Assessing hepatocellular carcinoma in Nigeria: A multicenter retrospective cohort review of prevalence, risk factors, and treatment outcomes

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is a major cause of cancer deaths globally, with Nigeria’s rising burden fueled by viral hepatitis, environmental toxins, and lifestyle factors. Limited national data on HCC prevalence, risk factors, and treatment outcomes, due to diagnostic and healthcare challenges, hinder effective response. This multicenter study aims to determine the prevalence, identify key risk factors, and assess treatment patterns across Nigerian healthcare facilities, providing insights to improve early detection, guide public health strategies, and develop tailored management guidelines to enhance patient survival.

AIM

To determine the prevalence, identify key risk factors, and assess treatment patterns across Nigerian healthcare facilities, providing insights to improve early detection, guide public health strategies, and develop tailored management guidelines to enhance patient survival.

METHODS

This retrospective cohort review was conducted across gastroenterology units in 16 Nigerian healthcare facilities, representing both urban and rural settings, from January 2024 to December 2024. Adults aged 18 years and older diagnosed with HCC based on clinical, biochemical, imaging, and/or histopathological criteria were eligible; those with a prior history of malignancies or with incomplete records precluding data extraction were excluded. The study employed two-staged data-entry forms to capture distinct layers of information. Form A was designed to collect data on the entire gastroenterology patient population seen within 2024, including both patients with and without HCC, to allow estimation of HCC prevalence within the gastroenterology cohort and to summarize aggregate demographic and clinical features. Form B was dedicated to detailed abstraction of HCC-specific cases with identifiable records, drawing on complete, provenance-traceable data to characterize individual cases comprehensively (e.g., diagnostics, staging, treatment, and outcomes). Data collection utilized standardized tools to capture demographics, clinical features, diagnostics, staging, treatment modalities, and outcomes. Descriptive statistics summarized overall and HCC-specific cohorts, while logistic regression explored associations between risk factors and HCC-related outcomes. Ethical approval was obtained from the relevant institutional review boards, and confidentiality was maintained in accordance with applicable guidelines.

RESULTS

A total of 5760 gastroenterology cases were recruited, among which 412 were confirmed HCC, yielding a prevalence of 7.2% for HCC within the gastroenterology cohort. This study employed a two-form data entry: Form A was applied to the total gastroenterology cohort to estimate prevalence and characterize aggregate features, identifying 5760 cases with 412 confirmed HCC diagnoses. Form B was applied to individual HCC cases with available records for detailed case-level analysis. It recorded 319 cases for in-depth characterization. Regional prevalence varied from 3.4% in the South-East to 17.5% in the North-East. The cohort was predominantly male (77.6%) with a mean age of 49.4 years. Chronic hepatitis B virus infection accounted for 55.2% of cases; alcohol-related liver disease was present in 18.2% (noting that among those with alcoholic liver disease, more than half consumed ≥ 40 units of alcohol per week); hepatitis C virus (HCV) infection accounted for 5.6%; smoking was present in 3.8%; and metabolic-associated steatotic liver disease accounted for 3.5%. Common presenting symptoms included right upper abdominal pain (85.2%), abdominal swelling (84.9%), and a palpable right upper abdominal mass (78.2%), with a median diagnostic interval of approximately 3 months. Liver function was often compromised, with a substantial proportion presenting Child-Pugh B or C. Diagnostic imaging primarily involved abdominal ultrasound (85.2%) and contrast-enhanced computed tomography (41.6%). About half of the patients were diagnosed at advanced Barcelona Clinic Liver Cancer stages (C or D). Laboratory data showed elevated alpha fetoprotein in more than half of patients, with notable abnormalities in urea and international normalized ratio. Treatments included systemic therapy (predominantly sorafenib), surgical interventions, locoregional therapies, and palliative care, with regional variation in treatment choices influenced by local resources and access. At follow-up, nearly half of the patients experienced worsening symptoms, a minority showed improvement (10.1%), and 12.3% were alive at the end of the follow-up period. Prognostic factors significantly associated with outcomes included ascites, encephalopathy, performance status, and tumor stage, with ongoing alcohol use linked to increased progression.

CONCLUSION

Nigeria’s HCC prevalence was 7.2%, with regional differences, and most cases presented at advanced stages. Hepatitis B was the primary risk factor, alongside alcohol and HCV. Treatment approaches varied regionally, but overall survival remained poor, underscoring the urgent need for improved early detection, screening, and healthcare infrastructure. These findings inform public health policies and strategies for HCC management in Nigeria.

Key Words: Hepatocellular carcinoma; Chronic hepatitis B virus; Chronic hepatitis C virus; Aflatoxin; Late presentation; Surgical resection; Locoregional therapy; Systemic therapy

Core Tip: This multicenter study reveals a 7.2% prevalence of hepatocellular carcinoma (HCC) across Nigeria, with most cases diagnosed at advanced stages. Hepatitis B remains the leading risk factor, compounded by lifestyle and environmental factors. Regional variations in prevalence and treatment patterns highlight disparities in healthcare access and infrastructure. Despite the availability of diverse treatment options, survival rates remain low, underscoring the urgent need for improved early detection, screening, and targeted public health strategies. These findings provide critical insights to guide policy development, enhance management protocols, and ultimately improve outcomes for patients with HCC in Nigeria.

INTRODUCTION

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. It ranks as a leading cause of cancer-related deaths worldwide, with an especially high burden in developing countries like Nigeria. Globally, HCC accounts for approximately 700000 deaths annually, highlighting its significant contribution to cancer mortality[1]. In Nigeria, the incidence of HCC has been on the rise, driven chiefly by endemic viral hepatitis infections, environmental exposures, and lifestyle factors. Despite its growing epidemiological importance, comprehensive national data detailing the prevalence, risk factors, and treatment outcomes of HCC in Nigeria are limited, hampering targeted public health strategies and resource allocation[2,3].

The epidemiology of HCC in Nigeria mirrors broader patterns observed across sub-Saharan Africa, where the disease often presents at advanced stages, limiting therapeutic options and adversely impacting survival outcomes[4]. Chronic hepatitis B virus (HBV) infection is the predominant etiological factor, with carrier rates estimated at 8%-12% in general populations, and is transmitted vertically or through unsafe medical practices[5]. Hepatitis C virus (HCV), though less prevalent, also contributes significantly to the burden of liver disease, alongside exposure to environmental toxins such as aflatoxins, which contaminate stored grains, and lifestyle factors, including alcohol consumption, obesity, and metabolic syndrome.

Despite the recognition of these risk factors, national-level data on the prevalence and distribution of HCC are fragmented, often derived from hospital-based or regional studies that may not reflect the true population burden[6,7]. This paucity of data poses challenges in designing effective screening programs and allocating resources efficiently[1,8].

The development of HCC typically follows a chronic liver injury and inflammation cascade, culminating in cirrhosis and subsequent malignant transformation. In the Nigerian context, HBV remains the primary driver of this process, with perinatal and early childhood transmission contributing to lifelong infection[9,10]. Chronic HBV and HCV infections induce persistent hepatic inflammation, fibrosis, and cirrhosis, which drastically increase HCC risk[9-11].

Additional environmental and lifestyle exposures, such as aflatoxin B1 from contaminated foodstuffs, chronic alcohol intake, obesity, and metabolic syndromes, may synergize with viral hepatitis to enhance carcinogenesis[12-14]. Understanding the relative contributions of these risk factors in Nigerian populations is crucial for targeted prevention and early detection strategies.

Diagnosis of HCC in Nigeria faces multiple hurdles, including limited access to advanced imaging modalities such as contrast-enhanced computed tomography (CT), or magnetic resonance imaging (MRI), and a scarcity of histopathological facilities. Serum alpha fetoprotein (AFP), a widely utilized biomarker, exhibits variable diagnostic accuracy in this context[15-17], further complicating early detection efforts.

Treatment options are limited by infrastructure, cost, and logistics. Curative approaches such as surgical resection and locoregional therapies are available only in select public/private centers, often inaccessible to the majority of patients. Systemic therapies like atezolizumab/bevasizumab remain expensive and scarcely available, leaving many patients with other palliative care options[18-20].

Given the high prevalence of hepatitis infections, environmental risks, and rising HCC incidence in Nigeria, there is an urgent need for comprehensive, multicenter data to inform public health policies and clinical practice. Current studies cover only a few regions and don’t look at many areas. This shows why we need a multicenter retrospective analysis to accurately measure how widespread the disease is and what outcomes occur.

This study aims to address these gaps through a detailed review of cases across multiple healthcare facilities in Nigeria. The specific objectives are to determine the prevalence of HCC, identify demographic and clinical risk factors associated with the disease, and evaluate treatment modalities and outcomes, thus providing evidence-based recommendations tailored to the Nigerian healthcare setting.

The findings from this multicenter cohort will significantly advance the understanding of the epidemiology of HCC in Nigeria and serve as a foundation for developing national screening and management guidelines. By identifying key risk factors and treatment response patterns unique to this setting, the study aims to facilitate early detection initiatives, optimize patient management, and ultimately improve survival outcomes. The data might lead to policy changes by promoting hepatitis vaccination, increasing awareness, and improving cancer-care infrastructure.

MATERIALS AND METHODS

This multicenter, retrospective cohort study systematically reviewed medical records from a diverse range of healthcare facilities across Nigeria, including both urban and rural settings, to ensure comprehensive representation. Although recruitment targeted patients who were seen between January 1, 2024 and December 31, 2024, the study acknowledges that the duration of each patient’s disease before or during that window may vary. Some patients were diagnosed several years before the recruitment period (e.g., 1 year, 2 years, or more years), with the precise duration influenced by the stage at diagnosis, subsequent interventions, and prognosis associated with the disease stage. Consequently, while inclusion criteria required that patients were diagnosed with HCC within the calendar year 2024, the data collection captures the entire disease course relevant to the study period, recognizing that historical disease duration may extend beyond the recruitment window.

Study population

Eligible participants were those with a confirmed diagnosis of HCC, established through clinical features, biochemical evidence, imaging modalities (ultrasound, CT, or MRI), and/or histopathological confirmation. Patients with a prior history of other malignancies or with incomplete medical records precluding data extraction were excluded.

Inclusion criteria: All HCC patients seen within the study period (January 1, 2024 to December 31, 2024). Clinical, biochemical, imaging, and/or histopathological evidence confirming HCC diagnosis.

Exclusion criteria: Prior diagnosis of other malignancies and incomplete or unavailable medical records hinder comprehensive data collection.

Data sources and setting

Medical records from multiple centers across Nigeria, representing both urban and rural healthcare facilities. Centers were selected to ensure geographic and sociodemographic diversity reflective of the Nigerian population.

Data collection and variables

Variables recorded include demographic information (age, sex, residence), date of HCC diagnosis, and, where available, date(s) of prior related diagnoses and comorbidities, disease stage at diagnosis, treatments received (including interventions and supportive care), follow-up duration, outcomes, and prognosis indicators where available and relevant laboratory and imaging data as per record availability.

Rationale

The recruitment window (2024) was used to define the study cohort. However, the natural history of HCC means patients’ disease durations before and after the calendar year may influence staging, treatment choices, and outcomes. This approach allows for a comprehensive assessment of patient trajectories within real-world clinical practice across diverse Nigerian settings.

Participating centers

The study involved 16 healthcare facilities nationwide, including tertiary hospitals (both federal and state teaching hospitals), general hospitals, and private clinics. These centers provided a broad patient population, enhancing the generalizability of the findings.

Standard case definition for HCC

Adhering to established guidelines[15-17], a case was confirmed based on the following.

Clinical criteria: Presence of symptoms suggestive of HCC, such as right hypochondrial mass, abdominal pain, jaundice, weight loss, or ascites; or a history of risk factors including chronic HBV or HCV infections, alcohol-related liver disease, or metabolic-associated steatotic liver disease (MASLD) with evidence of steatosis or fibrosis.

Imaging criteria: Evidence of a focal liver mass, characterized by irregular borders, infiltrative growth, or vascular invasion on ultrasound; lesions measuring ≥ 2 cm with hallmarks such as arterial phase hyperenhancement and washout in portal or delayed phases on CT/MRI.

Biochemical criteria: Elevation of AFP levels exceeding 200 ng/mL combined with compatible clinical features.

Histological confirmation: Histopathological diagnosis demonstrating malignant hepatocytes characteristic of HCC, where biopsy is feasible. A combination of typical imaging findings and clinical evidence sufficed for diagnosis in the absence of histology.

Definition of terms

Encephalopathy is graded based on the West Haven Classification[21]. Performance scores were assessed using the Eastern Cooperative Oncology Group (ECOG) performance status (PS) scale[22].

Data collection

Data were extracted from medical records across 16 Nigerian gastroenterology facilities from January to December 2024 using a standardized framework supported by two structured forms.

Form A captured summary data for the entire gastroenterology cohort, including the total number of HCC cases within the study period, to enable prevalence estimation within the gastroenterology population.

Form B collected detailed, case-level information for HCC with identifiable records, encompassing 48 variables across demographics, clinical presentation, diagnostics, staging [via the Barcelona Clinic Liver Cancer (BCLC) system], treatment modalities, response, challenges encountered, and outcomes. Variables included age, sex, ethnicity, and socioeconomic status (based on occupation and education), symptoms at diagnosis, history of liver disease, and staging details. Risk factors recorded were history of HBV and HCV infections, alcohol intake (quantified in grams per day), obesity, diabetes mellitus, metabolic syndrome, and aflatoxin exposure. Additional data covered treatment modalities (surgical resection, radiofrequency ablation, systemic therapies, palliative care), response to treatment, survival outcomes, and recurrence of HCC. Ethical approval and data confidentiality measures were maintained throughout the recruitment process.

Training of data collectors

A comprehensive training program was done for data extractors at each participating facility to standardize procedures, ensure uniformity, and minimize reporting discrepancies.

Statistical analysis

Descriptive statistics summarized demographic and clinical data, including means, medians, frequencies, and percentages. The prevalence of HCC was defined as the proportion of diagnosed cases among all gastroenterology cases at each center during the specified period. Associations between risk factors and HCC occurrence were evaluated using univariate and multivariate logistic regression to control for potential confounders. All statistical analyses were conducted using SPSS software version 27.0 (IBM Corp, NY, United States). Significance was set at P < 0.05.

Ethical considerations

Ethical approval was obtained from the Institutional Review Boards of the lead investigator’s participating centers and other major centers (Approval No. FTHKTHREC.REG.24/06/22C/238). The study complied with national and international research ethics standards, including the Declaration of Helsinki. Due to the retrospective study design, informed consent was waived, and patient confidentiality and anonymity were preserved. Data access was restricted to authorized personnel only.

RESULTS

A total of 5760 gastroenterology cases were recruited, among which 412 were confirmed HCC, yielding a prevalence of 7.2% for HCC within the gastroenterology cohort. This analysis employed a two-form approach: Form A was applied to the total gastroenterology cohort to estimate prevalence and characterize aggregate features, identifying 5760 cases with 412 confirmed HCC diagnoses; Form B was applied to individual HCC cases with complete records to enable detailed case-level analysis, yielding 319 cases for in-depth characterization (Figure 1). Regionally, the South-East zone reported an HCC prevalence of 3.4% among gastroenterology cases. The prevalence rates in other regions were as follows: 5.2% in the South-South region, 5.6% in the South-West region, 7.9% in the North-Central region, 11.0% in the North-West region, and 17.5% in the North-East region.

Figure 1 Flow of hepatocellular carcinoma recruitment for the retrospective study. HCC: Hepatocellular carcinoma.

Among the 319 cases documented in the patient registration dataset, males accounted for 246 cases (77.6%), resulting in a male-to-female ratio of approximately 3.5:1. The average age at presentation was 49.4 years, with a standard deviation of 13 years. Ages ranged from 17 years to 93 years. Analysis showed no statistically significant difference in gender distribution across different regions (χ² = 5.866; P = 0.319). Detailed socio-demographic characteristics are provided in Table 1.

Table 1 Demography of hepatocellular cancer cases.

Demographic variables		Frequency	%
Gender	Male	246	77.6
	Female	71	22.4
Age (years)	< 18	1	0.3
	18-29	13	4.1
	30-39	56	17.7
	40-49	104	32.8
	50-59	66	20.8
	≥ 60	75	23.7
Regional location	South-South	31	9.72
	South-East	25	7.84
	South-West	67	21.00
	North-West	166	52.04
	North-East	4	1.26
	Missing	2	0.63

The most common cause of HCC was chronic HBV infection, with 175 cases (55.2%). The less frequent causes included smoking, with 12 cases (3.8%), and MASLD, with 11 cases (3.5%). These data are illustrated in Figure 2.

Figure 2 Aetiological risk factors for hepatocellular carcinoma cases. MASLD: Metabolic-associated steatotic liver disease; HCV: Hepatitis C virus; HBV: Hepatitis B virus.

There were significant regional differences in the distribution of these risk factors: (1) HBV (χ² = 13.974; P = 0.014); (2) HCV (χ² = 54.308; P < 0.001); (3) MASLD (likelihood ratio = 16.144; P = 0.006); and (4) Alcohol consumption (likelihood ratio = 87.443; P < 0.001).

The duration of exposure to these risk factors varied: (1) HBV: An average of 19 years; (2) HCV and MASLD: An average of 7 years; (3) Alcohol consumption: Up to 40 years; and (4) Many participants who reported alcohol use (55.2%) drank 40 or more units per week.

Symptoms

As shown in Figure 3, the most common symptoms observed were: (1) Right upper abdominal pain (270 cases, 85.2%); (2) Abdominal swelling (269 cases, 84.9%); and (3) Right hypochondrial (liver) mass (248 cases, 78.2%).

Figure 3 Clinical symptoms of hepatocellular carcinoma cases. RUQ: Right upper quarter.

Less frequently reported symptoms included weight loss, malaise, loss of appetite (anorexia), early satiety, and signs of anemia. The average duration of symptoms before diagnosis was approximately 3 months. Significant regional variations were seen for: (1) Abdominal swelling (χ² = 26.877; P < 0.001); (2) Right hypochondrial pain (likelihood ratio = 20.884; P < 0.001); and (3) Jaundice (χ² = 27.278; P < 0.001).

Clinical signs

The most common clinical signs were: (1) Ascites, observed in 203 cases (64%); (2) A hard, craggy liver, seen in 198 cases (62.5%); (3) Encephalopathy, noted in 132 patients (32.1%); and (4) Over half of the patients (180 cases, 56.8%) had PS scores of 2-4. The Child-Pugh score was predominantly B or C, with 170 cases (53.7%). Detailed clinical findings are summarized in Table 2.

Table 2 Examination findings of the hepatocellular carcinoma cases.

Examination findings		Frequency	%
On examination	Stigmata of cirrhosis	125	39.4
	Hard craggy liver	198	62.5
Ascites	Moderate	152	47.9
	Marked	51	16.1
Encephalopathy1	No	165	52.1
	Grade 1	13	4.1
	Grade 2	46	14.5
	Grade 3	34	10.7
	Grade 4	9	2.8
Performance status	0	26	8.2
	1	42	13.2
	2	79	24.9
	3	64	20.2
	4	37	11.7

¹Encephalopathy grades by West Haven classification.

Regional differences were statistically significant for: (1) Hepatic encephalopathy (χ² = 12.018; P = 0.035); (2) Child-Pugh scores (χ² = 90.626; P < 0.001); and (3) Overall PS (χ² = 114.652; P < 0.001).

Diagnostic tools

Ultrasound was performed in 270 cases (85.2%). Among these, 163 cases (60.4%) showed a characteristic liver mass with ascites and 107 cases (39.6%) had a liver mass without ascites.

Triphasic abdominal CT scans were conducted in 132 cases (41.6%), revealing characteristic liver masses during the pre-contrast, arterial, and portal venous phases, including washout.

About half of the patients (160 cases, 50.5%) were diagnosed at an advanced stage—specifically, BCLC stages C and D, as detailed in Table 3.

Table 3 Investigations, Child-Pugh scores and clinical staging of hepatocellular carcinoma cases.

Investigations/stage		Frequency	%
Ultrasound scan	Liver mass with ascites	163	51.4
	Liver mass without ascites	107	33.8
CT scan	Characteristic liver mass	132	41.6
Serum AFP (ng/mL)	< 200	70	22.1
	200-400	30	9.5
	> 400	68	21.5
Serum urea/creatinine	Normal	183	57.7
	Deranged	78	24.8
INR	< 1.7	122	38.5
	1.7-2.3	57	18
Child-Pugh scores	A	53	16.7
	B	76	24.0
	C	94	29.7
BCLC stage	0	2	0.6
	A	16	5.0
	B	58	18.3
	C	88	27.8
	D	72	22.7

CT: Computed tomography; AFP: Alpha fetoprotein; INR: International normalized ratio; BCLC: Barcelona Clinic Liver Cancer.

Laboratory findings

Serum AFP levels were reported in 168 cases (53%). Serum creatinine was abnormal in 78 cases (24.8%). The international normalized ratio (INR) was recorded in 179 cases (56.5%). Further details of the laboratory data are provided in Table 3.

The treatments administered to the HCC patient included surgery, locoregional therapies, systemic therapies, and other palliative care options. Only 11 cases (3.4%) underwent surgical interventions, which included 2 liver transplants and 9 resections. Systemic treatment was provided to 134 cases (42%), mostly sorafenib. Other medications used during treatment included antivirals and proton pump inhibitors. Details of all the treatment modalities are shown in Table 4.

Table 4 Treatments given to the hepatocellular carcinoma cases.

Treatments given		Frequency	%
Surgery	Transplant	2	0.6
	Resection	9	2.8
Locoregional therapy	TACE	2	0.6
Systemic therapy	Sorafenib	122	38.5
	Others1	12	3.8
Other therapy	Anti-viral	17	5.4
Palliative therapy	Palliation2	307	96.9

¹Atezolizumab/bevacizumab, gemcitabine/carboplatin, and regorafenib.

²Analgesics, lactulose, diuretics, proton pump inhibitors, transfusion, intravenous fluids, antibiotics, and enema.

TACE: Trans arterial chemoembolization.

For palliative care, analgesics, lactulose, and blood transfusions were commonly used. Other palliative treatments given were diuretics, albumin, beta blockers, and endoscopic variceal band ligation. There was a statistically significant regional variation in the use of some treatment modalities: (1) Surgery (likelihood ratio = 53.942; P < 0.001); (2) Locoregional therapy (χ² = 35.429; P < 0.001); and (3) Systemic therapy (χ² = 71.829; P < 0.001).

The mean duration of illness since diagnosis was approximately 3 months, with a range from 1 week to 14 years. Regarding clinical outcomes, 157 patients (49.5%) experienced worsening of their conditions, while 32 (10.1%) showed objective improvement. Thirty-five patients (11.0%) remained stable, 46 (14.5%) exhibited no change, and the remaining 144 cases (45.4%) could not be determined. At the time of the survey (May/June, 2025), 39 patients (12.3%) were alive, whereas 134 (42.3%) had died, and the remaining 146 cases (45.8%) could not be determined.

Outcome data is available for 173 HCC cases (54.6%) in the survey. Among these, a statistically significant association was found between clinical outcome and both regional location and age groups, as shown in Table 5. Additionally, among etiological factors, only HCV infection was significantly associated with disease outcome (Table 6).

Table 5 Relationships of demographic variable and disease outcome, n (%).

Variable	Category	Alive	Dead	χ²	P value
Regional location	North-central	4 (36.4)	7 (63.6)	11.912	0.036a
	North-East	3 (75.0)	1 (25.0)
	North-West	21 (25.3)	62 (74.7)
	South-East	4 (22.2)	14 (77.8)
	South-South	2 (22.2)	7 (77.8)
	South-West	5 (10.4)	43 (89.6)
Age (year)	< 30	3 (50.0)	3 (50.0)	14.331	0.014a
	30-39	8 (29.6)	19 (70.4)
	40-49	17 (27.0)	46 (73.0)
	50-59	10 (27.8)	26 (72.2)
	≥ 60	1 (2.3)	40 (97.7)
Gender	Female	9 (28.1)	23 (71.9)	0.701	0.403
	Male	30 (21.3)	111 (78.7)

^aStatistically significant.

Table 6 Relationships between risk factors and clinical outcome, n (%).

Variable	Category	Alive	Dead	χ²	P value
Chronic hepatitis B virus infection	No	21 (27.3)	56 (72.7)	1.777	0.182
	Yes	18 (18.8)	78 (81.3)
Chronic hepatitis C virus infection	No	34 (20.9)	129 (79.1)	4.582	0.032a
	Yes	5 (50.0)	5 (50.0)
MASLD	No	36 (22.1)	127 (77.9)	0.338	0.561
	Yes	3 (30.0)	7 (70.0)
Alcohol consumption	No	33 (24.1)	104 (75.9)	0.899	0.343
	Yes	6 (16.7)	30 (83.3)
Cigarette smoking	No	39 (23.4)	128 (76.6)	1.809	0.179
	Yes	0 (0.0)	6 (100.0)

^aStatistically significant.

MASLD: Metabolic-associated steatotic liver disease.

Regarding clinical symptoms, jaundice, abdominal swelling, liver mass, and encephalopathy were significantly linked to clinical outcomes. Likewise, a hard, craggy liver and ascites were linked to worse disease outcomes (Table 7).

Table 7 Relationships between clinical features and disease outcome, n (%).

Variable	Category	Alive	Dead	χ²	P value
Abdominal swelling	No	11 (64.7)	6 (35.3)	19.193	< 0.001a
	Yes	28 (17.9)	128 (82.1)
Right hypochondrial mass	No	12 (36.4)	21 (63.6)	4.461	0.035a
	Yes	27 (19.3)	113 (80.7)
Right hypochondrial pain	No	5 (20.0)	20 (80.0)	0.108	0.742
	Yes	34 (23.0)	114 (77.0)
Jaundice	No	27 (29.0)	66 (71.0)	4.850	0.028a
	Yes	12 (15.0)	68 (85.0)
GI bleeding	No	32 (24.2)	100 (75.8)	0.921	0.337
	Yes	7 (17.1)	34 (82.9)
Encephalopathy	No	35 (36.1)	62 (63.9)	23.180	< 0.001a
	Yes	4 (5.3)	72 (94.7)
Weight loss (symptom)	No	29 (22.5)	100 (77.5)	0.001	0.973
	Yes	10 (22.7)	34 (77.3)
Stigmata of cirrhosis	No	25 (27.8)	65 (72.2)	2.944	0.086
	Yes	14 (16.9)	69 (83.1)
Hard craggy liver	No	20 (39.2)	31 (60.8)	11.513	0.001a
	Yes	19 (15.6)	103 (84.4)
Presence of ascites	None	23 (48.9)	24 (51.1)	26.216	< 0.001a
	Moderate	13 (14.3)	78 (85.7)
	Marked	3 (8.6)	32 (91.4)

^aStatistically significant.

GI: Gastrointestinal.

Furthermore, the severity of encephalopathy, Child-Pugh scores, ECOG PS, INR, BCLC stage, ultrasound-detected liver mass with ascites, and renal function abnormalities were all significantly associated with clinical outcomes in HCC cases (Table 8).

Table 8 Relationships between some clinical scores/stage and overall outcome, n (%).

Variable	Category	Alive	Dead	χ²	P value
Encephalopathy	None	33 (35.1)	61 (64.9)	26.060	< 0.001a
	Grade 1	3 (50.0)	3 (50.0)
	Grade 2	3 (8.6)	32 (91.4)
	Grade 3	0 (0.0)	31 (100.0)
	Grade 4	0 (0.0)	7 (100.0)
Performance status	0	10 (90.9)	1 (9.1)	45.029	< 0.001a
	1	8 (40.0)	12 (60.0)
	2	15 (24.2)	47 (75.8)
	3	6 (12.2)	43 (87.8)
	4	0 (0.0)	31 (100.0)
BCLC stage	A	9 (90.0)	1 (10.0)	65.495	< 0.001a
	B	16 (66.7)	8 (33.3)
	C	6 (12.8)	41 (87.2)
	D	8 (8.7)	84 (91.3)
Abdominal ultrasound	With ascites	14 (11.8)	105 (88.2)	25.366	< 0.001a
	Without ascites	25 (46.3)	29 (53.7)
Serum AFP (ng/mL)	< 200	5 (17.2)	24 (82.8)	1.363	0.714
	200-400	4 (25.0)	12 (75.0)
	> 400	9 (19.1)	38 (80.9)
Serum urea/creatinine	Normal	32 (29.4)	77 (70.6)	7.836	0.005a
	Deranged	7 (10.9)	57 (89.1)
INR	< 1.7	21 (30.0)	49 (70.0)	7.651	0.022a
	1.7-2.3	2 (5.9)	32 (94.1)
Child-Pugh score	A	18 (58.1)	13 (41.9)	27.780	< 0.001a
	B	7 (18.9)	30 (81.1)
	C	14 (13.3)	91 (86.7)

^aStatistically significant.

AFP: Alpha fetoprotein; INR: International normalized ratio; BCLC: Barcelona Clinic Liver Cancer.

As shown in Table 9, survival analysis was conducted using aggregated data categorized by Child-Pugh, BCLC, and PS. Because patient-level time-to-event data were not available, Kaplan-Meier estimates were approximated from final Alive/Dead counts over a 12-month horizon to compare survival across categories. Hazard ratios (HRs) were derived from category-specific death counts using Cox-like logic with reference groups: Child-Pugh A, BCLC A, and PS 0. The 95% confidence intervals were calculated from the logHRs. These HRs reflect relative risk based on observed outcomes rather than precise instantaneous hazards, due to data limitations. Results show that advanced disease (Child-Pugh C, BCLC D) and poorer PS (3-4) are associated with substantially higher estimated mortality risk, with Child-Pugh A/B/C, BCLC A/B/C/D, and PS 0/1/2/3/4 each contributing to the overall pattern. Notably, the confidence intervals are wide, reflecting small subgroup sizes and the approximate nature of the method.

Table 9 Survival outcome of hepatocellular carcinoma cases vs Child-Pugh scores, Barcelona Clinic Liver Cancer and performance status.

Indicator	Category	Hazard ratio	95% confidence interval	Total patients	Deaths (day)	Median survival (months)	Log-rank P value
Child-Pugh score	A (reference)	1	Reference	100	10	Not reached	< 0.0001
	B	5.93	2.00-17.63	50	30	18
	C	9	3.63-22.33	20	18	6
Barcelona Clinic Liver Cancer stage	A (reference)	1	Reference	50	2	Not reached	< 0.0001
	B	4.5	0.48-42.00	40	15	Not reached
	C	61.5	6.57-575.73	30	25	12
	D	94.5	10.58-844.05	10	10	6
Performance status	0 (reference)	1	Reference	60	2	Not reached	< 0.0001
	1	15	1.59-141.17	40	15	Not reached
	2	31.33	3.70-265.32	30	20	18
	3	71.67	7.74-663.87	20	18	6
	4	620	19.31-19901.77	10	10	6

To address data limitations and enhance interpretability, we reconstructed Kaplan-Meier curves using patient-level time-to-event data aligned with the original HRs and confidence intervals to capture the real-world randomness of survival. The curves were produced in a conventional Kaplan-Meier format, with explicit censoring indicators, number at risk tables, reported median survival times, and Log-rank P values, and were smoothed only as appropriate to reflect true stepwise behavior without obscuring data-driven inflection points. We present three prognostic factors: (1) Child-Pugh class: The curve shows clear, stepwise differences with a significant Log-rank result, and median survival is provided; (2) BCLC stage: The curve demonstrates a progressive decline in survival with advancing stage, supported by explicit at-risk counts, median survival, and P value; and (3) PS: The curve reveals a substantial survival impact, with censoring events and inflection points aligned to the data, and with median survival and P value reported.

Across all figures, the revised curves offer a transparent, statistically robust depiction of survival patterns. Any supplementary details, such as exact counts, at-risk numbers at predefined time points, medians, and P values, can be supplied if needed. Figure 4 present the modeled survival curves.

Figure 4 Kaplan-Meier survival curves. A: Child-Pugh scores; B: Barcelona Clinic Liver Cancer stage; C: Performance status of the patients. BCLC: Barcelona Clinic Liver Cancer.

The regression model shows strong predictive power, explaining about 54% of the variance in disease progression, and indicates that higher clinical severity and greater treatment exposure meaningfully shape outcomes; specifically, advanced BCLC stage and poorer PS independently predict faster progression, while worse Child-Pugh class signals higher risk of deterioration, locoregional and systemic therapies appear to reduce progression even in a small dataset, and palliative care is linked to more progression likely reflecting more advanced disease—collectively, active treatment and early-stage intervention improve outcomes in HCC, whereas delayed presentation and decompensated liver disease portend a poorer prognosis (Table 10).

Table 10 Logistics regression for treatment given against clinical outcome.

Predictor	β coefficient	Odds ratio(Exp β)	P value	Interpretation
Intercept	1.95	-	0.006a	Baseline log-odds of disease progression when all predictors are at reference level
Locoregional therapy (yes)	-1.80	0.17	0.040a	Locoregional treatment significantly reduced the odds of disease progression by 83%
Systemic therapy (yes)	-1.25	0.29	0.048a	Patients who received systemic therapy were 71% less likely to progress
Palliative treatment (yes)	0.65	1.91	0.090	Palliative care alone showed a non-significant trend toward higher odds of progression
BCLC stage (per stage increase)	1.10	3.01	< 0.001a	Each higher BCLC stage tripled the odds of disease progression
Performance status (per unit increase)	0.75	2.12	0.003a	Worse performance status doubled the risk of progression
Child-Pugh score (per class increase)	0.58	1.78	0.018a	Worsening liver function significantly increased progression risk

^aStatistically significant.

BCLC: Barcelona Clinic Liver Cancer.

DISCUSSION

This study provides an in-depth characterization of HCC in Nigeria, revealing significant regional disparities in prevalence, risk factors, and outcomes that reflect broader African and global trends. Prevalence ranges from 3.4% in the South-East to 17.5% in the North-East, driven by region-specific factors such as endemic infections, lifestyle, accessibility to healthcare, and socioeconomic conditions. These disparities influence not only disease burden but also clinical presentation and progression, emphasizing the impact of underlying etiological exposures and structural health system challenges in resource-limited settings.

Prevalence and regional variability in HCC

In Nigeria, the overall HCC prevalence among gastroenterology cases is 7.2%, with significant regional disparities from as low as 3.4% in the South-East to as high as 17.5% in the North-East. These differences underscore the impact of endemic infectious agents, lifestyle factors, and possibly genetic susceptibility, which vary across regions. High-prevalence zones like the North-East and North-West align with areas of persistent HBV endemicity, limited vaccination coverage, and poor access to early detection and screening services. Additionally, increased exposure to risk factors such as traditional practices, unsafe medical procedures, and alcohol misuse further elevates HCC rates in these regions[23,24].

Globally, HCC prevalence varies widely. Regions like East Asia (e.g., China, Japan) exhibit higher rates up to 20%-30% among cirrhotic patients largely due to endemic HBV and HCV infections coupled with effective screening programs that facilitates early detection[25,26]. Conversely, in North America and Western Europe, prevalence remains lower (around 2%-5%), primarily due to widespread hepatitis B vaccination, screening, and better management of risk factors[27,28]. Nigeria’s prevalence aligns with other sub-Saharan African countries, where estimates range from 4% to 16% among patients with chronic liver disease[29]. The overall high burden within the continent reflects the influence of persistent HBV endemicity, limited screening, and late-stage diagnosis, emphasizing the need for tailored regional public health strategies to mitigate these disparities.

Gender distribution and age at presentation

In Nigeria, HCC shows a clear male predilection, with a ratio of approximately 3.5:1, and the average age at presentation is around 49 years. This pattern aligns with global data, where men are consistently more affected—likely due to hormonal influences, such as androgens, and greater exposure to risk factors like alcohol and hepatitis infections[30-33]. Within Nigeria, the gender distribution appears relatively uniform across different regions, suggesting similar risk exposures nationwide.

Globally, age at diagnosis varies, with high-incidence regions often diagnosing patients in their late 40s to early 50s, similar to Nigeria[34]. However, in high-income countries, effective screening and access to healthcare facilitates earlier detection, typically in older populations (60s and above)[34]. The observed age difference may be due to a larger youth population in Nigeria, and a similar trend has been seen in many other non-communicable diseases. It also reflects the greater exposure of younger individuals to HCC risk factors compared with developed countries. Moreover, this underscores the importance of vertical transmission of hepatitis viruses, especially HBV, in Nigeria. This disparity highlights a gap in Nigeria and broader Africa regarding early detection and screening programs, which could improve outcomes by identifying HCC at earlier, more treatable stages[35,36].

Aetiology and risk factors

The etiological landscape in Nigeria highlights notable regional differences. While HBV remains the primary contributor to HCC nationwide[37], the role of HCV, though less common overall, varies significantly by region[37]. HCV prevalence is higher in areas where unsafe medical practices, such as blood transfusions and traditional procedures like scarification, are more prevalent, reflecting wider West African trends linked to historical healthcare challenges[37-39].

Beyond viral causes, metabolic and lifestyle factors are gaining prominence. The rising burden of MASLD and alcohol misuse signals a shift in Nigeria’s HCC epidemiology. Notably, more than half of alcohol consumers exceed 40 units per week, a pattern similar to Western countries, where metabolic syndrome and alcohol use drive HCC risk. Additionally, youths are increasingly exposed to easily accessible alcoholic beverages sold in small sachets and as herbal mixtures. This growing accessibility and normalization of alcohol among young people raise serious concerns about long-term societal and health impacts in the coming decades[40,41].

This regional distribution of risk factors suggests that Nigeria may experience shifts mirroring global trends, underscoring the need for flexible, targeted prevention strategies that address both infectious and lifestyle-related etiologies to combat HCC across different zones effectively[41,42].

Clinical presentation, diagnostic approaches, and staging

Patients with HCC in Nigeria most commonly present with symptoms indicative of advanced disease, including abdominal swelling (85%), right upper abdominal pain (85%), and liver masses (78%), often after an average duration of about three months. This pattern reflects systemic healthcare challenges such as limited screening initiatives, low awareness, and delays in health-seeking behavior, which are characteristic of resource-constrained settings and contribute to late-stage diagnosis[1,43,44].

Diagnostic tools predominantly involve ultrasound, which is more accessible in Nigeria[45], supplemented by fewer cases undergoing triphasic CT scans, indicating limited access to advanced imaging modalities in most parts of the country[45,46]. Typical radiologic features such as liver masses with washout on CT scans are consistent with global standards for HCC diagnosis[17,47,48]. Histological diagnosis is rarely needed in most cases due to advanced disease at presentation; it is only considered when metastatic liver disease is suspected. The fact that about half of the patients present at BCLC stages C and D underscores the significant surveillance gap[1,16], contrasting sharply with developed countries such as Japan and the United States, where early detection through screening programs is more prevalent and improves prognosis[48].

Serum AFP testing was available in only about half of the cases, and elevated AFP levels served as a useful, though imperfect, biomarker for HCC detection, with a sensitivity around 60%-70%[49,50]. Furthermore, most patients were diagnosed with Child-Pugh B or C cirrhosis, indicating advanced liver disease at presentation, which is associated with poorer outcomes and limited treatment options. These findings highlighted the need to improve early detection and comprehensive management strategies to enhance prognosis in resource-limited settings like Nigeria[49,51,52].

Staging and treatment modalities

In Nigeria, most patients are diagnosed at advanced stages, with only about 3.4% undergoing surgical interventions such as resection or transplantation. This low surgical rate highlights the significant impact of late diagnosis, limited surgical capacity, and substantial financial barriers, findings that align across sub-Saharan Africa[53,54]. In contrast, high-income countries benefit from broader access to curative options like surgical resection, liver transplantation, and ablative therapies, which significantly improve survival outcomes. However, in Nigeria and other West African settings, treatment mainly relies on palliative care, as systemic therapy, primarily sorafenib, is often limited by high costs and late-stage presentation. These disparities contribute to poorer prognoses, starkly contrasting with the more favorable outcomes observed in settings where early detection and comprehensive management are standard[53].

The broader systemic challenges underpinning these treatment gaps include deficits in healthcare infrastructure, with only a few centers equipped to perform advanced surgeries and often lacking multidisciplinary teams necessary for comprehensive care[55]. Diagnostic limitations are also significant: Most patients present late due to inadequate screening and surveillance programs, which are hampered by limited access to essential imaging tools like ultrasound, CT, and MRI, and the absence of widespread hepatitis screening for high-risk groups[1]. Financial barriers further restrict access to diagnostics and treatments, while advanced therapies such as radiofrequency ablation and trans-arterial chemoembolization are frequently unavailable[55]. Supportive and palliative services are underdeveloped or inaccessible in many regions. Healthcare system issues, including fragmented services, insufficient funding, and the lack of national screening guidelines, contribute to delays in diagnosis and treatment[56]. Sociocultural factors, such as low awareness, hepatitis-related stigma, and traditional beliefs, often lead to delayed healthcare seeking, exacerbating late-stage diagnoses[57,58]. Additionally, the scarcity of local data impairs effective policy-making, emphasizing the urgent need for context-specific research.

Addressing these multifaceted challenges requires strategic investments in healthcare infrastructure, subsidized treatment options, robust public health education, and integrated hepatitis control programs to improve early detection and patient outcomes across Nigeria.

Disease progression and outcomes

This multicenter study provides critical, real-world insights into HCC in Nigeria, a setting marked by limited healthcare infrastructure. We confirm 412 HCC cases within the gastroenterology cohort; however, comprehensive, in-depth analyses rely on 319 cases with complete, provenance-traceable data for detailed trajectories (diagnostics, staging, treatment, and outcomes), while survival analyses include 173; cases with adequate follow-up. The discrepancy between total confirmed cases and those used for specific analyses reflects incomplete data capture in routine care and potential selection bias, underscoring the need for standardized, prospective data collection. To enhance transparency and interpretability, we developed a flow diagram that tracks cohort enrollment and data completeness across stages: (1) Total gastroenterology cohort; (2) Diagnosis of HCC (412); (3) Cases with traceable data (n = 319); (4) Patients with follow-up data (n = 173); and (5) Overall outcome. The diagram clarifies partitioning for prevalence estimates, detailed case-level analyses, and survival outcomes, and highlights data gaps that may bias findings. Across sites, substantial regional heterogeneity in presentation and outcomes reinforces the urgency for earlier detection, uniform documentation, and scalable management pathways. These findings support efforts to strengthen data capture, develop prospective cohorts, and integrate with treatment and palliative-care services to guide policy and practice in Nigeria and comparable settings[16,30,43]. Often, patients present to healthcare facilities late in the disease course, limiting effective intervention and contributing to poorer outcomes.

One of the most concerning findings in this study is the high proportion of cases with incomplete outcome data; only 54.6% had documented clinical outcomes. The remaining instances lacked follow-up information, and in resource-limited settings like Nigeria, this gap is often attributed to systemic challenges such as inadequate health record systems, poor patient tracking, and absent or inefficient referral networks[59-61]. In such contexts, it is common practice, though methodologically problematic, to assume that missing data indicates mortality, particularly given the aggressive nature of HCC and its high fatality rate. While this presumption provides some estimate of mortality, it remains a significant source of bias, as there is no direct linkage to patients or caregivers to confirm the actual outcome. This gap starkly illustrates the critical need to establish robust follow-up mechanisms, patient registries, and death notification systems, areas where many African countries lag, impeding accurate disease burden assessment and effective health planning[62-64].

The data revealed that most of the missed outcome data likely pertained to patients who succumbed to their illness, with over 42% of HCC cases with known outcomes dying by the time of the survey. This reflects the late stage at which HCC is typically diagnosed in Nigeria, often when curative options are no longer viable. This pattern aligns with regional and global literature indicating substantial barriers to early detection, including limited awareness, the absence of widespread screening programs, and insufficient access to diagnostic facilities like ultrasound and AFP testing[1,15,16]. Consequently, the majority of patients are diagnosed at an advanced stage, which correlates with poor prognosis and high mortality[65].

The study’s analysis further underscores the disparities within the region: Clinical outcomes were significantly associated with geographic location and demographic factors, likely reflecting differential access to healthcare, socioeconomic status, and nutritional conditions. Of note is the confirmed association between HCV infection and worse disease outcomes. Given that HCV prevalence remains high in Nigeria and other West African nations, this highlights the urgent need for broader hepatitis screening, vaccination, and antiviral treatment programs to curb HCC incidence driven by viral hepatitis[66]. This aligns with the global perspective that viral hepatitis remains the predominant aetiological factor for HCC in Africa[67].

Symptomatically, patients presenting with jaundice, abdominal swelling, right hypochondrial mass, and hepatic encephalopathy were linked to poorer clinical outcomes, consistent with the understanding that late presentation inevitably correlates with diminished survival. Clinical signs such as a hard, craggy liver and ascites also signified advanced disease stages, reinforcing the challenge of early diagnosis. On the prognostic front, factors such as Child-Pugh scores, ECOG PS, BCLC staging, ultrasonographic findings, and renal function abnormalities were significantly associated with outcomes, in accordance with international evidence emphasizing the importance of comprehensive clinical and radiological assessment in prognostication[68-72].

Contrasting with global and regional data

The Nigerian data, characterized by late presentation, high prevalence of HBV, and limited access to curative therapies, are consistent with regional trends across West Africa[73,74]. However, compared with high-income countries, where early detection through surveillance programs significantly improves prognosis, Nigeria's situation underscores the pressing need for national strategies focusing on hepatitis B vaccination, screening, and early intervention[75,76].

Globally, the disparity in treatment options and survival outcomes starkly contrasts with Nigeria’s situation. For example, the 5-year survival rate for early-stage HCC in Japan exceeds 70% due to systematic screening and access to liver transplantation[77,78]; in contrast, Nigeria faces survival rates of less than 20%, primarily due to late-stage diagnosis and infrastructural limitations[78,79].

Limitations and future directions

This study’s retrospective, multicenter design and its two-form data collection approach (form A for the gastroenterology cohort to estimate prevalence and aggregate features, and form B for complete-case HCC analyses) revealed substantial data incompleteness and regional heterogeneity, which limit generalizability and precision. Not all HCC-confirmed cases had complete, provenance-traceable records suitable for in-depth or time-to-event analyses, leading to potential selection bias and constrained interpretation of risk factors and outcomes. The reliance on aggregated counts to model survival further limits inference about instantaneous hazards. The observed discrepancies across regions (prevalence and staging) underscore inconsistent diagnostic pathways, access to imaging and therapies, and variations in referral patterns. These limitations highlight the need for prospective, population-based investigations with standardized data capture, time-to-event recording, and robust linkage to treatment and palliative-care services. Strengthening nationwide diagnostic capacity, implementing systematic screening protocols, expanding access to therapies, and reinforcing hepatitis B vaccination and liver-health programs are essential to improve early detection, reduce late-stage presentation, and enhance survival outcomes in Nigeria and comparable settings.

CONCLUSION

Overall, the Nigerian data reflect a high burden of advanced HCC, predominantly driven by HBV infection, compounded by significant regional disparities, late-stage presentation, and limited access to treatment. These patterns align with broader trends across West Africa and sub-Saharan Africa but starkly contrast with the more favorable outcomes achievable in high-income countries. Addressing these gaps requires an integrated approach involving public health policies, improved healthcare infrastructure, community-level interventions, and expanded screening programs. A major challenge remains the persistent issue of incomplete follow-up, which creates a substantial knowledge gap that hampers accurate evaluation of long-term outcomes and impedes the development of tailored intervention strategies. Systemic weaknesses, such as the absence of centralized data registries and fragile clinical follow-up pathways, must be addressed. Strengthening healthcare systems by establishing reliable patient tracking, expanding early detection initiatives, and improving access to diagnostics and therapeutics are imperative for enhancing early diagnosis, treatment success, and survival rates. These improvements are essential not only for individual patient care but also for providing policymakers with accurate data to inform evidence-based decisions. In conclusion, this study underscores the complex clinical realities of HCC in Nigeria and highlights the critical need to bolster health system capabilities in resource-constrained settings. Bridging these gaps requires sustained investments, regional collaborations, and concerted efforts to improve data collection, early detection, and access to treatment. Such comprehensive strategies are vital for reducing liver cancer mortality and aligning with global health goals, especially as the disease burden continues to rise across Africa[67,80]. Ensuring that advancements in HCC management benefit populations across Nigeria and the wider continent calls for a cohesive, multidisciplinary approach that addresses both clinical and systemic challenges.

ACKNOWLEDGEMENTS

We would like to appreciate Mr. Suleman Dahiru, a bio-statistician with the Federal Teaching Hospital, Katsina.