Viral hepatitis Part 2: from Chronic Hepatitis to Cirrhosis and Liver Cancer 🧬

 While many patients recover completely from an episode of acute hepatitis, certain hepatitis viruses—especially Hepatitis B (HBV) and Hepatitis C (HCV)—fail to be cleared from the body. This persistence triggers a continuous inflammatory cascade in the liver, laying the groundwork for progressive scarring and, eventually, the development of hepatocellular carcinoma (HCC). 

In this post, we will explore:

• What defines chronic hepatitis
• How and why the liver progresses from inflammation to fibrosis, cirrhosis, and cancer
• The clinical features of chronic hepatitis and cirrhosis
• Risk factors, surveillance, and management strategies

🔁 What is Chronic Hepatitis?

Chronic hepatitis is defined as persistent liver inflammation lasting longer than six months. Unlike acute hepatitis—which is usually self-limiting—the immune system’s inability to fully eradicate the virus results in ongoing injury. 

Two viral agents are notorious in this regard:

• Hepatitis B: Approximately 5–10% of adults (and >90% of perinatally infected individuals) fail to clear the virus, resulting in chronic infection.
• Hepatitis C: For untreated acute HCV, up to 75–85% of patients develop chronic infection.

In these persistent infections, the virus is never fully cleared, and the immune system continuously attacks infected hepatocytes, fuelling a cycle of hepatocyte injury, fibrosis and repair that sets the stage for long-term complications.

🧬 Pathophysiology of Progression How and Why Chronic Hepatitis Leads to Liver Damage

The transformation from chronic hepatitis to cirrhosis and liver cancer is a multi-step process involving several key mechanisms:

1. Chronic Inflammation: (Repeated immune-mediated damage to hepatocytes.)

How it Happens:

The ongoing presence of HBV or HCV triggers a sustained immune response. Cytotoxic CD8+ T lymphocytes and inflammatory cytokines (such as tumor necrosis factor-α, interleukins, and interferon-γ) are persistently activated as they attempt to clear infected hepatocytes.

Why it Matters:

Although this immune response is aimed at eradicating the virus, continuous attack results in collateral damage. Every episode of immune-mediated cell destruction leads to the release of inflammatory mediators, which further amplify the injury

2. Fibrosis: (Activation of hepatic stellate cells leads to extracellular matrix deposition and scarring.)

How it Happens:

With repeated cycles of hepatocyte injury and death, the liver’s natural repair mechanisms kick in. Hepatic stellate cells (HSCs)—normally quiescent cells found in the space of Disse—become activated in response to cytokines like transforming growth factor-beta (TGF-β). Once activated, HSCs transform into myofibroblast-like cells that secrete collagen and other extracellular matrix proteins.

Why it Matters:

Initially, fibrosis is a protective, wound-healing response designed to seal off sites of injury. Over time, however, this collagen deposition becomes excessive. The resulting scar tissue disrupts the normal architecture of the liver, impairing blood flow and hepatocyte function.

3. Cirrhosis: (Widespread fibrosis disrupts normal liver architecture and blood flow.)

How it Happens:

When fibrosis becomes widespread, the liver’s normal lobular structure is replaced by regenerative nodules interspersed with fibrous bands. This process is known as cirrhosis.

Why it Matters:

As the architecture is distorted, the liver’s ability to process toxins, produce proteins, and regulate metabolism is compromised. This gives rise to portal hypertension (increased pressure in the portal venous system), which can result in complications such as ascites, varices, and splenomegaly. Importantly, many patients remain asymptomatic during the compensated stage until a decompensation event occurs.

4. Liver Failure and Hepatocellular Carcinoma (HCC): (Loss of function and malignant transformation due to chronic regenerative stress.)

How it Happens:

With cirrhosis, the liver’s functional reserve is critically reduced. Coupled with continual cycles of injury and regeneration, there is an increased likelihood of genetic mutations. In HBV infections, the virus can even integrate its DNA into host cells, directly promoting oncogenesis.

Why it Matters:

The constant regenerative stimuli create a mutagenic environment. Over years or decades, this can lead to the emergence of malignant cells and the development of HCC—a cancer that is challenging to treat and a leading cause of death in patients with chronic liver disease.

Key drivers of progression:

• Viral factors: Viral load, genotype, coinfection (e.g. HBV + HDV)

• Host factors: Immune status, alcohol use, metabolic syndrome

• Time: Fibrosis accumulates slowly over years to decades

Why Do Hepatitis B and C Become Chronic?

Many viruses cause self-limiting infections, where the immune system clears the virus entirely after an acute phase. However, HBV and HCV are unique—they often persist in the body long-term, leading to chronic infection. This happens because these viruses have distinct ways of evading the immune system and preventing full clearance.

🔬 Hepatitis B (HBV): Immune Evasion & Viral Integration

Hepatitis B infects liver cells (hepatocytes) but does not directly kill them. Instead, the immune response plays the main role in liver damage. Here’s how HBV manages to persist:

1. Weak Innate Immune Activation

• Normally, when cells are infected, they release interferons (which help trigger an antiviral response).
• HBV does not strongly stimulate interferon production, meaning the early immune response is delayed or ineffective.

2. Host Immune Dysfunction

• In adults, a strong CD8+ T-cell response helps clear HBV by destroying infected hepatocytes. 
•  If this T-cell response is weak or exhausted, HBV isn’t cleared properly, leading to chronic infection.

3. Perinatal Infection Leads to Immune Tolerance

• When HBV is transmitted at birth, the baby’s immune system fails to recognize HBV as foreign.
• This leads to immune tolerance, where HBV replicates freely without strong immune clearance.
• That’s why >90% of perinatally infected infants develop chronic HBV, compared to only 5–10% of adults.

4. HBV DNA Integration into Host Genome

• HBV is a DNA virus, which means it can integrate parts of its genetic material into human DNA.
• Even if a patient’s immune response suppresses HBV replication, some viral DNA remains in liver cells.
• This allows persistent low-level infection, increasing the risk of cirrhosis and hepatocellular carcinoma (HCC).

🧬 Hepatitis C (HCV): Mutation & Immune Exhaustion

HCV is an RNA virus, and unlike HBV, it does not integrate into human DNA. However, HCV is highly mutagenic, allowing it to escape immune clearance. Here’s how:

1. No Effective Neutralizing Antibody Response

• Normally, the immune system produces antibodies that recognize viruses and help destroy them.
• HCV has a high genetic diversity, so it constantly changes its surface proteins.
• This makes it difficult for the immune system to generate lasting antibodies, allowing HCV to persist.

2. Rapid Mutation & Quasi-Species Formation

• HCV mutates at an extremely high rate, creating quasi-species—slightly different versions of itself.
• Each time the immune system targets one strain, new mutated variants appear, making clearance almost impossible.

3. Dysfunctional CD8+ T-Cell Response

• A strong CD8+ T-cell attack is needed to clear viruses from infected cells.
• In chronic HCV infection, these T-cells become exhausted, losing their ability to function.
• This allows persistent infection, leading to chronic hepatitis, fibrosis, and cirrhosis.

4. Continuous Replication Without Latency

• Unlike HBV, HCV does not have a latent phase (it doesn’t hide in host DNA).
• Instead, it maintains chronic replication, continuously damaging liver cells.
• This slow, ongoing inflammatory response leads to fibrosis and cirrhosis over years.

🔎 Key Differences in Chronicity Between HBV & HCV

Virus	Mechanism Driving Chronic Infection	Risk of Chronicity
HBV	Immune evasion, perinatal immune tolerance, DNA integration	90% perinatal, 5–10% adults
HCV	Rapid mutation, immune exhaustion, ongoing replication	75–85% become chronic

💊 Why Does This Matter Clinically?

• Chronic HBV patients need lifelong monitoring because the virus remains latent and carries a high risk of HCC.
• Chronic HCV can now be cured with direct-acting antivirals (DAAs), but detection is key because it progresses silently.

(a) Most chronic HBV infections result from vertical transmission from infected mother to neonate or young infant. Anti-HBc, antibodies against HBV core antigen; anti-HBe, antibodies against the extracellular form of HBc. (b) Most chronic HCV infections result from horizontal transmission during adulthood. Whereas patients with chronic HBV infection experience multiple phases with distinct viremia and pathology patterns, these parameters tend to be less pronounced and more stable in chronic HCV infection.

🧠 Key Takeaway

Hepatitis B and C both evade the immune system, but in different ways. HBV suppresses immune activation and integrates into human DNA, while HCV constantly mutates to avoid recognition. Understanding these mechanisms helps clinicians predict chronicity, tailor screening protocols, and select the right treatment strategies.

🩺 Clinical Features and Investigations in Chronic Hepatitis

Clinical Features

Chronic hepatitis is often asymptomatic for years. Subtle signs include:

General Symptoms:

Fatigue, malaise, and vague right upper quadrant (RUQ) discomfort.

Physical Findings:

Mild hepatomegaly or a firm liver detected on examination. In advanced cases, signs of cirrhosis—such as jaundice, ascites, and spider angiomas—may be present.

Laboratory Findings:

• Liver Function Tests (LFTs): Mild elevations in ALT and GGT, with ALT often remaining higher than AST in earlier stages.
• Synthetic Function: In later disease, markers of synthetic liver function (albumin, coagulation parameters) may become abnormal.

Diagnosis is often made incidentally, e.g. during screening, antenatal testing, or abnormal bloods.

🧪 Investigation and Monitoring

A structured evaluation is vital for chronic hepatitis:

Test	Purpose
LFTs	Monitor ongoing inflammation and liver function (ALT, AST, bilirubin, albumin)
HBV Serology / HCV RNA	Confirm chronic infection and assess infectiousness
Fibroscan/Biopsy	Evaluate the degree of fibrosis and staging of cirrhotic progression
Alpha-Fetoprotein (AFP)	Tumour surveillance marker used in the monitoring of hepatocellular carcinoma (HCC)
Liver Ultrasound	Non-invasive imaging to screen for cirrhosis-related complications and HCC

🏥 Cirrhosis: The scarring endgame

Cirrhosis represents the culmination of prolonged fibrosis and it is associated with significant clinical consequences:

Portal Hypertension:

The fibrotic liver impedes blood flow, leading to increased pressure in the portal venous system. This results in the formation of varices (which risk life-threatening bleeding), ascites (fluid accumulation in the abdomen), and splenomegaly (enlarged spleen).

Hepatic Synthetic Failure:

As liver tissue is replaced by scar, the liver’s capacity to synthesize proteins (like albumin, clotting factors, etc.) diminishes, predisposing to coagulopathy and oedema.

Hepatic Encephalopathy:

Toxic substances (such as ammonia) accumulate as the liver loses its detoxification capacity, leading to neuropsychiatric disturbances.

Silent Progression & Decompensation:

A key point for clinicians is that many patients with cirrhosis remain asymptomatic until decompensation occurs—a sudden drop in liver function that manifests with symptoms like jaundice, ascites, variceal bleeding, or encephalopathy.

Decompensated cirrhosis presents with:

• Jaundice
• Ascites
• Variceal bleeding
• Encephalopathy

🧠 Key point: Cirrhosis can be silent — patients may not realise they have it until a decompensation event.

🔬 Hepatocellular Carcinoma (HCC) The Malignant Transformation

Hepatocellular carcinoma is the most common primary liver cancer, usually emerging against a background of chronic liver injury and cirrhosis. Chronic hepatitis B and C infections are major risk factors, as they create an environment of ongoing inflammation, fibrosis, and regenerative stress that predisposes to malignant transformation. In HBV, the virus may also directly contribute via integration into host DNA.

Clinical Presentation

HCC is notoriously insidious in its early stages, which is why many cases are detected during routine surveillance in high-risk patients. Key aspects include:

Early-Stage (Asymptomatic):

• Frequently picked up on imaging (ultrasound, CT, or MRI) during scheduled surveillance in patients with chronic liver disease or cirrhosis.
• May be identified as a small solitary nodule without systemic signs.

Symptomatic Disease (Advanced Stage):

• Non-specific systemic symptoms: Unexplained weight loss, fatigue, and anorexia.
• Abdominal symptoms and signs:
• Right upper quadrant pain or discomfort.
• A palpable mass on physical examination.
• Worsening ascites or new-onset jaundice (if the tumour affects liver synthetic function).
• Paraneoplastic syndromes: Rarely, patients may develop polycythaemia or hypercalcaemia.

Pathogenesis 

Chronic Inflammation and Regeneration:

The continuous cycle of damage and repair creates a mutation-prone environment. This genomic instability can drive malignant transformation.

Viral Integration (HBV-Specific):

HBV has the unique ability to integrate its DNA into host hepatocytes, further increasing the risk of oncogenic mutations even in the absence of cirrhosis.

Risk Factors:

• Cirrhosis: Irrespective of the underlying cause, cirrhosis dramatically increases HCC risk.
• Chronic HBV Infection: Even without cirrhosis, chronic HBV carries a higher risk due to direct viral oncogenesis.
• Coinfections and Environmental Exposures: Co-infection with HDV or HIV, family history of HCC, and exposure to aflatoxins all compound risk

Surveillance Strategies

Screening:

High-risk patients (e.g., those with cirrhosis or chronic HBV) should receive 6-monthly ultrasounds, often combined with AFP measurements.

Rationale:

Early detection improves the likelihood of curative treatments such as resection, liver transplantation, or local ablative therapies.

Prognosis

The prognosis in HCC varies greatly depending on the stage at diagnosis and underlying liver function:

Early-Stage HCC:

• When detected early, potentially curative interventions (surgical resection, ablation, or transplantation) can result in 5-year survival rates that are considerably higher.

Advanced HCC:

• For patients with large, multifocal tumours or vascular invasion, the prognosis is generally poor, with median survival often measured in months.
• Prognosis also depends on the degree of underlying cirrhosis, as a compromised liver can restrict treatment options and worsen outcomes.

Metastatic Behaviour:

• Initially, HCC tends to spread locally by vascular invasion, particularly into the portal and hepatic veins. 
• Distant metastases (e.g., to the lungs, bones, or, less commonly, the brain) typically occur in advanced stages.
• HCC is often less likely to metastasize early because the liver’s anatomy and unique blood supply tend to confine the disease for a period. However, aggressive variants with rapid vascular invasion can lead to early dissemination.

Aspect	Details
Presentation	Often asymptomatic early; later, RUQ pain, weight loss, palpable mass, new/worsening ascites, jaundice
Prognosis	Highly variable; early-stage disease may be curable, while advanced disease carries a poor prognosis
Metastases	Tends to spread locally via vascular invasion; distant metastases (lungs, bones) in later stages
Management	Curative options (surgical resection, transplant, ablation) for early-stage; TACE, systemic therapies in advanced stages
Surveillance	6-monthly ultrasound ± AFP in high-risk patients to detect early lesions

Hepatocellular carcinoma is a devastating complication of chronic liver disease that underscores the importance of early detection and intervention. Understanding its subtle early presentations, natural history of spread, and the rationale behind various management strategies is essential in guiding treatment decisions and ultimately improving patient outcomes. By employing regular surveillance in high-risk populations, clinicians can catch HCC before it becomes too advanced, offering a chance for curative treatment.

💊 Management Principles for chronic hepatitis

Effective management of chronic hepatitis and its complications revolves around several key strategies:

Aim	Intervention
Suppress Viral Replication	Use of antivirals (e.g., tenofovir or entecavir for chronic HBV; direct-acting antivirals for HCV)
Monitor and Mitigate Fibrosis	Regular non-invasive assessments (Fibroscan, serial LFTs) and potentially liver biopsy if needed
Prevent Complications	Lifestyle modifications (alcohol avoidance, weight management) and comorbidity control (diabetes, hypertension)
Screen for HCC	Routine surveillance with 6-monthly ultrasound ± AFP in high-risk individuals
Reduce Transmission	Vaccination of at-risk contacts (especially for HBV) to contain the spread and protect the community

Management goals will change with disease stage and clinical features 

Stage	Features	Management Focus
Chronic Hepatitis	Persistent infection; mild ALT rise; low-grade inflammation	Antiviral therapy; lifestyle modification; regular monitoring of liver enzymes and viral load
Compensated Cirrhosis	Significant fibrosis; preserved liver function; may be asymptomatic	Prevent progression; begin HCC surveillance; tailored lifestyle and comorbidity management
Decompensated Cirrhosis	Signs of liver failure (ascites, varices, encephalopathy); synthetic dysfunction	Manage complications aggressively; consider liver transplantation; optimize supportive care
HCC	May be clinically silent or cause pain, weight loss, or decompensation	Early detection via surveillance; curative resection, transplantation, or palliative care based on stage

Clinical cases for consideration

Case 1 : Chronic Hepatitis C  

Patient:

David, a 58-year-old construction worker, presents to his GP for a routine check-up.

History of Present Illness

David reports no major symptoms, though he occasionally feels tired and sluggish. He attributes this to his long work hours. He has no jaundice, RUQ pain, or nausea.

However, on routine bloodwork during an insurance medical review, mildly elevated ALT was noted, prompting further investigation.

Past Medical History

• No known liver disease.
• History of IV drug use in his late 20s (occasional, stopped years ago).
• No prior hepatitis screening or vaccination history.
•  No history of hazardous alcohol use.

Social History

• Works full-time in construction, physically active.
• No regular medications, drinks socially.
• No recent travel history or high-risk behaviours.

Examination Findings

General:

• Well-looking, no obvious jaundice or pallor.

Vital Signs:

• BP: 128/80 mmHg
• HR: 78 bpm
• Temp: 36.8°C
• RR: 16 breaths/min
•  SpO₂: 99%

Abdominal Examination:

• Mild hepatomegaly, no tenderness.
• No splenomegaly or signs of ascites.
• No asterixis or other signs of hepatic encephalopathy.

Laboratory Investigations

Test	Result	Normal Range
White Cell Count	6.2 x 10⁹/L	4.0 – 11.0 x 10⁹/L
Haemoglobin	14.0 g/dL	13.5 – 17.5 g/dL
Platelets	140 x 10⁹/L	150 – 400 x 10⁹/L
ALT	78 U/L	< 40 U/L
AST	65 U/L	< 40 U/L
Total Bilirubin	15 µmol/L	< 20 µmol/L
ALP	110 U/L	30 – 130 U/L
Anti-HCV Antibody	Positive	Negative
HCV RNA (Viral Load)	6.5 x 10⁶ IU/mL	Undetectable/Very low
INR	1.1	0.8 – 1.2

Note: Mild transaminase elevation with positive anti-HCV and high HCV RNA viral load confirms chronic HCV infection.

Diagnosis

✅ Chronic Hepatitis C infection

✅ Likely subclinical for decades, detected incidentally

✅ Platelets on the lower end of normal—potential early portal hypertension?

Next Steps in Management

1️⃣ Staging & Fibrosis Assessment:

• Fibroscan or liver biopsy to assess degree of fibrosis or cirrhosis risk.
• Abdominal ultrasound to check for structural liver abnormalities.

2️⃣ Initiation of Direct-Acting Antiviral (DAA) Therapy:

• Treatment with antiviral therapy for 12 weeks.
• High cure rates (>95%), eliminating viral replication and preventing disease  progression.

3️⃣     Monitoring & Surveillance:

• LFTs & HCV RNA at 4 weeks, 12 weeks, and post-treatment clearance check.
• Surveillance for HCC if cirrhosis is present (6-monthly ultrasound ± AFP).

4️⃣     Lifestyle & Risk Reduction:

• Avoid alcohol to minimize liver damage.
• Counsel on vaccination (HBV, HAV) to prevent co-infections.
• Education on liver health and long-term risks.

Summary

David’s chronic hepatitis C infection remained undiagnosed for decades due to its silent nature. Only mild ALT elevation hinted at underlying fibrosis. Screening led to early detection, allowing curative treatment with DAAs before progression to cirrhosis.

Case 2: Chronic Hepatitis B

Patient:

Jason, a 43-year-old truck driver, presents to the emergency department with progressive fatigue, abdominal swelling, and shortness of breath over the past few weeks.

History of Present Illness

Jason reports worsening tiredness, nausea, and decreased appetite for several months but never sought medical care. Over the last 2 weeks, his legs have become swollen, and his abdomen feels increasingly distended. He has also noticed yellowing of his eyes and episodes of confusion—sometimes forgetting basic tasks at work.

He has never been tested for hepatitis, and this is his first time hearing about liver disease.

Past Medical History

•  No previous hospitalizations or chronic illnesses.
• Born in China, a region with high HBV prevalence, but has lived in Australia since his early 20s.
• No history of IV drug use, occasional alcohol consumption.
• No known family history of liver disease or hepatitis.

Social History

• Works long hours driving, limited access to healthcare.
• No prior health screenings.
• Married with two children (who have not been screened for HBV).

Examination Findings

General Appearance:

• Jaundiced, thin with muscle wasting.
• Distended abdomen with fluid wave (suggestive of ascites).

Vital Signs:

•  BP: 100/65 mmHg
• HR: 96 bpm
• Temp: 37.2°C
• RR: 18 breaths/min
• SpO₂: 97% on room air

Abdominal Examination:

• Massive ascites, flank dullness, no tenderness.
• Hepatomegaly with nodular texture, consistent with cirrhosis.
• Splenomegaly, suggesting portal hypertension.

Neurological Examination:

• Asterixis (flapping tremor), mild confusion—suggesting hepatic encephalopathy.

Laboratory Investigations

Test	Result	Normal Range
White Cell Count	5.8 x 10⁹/L	4.0 – 11.0 x 10⁹/L
Haemoglobin	12.1 g/dL	13.5 – 17.5 g/dL
Platelets	98 x 10⁹/L	150 – 400 x 10⁹/L
ALT	45 U/L	< 40 U/L
AST	80 U/L	< 40 U/L
Total Bilirubin	65 µmol/L	< 20 µmol/L
ALP	190 U/L	30 – 130 U/L
Albumin	26 g/L	35 – 50 g/L
INR	1.6	0.8 – 1.2
HBsAg	Positive	Negative
Anti-HBc IgG	Positive	Negative
HBeAg	Negative	Negative
HBV DNA (Viral Load)	2.5 x 10⁶ IU/mL	Undetectable
AFP	38 ng/mL (elevated)	< 10 ng/mL
Fibroscan Score	F4 (Advanced Fibrosis/Cirrhosis)	Normal ≤ F1

Diagnosis

✅ Previously undiagnosed chronic hepatitis B (likely perinatally acquired)

✅ Advanced cirrhosis with portal hypertension and ascites

✅ Hepatic encephalopathy (suggested by confusion, asterixis)

✅ Possible hepatocellular carcinoma (based on elevated AFP)

Next Steps in Management

1️⃣     Immediate Hospital Admission & Stabilization

• Diuretics (e.g., spironolactone, furosemide) for ascites management.
• IV albumin & antibiotics if spontaneous bacterial peritonitis suspected.
• Lactulose for hepatic encephalopathy to reduce ammonia buildup.

2️⃣     Cancer Screening & Liver Imaging

• Urgent CT/MRI to assess for hepatocellular carcinoma (HCC) given elevated AFP and cirrhosis.
• If HCC confirmed, consider surgery or transplant depending on tumour stage.

3️⃣     Long-Term Antiviral Therapy for HBV

• Long term antivirals to suppress HBV replication and slow further disease progression.

4️⃣     Planning for Liver Transplant Evaluation

• If decompensated cirrhosis progresses, referral for transplant must be considered.

5️⃣     Family Screening & Public Health Measures

• Immediate HBV screening for his wife and children, plus vaccination if HBsAg-negative.
• Notify public health authorities, as chronic hepatitis B is a notifiable disease.

Summary

Jason’s undiagnosed chronic hepatitis B progressed silently over decades until complications like cirrhosis, ascites, and possibly hepatocellular carcinoma emerged. This case highlights the importance of early HBV screening, particularly for immigrants from endemic regions and those born to HBV-positive mothers.

Remember

• HBV acquired at birth can remain silent for decades.
• Patients may present with cirrhosis before ever realizing they had chronic infection.
• AFP elevation + cirrhosis always raises suspicion for HCC.
• Antiviral therapy can slow progression, but screening is essential to catch complications early.

Case 3:  Hepatocellular Carcinoma (HCC)

 Patient:

Michael, a 58-year-old retired teacher, presents with weight loss, worsening right upper quadrant (RUQ) pain, and new onset jaundice.

History of Present Illness

Michael reports unintentional weight loss of 7 kg over the past three months. He has noticed increasing fatigue, nausea, and reduced appetite, along with a vague dull RUQ pain that has been persistent for several weeks. His wife also noticed that his eyes looked yellow and that he had mild abdominal swelling.

He has never been diagnosed with liver disease and has never been tested for hepatitis, as he never felt unwell before.

Past Medical History

• Hypertension, well controlled.
• No history of jaundice, bleeding disorders, or previous liver disease.
• Born in Egypt, where HBV and HCV prevalence is high, but never screened.
•  Occasional social drinker - 1-2 drinks per week.

Social History

• Previously worked as a teacher, now retired.
• No IV drug use, no known history of hepatitis.
• Married, two adult children (none screened for HBV or HCV).

Examination Findings

General Appearance:

• Mild jaundice, visible scleral icterus.
• Cachexia (muscle wasting).
• Palpable right upper quadrant mass.

Vital Signs:

• BP: 110/70 mmHg
•  HR: 85 bpm
• Temp: 37.4°C
• RR: 18 breaths/min
• SpO₂: 98%

Abdominal Examination:

• Firm, irregular RUQ mass, suspicious for a hepatic tumor.
• Mild ascites, fluid wave present.
• Hepatomegaly, with nodular liver edge.
• No splenomegaly.

Laboratory Investigations

Test	Result	Normal Range
White Cell Count	6.5 x 10⁹/L	4.0 – 11.0 x 10⁹/L
Haemoglobin	12.8 g/dL	13.5 – 17.5 g/dL
Platelets	105 x 10⁹/L	150 – 400 x 10⁹/L
ALT	60 U/L	< 40 U/L
AST	85 U/L	< 40 U/L
Total Bilirubin	40 µmol/L	< 20 µmol/L
ALP	220 U/L	30 – 130 U/L
Albumin	28 g/L	35 – 50 g/L
INR	1.4	0.8 – 1.2
HBsAg	Negative	Negative
Anti-HCV Antibody	Positive	Negative
HCV RNA (Viral Load)	Undetectable (likely spontaneous clearance years ago)	Undetectable
AFP	685 ng/mL (markedly elevated)	< 10 ng/mL
CT Abdomen Findings	Large 8 cm hepatic mass, irregular margins, portal vein invasion	N/A
Fibroscan Score	F4 (Cirrhosis)	Normal ≤ F1

Diagnosis

✅ Hepatocellular carcinoma (HCC), presenting as first clinical manifestation

✅ Previously undiagnosed cirrhosis, likely due to remote HCV exposure

✅ Portal vein invasion, suggesting advanced disease

✅ Markedly elevated AFP, supporting HCC diagnosis

Next Steps in Management

1️⃣     Confirm Diagnosis & Tumour Staging

• CT/MRI abdomen for tumour characterization, vascular invasion, and metastases.
• Consider biopsy if diagnosis is uncertain (though often unnecessary in classic HCC cases).

2️⃣     Assess Treatment Options Based on Staging

• Curative options (only if early-stage):
• Resection or liver transplant—unlikely in this case due to advanced disease.
• Locoregional therapy (if intermediate stage):
• Transarterial chemoembolization (TACE) for tumour control.
• Transarterial radioembolization (TARE) if available
• Systemic therapy (if advanced stage):
• Tyrosine kinase inhibitors (sorafenib, lenvatinib) for metastatic disease.
• Immunotherapy (checkpoint inhibitors) under investigation.

3️⃣     Palliative and Symptom Management

• Manage ascites (diuretics, paracentesis if necessary).
• Nutrition support, given cachexia and fatigue.
• Consider hospice/palliative care discussion if prognosis is poor.

4️⃣     Screening & Family Testing

• HCV screening for family members (spouse, children).
• Surveillance advice for close contacts with HBV risk factors.

Summary

Michael remained unaware of his past HCV exposure, leading to silent progression to cirrhosis and hepatocellular carcinoma. His first symptom of liver disease was actually HCC, highlighting the importance of screening for chronic hepatitis and cirrhosis before complications arise.

Remember

• HCC can be the first clinical presentation in patients who never knew they had chronic hepatitis.
• Remote exposure to HCV can still result in cirrhosis decades later, even with undetectable viral RNA.
• Advanced HCC with vascular invasion limits curative treatment options—early detection is critical.
• AFP is often elevated but not always—imaging remains the gold standard for HCC diagnosis.

Final summary 

Chronic hepatitis represents a silent but progressive assault on the liver. Repeated cycles of immune-mediated injury, fibrosis, and regenerative stress set the stage for cirrhosis and hepatocellular carcinoma. Early detection through vigilant screening, prompt initiation of antiviral therapies, and proactive lifestyle modifications are keys to altering the natural history of the disease. By understanding the “how” and “why” of these processes, clinicians can better protect liver health in patients with chronic viral hepatitis.