16(17):2109-19. [PubMed ID: 20440851]. [PubMed Central ID: PMC2864836]. https://doi.org/10.3748/wjg.v16.i17.2109.

  • 41.

    Volk M, Strotzer M, Lenhart M, Techert J, Seitz J, Feuerbach S. Frequency of benign hepatic lesions incidentally detected with contrast-enhanced thin-section portal venous phase spiral CT. Acta Radiol. 2001;42(2):172-5. [PubMed ID: 11259945]. https://doi.org/10.1034/j.1600-0455.2001.042002172.x.

  • 42.

    Kreft B, Pauleit D, Bachmann R, Conrad R, Kramer A, Schild HH. [Incidence and significance of small focal liver lesions in MRI]. Rofo. 2001;173(5):424-9. German. [PubMed ID: 11414150]. https://doi.org/10.1055/s-2001-13340.

  • 43.

    Soyer P, Bluemke DA, Vissuzaine C, Beers BV, Barge J, Levesque M. CT of hepatic tumors: prevalence and specificity of retraction of the adjacent liver capsule. AJR Am J Roentgenol. 1994;162(5):1119-22. [PubMed ID: 8165994]. https://doi.org/10.2214/ajr.162.5.8165994.

  • 44.

    Dill-Macky MJ, Burns PN, Khalili K, Wilson SR. Focal hepatic masses: enhancement patterns with SH U 508A and pulse-inversion US. Radiology. 2002;222(1):95-102. [PubMed ID: 11756711]. https://doi.org/10.1148/radiol.2221010092.

  • 45.

    Koea JB. Hepatic incidentaloma: the rule of tens. HPB (Oxford). 2013;15(5):379-83. [PubMed ID: 23557409]. [PubMed Central ID: PMC3633040]. https://doi.org/10.1111/j.1477-2574.2012.00595.x.