L19 - Liver pathology Flashcards
Reviewing the anatomy and histology of the liver Introducing the most common epithelial malignancy of the liver Describing the conditions leading to liver carcinoma
Why is the liver unique in its ability to regenerate
🔄 The liver is one of the few organs in the human body that can regenerate after partial removal. This is because hepatocytes (liver cells) can proliferate in response to injury or resection. Up to 70% of the liver can be removed, and the remaining portion can regenerate within weeks, provided the liver is otherwise healthy. This regenerative capacity is why partial liver donation is possible.
What is the first question to consider when a liver mass is detected?
🧐 The primary concern is whether the mass is primary or metastatic. The liver is a common site for metastases from other cancers (e.g., colorectal, breast), so metastatic tumors are more frequent than primary liver tumors. The diagnosis influences treatment decisions, as metastatic liver tumors usually originate from other organs and require different management than primary liver cancers
What are the most common primary liver tumours?
🏥 The most common primary liver tumor is hepatocellular carcinoma (HCC), which arises from hepatocytes. Other primary liver cancers include cholangiocarcinoma (bile duct cancer) and, less commonly, angiosarcomas and hepatoblastomas. However, most liver tumors are metastatic rather than primary.
What conditions predispose individuals to primary liver cancer?
⚠️ Several conditions increase the risk of primary liver cancer, including:
Chronic liver disease (e.g., cirrhosis) 🌀 – often due to hepatitis B/C or alcohol-related liver damage
Non-alcoholic fatty liver disease (NAFLD) 🍔 – associated with obesity and metabolic syndrome
Aflatoxin exposure 🍄 – a carcinogen found in contaminated food
Genetic disorders 🧬 – such as hereditary hemochromatosis
Chronic inflammation and fibrosis 🏗️ – contribute to cancer development
How does the liver’s vascular supply influence tumour resection?
🩸 The liver has a segmental vascular structure, meaning each segment has its own blood supply. This allows segmental resection of the liver (removing a part while preserving function). Surgeons can clamp off blood vessels to a particular segment without affecting the rest of the liver, making tumor resection more feasible while minimizing complications.
How can liver tumours be detected through physical examination?
🤲 The liver’s lower edge is palpable beneath the right ribcage. If the liver is enlarged or has an irregular texture, thick can be delt during an abdominal exam.
What do signs of a liver tumour include during an abdominal examination
📏Hepatomegaly (liver enlargement) - suggests swelling due to cancer, cirrhosis or congestion
🪨 Firm or nodular texture - may indicate a tumour
❌ Tenderness on palpitation - Could signal inflammation or malignancy
What is the functional unit of the liver?
🏗️ The hepatic lobule is the functional unit of the liver
How is the liver vascularised?
The liver has dual vascularization:
1️⃣ Hepatic artery – delivers oxygenated blood to the liver.
2️⃣ Portal vein – carries nutrient-rich but poorly oxygenated blood from the GI tract to the liver for processing and detoxification.
This unique circulation makes the liver highly vulnerable to metabolic stress, drug toxicity, and viral infections.
Why is the liver a key organ for drug metabolism and detoxification?
💊 because the liver plays a key role in modifying, detoxifying or activating drugs before they reach the circululation. If the liver function is impaired in any way (e.g. liver disease or cirrhosis), drugs can accumulate which results in toxicity or reduced therapeutic effect.
What is an example of another organ that contributes to drug exertion
The kidneys also contribute to drug excretion, but the liver is the primary site of metabolism.
How does liver function affect vitamin D metabolism?
☀️ Vitamin D metabolism occurs in multiple steps:
1️⃣ Sunlight activates vitamin D precursors in the skin.
2️⃣ Liver hydroxylation (first step) – Converts vitamin D into an intermediate form.
3️⃣ Kidney hydroxylation (final step) – Produces the active form of vitamin D.
If liver function is impaired, vitamin D activation is disrupted, leading to deficiency and possible bone-related disorders (e.g., osteomalacia).
What are hepatocytes
Hepatocytes are the main functional cells of the liver
What is the structure of hepatocyes
1️⃣ Large, modified epithelial cells with a granular, pink cytoplasm (rich in mitochondria and organelles for detoxification).
2️⃣Arranged in trabecular patterns with a single line of hepatocytes separated by sinusoidal vessels (lined by endothelial cells).
3️⃣ Connected to a canalicular system, which transports bile to the biliary tract.
what are the two types of epithelial cells in the liver?
1️⃣ Hepatocytes – The main functional cells responsible for metabolism, detoxification, and protein synthesis.
2️⃣ Biliary epithelial cells – Line the biliary tract, facilitating bile transport from hepatocytes to the gallbladder and intestines.
How is the liver anaotomically divided?
🏥 The liver is divided into eight segments, following the Couinaud classification:
1️⃣ Segment 1 (Caudate lobe) – Located posteriorly, near the IVC.
2️⃣ Segments 2 & 3 – Found in the left lateral lobe.
3️⃣ Segment 4 – Medial part of the left lobe, divided into 4a (superior) and 4b (inferior).
4️⃣ Segments 5 to 8 – Located in the right lobe:
5 & 6 – Below the horizontal plane of the portal vein (PV).
7 & 8 – Above the portal vein.
7 & 8 are more posterior, while 5 & 6 are more anterior.
The portal vein (PV), hepatic artery, and bile ducts supply and drain each segment independently, making segmental resection possible in liver surgery.
What is the most common primary liver maliganacy worldwide?
🏥 Hepatocellular carcinoma (HCC) is the most common primary epithelial cancer of the liver, accounting for >80% of primary liver malignancies worldwide
How common is hepatocellular carcinoma (HCC) globally?
🌍 HCC is the 5th most common malignancy worldwide, with a male-to-female ratio of 3:1.
What is the most common risk factor for hepatocellular carcinoma (HCC)
🍺 Cirrhosis is the biggest risk factor—~80% of HCC cases arise in cirrhotic livers. Cirrhosis leads to regenerative nodules separated by fibrosis, creating a structurally abnormal liver.
What is the normal histological structure of the liver?
🏗 The liver lobule consists of:
🩸 Portal triad (periphery): Portal vein, hepatic artery, and bile duct.
🌊 Central vein (centre of the lobule).
Minimal fibrous tissue—mostly found in the portal areas.
what is the homogenous texture of the liver?
the liver is soft, dark brown and lacks a significant fibrous component in normal conditions
How does hepatocellular carcinoma (HCC) appear macroscopically?
🔬HCC forms an expansile mass with altered colour and texture, more fibrous tissue in between tumour cells, ink-marked resection margins *sued in pathology to assess complete tumour removal), disrupted normal liver structure
What factors are contributing to the increasing prevalence of HCC
📈 due to increasing cases of chronic liver disease e.g. Hepatitis B and C, NAFLD/NASH, Alcohol-related cirrhosis and metabolic disorders e.g. diabetes, obsesity-associated liver disease
Which region has the highest incidence of hepatocellular carcinoma?
🌏 Asia (72.5%) has the highest incidence, followed by:
Europe (9.8%)
Africa (7.7%)
North America (5%)
Latin America & the Caribbean (4.6%)
Oceania (0.4%)
How does the median age of onset for HCC vary geographically?
📊 North America & Europe: Older than the 6th decade
📊Asia & Africa: Between the 3rd and 6th decades (younger)
What are the main risk factors for hepatocellular carcinoma?
🚨 Chronic liver disease leading to cirrhosis, caused by:
🦠Infectious: Viral hepatitis (HBV, HCV)
⚖️Metabolic: NAFLD (obesity, diabetes), Hemochromatosis
🍷Environmental: Aflatoxin, alcohol, steroids, oral contraceptives
🧬Developmental/congenital: Abernethy malformation, Alagille syndrome
What is the leading global cause of hepatocellular carcinoma?
🦠 Chronic viral hepatitis (HBV & HCV) is the leading cause of HCC worldwide.
How is viral hepatitis transmitted?
💉 Hepatitis B & C: Blood & body fluids
🍽️ Hepatitis A: Fecal-oral route
how does aflatoxin exposure increase HCC risk?
🍄 Aflatoxin is a toxin produced by fungi in contaminated grain supplies, particularly in warm, humid environments. It contributes to the high HCC rates in Asia…..it gets metabolised into reactive intermediates that bind to DNA (DNA adducts) which lead to mutations e.g. p53 mutations promoting uncontrolled cell growth
How has climate change affected aflatoxin risk?
🌍 Rising temperature & humidity in regions like Northern Europe may increase aflatoxin contamination, posing a greater HCC risk.
What was Thorotrast, and how did it affect liver cancer risk?
🏥 Thorotrast, a contrast agent in X-rays used in the 1950s, was linked to increased risks of cholangiocarcinoma, cirrhosis, and HCC (because of its radioactivity and the accumulation of thorium dioxide in the liver), leading to its removal from medical use.
What are the classic signs of liver dysfunction in HCC patients?
💧 Ascites (fluid accumulation in the abdomen)
🩸Caput medusae (dilated superficial abdominal veins)
🟡 Jaundice (yellow skin & eyes)
🩹Easy bruising (due to impaired coagulation)
What are the main diagnostic methods for HCC?
Imaging: CT/MRI with contrast 🖥️
Biopsy: Histological confirmation 🔬
Serum markers: Alpha-fetoprotein (AFP) 📊
Why is imaging preferred over biopsy in HCC diagnosis?
🩻 Biopsies carry a risk of tumor seeding, so CT/MRI with contrast is often sufficient for diagnosis.
What is the role of alpha-fetoprotein (AFP) in HCC?
📊 AFP is an HCC biomarker, but it is not specific and may be normal in early-stage HCC.
: What staging system is commonly used for HCC?
🏥 The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly used to determine treatment options.
What factors affect the prognosis of hepatocellular carcinoma?
Tumor size & spread 📏
Presence of vascular invasion 🩸
Underlying liver function (Cirrhosis, Child-Pugh score) 🍷
What should be considered when a solid liver mass is detected?
🏥 Solid masses require further evaluation, considering:
Size 📏
Growth over time ⏳
Cirrhosis status 🍷
What is the typical survival rate for untreated HCC?
⏳ Median survival without treatment is 6 months in advanced cases.
How can the risk of hepatocellular carcinoma be reduced?
🛡️ Prevention strategies include:
HBV vaccination 💉
HCV antiviral therapy 💊
Aflatoxin exposure reduction 🚫🍞
Alcohol moderation 🍷
Regular screening for high-risk patients 🩻
What are the first considerations when a hepatic mass is suspected?
You need to consider whether the mass is benign or malignant , the background liver condition (e.g. cirrhosis) and the lesion type (solid vs vascular)
Are benign hepatic lesions more common than malignant ones?
✅ Yes, benign hepatic lesions are more common than malignant ones.
What are some examples of benign non-epithelial hepatic lesions>
🩸 Hemangiomas are benign vascular lesions of the liver.
What is the recommended approach for small liver lesions?
🔎 Monitor small lesions to check for changes in size.
When is a liver biopsy considered?
📏 The lesion is >1 cm
🩻Imaging features are unclear
🩸The patient has good coagulative capacity
What is a key limitation of liver biopsies?
💉 The accuracy depends on the biopsy sample quality and the operator’s skill.
What is the initial step if a hepatic mass/ nodule is detected on imaging?
🩻 you assess the size:
<1 cm → Repeat ultrasound in 4 months
>1 cm → Perform multiphasic contrast-enhanced imaging (CT/MRI)
What is the next step if a <1cm hepatic lesion remains stable?
✅ Continue monitoring with repeat imaging.
What if a <1cm hepatic lesion shows a growing/changing pattern?
🔬 Consider further imaging or biopsy.
What imaging techniques help detect HCC hallmarks?
🏥 Multiphasic contrast-enhanced CT, MRI, or gadoxetic-enhanced MRI.
What happens if one imaging technique detects HCC hallmarks?
✅ Diagnosis of HCC confirmed.
What if the first imaging technique does not detect HCC hallmarks?
Another modality (CT/MRI/ contrast-enhanced ultrasound) for confirmation
If a second imaging technique is also negative, what is the next step?
🔬 Biopsy is needed for further evaluation.
why might a biopsy be needed despite negative imaging?
🔬 Imaging can miss atypical cases, requiring histological confirmation
What happens if a biopsy results is unclear?
🔄 Consider re-biopsy.
Why is a multu-step imaging process used for HCC diagnosis?
🔄 HCC progression is gradual—from dysplastic nodules to malignancy. Multiple imaging steps ensure accurate detection at different stages.
What is the stepwide progression of helaptocellular carcinoma (stages 1-4)
🧬 Stages:
1️⃣ Low-grade dysplastic nodule
2️⃣ High-grade dysplastic nodule
3️⃣ Early hepatocellular carcinoma
4️⃣ Progressed hepatocellular carcinoma
What molecular alterations are linked to HCC progression
🧬 telomere shortening
⚙️ TERT activation
🚦CEll cycle checkpoint inhibition
What is TERT
Telomerase reverse transcriptase (TERT) which is a frequent and early event promoting cell proliferation and tumour growth by maintaining telomere length and enabling cellular immortalisation
What is a key mutation in HCC progression
🔑 TERT promoter mutation is a crucial event in HCC progression.
What are the three major molecular clusters in HCC?
molecular subtypes
1️⃣ CTNNB1-cluster (leads to aberrant Wnt signalling)
2️⃣ AXIN1-cluster (tumours with mutations in the AXIN1 gene impacting Wnt signalling)
3️⃣ TP53-cluster (tumours with mutations in the TP53 gene so has compromised tumour suppression)
How do these genetic clusters influence HCC behavious
🏥 Different mutations affect tumor progression, treatment response, and prognosis.
Why do some genetic mutations overlap in HCC?
🔄 Some mutations co-exist, leading to complex tumor behavior and different molecular subtypes.
Why is identifying HCC subtypes important?
🩺 Different subtypes have unique behaviors and may occur at younger ages (but can be easily mistaken for benign lesions)
Why should clinicians consider HCC in younger patients?
⚠️ HCC typically occurs in the 5th or 6th decade, but certain subtypes can appear earlier.
What factors influence whether a liver lesion is benign or malignant?
🏥 Clinical history, imaging features, and biopsy results determine risk.
What genetic mutation is associated with the serous subtype of HCC?
🧬 TSC1 and TSC2 mutations are linked to the serous subtype of HCC.
What molecular pathway is activated in the atopatic subtype of HCC?
🔥 IL-6 (Interleukin-6) and JAK-STAT pathway activation drive the atopatic subtype.
Which genetic mutations are associated with the macrotrabecular subtype of HCC?
🧬 TP53 mutation is a key driver of the macrotrabecular subtype.
What is the characteristic genetic alteration in fibrolamellar HCC?
🧬 The DNAJB1-PRKACA fusion gene is the hallmark of fibrolamellar HCC.
Why is fibrolamellar HCC an important differential diagnosis in younger patients?
🏥 Fibrolamellar HCC occurs earlier than other HCC subtypes and should be considered in younger patients presenting with liver masses.
How does the morphology of fibrolamellar HCC differ from typical HCC?
🔬 Fibrolamellar HCC is more organised than conventional HCC, though it still lacks normal trabecular architecture.
What histological feature distinguishes normal hepatocytes from HCC cells?
🔬 Normal hepatocytes are arranged in a trabecular system with each trabecula consisting of a single layer of hepatocytes. HCC disrupts this structure, forming clusters of cells.
How do the nuclei of HCC cells differ from normal liver cells?
🔬 HCC cells often have larger nuclei, double nuclei, or prominent eosinophilic nucleoli, indicating cellular atypia.
What histological features indicate HCC with cirrhosis
🔬 A circumscribed tumour in the presence of cirrhotic liver changes suggests HCC rather than benign lesions.
How does the background liver tissue help differentiate fibrolamellar HCC from conventional HCC
🏥 Fibrolamellar HCC is NOT associated with chronic liver disease or cirrhosis. If a younger patient has cirrhosis, consider HCC first. If a solid liver nodule is present in a younger patient with no cirrhosis, a broader differential must be considered.
What is the prognosis of fibrolamellar HCC compared to conventional HCC?
📈 Fibrolamellar HCC has a better prognosis than conventional HCC, but still requires early diagnosis and treatment.
Which HCC subtypes are linked to a worse prognosis?
⚠️ More aggressive HCC subtypes include:
🧬 Sarcomatoid carcinoma
🧬 Carcinosarcoma
🔬 Macrotrabecular HCC
🦠 Cirrhotomimetic HCC
🏥 Neutrophil-rich HCC
Which HCC subtypes have a similar or better prognosis than conventional HCC?
🫀 Steatohepatitic HCC
🔬 Clear cell HCC
🏥 Chromophobe HCC
📈 Fibrolamellar HCC
🦠 Lymphocyte-rich HCC
Which HCC subtype has an unpredictable prognosis?
❓ Scirrhous HCC can behave variably, sometimes more aggressively and sometimes more indolently.
What is the histological appearance of aggressive sarcomatoid carcinoma and carcinosarcoma?
🔬 These high-grade, undifferentiated tumours show:
Severe loss of normal liver architecture
Highly pleomorphic cells
Sarcomatoid or spindle-cell differentiation
How does macrotrabecular HCC compare in prognosis?
🏥 Macrotrabecular HCC is more aggressive and associated with a worse prognosis than conventional HCC.
how does immune infiltration affect HCC prognosis?
🦠 Neutrophil-rich HCC tends to have a worse prognosis, while lymphocyte-rich HCC has a better prognosis.
What is cholangiocarcinoma, and where does it arise from?
🏥 Cholangiocarcinoma is an adenocarcinoma that arises from bile duct epithelial cells. It can be intrahepatic (within the liver) or extrahepatic (outside the liver, extending to the bile ducts and gallbladder).
How is cholangiocarcinoma diagnosed?
🔬 Diagnosis of exclusion—must first rule out metastatic adenocarcinoma before confirming primary cholangiocarcinoma.
What is the age group most affected by cholangiocarcinoma?
📅 Typically affects patients aged 60–70 years.
Is there a gender preference for cholangiocarcinoma?
⚖️ Male = Female (unlike hepatocellular carcinoma, which is more common in men).
What is the prognosis of cholangiocarcinoma?
❌ Poor prognosis—often associated with chronic liver disease and cirrhosis.
What are the infectious cases of cholangiocarcinoma
🦠 Viral hepatitis (HBV, HCV).
What metabolic conditions increase the risk of cholangiocarcinoma?
⚡ Non-alcoholic fatty liver disease (linked to obesity & diabetes), hemochromatosis, and alpha-1 antitrypsin deficiency.
What environmental exposure increases the risk of cholangiocarcinoma?
☢️ Aflatoxin, alcohol, steroids, oral contraceptives, tobacco, and Thorotrast (a past radiographic contrast agent).
What congenital or developmental conditions are linked to cholangiocarcinoma?
🧬 Abernethy malformation, Alagille syndrome, Ataxia telangiectasia
What are the histological characteristics of cholangiocarcinoma?
🔬 The tumour consists of small, bluish cells forming glandular structures, in contrast to hepatocytes, which are larger and pinkish with granular cytoplasm.
What is the most important step when seeing a glandular tumour in the liver?
🛑 First rule out metastatic adenocarcinoma! Only after excluding metastases can cholangiocarcinoma be diagnosed.
How does a cirrhotic liver differ from a normal liver in size and consistency
🏥 A cirrhotic liver is smaller, harder, and has a sharp edge upon palpation.
What does the surface of a cirrhotic liver look like?
🌰 It is irregular and covered in hepatocyte nodules which are surrounded by fibrous tissue strands, unlike the smooth surface of a healthy liver (very disorganised)
What are the two types of nodules seen in cirrhosis?
🔬 Micro-nodules and macro-nodules, which are separated by strands of fibrous tissue.
what is the difference between micronodular and macronodular cirrhosis?
🔬 micronodular cirrhosis has nodules smaller than 3mm, while macronodular cirrhosis has nodules larger than 3mm
How does cirrhosis affect liver function at a cellular level?
🚫 Even though hepatocytes are still present, their disorganized arrangement prevents proper liver function.
What percentage of hepatitis cases in the US are caused by Hepatitis B?
40% of hepatitis cases are Hepatitis B in the US
What are the key features of Hepatitis B infection?
⚠️ Fulminant hepatic failure (severe, rapid liver damage)
🏥 Chronic liver disease and cirrhosis
🔄 Fibrosing cholestatic hepatitis (severe form in liver transplant recipients)
🎗️ Hepatocellular carcinoma risk: 40% in men, 15% in women
How is Hepatitis B transmitted?
🩸 Via infected blood, sexual contact, intravenous drug use, contaminated instruments, or mother-to-child during delivery.
What defines a Hepatitis B carrier state (chronic hepatitis B) ?
🛑 This occurs when someone remains infected with hepatitis B / hepatitis B antigenemia lasting >6 months, whilst they still have normal ALT & AST, and no symptoms (occurs in 10% of cases).
what are ALT And AST
ALT (alanine transaminase) and AST (aspartate transaminase) are enzymes found in the liver, and when the liver is damaged, they leak into the bloodstream, indicating potential liver problems.
What kind of virus is Hepatitis C?
🦠 Flavivirus, enveloped RNA virus.
What percentage of non-A, non-B hepatitis cases are caused by Hepatitis C?
📊 90%.
What percentage of transfusion associated hepatitis cases are due to hepatitis C?
💉 75-95%.
What are the main transmission routes for Hepatitis C?
💉 35% IV drug use
🏠 15% household/heterosexual exposure
🩸 5% blood transfusion
❓ 45% unknown cause
Is acute liver failure common in Hepatitis C?
🚫 No, it is rare.
What is the risk of developing hepatocellular carcinoma (HCC) in Hepatitis C patients with alcoholic cirrhosis?
🍺 57% at 10 years.
Can hepatitis C cause hepatocellular carcinoma (HCC) without cirrhosis?
❌ No, unlike Hepatitis B, HCC from Hepatitis C is only seen after cirrhosis has developed.
What histological features are associated with Hepatitis C
Sinusoidal lymphocytic infiltrate
Lymphoid follicles surrounding damaged bile ducts
Portal tract involvement
Mallory hyaline
Mild focal macrovesicular steatosis
Minimal necrosis
what is sinusoidal lymphocytic infiltrate (Hep C)
🦠 Lymphocytes (a type of white blood cell) accumulating in the liver sinusoids (small blood vessels in the liver), indicating chronic inflammation and immune response.
What is lymphoid folliclesWhat is portal tract involvement in Hepatitis C?
🏗️ Inflammatory cells expanding the portal tracts, leading to fibrosis and progressive liver damage.
What is Mallory hyaline (Hep C)
🏵️ Abnormal, tangled cytoplasmic protein deposits found in hepatocytes, often seen in alcoholic liver disease but also present in Hepatitis C.
What is mild focal macrovesicular steatosis (hep C)
🫧 Fat accumulation (large lipid droplets) in liver cells, occurring in patches (‘focal’), indicating metabolic stress on the liver.
What is minimal necrosis in Hep C?
💀 Only slight death of hepatocytes, suggesting that the infection causes slow, chronic damage rather than severe acute liver failure.
What is a specific but insensitive histological marker of Hep C
🔍 Lymphoid aggregates (specific but only 50% sensitive).
What type of fibrosis is common in Hep C
🏗️ Portal fibrosis.
Why is hepatitic C becoming more common
📈 Due to increased protection against Hepatitis B, leading to a shift in prevalence.
What are the key features of hepatitis D (HDV)
🦠 Defective RNA virus that requires Hepatitis B (HBV) for replication
💉 IV drug use is a major risk factor
🔄 Co-infection or superinfection with HBV
⚠️ May cause acute or fulminant hepatitis
How is Hepatitis E (HEV) transmitted?
🚰 Faeco-oral transmission via contaminated water
Why is Hepatitis E (HEV) dangerous in pregnancy?
🤰 Poor outcome in pregnant women, with up to 22% mortality
⚠️ Can cause fulminant hepatitis
🩸 Associated with disseminated intravascular coagulation (DIC)
What is (Non) Alcholoc Fatty liver disease (NAFLD / AFLD)
🏥 Hepatic steatosis (Condition where fat builds up around the liver) associated with obesity, type 2 diabetes, or metabolic dysregulation
🍺 Alcoholic Fatty Liver Disease (AFLD) has the same morphology but is caused by alcohol
🔍 Can occur with or without inflammation/fibrosis
How does a fatty liver appear?
🟡 Soft, yellow, and greasy
🏋️ Liver is enlarged
✨ Shiny surface without cirrhotic nodules
What are the histological features of fatty liver disease?
🔬 Predominantly macrovesicular steatosis (≥5% hepatocytes under low magnification)
🔥 Lobular inflammation
🎈 Ballooning degeneration
🧶 Fibrosis (if disease progresses)
Why does fatty liver disease progress to fibrosis?
🛢️ Lipid vacuoles rupture which triggers inflammation and fibrosis to form
How is NAFLD severity evaluated
📊 Scored by:
🛢️ Lipid content (steatosis)
🔥 Presence of inflammation
🎈 Cell deformation (ballooning degeneration)
🧶 Degree of fibrosis
What is Primary biliary Cholangitis (PBC)
🏥 Chronic, progressive cholestatic liver disease where granulomatous destruction of interlobular bile duct leads to fibrosis and later cirrhosis
Who is most affected by Primary billary cholangitis (PBC)
👩 Middle-aged women (rare in children)
What autoimmune conditions are associated with PBC?
🦷 Sjogren syndrome (autoimmune disease where the immune system attacks tear and saliva glands)
🦋 Systemic lupus erythematosus (SLE)
🦠 Thyroiditis
🖐️ Raynaud’s phenomenon
What lab findings are characteristics of PBC?
⬆️ Alkaline phosphatase (ALP)
⬆️ IgM
🧪 Antimitochondrial antibody (AMA) positive (classic marker)
What are the histological features of PBC`
🌸 Florid duct lesions (pathognomonic)
🎯 Patchy involvement of interlobular bile ducts & canals of Hering
❌ Does not affect larger bile ducts
How does PBC differ from primary sclerosing cholangitis?
Both are diseases affecting bile ducts but
PBC: primarily targets small intrahepatic bile ducts, Granulomatous destruction, patchy inflammation, AMA positive
PSC: affects both intrahepatic and extrahepatic bile ducts and leads to progressive structuring of the biliary tree, minimal inflammation, risk of cholangiocarcinoma, classic imaging findings
what is drug-induced liver injury (DILI)
💊 Liver damage caused by medications, herbs, or toxins which is diagnosed through exclusion and can present with any histological pattern
What is a key feature often associated with DILI
🚦 Cholestasis (impaired bile flow)
Why is drug history important in diagnosing DILI?
📋 Because morphology is nonspecific, history helps identify potential hepatotoxic drugs
What types of drigs are known to cause liver damage?
⚠️ Antibiotics (e.g., amoxicillin-clavulanate)
⚠️ Steroids
⚠️ NSAIDs
⚠️ Anticonvulsants (e.g., valproate)
⚠️ Herbal supplements e.g. turmeric, Garcinia cambogia, green tea extract, kava, black cohosh, and certain products containing red yeast rice
What is Wilson’s disease?
🧬 Autosomal recessive disorder causing copper accumulation
🏥 1 in 30,000 people affected
🏡 Tends to present in childhood
What causes liver damage in Wilson’s disease?
🧪 Copper accumulation exceeds ceruloplasmin binding capacity, leading to toxicity and liver injury
🏚️ Lysosomal buildup → Fibrosis → Cirrhosis
What are the neurological symtoms of Wilson’s Disease?
🧠 Putamen copper accumulation → Psychosis or Parkinsonian symptoms
What is the eye finding in Wilson’s disease?
👁️ Kayser-Fleischer Rings (copper deposition in the cornea)
What other organs are affected in Wilson’s Disease?
👁️ Cornea (Kayser-Fleischer rings)
🦴 Bones & joints
🩺 Kidneys
🦴 Parathyroid gland (hormonal effects)
What is haemochromatosis?
⚙️ Excessive iron accumulation in the body ( happens over time)
What are the major organs affected by hemochromatosis?
🏥 Liver, pancreas, heart
Liver → Cirrhosis, fibrosis
Pancreas → Diabetes-like symptoms
Heart → Cardiomyopathy, arrhythmias
What are the two types of haemochromatosis?
Primary (Hereditary): Autosomal recessive disorder
📅 Presents earlier in males
👩⚕️ Menstruation delays iron accumulation in females
Secondary: Due to repeated transfusions (e.g., chronic anaemia e.g. sickle cell, thalassemia)
What are the complications of iron accumulation in haemochromatosis?
⚠️ Cirrhosis, diabetes-like symptoms (pancreatic damage), cardiac abnormalities (myocardium involvement)
🏥 Increases risk of hepatocellular carcinoma (HCC)
What are the clinical symtoms of haemochromatosis?
🩸 Fatigue, diabetes symptoms, joint pain, skin pigmentation (“bronze diabetes”)
Early: Non-specific symptoms (fatigue, joint pain)
Late: Cirrhosis, diabetes, cardiomyopathy, arthritis
What is the main diagnostic test for hemochromatosis?
🧪 Serum ferritin & transferrin saturation
High ferritin (iron storage protein)
High transferrin saturation (>45%)
What is the treatment for hemochromatosis
💉 Regular phlebotomy (removes excess iron)
🏥 Iron chelation (for severe cases)
What is alpha-1 Antitrupsin Deficiency (AATD)
🏥 Genetic metabolic disorder → Deficiency of Alpha-1 Antitrypsin (AAT)
🧬 Autosomal recessive disease
What happens when AAT accumulates in the liver?
🏚️ mutant AAT accumulates in hepatocytes → Fibrosis and cirrhosis
🔬 Eosinophilic intracytoplasmic globules in periportal hepatocytes (Zone 1)
What is AAT
Alpha-1 antitrypsin which inhibits neurtophil elastase, protecting lung and liver from damage
what type of inheritance is AATD
Autosomal recessive
What are the histological features of AATD in the liver?
🩸 Mild portal inflammation (mainly lymphocytic)
🟡 Mild steatosis (periportal hepatocytes)
🏗️ Diffuse nodulation (fibrous bands dividing liver into regenerative nodules)
How does AATD affect the lungs?
🫁 Early-onset emphysema (especially in lower lobes) due to lack of AAT protection against oxidative damage. This is exacerbated by smoking
What are the long-term risks of AATD?
⚠️ Cirrhosis and increased risk of hepatocellular carcinoma (HCC)
What are the histological features of AATD?
Eosinophilic PAS-positive globules in Zone 1 hepatocytes
Mild portal inflammation (lymphocytic)
Periportal fibrosis → cirrhosis
What are the main diagnostic tests for AATD?
🩸 Serum AAT levels, Genetic testing for PiZZ mutation
Low AAT levels → Suggestive of disease
What are the treatment options for AATD
💨 Lung: AAT replacement therapy, smoking cessation
🏥 Liver: Liver transplant if cirrhosis develops
