A 58-year-old man with a 15-year history of hepatitis B infection presents with a solitary liver mass. Imaging and biopsy confirm hepatocellular carcinoma. Which of the following is the most common aetiological factor for HCC in this patient?

Question

Accepted Answer

C. Hepatitis B virus infection. ## Aetiological Factors in HCC

**Key Point:** Hepatitis B virus (HBV) infection is the most common cause of hepatocellular carcinoma globally, accounting for approximately 50–55% of all HCC cases worldwide. In India and Southeast Asia, HBV is the predominant aetiological agent.

### Global Epidemiology of HCC Causes

| Aetiological Factor | Global Prevalence | Mechanism | Geographic Distribution |
| --- | --- | --- | --- |
| **Hepatitis B** | 50–55% | Chronic inflammation, integration of HBV DNA, cirrhosis | Asia, Africa, India |
| Hepatitis C | 20–25% | Chronic inflammation, cirrhosis | Europe, North America, Japan |
| Alcoholic cirrhosis | 10–15% | Oxidative stress, fibrosis, cirrhosis | Western countries |
| NAFLD | 5–10% | Metabolic dysfunction, steatosis, cirrhosis | Developed nations (rising) |
| Other (hemochromatosis, PBC, PSC) | <5% | Specific pathogenic mechanisms | Variable |

**High-Yield:** In the Indian subcontinent and most of Asia, HBV accounts for >60% of HCC cases. HBV can cause HCC even in the absence of cirrhosis (integration of viral DNA into host genome).

**Clinical Pearl:** HBV-related HCC typically develops after 20–30 years of chronic infection. The presence of HBsAg and elevated HBV DNA are strong risk factors. HBV vaccination has significantly reduced HCC incidence in vaccinated cohorts.

### Pathogenic Mechanisms

1. **Chronic inflammation** → hepatocyte necrosis and regeneration → genomic instability
2. **HBV DNA integration** → insertional mutagenesis, disruption of tumour suppressor genes (p53, Rb)
3. **HBx protein** → transactivation of oncogenic pathways, inactivation of p53
4. **Cirrhosis development** → architectural distortion, portal hypertension, increased HCC risk

**Warning:** Do not confuse "most common cause" with "most common in cirrhotic patients." While HBV causes HCC in both cirrhotic and non-cirrhotic livers, HCV-related HCC almost always occurs in the setting of cirrhosis.

Answer

A. Hepatitis C virus infection

Answer

B. Alcoholic cirrhosis

Answer

D. Non-alcoholic fatty liver disease

A 58-year-old man with a 15-year history of hepatitis B infection presents with a solitary liver mass. Imaging and biopsy confirm hepatocellular carcinoma. Which of the following is the most common aetiological factor for HCC in this patient?

Explanation

Aetiological Factors in HCC

Global Epidemiology of HCC Causes

Pathogenic Mechanisms

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Aetiological Factor	Global Prevalence	Mechanism	Geographic Distribution
Hepatitis B	50–55%	Chronic inflammation, integration of HBV DNA, cirrhosis	Asia, Africa, India
Hepatitis C	20–25%	Chronic inflammation, cirrhosis	Europe, North America, Japan
Alcoholic cirrhosis	10–15%	Oxidative stress, fibrosis, cirrhosis	Western countries
NAFLD	5–10%	Metabolic dysfunction, steatosis, cirrhosis	Developed nations (rising)
Other (hemochromatosis, PBC, PSC)	<5%	Specific pathogenic mechanisms	Variable