liver The largest single organ in the human body. In an adult, it weighs about three pounds and is roughly the size of a football. Located in the upper right-hand part of the abdomen, behind the lower ribs

Supplied with blood via the protal vein and hepatic artery. The liver is divided) into four lobes: the right (the largest lobe), left, quadrate and caudate lobes. Supplied with blood via the protal vein and hepatic artery. Blood carried away by the hepatic vein. It is connected to the diaphragm and abdomainal walls by five ligaments. Gall Bladder Muscular bag for the storage, concentration, acidification and delivery of bile to small intestine The liver is the only human organ that has the remarkable property of self-regeneration. If a part of the liver is removed, the remaining parts can grow back to its original size and shape.

LIVER FUNCTION TESTS Alanine transaminse (ALT) Aspartate transaminase (AST ) ALKALINE PHOSPHATASE BILIRUBIN

ALT and AST Enzymes, found in Hepatocytes Released when liver cells damaged ALT is specific for liver injury AST (SGOT) is also found in skeletal and cardiac muscle

Transaminitis: < 5 x normal ALT predominant Chronic Hep B / C Acute A-E, EBV, CMV Hemochromatosis Medications / Toxins Autoimmune Hepatitis Alpha-1-antitrypsin Wilson’s Disease Celiac Disease

ALKALINE PHOSPHATASE Found in hepatocytes that line the bile canaliculi Level is raised in Biliary obstruction (causes stretch of the bile canaliculi) BUT also found in BONE and PLACENTA GGT is also found in bile canaliculi and therefore can be used in conjunction with Alk Phos for predicting liver origin BUT GGT can be raised by many drugs including Alcohol and therefore non specific

BILIRUBIN Water insoluble product of heme metabolism Taken up by liver and conjugated to become water soluble so it can be excreted in bile and into bowel. Patient looks Jaundiced if bilirubin >2.5 If patient is vomiting GREEN, then they have bowel obstruction below the level of the Ampulla of Vater.

WHAT IS THE DEAL WITH DIRECT AND INDIRECT BILIRUBIN? Prehepatic disease (eg hemolysis) causes high bilirubin which is non conjugated ie. Indirect fraction higher Hepatic disease causes increased conjugated and unconjugated bilirubin Post hepatic disease eg. Gallstones have increased conjugated (direct) bilirubin and lead to dark urine and pale stool

TESTS OF LIVER FUNCTION PROTHROMBIN TIME/ INR ALBUMIN

PROTHROMBIN TIME/INR Measure of the Vitamin K dependent clotting factors ie. II, VII, IX and X. The liver is involved in activating Vitamin K. Therefore in liver damage, these clotting factors cannot be produced. Before you believe that prolonged INR is due to liver disease just make sure the patient has adequate Vitamin K by giving 10mg sc. Giving Vitamin K has no effect on INR if patient has impaired synthetic function.

ALBUMIN Albumin has a half life of 21 days, so the drop that occurs with hepatic dysfunction does not occur acutely That said, acute illness can cause albumin to drop rapidly – a process thought to be due to cytokines increasing the rate of albumin metabolism HOWEVER, don’t forget that low albumin also occurs in NEPHROTIC syndrome, so always check the urine for protein

Radiological examination of the liver Ultrasound of the liver. Ultrasound of normal liver. Longitudinal scan showing uniform echo pattern interspersed with bright echoes of portal triads and echo-free areas of hepatic and portal veins. D, diaphragm; K, right kidney

CT.scan CT scan showing unopacified hepatic veins (arrows) which should not be confused with metastases.

MRI of the liver Magnetic resonance imaging is used as a problem-solving technique to give additional information to ultrasound and CT. Axial sections give images akin to CT but images can also be obtained in the coronal and sagittal planes. By using special sequences information can also be obtained on the arterial and venous circulation of the liver.

Radionuclide liver imaging Radionuclide liver scanning (99mTc-labelled sulphur or tin colloid) has been almost completely replaced by ultrasound, CT and MRI. The hepatobiliary agents which also show the liver parenchyma, but their primary indication is to show disease of the extrahepatic biliary system.

Percutaneous transhepatic cholangiography Percutaneous transhepatic cholangiography is accomplished by injecting contrast material under fluoroscopic vision through a narrow gauge needle placed in the parenchyma of the liver. has the advantage of allowing the operator to institute biliary drainage if necessary. It is increasingly reserved for patients with biliary obstruction who need permanent or temporary biliary drainage. Needle biopsy of masses, drainage of fluid collections, and placement of external and internal drainage (choledochoduodenal) stents all can be accomplished percutaneously. Magnetic resonance cholangiopancreatography (MRCP) Special sequences enable the biliary duct system to be visualized directly without the need for any contrast agent

Liver trauma Largest organ, 2nd most common injured, Blunt trauma most common Friable parenchyma, thin capsule, fixed position in relation to spine  prone to blunt injury . Right lobe larger, closer to ribs. more injury In children compliant ribs, transmitted force

Mechanisms of injury:- simple compression against ribs, spine, ligamentous attachment to diaphragm and the posterior abdominal wall ,shear forces during deceleration injury High-velocity bullet injuries burst injuries with distant contusions and parenchymal disruption. Associations

management Initial resuscitation as per ATLS protocol It is important to note the mechanism of injury Clinical picture may vary from mild RUQ pain through to peritonism to haemorrhagic shock Stable patients undergo CT imaging Unstable patients require resuscitation and laparotomy

Types of injury 1.Stab wounds 2.percutaneous biopsy 3.cholangiography Low-velocity penetrating injury 1.Stab wounds 2.percutaneous biopsy 3.cholangiography 4.biliary drainage, capsular tears, hematoma, bile leaks, arteriobiliary fistulas, and hemoperitoneum, arterial aneurysms Types of injury Parenchymal damage Subcapsular hematoma Laceration Contusion Hepatic vascular disruption Bile duct injury

CT Scans Accurate in localizing the site of liver injury and any associated injuries Used to monitor healing CT criteria for staging liver trauma uses AAST liver injury scale Grades 1-6

Classification (AAST I-Subcapsular hematoma<1cm, superficial laceration<1cm deep.

Treatment Conservative Surgical Blunt liver trauma, Haemodynamically stable No other injuries requiring surgery Surgical Penetrating injuries Haemodynamically unstable Other injuries requiring surgery

HYDATID CYST DISEASE Hydatid disease is a worldwide zoonosis produced by the larval stage of the Echinococcus tapeworm . The two main types of hydatid disease are caused by E granulosus and E multilocularis. E granulosus is commonly seen in the great grazing regions of the world—particularly the Mediterranean region, Africa, South America, the Middle East, Australia, and New Zealand—and is the most frequently encountered type of hydatid disease in humans

The hydatid cyst has three layers: (a) the outer pericyst, composed of modified host cells that form a dense and fibrous protective zone; (b) the middle laminated membrane, which is acellular and allows the passage of nutrients; (c) the inner germinal layer, where the scolices (the larval stage of the parasite) and the laminated membrane are produced.

Daughter vesicles (brood capsules) are small spheres that contain the protoscolices and are formed from rests of the germinal layer. Before becoming daughter cysts, these daughter vesicles are attached by a pedicle to the germinal layer of the mother cyst. At gross examination, the vesicles resemble a bunch of grapes

Hydatid disease involves the liver in approximately 75% of cases, the lung in 15%, and other anatomic locations in 10% The clinical features are highly variable. The spectrum of symptoms depends on the following: Involved organs Size of cysts and their sites within the affected organ or organs Interaction between the expanding cysts and adjacent organ structures, particularly bile ducts and the vascular system of the liver Symptoms due to pressure usually take a long time to manifest, except when they occur in the brain . Most symptomatic cysts are larger than 5 cm in diameter. Bacterial infection of cysts and spread of protoscolices and larval material into bile ducts or blood vessels Immunologic reactions such as asthma, anaphylaxis, or membranous nephropathy secondary to release of antigenic material

The right lobe is the most frequently involved portion of the liver. Once in the human liver, cysts grow to 1 cm during the first 6 months and 2–3 cm annually thereafter, depending on host tissue resistance.

Clinical presentation of liver disease

Work Up Generally, routine laboratory tests do not show specific results. In patients with rupture of the cyst in the biliary tree, marked and transient elevation of cholestatic enzyme levels occurs, often in association with hyperamylasemia and eosinophilia (as many as 60%). Indirect hemagglutination test and enzyme-linked immunosorbent assay are the most widely used methods for detection of anti-Echinococcus antibodies (immunoglobulin G [IgG]).These tests give false positive results in cases of schistosomiasis and nematode infestations that is why they are not specific for diagnosing hydatidosis. Immunoelectrophoresis : depends on the formation of specific arc of precipitation ( called arc 5 ) which is highly specific and can be used to exclude cross-reactions caused by noncestode parasites

Imaging Studies: Plain radiography Ultrasound examination CT scaning MRI

Management Options Medical . Surgery. PAIR.

Medical treatment Indications: Chemotherapy is indicated in patients with primary liver or lung cysts that are inoperable (because of location or medical condition), patients with cysts in 2 or more organs, and peritoneal cysts. Chemotherapeutic agents: Two benzimidazoles are used, albendazole and mebendazole. Albendazole is administered in several 1-month oral doses (10-15 mg/kg/d) separated by 14-day intervals. The optimal period of treatment ranges from 3-6 months, with no further increase in the incidence of adverse effects if this period is prolonged. Mebendazole is also administered for 3-6 months orally in dosages of 40-50 mg/kg/d

Contraindications: Early pregnancy, bone marrow suppression, chronic hepatic disease, large cysts with the risk of rupture, and inactive or calcified cysts are contraindications. A relative contraindication is bone cysts because of the significantly decreased response. Outcome : Response rates in 1000 treated patients were that 30% had cyst disappearance (cure), 30-50% had a decrease in the size of the cyst (improvement), and 20-40% had no changes. Also, younger adults responded better than older adults

PAIR This technique, performed using either ultrasound or CT guidance, involves aspiration of the contents via a special cannula, followed by injection of a scolicidal agent for at least 15 minutes, and then reaspiration of the cystic contents. The cyst is then filled with isotonic sodium chloride solution. Perioperative treatment with a benzimidazole is mandatory (4 d prior to the procedure and 1-3 mo after). The cysts should be larger than 5 cm in diameter

Indications: Inoperable patients; patients refusing surgery; multiple cysts in segment I, II, and III of the liver; and relapse after surgery or chemotherapy are indications for the PAIR technique Contraindications: Early pregnancy, lung cysts, inaccessible cysts, superficially located cysts (risk of spillage), and cysts communicating with the biliary tree (risk of sclerosing cholangitis from the scolecoidal agent).

Surgical Management Indications: 1-Large liver cysts with multiple daughter cysts; superficially located single liver cysts that may rupture (traumatically or spontaneously). 2-liver cysts with biliary tree communication or pressure effects on vital organs or structures. 3-infected cysts . 4-cysts in lungs, brain, kidneys, eyes, bones

Concomitant treatment with benzimidazoles (albendazole or mebendazole) has been reported to reduce the risk of secondary echinococcosis. Treatment is started 4 days preoperatively and lasts for 1 month. Contraindications: General contraindications to surgical procedures (eg, extremes of age, pregnancy, severe preexisting medical conditions); multiple cysts in multiple organs; cysts that are difficult to access; dead cysts; calcified cysts; and very small cysts are contraindications.

Complications 1-All the usual complications related to the surgical procedure and anesthesia 2-Related to the parasite Recurrence Metastasis Infection Spillage and seeding (secondary echinococcosis) - Allergic reaction or anaphylactic shock 3-Related to the medical treatment Hepatotoxicity Anemia Thrombocytopenia Alopecia Embryotoxicity Teratogenicity

Complications , cont 4-Related to PAIR Hemorrhage Mechanical damage to other tissue Infections Allergic reaction or anaphylactic shock Persistence of daughter cysts Sudden intracystic decompression leading to biliary fistulas 5-Related to scolicidal agents - Chemical sclerosing cholangitis

Liver tumor Benign Malignant Hemangioma Focal nodular hyperplasia Adenoma Liver cysts Primary liver cancers Hepatocellular carcinoma Fibrolamellar carcinoma Hepatoblastoma 2. Metastases

Benign Liver Lesions Hemangioma Focal nodular hyperplasia Adenoma Cysts

Hemangioma Clinical Features The commonest liver tumor 5% of autopsies Usually single small Well demarcated capsule Usually asymptomatic

Diagnosis and Management US: echogenic spot, well demarcated CT: venous enhancement from periphery to center MRI: high intensity area No need for FNA Treatment No need for treatment

Focal Nodular Hyperplasia (FNH) Clinical Features Benign nodule formation of normal liver tissue Central stellate scar More common in young and middle age women No relation with sex hormones Usually asymptomatic May cause minimal pain

Focal Nodular Hyperplasia (FNH) Diagnosis and Management US: Nodule with varying echogenicity CT: Hypervascular mass with central scar MRI: iso or hypo intense FNA: Normal hepatocytes and Kupffer cells with central core. Treatment: No treatment necessary Pregnancy and hormones OK

Hepatic Adenoma Clinical features Benign neoplasm composed of normal hepatocytes no portal tract, central veins, or bile ducts More common in women Associated with contraceptive hormones Usually asymptomatic but may have RUQ pain May presents with rupture, hemorrhage, or malignant transformation (very rare)

Hepatic Adenoma Diagnosis and Management DX US: filling defect CT: Diffuse arterial enhancement MRI: hypo or hyper intense lesion FNA : may be needed Tx Stop hormones Observe every 6m for 2 y If no regression then surgical excision

Malignant Liver Tumors Hepatocellular carcinoma (HCC) Fibro-lamellar carcinoma of the liver Hepatoblastoma Intrahepatic cholangiocarcinoma Others

HCC: Incidence The most common primary liver cancer Increasing in US and all the world

HCC: Risk Factors The most important risk factor is cirrhosis from any cause: Hepatitis B (integrates in DNA) Hepatitis C Alcohol Aflatoxin Other

HCC: labs Labs of liver cirrhosis AFP (Alfa feto protein) Is an HCC tumor marker Values more than 100ng/ml are highly suggestive of HCC Elevation seen in more than 70% of pt

HCC: Diagnosis Clinical presentation Elevated AFP US Triphasic CT scan: very early arterial perfusion MRI Biopsy

HCC: Resection Feasible for small tumors with preserved liver function (no jaundice or portal HTN) Recurrence rate is high

Secondary Liver Metastases The most common site for blood born metastases Common primaries : colon, breast, lung, stomach, pancreases, and melanoma Mild cholestatic picture (ALP, LDH) with preserved liver function Dx imaging or FNA Treatment depends on the primary cancer In some cases resection or chemoembolization is possible