L19 - Liver pathology

Question 1

Why is the liver unique in its ability to regenerate

Answer 1

🔄 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.

Question 2

What is the first question to consider when a liver mass is detected?

Answer 2

🧐 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

Question 3

What are the most common primary liver tumours?

Answer 3

🏥 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.

Question 4

What conditions predispose individuals to primary liver cancer?

Answer 4

⚠️ 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

Question 5

How does the liver’s vascular supply influence tumour resection?

Answer 5

🩸 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.

Question 6

How can liver tumours be detected through physical examination?

Answer 6

🤲 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.

Question 7

What do signs of a liver tumour include during an abdominal examination

Answer 7

📏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

Question 8

What is the functional unit of the liver?

Answer 8

🏗️ The hepatic lobule is the functional unit of the liver

Question 9

How is the liver vascularised?

Answer 9

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.

Question 10

Why is the liver a key organ for drug metabolism and detoxification?

Answer 10

💊 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.

Question 11

What is an example of another organ that contributes to drug exertion

Answer 11

The kidneys also contribute to drug excretion, but the liver is the primary site of metabolism.

Question 12

How does liver function affect vitamin D metabolism?

Answer 12

☀️ 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).

Question 13

What are hepatocytes

Answer 13

Hepatocytes are the main functional cells of the liver

Question 14

What is the structure of hepatocyes

Answer 14

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.

Question 15

what are the two types of epithelial cells in the liver?

Answer 15

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.

Question 16

How is the liver anaotomically divided?

Answer 16

🏥 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.

Question 17

What is the most common primary liver maliganacy worldwide?

Answer 17

🏥 Hepatocellular carcinoma (HCC) is the most common primary epithelial cancer of the liver, accounting for >80% of primary liver malignancies worldwide

Question 18

How common is hepatocellular carcinoma (HCC) globally?

Answer 18

🌍 HCC is the 5th most common malignancy worldwide, with a male-to-female ratio of 3:1.

Question 19

What is the most common risk factor for hepatocellular carcinoma (HCC)

Answer 19

🍺 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.

Question 20

What is the normal histological structure of the liver?

Answer 20

🏗 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.

Question 21

what is the homogenous texture of the liver?

Answer 21

the liver is soft, dark brown and lacks a significant fibrous component in normal conditions

Question 22

How does hepatocellular carcinoma (HCC) appear macroscopically?

Answer 22

🔬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

Question 23

What factors are contributing to the increasing prevalence of HCC

Answer 23

📈 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

Question 24

Which region has the highest incidence of hepatocellular carcinoma?

Answer 24

🌏 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%)

Question 25

How does the median age of onset for HCC vary geographically?

Answer 25

📊 North America & Europe: Older than the 6th decade 📊Asia & Africa: Between the 3rd and 6th decades (younger)

Question 26

What are the main risk factors for hepatocellular carcinoma?

Answer 26

🚨 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

Question 27

What is the leading global cause of hepatocellular carcinoma?

Answer 27

🦠 Chronic viral hepatitis (HBV & HCV) is the leading cause of HCC worldwide.

Question 28

How is viral hepatitis transmitted?

Answer 28

💉 Hepatitis B & C: Blood & body fluids 🍽️ Hepatitis A: Fecal-oral route

Question 29

how does aflatoxin exposure increase HCC risk?

Answer 29

🍄 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

Question 30

How has climate change affected aflatoxin risk?

Answer 30

🌍 Rising temperature & humidity in regions like Northern Europe may increase aflatoxin contamination, posing a greater HCC risk.

Question 31

What was Thorotrast, and how did it affect liver cancer risk?

Answer 31

🏥 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.

Question 32

What are the classic signs of liver dysfunction in HCC patients?

Answer 32

💧 Ascites (fluid accumulation in the abdomen) 🩸Caput medusae (dilated superficial abdominal veins) 🟡 Jaundice (yellow skin & eyes) 🩹Easy bruising (due to impaired coagulation)

Question 33

What are the main diagnostic methods for HCC?

Answer 33

Imaging: CT/MRI with contrast 🖥️ Biopsy: Histological confirmation 🔬 Serum markers: Alpha-fetoprotein (AFP) 📊

Question 34

Why is imaging preferred over biopsy in HCC diagnosis?

Answer 34

🩻 Biopsies carry a risk of tumor seeding, so CT/MRI with contrast is often sufficient for diagnosis.

Question 35

What is the role of alpha-fetoprotein (AFP) in HCC?

Answer 35

📊 AFP is an HCC biomarker, but it is not specific and may be normal in early-stage HCC.

Question 36

: What staging system is commonly used for HCC?

Answer 36

🏥 The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly used to determine treatment options.

Question 37

What factors affect the prognosis of hepatocellular carcinoma?

Answer 37

Tumor size & spread 📏 Presence of vascular invasion 🩸 Underlying liver function (Cirrhosis, Child-Pugh score) 🍷

Question 38

What should be considered when a solid liver mass is detected?

Answer 38

🏥 Solid masses require further evaluation, considering: Size 📏 Growth over time ⏳ Cirrhosis status 🍷

Question 39

What is the typical survival rate for untreated HCC?

Answer 39

⏳ Median survival without treatment is 6 months in advanced cases.

Question 40

How can the risk of hepatocellular carcinoma be reduced?

Answer 40

🛡️ Prevention strategies include: HBV vaccination 💉 HCV antiviral therapy 💊 Aflatoxin exposure reduction 🚫🍞 Alcohol moderation 🍷 Regular screening for high-risk patients 🩻

Question 41

What are the first considerations when a hepatic mass is suspected?

Answer 41

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)

Question 42

Are benign hepatic lesions more common than malignant ones?

Answer 42

✅ Yes, benign hepatic lesions are more common than malignant ones.

Question 43

What are some examples of benign non-epithelial hepatic lesions>

Answer 43

🩸 Hemangiomas are benign vascular lesions of the liver.

Question 44

What is the recommended approach for small liver lesions?

Answer 44

🔎 Monitor small lesions to check for changes in size.

Question 45

When is a liver biopsy considered?

Answer 45

📏 The lesion is >1 cm 🩻Imaging features are unclear 🩸The patient has good coagulative capacity

Question 46

What is a key limitation of liver biopsies?

Answer 46

💉 The accuracy depends on the biopsy sample quality and the operator’s skill.

Question 47

What is the initial step if a hepatic mass/ nodule is detected on imaging?

Answer 47

🩻 you assess the size: <1 cm → Repeat ultrasound in 4 months >1 cm → Perform multiphasic contrast-enhanced imaging (CT/MRI)

Question 48

What is the next step if a <1cm hepatic lesion remains stable?

Answer 48

✅ Continue monitoring with repeat imaging.

Question 49

What if a <1cm hepatic lesion shows a growing/changing pattern?

Answer 49

🔬 Consider further imaging or biopsy.

Question 50

What imaging techniques help detect HCC hallmarks?

Answer 50

🏥 Multiphasic contrast-enhanced CT, MRI, or gadoxetic-enhanced MRI.

Question 51

What happens if one imaging technique detects HCC hallmarks?

Answer 51

✅ Diagnosis of HCC confirmed.

Question 52

What if the first imaging technique does not detect HCC hallmarks?

Answer 52

Another modality (CT/MRI/ contrast-enhanced ultrasound) for confirmation

Question 53

If a second imaging technique is also negative, what is the next step?

Answer 53

🔬 Biopsy is needed for further evaluation.

Question 54

why might a biopsy be needed despite negative imaging?

Answer 54

🔬 Imaging can miss atypical cases, requiring histological confirmation

Question 55

What happens if a biopsy results is unclear?

Answer 55

🔄 Consider re-biopsy.

Question 56

Why is a multu-step imaging process used for HCC diagnosis?

Answer 56

🔄 HCC progression is gradual—from dysplastic nodules to malignancy. Multiple imaging steps ensure accurate detection at different stages.

Question 57

What is the stepwide progression of helaptocellular carcinoma (stages 1-4)

Answer 57

🧬 Stages: 1️⃣ Low-grade dysplastic nodule 2️⃣ High-grade dysplastic nodule 3️⃣ Early hepatocellular carcinoma 4️⃣ Progressed hepatocellular carcinoma

Question 58

What molecular alterations are linked to HCC progression

Answer 58

🧬 telomere shortening ⚙️ TERT activation 🚦CEll cycle checkpoint inhibition

Question 59

What is TERT

Answer 59

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

Question 60

What is a key mutation in HCC progression

Answer 60

🔑 TERT promoter mutation is a crucial event in HCC progression.

Question 61

What are the three major molecular clusters in HCC?

Answer 61

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)

Question 62

How do these genetic clusters influence HCC behavious

Answer 62

🏥 Different mutations affect tumor progression, treatment response, and prognosis.

Question 63

Why do some genetic mutations overlap in HCC?

Answer 63

🔄 Some mutations co-exist, leading to complex tumor behavior and different molecular subtypes.

Question 64

Why is identifying HCC subtypes important?

Answer 64

🩺 Different subtypes have unique behaviors and may occur at younger ages (but can be easily mistaken for benign lesions)

Question 65

Why should clinicians consider HCC in younger patients?

Answer 65

⚠️ HCC typically occurs in the 5th or 6th decade, but certain subtypes can appear earlier.

Question 66

What factors influence whether a liver lesion is benign or malignant?

Answer 66

🏥 Clinical history, imaging features, and biopsy results determine risk.

Question 67

What genetic mutation is associated with the serous subtype of HCC?

Answer 67

🧬 TSC1 and TSC2 mutations are linked to the serous subtype of HCC.

Question 68

What molecular pathway is activated in the atopatic subtype of HCC?

Answer 68

🔥 IL-6 (Interleukin-6) and JAK-STAT pathway activation drive the atopatic subtype.

Question 69

Which genetic mutations are associated with the macrotrabecular subtype of HCC?

Answer 69

🧬 TP53 mutation is a key driver of the macrotrabecular subtype.

Question 70

What is the characteristic genetic alteration in fibrolamellar HCC?

Answer 70

🧬 The DNAJB1-PRKACA fusion gene is the hallmark of fibrolamellar HCC.

Question 71

Why is fibrolamellar HCC an important differential diagnosis in younger patients?

Answer 71

🏥 Fibrolamellar HCC occurs earlier than other HCC subtypes and should be considered in younger patients presenting with liver masses.

Question 72

How does the morphology of fibrolamellar HCC differ from typical HCC?

Answer 72

🔬 Fibrolamellar HCC is more organised than conventional HCC, though it still lacks normal trabecular architecture.

Question 73

What histological feature distinguishes normal hepatocytes from HCC cells?

Answer 73

🔬 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.

Question 74

How do the nuclei of HCC cells differ from normal liver cells?

Answer 74

🔬 HCC cells often have larger nuclei, double nuclei, or prominent eosinophilic nucleoli, indicating cellular atypia.

Question 75

What histological features indicate HCC with cirrhosis

Answer 75

🔬 A circumscribed tumour in the presence of cirrhotic liver changes suggests HCC rather than benign lesions.

Question 76

How does the background liver tissue help differentiate fibrolamellar HCC from conventional HCC

Answer 76

🏥 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.

Question 77

What is the prognosis of fibrolamellar HCC compared to conventional HCC?

Answer 77

📈 Fibrolamellar HCC has a better prognosis than conventional HCC, but still requires early diagnosis and treatment.

Question 78

Which HCC subtypes are linked to a worse prognosis?

Answer 78

⚠️ More aggressive HCC subtypes include: 🧬 Sarcomatoid carcinoma 🧬 Carcinosarcoma 🔬 Macrotrabecular HCC 🦠 Cirrhotomimetic HCC 🏥 Neutrophil-rich HCC

Question 79

Which HCC subtypes have a similar or better prognosis than conventional HCC?

Answer 79

🫀 Steatohepatitic HCC 🔬 Clear cell HCC 🏥 Chromophobe HCC 📈 Fibrolamellar HCC 🦠 Lymphocyte-rich HCC

Question 80

Which HCC subtype has an unpredictable prognosis?

Answer 80

❓ Scirrhous HCC can behave variably, sometimes more aggressively and sometimes more indolently.

Question 81

What is the histological appearance of aggressive sarcomatoid carcinoma and carcinosarcoma?

Answer 81

🔬 These high-grade, undifferentiated tumours show: Severe loss of normal liver architecture Highly pleomorphic cells Sarcomatoid or spindle-cell differentiation

Question 82

How does macrotrabecular HCC compare in prognosis?

Answer 82

🏥 Macrotrabecular HCC is more aggressive and associated with a worse prognosis than conventional HCC.

Question 83

how does immune infiltration affect HCC prognosis?

Answer 83

🦠 Neutrophil-rich HCC tends to have a worse prognosis, while lymphocyte-rich HCC has a better prognosis.

Question 84

What is cholangiocarcinoma, and where does it arise from?

Answer 84

🏥 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).

Question 85

How is cholangiocarcinoma diagnosed?

Answer 85

🔬 Diagnosis of exclusion—must first rule out metastatic adenocarcinoma before confirming primary cholangiocarcinoma.

Question 86

What is the age group most affected by cholangiocarcinoma?

Answer 86

📅 Typically affects patients aged 60–70 years.

Question 87

Is there a gender preference for cholangiocarcinoma?

Answer 87

⚖️ Male = Female (unlike hepatocellular carcinoma, which is more common in men).

Question 88

What is the prognosis of cholangiocarcinoma?

Answer 88

❌ Poor prognosis—often associated with chronic liver disease and cirrhosis.

Question 89

What are the infectious cases of cholangiocarcinoma

Answer 89

🦠 Viral hepatitis (HBV, HCV).

Question 90

What metabolic conditions increase the risk of cholangiocarcinoma?

Answer 90

⚡ Non-alcoholic fatty liver disease (linked to obesity & diabetes), hemochromatosis, and alpha-1 antitrypsin deficiency.

Question 91

What environmental exposure increases the risk of cholangiocarcinoma?

Answer 91

☢️ Aflatoxin, alcohol, steroids, oral contraceptives, tobacco, and Thorotrast (a past radiographic contrast agent).

Question 92

What congenital or developmental conditions are linked to cholangiocarcinoma?

Answer 92

🧬 Abernethy malformation, Alagille syndrome, Ataxia telangiectasia

Question 93

What are the histological characteristics of cholangiocarcinoma?

Answer 93

🔬 The tumour consists of small, bluish cells forming glandular structures, in contrast to hepatocytes, which are larger and pinkish with granular cytoplasm.

Question 94

What is the most important step when seeing a glandular tumour in the liver?

Answer 94

🛑 First rule out metastatic adenocarcinoma! Only after excluding metastases can cholangiocarcinoma be diagnosed.

Question 95

How does a cirrhotic liver differ from a normal liver in size and consistency

Answer 95

🏥 A cirrhotic liver is smaller, harder, and has a sharp edge upon palpation.

Question 96

What does the surface of a cirrhotic liver look like?

Answer 96

🌰 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)

Question 97

What are the two types of nodules seen in cirrhosis?

Answer 97

🔬 Micro-nodules and macro-nodules, which are separated by strands of fibrous tissue.

Question 98

what is the difference between micronodular and macronodular cirrhosis?

Answer 98

🔬 micronodular cirrhosis has nodules smaller than 3mm, while macronodular cirrhosis has nodules larger than 3mm

Question 99

How does cirrhosis affect liver function at a cellular level?

Answer 99

🚫 Even though hepatocytes are still present, their disorganized arrangement prevents proper liver function.

Question 100

What percentage of hepatitis cases in the US are caused by Hepatitis B?

Answer 100

40% of hepatitis cases are Hepatitis B in the US

Question 101

What are the key features of Hepatitis B infection?

Answer 101

⚠️ 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

Question 102

How is Hepatitis B transmitted?

Answer 102

🩸 Via infected blood, sexual contact, intravenous drug use, contaminated instruments, or mother-to-child during delivery.

Question 103

What defines a Hepatitis B carrier state (chronic hepatitis B) ?

Answer 103

🛑 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).

Question 104

what are ALT And AST

Answer 104

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.

Question 105

What kind of virus is Hepatitis C?

Answer 105

🦠 Flavivirus, enveloped RNA virus.

Question 106

What percentage of non-A, non-B hepatitis cases are caused by Hepatitis C?

Answer 106

📊 90%.

Question 107

What percentage of transfusion associated hepatitis cases are due to hepatitis C?

Answer 107

💉 75-95%.

Question 108

What are the main transmission routes for Hepatitis C?

Answer 108

💉 35% IV drug use 🏠 15% household/heterosexual exposure 🩸 5% blood transfusion ❓ 45% unknown cause

Question 109

Is acute liver failure common in Hepatitis C?

Answer 109

🚫 No, it is rare.

Question 110

What is the risk of developing hepatocellular carcinoma (HCC) in Hepatitis C patients with alcoholic cirrhosis?

Answer 110

🍺 57% at 10 years.

Question 111

Can hepatitis C cause hepatocellular carcinoma (HCC) without cirrhosis?

Answer 111

❌ No, unlike Hepatitis B, HCC from Hepatitis C is only seen after cirrhosis has developed.

Question 112

What histological features are associated with Hepatitis C

Answer 112

Sinusoidal lymphocytic infiltrate Lymphoid follicles surrounding damaged bile ducts Portal tract involvement Mallory hyaline Mild focal macrovesicular steatosis Minimal necrosis

Question 113

what is sinusoidal lymphocytic infiltrate (Hep C)

Answer 113

🦠 Lymphocytes (a type of white blood cell) accumulating in the liver sinusoids (small blood vessels in the liver), indicating chronic inflammation and immune response.

Question 114

What is lymphoid folliclesWhat is portal tract involvement in Hepatitis C?

Answer 114

🏗️ Inflammatory cells expanding the portal tracts, leading to fibrosis and progressive liver damage.

Question 115

What is Mallory hyaline (Hep C)

Answer 115

🏵️ Abnormal, tangled cytoplasmic protein deposits found in hepatocytes, often seen in alcoholic liver disease but also present in Hepatitis C.

Question 116

What is mild focal macrovesicular steatosis (hep C)

Answer 116

🫧 Fat accumulation (large lipid droplets) in liver cells, occurring in patches (‘focal’), indicating metabolic stress on the liver.

Question 117

What is minimal necrosis in Hep C?

Answer 117

💀 Only slight death of hepatocytes, suggesting that the infection causes slow, chronic damage rather than severe acute liver failure.

Question 118

What is a specific but insensitive histological marker of Hep C

Answer 118

🔍 Lymphoid aggregates (specific but only 50% sensitive).

Question 119

What type of fibrosis is common in Hep C

Answer 119

🏗️ Portal fibrosis.

Question 120

Why is hepatitic C becoming more common

Answer 120

📈 Due to increased protection against Hepatitis B, leading to a shift in prevalence.

Question 121

What are the key features of hepatitis D (HDV)

Answer 121

🦠 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

Question 122

How is Hepatitis E (HEV) transmitted?

Answer 122

🚰 Faeco-oral transmission via contaminated water

Question 123

Why is Hepatitis E (HEV) dangerous in pregnancy?

Answer 123

🤰 Poor outcome in pregnant women, with up to 22% mortality ⚠️ Can cause fulminant hepatitis 🩸 Associated with disseminated intravascular coagulation (DIC)

Question 124

What is (Non) Alcholoc Fatty liver disease (NAFLD / AFLD)

Answer 124

🏥 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

Question 125

How does a fatty liver appear?

Answer 125

🟡 Soft, yellow, and greasy 🏋️ Liver is enlarged ✨ Shiny surface without cirrhotic nodules

Question 126

What are the histological features of fatty liver disease?

Answer 126

🔬 Predominantly macrovesicular steatosis (≥5% hepatocytes under low magnification) 🔥 Lobular inflammation 🎈 Ballooning degeneration 🧶 Fibrosis (if disease progresses)

Question 127

Why does fatty liver disease progress to fibrosis?

Answer 127

🛢️ Lipid vacuoles rupture which triggers inflammation and fibrosis to form

Question 128

How is NAFLD severity evaluated

Answer 128

📊 Scored by: 🛢️ Lipid content (steatosis) 🔥 Presence of inflammation 🎈 Cell deformation (ballooning degeneration) 🧶 Degree of fibrosis

Question 129

What is Primary biliary Cholangitis (PBC)

Answer 129

🏥 Chronic, progressive cholestatic liver disease where granulomatous destruction of interlobular bile duct leads to fibrosis and later cirrhosis

Question 130

Who is most affected by Primary billary cholangitis (PBC)

Answer 130

👩 Middle-aged women (rare in children)

Question 131

What autoimmune conditions are associated with PBC?

Answer 131

🦷 Sjogren syndrome (autoimmune disease where the immune system attacks tear and saliva glands) 🦋 Systemic lupus erythematosus (SLE) 🦠 Thyroiditis 🖐️ Raynaud’s phenomenon

Question 132

What lab findings are characteristics of PBC?

Answer 132

⬆️ Alkaline phosphatase (ALP) ⬆️ IgM 🧪 Antimitochondrial antibody (AMA) positive (classic marker)

Question 133

What are the histological features of PBC`

Answer 133

🌸 Florid duct lesions (pathognomonic) 🎯 Patchy involvement of interlobular bile ducts & canals of Hering ❌ Does not affect larger bile ducts

Question 134

How does PBC differ from primary sclerosing cholangitis?

Answer 134

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

Question 135

what is drug-induced liver injury (DILI)

Answer 135

💊 Liver damage caused by medications, herbs, or toxins which is diagnosed through exclusion and can present with any histological pattern

Question 136

What is a key feature often associated with DILI

Answer 136

🚦 Cholestasis (impaired bile flow)

Question 137

Why is drug history important in diagnosing DILI?

Answer 137

📋 Because morphology is nonspecific, history helps identify potential hepatotoxic drugs

Question 138

What types of drigs are known to cause liver damage?

Answer 138

⚠️ 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

Question 139

What is Wilson's disease?

Answer 139

🧬 Autosomal recessive disorder causing copper accumulation 🏥 1 in 30,000 people affected 🏡 Tends to present in childhood

Question 140

What causes liver damage in Wilson's disease?

Answer 140

🧪 Copper accumulation exceeds ceruloplasmin binding capacity, leading to toxicity and liver injury 🏚️ Lysosomal buildup → Fibrosis → Cirrhosis

Question 141

What are the neurological symtoms of Wilson's Disease?

Answer 141

🧠 Putamen copper accumulation → Psychosis or Parkinsonian symptoms

Question 142

What is the eye finding in Wilson's disease?

Answer 142

👁️ Kayser-Fleischer Rings (copper deposition in the cornea)

Question 143

What other organs are affected in Wilson’s Disease?

Answer 143

👁️ Cornea (Kayser-Fleischer rings) 🦴 Bones & joints 🩺 Kidneys 🦴 Parathyroid gland (hormonal effects)

Question 144

What is haemochromatosis?

Answer 144

⚙️ Excessive iron accumulation in the body ( happens over time)

Question 145

What are the major organs affected by hemochromatosis?

Answer 145

🏥 Liver, pancreas, heart Liver → Cirrhosis, fibrosis Pancreas → Diabetes-like symptoms Heart → Cardiomyopathy, arrhythmias

Question 146

What are the two types of haemochromatosis?

Answer 146

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)

Question 147

What are the complications of iron accumulation in haemochromatosis?

Answer 147

⚠️ Cirrhosis, diabetes-like symptoms (pancreatic damage), cardiac abnormalities (myocardium involvement) 🏥 Increases risk of hepatocellular carcinoma (HCC)

Question 148

What are the clinical symtoms of haemochromatosis?

Answer 148

🩸 Fatigue, diabetes symptoms, joint pain, skin pigmentation ("bronze diabetes") Early: Non-specific symptoms (fatigue, joint pain) Late: Cirrhosis, diabetes, cardiomyopathy, arthritis

Question 149

What is the main diagnostic test for hemochromatosis?

Answer 149

🧪 Serum ferritin & transferrin saturation High ferritin (iron storage protein) High transferrin saturation (>45%)

Question 150

What is the treatment for hemochromatosis

Answer 150

💉 Regular phlebotomy (removes excess iron) 🏥 Iron chelation (for severe cases)

Question 151

What is alpha-1 Antitrupsin Deficiency (AATD)

Answer 151

🏥 Genetic metabolic disorder → Deficiency of Alpha-1 Antitrypsin (AAT) 🧬 Autosomal recessive disease

Question 152

What happens when AAT accumulates in the liver?

Answer 152

🏚️ mutant AAT accumulates in hepatocytes → Fibrosis and cirrhosis 🔬 Eosinophilic intracytoplasmic globules in periportal hepatocytes (Zone 1)

Question 153

What is AAT

Answer 153

Alpha-1 antitrypsin which inhibits neurtophil elastase, protecting lung and liver from damage

Question 154

what type of inheritance is AATD

Answer 154

Autosomal recessive

Question 155

What are the histological features of AATD in the liver?

Answer 155

🩸 Mild portal inflammation (mainly lymphocytic) 🟡 Mild steatosis (periportal hepatocytes) 🏗️ Diffuse nodulation (fibrous bands dividing liver into regenerative nodules)

Question 156

How does AATD affect the lungs?

Answer 156

🫁 Early-onset emphysema (especially in lower lobes) due to lack of AAT protection against oxidative damage. This is exacerbated by smoking

Question 157

What are the long-term risks of AATD?

Answer 157

⚠️ Cirrhosis and increased risk of hepatocellular carcinoma (HCC)

Question 158

What are the histological features of AATD?

Answer 158

Eosinophilic PAS-positive globules in Zone 1 hepatocytes Mild portal inflammation (lymphocytic) Periportal fibrosis → cirrhosis

Question 159

What are the main diagnostic tests for AATD?

Answer 159

🩸 Serum AAT levels, Genetic testing for PiZZ mutation Low AAT levels → Suggestive of disease

Question 160

What are the treatment options for AATD

Answer 160

💨 Lung: AAT replacement therapy, smoking cessation 🏥 Liver: Liver transplant if cirrhosis develops