Liver and Biliary Pathology — MCQs

Liver and Biliary Pathology Indian Medical PG Practice Questions and MCQs

Question 111: What are the most likely histological findings on a liver biopsy from a 20-year-old male who died due to acetaminophen overdose?

A. Focal scattered necrosis
B. Midzonal necrosis
C. Centrizonal necrosis (Correct Answer)
D. Steatohepatitis

Explanation: **Explanation:** **Acetaminophen (Paracetamol) toxicity** is a classic cause of drug-induced liver injury [1]. The correct answer is **Centrizonal necrosis (Zone 3 necrosis)** because of the unique metabolic profile of the liver lobule [1]. 1. **Why Centrizonal Necrosis is Correct:** Acetaminophen is metabolized in the liver by the **Cytochrome P450 system** (specifically CYP2E1) into a highly reactive toxic metabolite called **NAPQI** [2]. The highest concentration of P450 enzymes is found in **Zone 3 (the centrizonal area)** surrounding the central vein [1]. Furthermore, Zone 3 has the lowest oxygen tension and the least amount of glutathione (which neutralizes NAPQI). Consequently, when glutathione stores are exhausted, NAPQI causes massive oxidative stress and covalent bonding to cellular proteins, leading to necrosis specifically in Zone 3 [1]. 2. **Why Other Options are Incorrect:** * **Focal scattered necrosis:** This is typical of viral hepatitis (spotty necrosis) rather than predictable dose-dependent toxins [1]. * **Midzonal necrosis (Zone 2):** This is extremely rare but can be seen in Yellow Fever. * **Steatohepatitis:** This is characterized by fat accumulation, Mallory-Denk bodies, and neutrophil infiltration, typically seen in Alcohol-associated Liver Disease or NAFLD/NASH, not acute acetaminophen poisoning [2]. **NEET-PG High-Yield Pearls:** * **Antidote:** N-acetylcysteine (NAC), which replenishes glutathione stores. * **Zonal Anatomy:** Zone 1 (Periportal) is affected first by phosphorus poisoning or Eclampsia; Zone 3 is affected by Ischemia ("Shock liver"), Halothane, and Acetaminophen [1]. * **Histology:** In severe cases, centrizonal necrosis can progress to **massive hepatic necrosis**, leading to a "shrunken" liver [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, p. 832. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 846-847.

Question 112: Microvascular steatosis is seen in all of the following conditions except?

A. Alcoholic liver disease (Correct Answer)
B. Acute fatty liver of pregnancy
C. Methotrexate toxicity
D. Reye syndrome

Explanation: **Explanation:** The distinction between **macrovesicular** and **microvesicular** steatosis is a high-yield concept in hepatic pathology. **1. Why Alcoholic Liver Disease (ALD) is the correct answer:** Alcoholic liver disease typically presents with **macrovesicular steatosis**. In this condition, large lipid droplets accumulate within the cytoplasm of hepatocytes, displacing the nucleus to the periphery [1]. While chronic alcohol use is the most common cause of macrovesicular steatosis globally, it does not typically cause the microvesicular form [2]. **2. Analysis of Incorrect Options (Causes of Microvesicular Steatosis):** In microvesicular steatosis, the cytoplasm is filled with tiny lipid vesicles that do not displace the nucleus, often due to mitochondrial dysfunction and impaired beta-oxidation of fatty acids. * **Acute Fatty Liver of Pregnancy (AFLP):** A life-threatening third-trimester emergency characterized by diffuse microvesicular fat. * **Reye Syndrome:** Occurs in children following a viral illness treated with aspirin; it features mitochondrial injury leading to microvesicular steatosis. * **Methotrexate Toxicity:** While methotrexate is primarily associated with hepatic fibrosis and cirrhosis, acute or high-dose toxicity can manifest as microvesicular steatosis. (Other drugs include Valproate and Tetracyclines). **Clinical Pearls for NEET-PG:** * **Macrovesicular Steatosis:** Most common causes are **Alcohol**, **Obesity/Diabetes (NAFLD)**, and **Hepatitis C (Genotype 3)** [1], [3]. * **Microvesicular Steatosis:** Think of the mnemonic **"MARS"** — **M**ethotrexate/Mitochondrial toxins, **A**FLP, **R**eye Syndrome, and **S**alicylates/Sodium Valproate. * **Histology Tip:** In microvesicular steatosis, the liver cells have a "foamy" appearance, but the nucleus remains central. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 848-850. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 389-390. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 852-854.

Question 113: A 1-month-old newborn presents with conjugated hyperbilirubinemia, intrahepatic cholestasis, and high alkaline phosphatase. Eosinophilic, PAS-positive cytoplasmic granules are seen in a liver biopsy specimen. What is the diagnosis?

A. Alpha-1-antitrypsin deficiency (Correct Answer)
B. Congenital hepatic fibrosis
C. Extrahepatic biliary atresia
D. Ductal plate abnormality

Explanation: **Explanation:** The clinical presentation of neonatal cholestasis (conjugated hyperbilirubinemia and high ALP) combined with the classic histological finding of **eosinophilic, PAS-positive, diastase-resistant cytoplasmic globules** in hepatocytes is pathognomonic for **Alpha-1-Antitrypsin (A1AT) Deficiency** [1]. 1. **Why A1AT Deficiency is correct:** A1AT is a protease inhibitor synthesized in the liver [1]. In the most common severe mutation (PiZZ), a single amino acid substitution causes the protein to misfold. These misfolded proteins cannot be secreted and instead aggregate within the endoplasmic reticulum of hepatocytes [1]. These aggregates appear as round-to-oval eosinophilic globules that stain positive with **Periodic Acid-Schiff (PAS)** and remain positive even after treatment with **diastase** (which digests glycogen). In infants, this leads to cholestatic jaundice and may progress to cirrhosis [1]. 2. **Why other options are incorrect:** * **Extrahepatic biliary atresia:** While it is the most common cause of neonatal cholestasis, the histology typically shows bile duct proliferation, portal fibrosis, and bile plugs, but *not* PAS-positive globules. * **Congenital hepatic fibrosis & Ductal plate abnormality:** These belong to the spectrum of fibropolycystic diseases. Histology shows "bridging" fibrosis and malformed, dilated bile ducts (ductal plate malformations) rather than intracellular protein accumulation. **High-Yield Pearls for NEET-PG:** * **Genetics:** Autosomal Codominant; localized on Chromosome 14 [1]. * **Stain:** PAS-positive, **Diastase-resistant** (crucial for differentiating from glycogen) [1]. * **Organ Involvement:** Liver (due to protein accumulation/toxicity) and Lungs (Panacinar emphysema due to lack of circulating protease inhibitor) [1]. * **Most common genetic cause** of liver disease in children. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 856-858.

Question 114: Midzonal necrosis in the liver may occur in which of the following conditions?

A. Enteric fever
B. Yellow fever (Correct Answer)
C. Scarlet fever
D. Rheumatic fever

Explanation: **Explanation:** The liver lobule is divided into three zones based on oxygenation and metabolic activity [1]. While most hepatotoxins cause Zone 3 (centrilobular) necrosis and certain toxins cause Zone 1 (periportal) necrosis, **Yellow Fever** is the classic and unique cause of **Zone 2 (midzonal) necrosis**. **Why Yellow Fever is correct:** In Yellow Fever, the virus causes characteristic midzonal necrosis. Histologically, this is accompanied by the presence of **Councilman bodies** (apoptotic, eosinophilic hepatocytes) [2] and **Torres bodies** (intranuclear inclusions). The sparing of the immediate periportal and pericentral areas is a hallmark of this viral infection. **Analysis of Incorrect Options:** * **Enteric Fever (Typhoid):** Characterized by "Typhoid nodules," which are small focal clusters of hepatocytes undergoing necrosis replaced by macrophages (Kupffer cells). It does not follow a midzonal pattern. * **Scarlet Fever:** Caused by *Streptococcus pyogenes*, it primarily manifests as a skin rash and "strawberry tongue." Liver involvement is rare and non-specific. * **Rheumatic Fever:** An autoimmune multi-system inflammatory disease following Group A Strep infection. While it affects the heart, joints, and CNS, it does not cause specific zonal liver necrosis. **High-Yield Clinical Pearls for NEET-PG:** * **Zone 1 (Periportal):** Affected by Phosphorus poisoning, Eclampsia, and Cocaine [1]. * **Zone 2 (Midzonal):** Classically **Yellow Fever**. * **Zone 3 (Centrilobular):** Most common site of injury. Affected by Ischemia (Shock liver), Paracetamol (Acetaminophen) toxicity [1], [3], and Carbon tetrachloride ($CCl_4$). * **Councilman Bodies:** Also seen in other viral hepatitides [2], but most famously associated with Yellow Fever in the context of midzonal patterns. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, p. 828. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 386-387. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, p. 832.

Question 115: Which of the following is false regarding Dubin-Johnson syndrome?

A. Liver is darkly pigmented
B. It is an autosomal recessive disorder
C. It causes unconjugated hyperbilirubinemia (Correct Answer)
D. It is caused by a mutation in the canalicular multidrug resistance protein 2

Explanation: **Explanation:** **Dubin-Johnson Syndrome (DJS)** is an autosomal recessive disorder characterized by a defect in the transport of bilirubin from hepatocytes into the bile canaliculi [1]. 1. **Why Option C is False (The Correct Answer):** DJS causes **conjugated hyperbilirubinemia**, not unconjugated [1]. In this condition, the liver can conjugate bilirubin with glucuronic acid normally, but it lacks the transport protein required to excrete the conjugated bilirubin into the bile. Consequently, conjugated bilirubin leaks back into the blood, leading to jaundice. 2. **Analysis of Other Options:** * **Option A (Liver Pigmentation):** This is a hallmark feature. Due to the impaired excretion of epinephrine metabolites (polymers of epinephrine), they accumulate in lysosomes, giving the liver a characteristic **grossly black/dark brown appearance** [1]. * **Option B (Inheritance):** DJS follows an **autosomal recessive** pattern of inheritance [1]. * **Option D (Molecular Defect):** The condition is caused by a mutation in the **ABCC2 gene**, which encodes the **Multidrug Resistance-associated Protein 2 (MRP2)** [1]. This protein is essential for the canalicular secretion of conjugated bilirubin and other organic anions. **High-Yield Clinical Pearls for NEET-PG:** * **Rotor Syndrome vs. DJS:** Both cause conjugated hyperbilirubinemia, but Rotor Syndrome **does not** feature a pigmented liver and has a different urinary coproporphyrin excretion pattern [1]. * **Urinary Coproporphyrin:** In DJS, total urinary coproporphyrin levels are normal, but **>80% is Coproporphyrin I** (normally, Coproporphyrin III predominates). * **Oral Cholecystography:** The gallbladder is typically **not visualized** in DJS due to the inability to excrete the contrast medium. * **Prognosis:** DJS is a benign condition and generally does not require treatment [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, p. 860.

Question 116: A patient with cirrhosis is positive for HBsAg and has increased levels of alpha-fetoprotein. What is the most probable diagnosis?

A. Submassive hepatic necrosis
B. Hepatocellular carcinoma (Correct Answer)
C. Massive hepatic necrosis
D. None of the above

Explanation: **Explanation:** The correct diagnosis is **Hepatocellular Carcinoma (HCC)**. This conclusion is based on the classic triad of risk factors and biomarkers presented in the question: 1. **Chronic Liver Disease (Cirrhosis):** Cirrhosis is the strongest predisposing factor for HCC, acting as a premalignant state due to continuous hepatocyte regeneration and oxidative stress [1]. 2. **Hepatitis B Infection (HBsAg positive):** HBV is a major oncogenic virus. It can cause HCC both indirectly (via cirrhosis) and directly (by integrating its DNA into the host genome, leading to genomic instability) [2], [3]. 3. **Tumor Marker (Alpha-fetoprotein):** AFP is the most specific serum marker for HCC [1]. While mild elevations can occur in hepatitis, significantly increased levels in a cirrhotic patient are highly suggestive of malignant transformation. **Analysis of Incorrect Options:** * **Options A & C (Submassive and Massive Hepatic Necrosis):** These refer to patterns of acute, severe liver injury (e.g., fulminant viral hepatitis or drug toxicity like Paracetamol). While they cause a rise in transaminases (AST/ALT), they do not typically present with elevated AFP or occur as a primary complication of chronic cirrhosis in this context. * **Option D:** Incorrect, as the clinical presentation perfectly fits the profile of HCC. **NEET-PG High-Yield Pearls:** * **Most common primary site of metastasis to the liver:** Colon. * **Most common primary malignant tumor of the liver:** Hepatocellular Carcinoma. * **Fibrolamellar Variant of HCC:** Occurs in young adults, is *not* associated with cirrhosis or HBV, and typically has a **normal AFP**. * **Screening:** Patients with cirrhosis should undergo screening every 6 months using Ultrasound and AFP levels [1]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 399-400. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 876-877. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 838-840.

Question 117: Sclerosing cholangitis is most likely seen in which of the following conditions?

A. Ulcerative colitis (Correct Answer)
B. Hemochromatosis
C. Wilson disease
D. Primary biliary cirrhosis

Explanation: **Explanation:** **Primary Sclerosing Cholangitis (PSC)** is a chronic cholestatic liver disease characterized by inflammation, obliterative fibrosis, and segmental narrowing of both intrahepatic and extrahepatic bile ducts [2]. 1. **Why Ulcerative Colitis (UC) is correct:** There is a very strong clinical association between PSC and Inflammatory Bowel Disease (IBD) [1]. Approximately **70-80% of patients with PSC have underlying Ulcerative Colitis** [2]. Conversely, about 4-5% of UC patients will develop PSC [2]. The pathogenesis is thought to involve immune-mediated injury, often presenting with the classic "onion-skin" fibrosis on biopsy and a "beaded appearance" of bile ducts on ERCP/MRCP [1], [2]. 2. **Why other options are incorrect:** * **Hemochromatosis:** This is a disorder of iron overload leading to micronodular cirrhosis, skin hyperpigmentation, and diabetes ("bronze diabetes"). It does not primarily affect the biliary tree. * **Wilson Disease:** This involves impaired copper excretion leading to copper accumulation in the liver (cirrhosis), brain (basal ganglia), and eyes (Kayser-Fleischer rings). It is not associated with sclerosing cholangitis. * **Primary Biliary Cholangitis (PBC):** While also a cholestatic disease, PBC primarily affects **small intrahepatic bile ducts** and is most commonly seen in middle-aged women. It is characterized by Anti-Mitochondrial Antibodies (AMA), which are typically absent in PSC. **High-Yield Pearls for NEET-PG:** * **Imaging Gold Standard:** MRCP/ERCP showing "string of beads" appearance [2]. * **Serology:** PSC is often associated with **p-ANCA** (positive in 60-80% of cases). * **Biopsy:** Characteristic **"Onion-skin" fibrosis** (periductal fibrosis) [1]. * **Malignancy Risk:** PSC significantly increases the risk of **Cholangiocarcinoma** and Colorectal Cancer. * **Gender:** Unlike PBC (females), PSC is more common in **males** (2:1 ratio) [2]. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 393-394. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 865-866.

Question 118: Anti-LKM antibodies are seen in which condition?

A. Type I Autoimmune hepatitis
B. Type II Autoimmune hepatitis
C. Drug-induced hepatitis (Correct Answer)
D. Chronic hepatitis D

Explanation: **Explanation:** The presence of **Anti-Liver Kidney Microsome (Anti-LKM) antibodies** is a classic marker for autoimmune-mediated liver injury, but their specific subtype determines the clinical association [1]. **Why Drug-induced Hepatitis is correct:** While Anti-LKM-1 is the hallmark of Type II Autoimmune Hepatitis (AIH) [1], **Anti-LKM-2** antibodies are specifically associated with **Drug-Induced Liver Injury (DILI)**, historically linked to the drug **Ticrynafen** (a diuretic) [1]. These antibodies are directed against Cytochrome P450 2C9. In the context of this specific question, "Drug-induced hepatitis" is a recognized association for the LKM antibody family [1]. **Analysis of Incorrect Options:** * **Type I Autoimmune Hepatitis:** This is the most common form of AIH. It is characterized by **Anti-Nuclear Antibodies (ANA)** and/or **Anti-Smooth Muscle Antibodies (ASMA)**, not Anti-LKM [1]. * **Type II Autoimmune Hepatitis:** This subtype is characterized by **Anti-LKM-1** antibodies (targeting CYP2D6) and Anti-Liver Cytosol type 1 (ALC-1) antibodies [1]. It typically affects children and young girls. * **Chronic Hepatitis D:** While some patients with Chronic Hepatitis C or D may transiently develop Anti-LKM-3 antibodies, it is not the primary diagnostic marker for Hepatitis D. **High-Yield Clinical Pearls for NEET-PG:** * **LKM-1:** Type II Autoimmune Hepatitis (Target: CYP2D6) [1]. * **LKM-2:** Drug-induced hepatitis (Target: CYP2C9). * **LKM-3:** Chronic Hepatitis D (Target: UDP-glucuronosyltransferase). * **SLA/LP (Soluble Liver Antigen):** Most specific marker for Autoimmune Hepatitis [1]. * **Type I AIH** is associated with **HLA-DR3 or DR4**, whereas **Type II** is associated with **HLA-DRB1 and DQB1**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 845-846.

Question 119: A macroscopic hepatic change known as nutmeg liver is indicative of?

A. Acute left-sided heart failure
B. Acute right-sided heart failure
C. Alcohol toxicity
D. Chronic congestive heart failure (Correct Answer)

Explanation: **Explanation:** **Nutmeg liver** is the classic macroscopic description for **Chronic Passive Congestion (CPC)** of the liver, most commonly caused by **Chronic Congestive Heart Failure (right-sided).** [1] **Why the correct answer is right:** In chronic right-sided heart failure, there is a "back-up" of blood into the inferior vena cava and hepatic veins. This leads to persistent venous congestion within the liver [2]. The increased pressure causes congestion and hemorrhage in the **centrilobular areas (Zone 3)**, which are furthest from the arterial blood supply [1]. Macroscopically, these congested red-brown areas contrast with the surrounding pale, fatty, or normal hepatocytes (Zones 1 and 2), creating a mottled appearance resembling the cut surface of a **nutmeg** [3]. **Why the other options are wrong:** * **Acute Heart Failure (A & B):** Acute failure typically results in sudden congestion and possibly centrilobular necrosis, but it does not provide enough time for the distinct, alternating mottled pattern of "nutmeg liver" to develop. * **Alcohol Toxicity (C):** Chronic alcohol consumption typically leads to steatosis (fatty liver), alcoholic hepatitis (Mallory-Denk bodies), or micronodular cirrhosis. While the liver may appear yellow and greasy, it does not show the red-mottled nutmeg pattern unless heart failure is also present. **High-Yield Clinical Pearls for NEET-PG:** * **Microscopic view:** Centrilobular (Zone 3) congestion, hemorrhage, and atrophy of hepatocytes [1]. * **Cardiac Cirrhosis:** If chronic congestion persists, it can lead to fibrosis, specifically "bridging fibrosis" between central veins, known as cardiac cirrhosis [3]. * **Zone 3 Vulnerability:** Zone 3 is the most susceptible to both congestion and hypoxia because it is the least oxygenated part of the hepatic acinus [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Hemodynamic Disorders, Thromboembolic Disease, and Shock, p. 126. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 401-402. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 870-872.

Question 120: All of the following are true about fibrolamellar hepatocellular carcinoma except?

A. Associated with raised Alpha-fetoprotein (AFP) (Correct Answer)
B. Recurrences are seen despite a better prognosis
C. Increased neurotensin and vitamin B12 binding globulin
D. Lymph node metastasis is seen

Explanation: **Explanation:** Fibrolamellar Hepatocellular Carcinoma (FL-HCC) is a distinct variant of hepatocellular carcinoma that typically occurs in young adults (20–40 years) without underlying cirrhosis or hepatitis virus infection. **1. Why Option A is the correct answer (The Exception):** Unlike conventional HCC, **Alpha-fetoprotein (AFP) levels are typically normal** in patients with fibrolamellar HCC. This is a classic diagnostic differentiator frequently tested in exams [1]. If a young patient presents with a large liver mass but normal AFP, FL-HCC should be the top differential. **2. Analysis of other options:** * **Option B:** While FL-HCC has a **better prognosis** and higher resectability rate than conventional HCC (due to the absence of cirrhosis), it still carries a significant risk of **late recurrences**, often requiring long-term follow-up [1]. * **Option C:** FL-HCC is associated with unique biochemical markers, specifically **elevated serum neurotensin** and **increased Vitamin B12 binding capacity** (transcobalamin I), which can serve as diagnostic clues. * **Option D:** Unlike conventional HCC, which primarily spreads hematogenously, FL-HCC has a higher propensity for **lymph node metastasis** at the time of diagnosis. **High-Yield Clinical Pearls for NEET-PG:** * **Morphology:** Characterized by large, polygonal cells with abundant eosinophilic cytoplasm (oncocytic) and prominent nucleoli, separated by **parallel lamellae of collagen bundles**. * **Genetics:** A highly specific molecular marker is the **DNAJB1-PRKACA gene fusion**. * **Gross Appearance:** Often presents as a single large hard mass with a **central stellate scar** (resembling Focal Nodular Hyperplasia). * **Gender:** Occurs equally in males and females (no male predominance). **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 399-400.

Practice by Chapter

Jaundice and Cholestasis

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Viral Hepatitis

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Alcoholic and Non-alcoholic Fatty Liver Disease

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Drug and Toxin Induced Liver Injury

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Cirrhosis and Its Complications

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Metabolic Liver Diseases

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Liver Tumors

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Gallbladder and Biliary Tract Diseases

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Congenital Liver Diseases

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Liver Transplantation Pathology

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