Role of Ultrasound in the Diagnosis of Hepatocellular Carcinoma in Patients with Chronic Liver Disease

Background: Hepatocellular carcinoma (HCC) is a common cancer in humans. Its mortality ranks third among human malignancies. Cirrhosis of liver is a major contributor to hepatocellular carcinoma, about in 80% of the affected individuals. Fine needle aspiration cytology (FNAC) of the liver which is a minimal invasive procedure is essential to sort out primary and secondary neoplasm of the liver. Objective: The aim of this cross-sectional study was to determine the accuracy of ultrasound for diagnosis of HCC in comparison with FNAC findings. Materials and Methods: This study was done in the Radiology & Imaging Department in Enam Medical College & Hospital, Savar, Dhaka in collaboration with the Department of Pathology of the same institution for FNAC correlation during October 2017 to November 2019. A total number of 50 patients with CLD with known hepatic mass, referred to the department were included in the study. Ultrasound was done with TOSHIBA using low frequency curvilinear probe of 3.5 MHz. USG-guided aspirations was performed using 18G needle under full aseptic measure. USG findings were validated by histopathology reports. Analysis was done by SPSS 19.0. Results: Mean age of the study population was 58.6 ± 10.9 years, of whom 37(74%) were male and 13 (26%) were female. Mean size of the hepatic lesions was 4.7 ± 1.08 cm. The lesions were characterized as iso-, hypo- and hyperechoic as compared with hepatic parenchyma. Doppler study shows both central and peripheral vascularity. Compared with FNAC findings, accuracy of USG findings was determined. Sensitivity of USG in detection of HCC was 97.7%, specificity was 66.7%, and positive prediction value 95.6% and negative prediction value 80%. Conclusion: Conventional USG can be used as a screening method in patients with CLD having hepatic masses. However, further workup is required for definite diagnosis.


Introduction
Liver cancer is the third most common cause of cancerrelated death in the world. 1 Among liver cancers, the hepatocellular carcinoma (HCC) is the most common primary liver cancer. 1 It is two to four times more prevalent in men 1 , rarely occurring before the age of 40 years, with the peak incidence at approximately the sixth to seventh decade of life. According to the International Agency for Research on Cancer (IARC), it is the fifth most frequent malignant neoplasm in men and the ninth most frequent in women. 2 Overall prognosis is poor with the average mortality to morbidity rate of 0.95.
Approximately 90% of cases of HCC develop in the setting of chronic liver disease, most commonly approximately 60% of HCC cases in developing countries, while only up to 20% in developed countries. 3 Probability of developing HCC increases with duration of liver cirrhosis and 1/3 of patients with known cirrhosis will develop HCC in due life course. 4 Research conducted on large groups of patients with a long-term follow-up allowed to distinguish factors indicative of increased risk of HCC in patients with liver cirrhosis. Smoking is considered an independent risk factor in development of HCC. 4

Materials and Methods
This cross sectional study was carried in the department of Radiology and Imaging of Enam Medical College & Hospital, Savar, Dhaka in collaboration with the department of Pathology of the same institution for histopathological correlation during October 2017 to November 2019. This study was carried out on consecutively selected 50 patients ranging from 41−75 years having chronic liver disease with hepatic SOL and supported by ultrasonogram.
Ultrasonogram was performed by Toshiba Aplio 500 low frequency (3.5 MHz) curvilinear transducer. USGguided aspiration was performed using 18G needle under full aseptic measure. Finally, ultrasonographic diagnoses of hepatic SOL were correlated with histopathological reports. The following outcome variables were observed.
Demographic: Age of the patient. Gender of the patients.
Imaging variables: Size of mass, site of lesion, type of lesion (solid/cystic), echogenicity, margin and Doppler findings.
The entire relevant data of patients were recorded in a predesigned structured questionnaire. Then all data were checked and edited after collection and entered into computer and analyzed with the help of SPSS (statistical package for social sciences) 19.0 version. For the validity of the study outcome sensitivity, specificity, accuracy, positive and negative predictive values were calculated out after confirmation of the diagnosis histopathologically.

Results
A total 50 consecutive cases diagnosed clinically as patients with chronic liver disease having hepatic mass who attended the department of Radiology and Imaging of EMCH for ultrasonography during the period from 1 st October 2017 to 30 th November 2019 were selected for this study. Mean age of the patients was 58.6 ± 10.9 years, ranging from 41 to 75 years. Among them 37 (74%) were male and 13 (26%) were female.
Sonographically hepatic SOLs were diagnosed as hepatocellular carcinoma having following criteriairregular shaped in 86% cases, margin were irregular in 90% cases, hypoechoic in 80% cases and central necrosis in 92% cases. Doppler study shows central and peripheral vascularity in 84% cases (Table I).
On ultrasonography, lesions were diagnosed as HCC in 90.0% cases and other than HCC in 10%. Among other lesions FNH was found in 2.0%, metastasis in 4.0%, abscess in 2.0%, hemangioma in 2.0% cases (Table II).
On histopathology, lesions were diagnosed as HCC in 88.0% cases and other than HCC in 12%. Among other lesions metastases were found in 44.0%, abscess in 6.0%, hemangioma in 8.0%, FNH in 4.0% and Hydatid cyst in 4% cases (Table III).   Sonographically 45 lesions were HCC; out of these 43 (95.5%) were also proved HCC histopathologically, and 2 (4.4%) other than HCC. Out of 5 cases who were sonographically diagnosed as other than HCC, one (20%) was diagnosed as HCC and 4 (80%) were proved other than HCC (Table IV).
Ultrasonographic findings were correlated with histopathological findings to evaluate the ultrasonographic characteristics of Hepatic SOL. Table  V shows that in diagnosis of HCC by ultrasonogram, sensitivity was 97.7%, specificity 66.7%, positive predictive value (PPV) 95.6%, negative predictive value 80% and accuracy was 94.0%. It has become a routine practice over the past four years in our hospital for any patient suspected with hepatic lesion to undergo a FNAC technique. The USSG-FNAC technique localized the tumour so that a high precision of the lesion aspirate is obtained. USSG-FNAC of the liver plays more roles in diagnosis and classification of liver disease than ultrasound alone, as it requires greater precision to reach diagnostic accuracy. 14 Huber & Heuhold 15 recorded a sensitivity In another study by Tanaka et al 21 the overall sensivity, specificity and accuracy of US was found to be 58.9%, 99.9%, and 99.3% respectively. In a study by Sbolli et al 22 138 patients underwent ultrasound followed by fine needle aspiration biopsy. The diagnosis of HCC was obtained in 132 cases with sensitivity of 95.6% and specificity of almost 100% and in this study the sensitivity closely resembles to this study. In a study by Takayasu et al 23 the sensitivity of ultrasound was found to be more sensitive (86%) and less specific (82%) in diagnosing HCC. The overall accuracy of procedure in the present study was 94.0%, which was comparable to the rate of accuracy reported in literature (78% to 97.82%). 2,14,24,25 The findings of the present study show that because of increased sensitivity conventional ultrasonography can be used as a screening tool in patients with chronic liver disease for surveillance purpose.