Hepatocellular Carcinoma in South Indian Population: Clinical Profile and AFP Correlation with Radiological Tumor Size

ABSTRACT

Objectives:

To study the clinical profile of hepatocellular carcinoma (HCC) in a tertiary care hospital and alpha fetoprotein correlation (AFP) with radiological tumor size.

Materials and Methods:

A prospective observational study was conducted from February 2023 to August 2024. There were 57 cases of HCC enrolled. Patient details were noted, such as demographics, clinical characteristics, tumor characteristics, disease severity and their treatment. The data was compiled and analyzed. The outcome measures were association of tumor size with AFP levels.

Results:

Patients had a mean age of 63.1 years and a BMI of 27.02 kg/m². Common risk factors were diabetes mellitus and alcohol in 47.4% and 43.9%, respectively. The common symptoms were abdominal pain (right hypochondrium) in 40 (70.2%) patients, abdominal distension in 36 (63.2%), jaundice in 19 (33.3%), weight loss in 10 (17.5%), fever in 8 (14.0%). Hepatomegaly was present in 29 (50.9%) patients, ascites in 27 (47.4%), splenomegaly in 10 (17.5%), liver bruit and pleural effusion in 6 (10.5%) patients each, and hepatic encephalopathy in 4 (7.0%) patients.

Conclusion:

HCC patients were primarily older men with diabetes and alcohol being common risk factors. Abdominal pain and distention remain common findings with complications of cirrhosis, esophageal varices, and pleural effusion. AFP levels and imaging modalities were the most important aids for the diagnosis, management and prognosis. Majority of the treatment remains supportive in the form of transarterial chemoembolization (TACE), transarterial radioembolization (TARE), stereotactic body radiation therapy (SBRT) etc. with few cases demanding interventional therapies.

INTRODUCTION

Hepatocellular carcinoma (HCC) is a significant primary liver cancer, seen in the world with a high mortality rate.[1,2] Among all cancers, it has been placed on 4^th position in terms of mortality, wherein around 8 lakh deaths are reported annually, with over 0.9 million new cases reported per year, accounting for 5^th position in terms of incidence.[3]

Among various liver cancers, HCC is responsible for around 90% of the cases. GLOBOCAN 2020 data says that India reported a mortality of 33,793 per year and case rate of 3% for 3 per year – giving India the 10^th position among the list of incidences of liver cancers throughout the world.[4]

The development of HCC involves multiple risk factors primarily being infections in terms of Hepatitis B, C and comorbidities that may affect the liver such as chronic liver disease, alcohol, diabetes, genetics, toxins, smoking, and carcinogens. All these may pathologically affect the liver cells causing necrosis and inflammation of the hepatocytes. Subsequently, the chronic nature of the pathology may lead to fibrosis and cirrhosis ultimately causing HCC.[5,6,7]

Symptomatically patients may have fever, pain upper abdomen, weight loss, loss of appetite, palpable mass, jaundice, malaise, edema, and ascites.[8] The diagnosis rests on the use of tumor markers like AFP, radiological investigations like Ultrasound (USG), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) that may identify the size, location and nature of the lesion along with the involvement of blood vessels and other organs.[9]

Biopsy is needed rarely to confirm the diagnosis, and pathological systems are used for grading the severity that include Barcelona chronic clinic liver cancer staging system (BCLC),[10] model of end stage liver disease (MELD) score,[11] and tumor node metastasis (TNM) staging system.[12]

The best approach to optimize the management of HCC is the role of a multidisciplinary team. HCC carries grave prognosis and poor survival rate of less than 20% due to late diagnosis. Early detection, thus, is very important as survival rates may increase to 70% at 5 years.[13]

The development and prognosis of HCC depends on various factors like age, gender of the patient, associated conditions such as viral hepatitis, cirrhosis, or chronic liver disease.[14,15] Knowing the clinical profile of the patients and the severity of the HCC helps in predicting the progression of the disease and managing the patient well. There is paucity of studies in India, thus, we conducted this study to determine the clinical and risk profile of HCC in a tertiary care hospital of India and the correlation of AFP levels with tumor size.

MATERIALS AND METHODS

A prospective observational study was conducted in Department of General Medicine in a tertiary care hospital of Manipal, India. The study was conducted over a period from February 2023 to August 2024 with inclusion criteria of any patient who was newly diagnosed with HCC with age of more than 18 years or an already diagnosed case of who was admitted to the hospital and managed. Exclusion criteria was age less than 18 years, patients with cancers other than HCC and pregnancy.

57 cases of HCC were enrolled in the current study who satisfied the eligibility criteria in the study period. They were explained about the study, and it was informed that the data will be obtained in a study form and reported for publication. Written informed consent was obtained. No changes in the diagnosis or treatment approach of the patient were required for the study. So, ethical clearance was waived off.

Patient details were noted, such as demographics, clinical characteristics, their symptoms and comorbidities. ECOG scoring was done from 0 to 4 and reported.[16] Child-Pugh scoring was also done.[17] All the investigations in terms of coagulation profile, glycemic parameters, liver function test, kidney function test, tumor markers such as AFP, viral markers by ELISA, chest X-ray, biopsy, cytology, USG, CECT scan, and MRI were reported. Pathologically HCC was graded into well, moderately, poorly differentiated. Certain cases that required upper GI endoscopy to notice esophageal varices were done. The outcome measures were association of tumor size with AFP levels.

Statistical analysis

The data was compiled and entered into an excel spreadsheet using Microsoft office. Numbers or frequencies and their corresponding percentages were recorded. For quantitative data, the mean was calculated along with the standard deviation, and the range was determined by identifying the minimum and maximum values. To assess associations between parameters, such as tumor size and AFP levels, the Chi-square test was employed, with the Fisher exact test used when cell values were less than 5. The Pearson correlation coefficient was calculated to explore the relationship between AFP levels and tumor size. A P value of less than 0.05 was considered statistically significant. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS), version 29, from IBM Corporation, New York.

RESULTS

Demographic characteristics

The mean age of the study patients was 63.1 ± 11.9 years with a mean BMI of 27.02 ± 3.96 kg/m². Common risk factors were diabetes mellitus and alcohol in 47.4% and 43.9%, respectively [Table 1].

Table 1.

Demographic and clinical characteristics (n=57)

Characteristics	Mean±SD	n (%)
Age (y)	63.1±11.9
Gender
Males		53 (93)
Females		4 (7)
BMI (kg/m2)	27.02±3.96
Risk factors
DM		27 (47.4)
Alcohol		25 (43.9)
HBV		12 (21.1)
Smoking		10 (17.5)
Pre-existing liver
disease		5 (8.8)
HCV		2 (3.5)

Clinical characteristics

The most common symptom was abdominal pain (right hypochondrium) in 40 (70.2%) patients, abdominal distension in 36 (63.2%), jaundice in 19 (33.3%), weight loss in 10 (17.5%), fever in 8 (14.0%), hematemesis and malena in 8 (14.0%), encephalopathy/altered sensorium in 4 (7.0%), pruritus in 2 (3.5%), and other symptoms (decreased appetite, backache, fatigue, cough, vomiting, pedal edema, and constipation) in 12 (21.1%) patients. This is shown in Figure 1.

Figure 1.

Symptoms distribution

On general examination, icterus and pedal edema were present in 19 (33.3%) patients each, signs of chronic liver cell failure (Spider Naevi, palmar erythema, testicular atrophy, and Dupuytren’s contracture etc.) in 10 (17.5%) patients, and pallor in 7 (12.3%) patients.

On systemic examination, hepatomegaly was present in 29 (50.9%) patients, ascites in 27 (47.4%), splenomegaly in 10 (17.5%), liver bruit and pleural effusion in 6 (10.5%) patients each, and hepatic encephalopathy in 4 (7.0%) patients.

Tumor severity assessment

A plethora of lab investigations were done, values of that are shown in Tables 2 and 3. On serology, HbsAg ELISA was reactive in 12 (21.1%), anti-HCV assay was reactive is 2 (3.5%), and HIV was reactive in none of the patients. On ascitic fluid analysis, SAAG was high in 15 (88.2%) and low in 2 (11.8%) patients. Malignant cytology was present in 1 (6.7%) patient. Chest X-ray was normal in 47 (87.0%) patients. Pleural effusion was present in 5 (9.3%) patients and metastasis in 2 (3.7%) patients.

Table 2.

Laboratory investigation findings

Laboratory investigations
	N	Minimum	Maximum	Mean	SD
Hb (gm/dL)	57	7.1	15.4	11.12	1.87
Platelet	57	46.0	595.0	209.53	131.00
White blood cells (WBC/uL of blood)	57	3.6	20.4	8.02	3.24
Albumin (g/dL)	57	2.22	4.58	3.35	0.60
Bilirubin (mg/dL)	57	0.26	32.01	2.81	4.61
AST (IU/L)	57	23.0	284.0	92.38	62.68
ALT (IU/L)	57	4.0	223.0	59.61	48.78
ALP (IU/L)	57	12.4	817.0	224.90	162.12
Urea (mg/dL)	57	9.0	111.0	30.86	18.08
Creatinine (mg/dL)	57	0.55	3.29	1.07	0.50
Na+ (mmol/L)	57	106.0	140.4	132.14	6.22
K+ (mmol/L)	57	3.2	6.5	4.54	0.60
HbA1c (%)	57	4.2	10.3	6.29	1.55
FBS (mg/dL)	21	41.0	255.0	127.71	53.53
PPBS (mg/dL)	56	47.0	372.0	158.84	75.69
PT (s)	57	10.0	20.3	12.80	1.89
INR	57	0.92	1.86	1.15	0.18
APTT (s)	38	21.1	42.9	30.27	4.19
AFP	57	3.20	60500.01	8717.96	17873.17
Tumor size (cm)	57	1.40	18.10	9.10	4.49

Table 3.

Other tumor related findings

Parameter	N (%)
SAAG
High	15 (88.2%)
Low	2 (11.8%)
Malignant cytology	1 (6.7%)
Chest X-ray normal	47 (87.0%)
Pleural effusion	5 (9.3%)
Metastasis (X-ray)	2 (3.7%)
Cirrhosis	33 (57.9%)
Ascites	27 (47.4%)
Metastasis/portal vein involvement	36 (63.2%)
PET scan (n=9) mets	5 (--)
Liver biopsy (n=26)
G1	6
G2	14
G3	6
Upper GI endoscopy
Large varices	8 (14%)
Small varices	16 (28.1%)

Cirrhosis was present in 33 (57.9%) patients. Ascites was present in 27 (47.4%) patients. Metastasis/portal vein involvement was present in 36 (63.2%) patients. Out of 57 patients, the majority had 8^th segment involved [29 (52.7%)], followed by 5^th segment [26 (47.3%)], and 7^th segment [24 (43.6%)]. Majority of the patients had ECOG performance score 1 [28 (49.1%)], followed by score 2 [17 (29.8%)], score 3 [6 (10.5%)], score 0 [4 (7.0%)], and score 4 [2 (3.5%)]. Child-Pugh scoring was done, where in maximum cases had A [26 (45.6%)], followed by B [25 (43.9%)], and C [6 (10.5%)] cases.

BCLC grading was done wherein A, B, C, and D stages had proportion of 6 (10.5%) cases, 12 (21.1%) cases, 34 (59.6%) cases and 5 (8.8%) cases, respectively.

Outcome variables

No significant association was found between AFP levels and tumor size (P = 0.497) as shown in Table 4. There was no significant correlation with r value = −0.012 P is equal to 0.93. [Figure 2]. The patients received treatment in the form of supportive care in 42 (72.4%) patients, resection in 5 (8.6%), TACE and lenvatinib in 4 (6.9%) patients each, SBRT, TARE, and radiofrequency ablation (RFA) in 1 (1.7%) patient each. Supportive care included SBRT, lenvatinib, palliative radiotherapy, palliative chemotherapy, debulking surgery etc.

Table 4.

Comparison of AFP range between tumor size by Pearson’s Chi-square test

			Tumor size (cm)			Total	χ2 - value	P
			<5	5–10	>10
AFP range (ng/ml)	< = 20	Count	3	5	8	16	9.371	0.497#
		%	18.8%	31.3%	50.0%	100.0%
	21–399	Count	6	4	6	16
		%	37.5%	25.0%	37.5%	100.0%
	400–1000	Count	1	2	1	4
		%	25.0%	50.0%	25.0%	100.0%
	1001–5000	Count	1	1	3	5
		%	20.0%	20.0%	60.0%	100.0%
	5001–10000	Count	0	3	0	3
		%	0.0%	100.0%	0.0%	100.0%
	>10000	Count	3	4	6	13
		%	23.1%	30.8%	46.2%	100.0%
Total		Count	14	19	24	57
%		24.6%	33.3%	42.1%	100.0%

^#No statistical significance at P > 0.05 level

Figure 2.

Correlations of AFP with tumor size by using Pearson correlation r = −0.012, P = 0.930

DISCUSSION

The present study is one of the significant landmark Indian studies that encompassed a wide clinical profile of patients presenting or admitted and diagnosed with HCC. The mean age of the study patients was 63.1 years with a standard deviation of 11.9 years showing that proportionately 50s and 60s were the major age group affected with HCC. The study findings were in line with mean ages reported in various studies that ranged from 45.5 to 57.4 years.[18,19,20,21]

Gender distribution showed male predominance with less than 10% females having HCC. The findings are in line with various other studies reporting male prevalence of HCC ranging from 71.7% to 92% with females having very low rate of HCC.[18,19,20,21] The preponderance of HCC in older men can be accounted by the presence of comorbidities like diabetes and habits of smoking and alcohol. In the present study, two commonest risk factors identified were presence of diabetes as seen in 47.4% cases and consumption of alcohol as seen in 43.9% cases.

Symptomatically, abdominal pain remains one of the commonest symptoms in 71.2% cases restricted to right hypochondriac region. The findings are in line with various other studies where commonest symptom was abdominal pain followed by other symptoms of fever, malaise, jaundice as seen in the previous study. Malena or bloody stools have also been reported in cases with esophageal varices.[18,19,21]

AFP remains one of the significant tumor markers that was done in the present study, and it was correlated with the tumor size. In the present study, there was no correlation between the AFP and size of the tumor (r = −0.012, P = 0.93). A few studies are corresponding with our studies showing no significant association between tumor size and AFP levels.[22,23,24] Although certain contrasting studies identified a positive relationship between them.[25,26] The discrepancy can be due to presence of cirrhosis in the study cohort or heterogeneous patient profile. However, this demands future research because AFP remains a significant tumor marker in relation to HCC.

Severity assessment is important from the point of view of management. Management may include surgical or non-surgical methods of treatment. Overall, it remains important that the patient is diagnosed early, and clinical profile is taken into account although managing the patient – to bring about good survival.[20]

Limitations

The study is limited by the fact that the sample cohort was not followed up. Once determining the survival outcomes and being a single-center study, the data cannot be applied to a wide area of population.

CONCLUSION

In conclusion, the patients had a mean age of 63.1 years and a BMI of 27.02 kg/m², with diabetes and alcohol consumption being the most common risk factors. Abdominal pain and distension were the most frequent presenting symptoms, along with jaundice, weight loss, and other signs of liver dysfunction. Hepatomegaly and ascites were prevalent in nearly half of the patients. Lab investigations revealed that 21.1% were reactive for HbsAg, although anti-HCV reactivity was low, and none tested positive for HIV. Cirrhosis and metastasis were common, affecting 57.9% and 63.2% of patients, respectively. Most patients had moderate performance status (ECOG 1 or 2), and Child-Pugh A classification was the most frequent. BCLC staging showed a predominance of advanced cases (stage C in 59.6% of patients). There was no significant correlation between AFP levels and tumor size. Treatment was primarily supportive care, with few patients undergoing resection or interventional therapies.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.