LIVER: A VITAL ORGAN

Liver diseases are now established as the fifth most common cause of death after heart disease, stroke, chest infections and cancer

PROF. M. S. KHUROO

Of late, diseases of the liver are often a focus of media attention. This article shall give an overview of the structure & functions of the liver and spectrum of the diseases, which affect this vital organ (Table). 
The liver is the largest organ of the human body, weighs around 1500 g and is placed in the right upper abdomen and protected by the ribcage (Fig 1).  Liver has distinction of a dual (portal vein-80% and hepatic arteries-20%)blood supplyentering at its hilum. Bile secreted by the liver leaves the organ through biliary channels and enters the duodenum. Blood leaves the liver through 3 hepatic veins, which enter the inferior vena cava.  Functional subdivision of the liver in to eight segments having independent vascular and biliary supplies hasbeen of great importance when liver resections are required.
Liver is composed of a principal cell type, the hepatocytes, which accounts for 60 percent of cell population arranged in plates, that are interconnected to form a continuous three dimensional lattice. Endothelial lining cells, perisinusoidal stellate cells and intraluminal Kupffer cells comprise the remaining of the liver cell population. 
Liver performs complex synthetic and metabolic functions. Bile is produced by hepatocytes and bile flow occurs through transepithelial movement of solutes and organic molecules. Hepatocytes synthesize liver specific proteins (mostly enzymes), which carry many synthetic and detoxifying functions of drugs and toxins delivered to the liver from the gut via the portal circulation. In addition hepatocytes synthesize all plasma proteins except immunoglobulins (synthesized by plasma cells). Hepatocytes are essential in maintaining blood glucose levels. Kupffer cells constitute the largest population of fixed macrophages of the body and are involved in phagocytosis of blood borne toxicants and particulates such as bacteria from circulation. 
Liver diseases are now established as the fifth most common cause of death after heart disease, stroke, chest infections and cancer.  Disturbing is the data that unlike other major causes of mortality, liver disease is increasing over the years rather than declining.
Liver diseases present clinically in a few distinct patterns whatever the underlying etiology. Many patients have no symptoms and such patients may be detected incidentally to have elevated liver tests or positive viral or serologic marker (HBsAg, anti-HCV, AMA etc.). Acute hepatitis is a self-limiting illness with constitutional symptoms, jaundice, elevated liver enzymes and eventual recovery. Acute hepatic failure is a devastating illness and is characterized by rapid and progressive deterioration of liver functions leading to encephalopathy and multiorgan failure. Chronic hepatitis presents with fatigue, jaundice and elevated liver tests. Cirrhosis may be clinically silent for several years before symptoms and signs of hepatocellular dysfunction and portal hypertension such as jaundice, encephalopathy, ascites and variceal bleeding develop (Fig 2). Acute on chronic liver failure (AoCLF) is a recently recognized entity wherein there is rapid decompensation once acute hepatic insult is superimposed on established stable chronic liver disease. Cholestatic liver disease patients present with jaundice, itching, clay stools and dark urine and substantial elevated serum alkaline phosphatase. 
Liver diseases are caused from diverse agents. Hepatitis viruses A to E are most important causes of liver diseases. Today we have a large pool of chronic carriers of hepatitis viruses across the globe. Estimated numbers of HBV & HCV infected worldwide are staggering -350 million and 500 million, with estimated one million and 5 million deaths annually respectively. Hepatitis E virus has turned out to be the most enigmatic human agent since we discovered the agent in 1980. HEV causes large-scale waterborne epidemics in developing countries involving hundreds and thousands of adult population. In recent years, hepatitis E is recognized as a clinical problem in industrialized countries and possibly is spread through food borne zoonotic transmission. Chronic and excessive alcohol ingestion is another major cause of liver disease. Alcoholic liver disease has spectrum of pathological changes including fatty liver, alcoholic hepatitis and alcoholic cirrhosis. Non-alcoholic fatty liver disease (NAFLD)as a manifestation of metabolic syndrome and consequent insulin resistance has taken us by storm globally. NAFLD is a potentially progressive liver disease and shall pose serious health problem to our community in near future. Pathological spectrum of NAFLD is similar to that of alcoholic liver disease and includes fatty liver, non-alcoholic steatohepatitis (NASH) and cirrhosis. Hepatocellular carcinoma (HCC; Liver cancer) is one of the most common malignancies worldwide with annual global incidence approximately 1 million cases. Factors associated with increased risk of HCC include cirrhosis of any cause, chronic HBV & HCV infections, alcoholic and non-alcoholic fatty liver disease & cirrhosis. Liver is a common site for metastases from tumors of the colon, stomach, pancreas and breast.  However, liver metastases can originate from any organ primary tumor. Drugs can cause liver injury and may result from direct toxic affect of the drug or result of idiosyncratic drug reaction. Recently misguided popularity of herbal medicines of unproven efficacy has been associated with toxic hepatitis. In addition to above, liver disease can occur from a wide variety of other causes.
Methodology to be followed forproper evaluation of liver diseases should follow a defined protocol. This includes a proper history, thorough physical examination, routine blood counts and serum chemistry including liver tests. Abnormal liver tests can be classified in to definite patterns namely hepatocellular (elevated serum bilirubin; elevated ALT/AST >500 IU; ALT>AST; normal to <3 times normal elevation of AP), cholestatic (elevated serum bilirubin, normal to <300 IU ALT/AST; more than 4 times normal elevation of AP), haemolytic/Gilbert’s syndrome (isolated elevation of unconjugated serum bilirubin rarely above 5 mg/dl); synthetic liver failure (elevated serum bilirubin, modest elevated ALT, AST & AP; low albumin, high globulins and high prothrombin time) and infiltrative (isolated more than 4 times normal elevation of  AP). Each pattern has different clinical connotations and defines corresponding further work up. Hepatobiliary ultrasound with Doppler is now considered an extension to clinical examination for hepatobiliary diseases and is strongly recommended as a part of primary evaluation. Ultrasound with Doppler is useful for detecting gallstones, thickened gallbladder, dilated bile ducts, cysts and masses within the liver, periportal fibrosis, hepatosplenomegaly and evidence of portal hypertension. Based on findings of these, further cost-effective, evidence-based laboratory tests; imaging tools like computed-tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP); or other invasive tests like liver biopsy or guided fine needle aspiration biopsies need to be employed.

Recently there have been major strides in prevention and management of a number of liver diseases. Implementing following 8 slogans can prevent spread of hepatitis viruses: i. Safe blood, ii. Safe needle, iii. Safe sex, iv. Safe pregnancy, v. safe food; vi. Safe portable water, vii. Safe shave, &viii. Safe tattoo (Fig 3).Universal hepatitis B vaccination at birth in endemic areas has been shown to be highly effective in reducing carrier rates in children as well as the incidence of end stage liver disease (ESLD) and liver cancer.  Hepatitis A vaccine is highly efficacious and combined HAV/HBV need to be implemented in industrialized countries and western travellers to endemic areas. Recently, Hepatitis E vaccine 239, Hecolin has been launched in China and raises hopes for control of this human python. There have been major strides in the drug treatment of HBV and HCV. However, drug treatment for both HBV and HCV is far from satisfactory because of low cure rates, prolonged therapy, adverse drug reactions and exceptional costs. Abstinence of alcohol should be encouraged for all patients with alcoholic liver disease. Life style modifications at present are the only way forward to control metabolic syndrome, insulin resistance and NAFLD. It is worth mentioning that for patients with ESLD and acute liver failure, liver transplant is the only hope for millions of such patients as of today. In spite of the shortage of organs and long waiting list of patients on cadaveric program liver transplant has substantially changed management of such patients. Live Donor Liver Transplant (LDLT) has removed many bottlenecks and strengthened such programs especially in India.
Author is Former Director, Chairman Dept. of Medicine, Professor Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India. Reach him at Khuroo@yahoo.com 

Table: Liver: A Vital Organ of the Human Body
Gross structure  Placement: Right upper abdomen; Weight: 1500 g; Blood supply: Portal vein (80%), hepatic arteries (20%); venous drainage: 3 hepatic veins; Bile drainage: hepatic ducts (right & left), Common bile duct, Gallbladder; Cells: hepatocytes (60%), endothelial cells, perisinusoidal stellate cells & Kupffer cells (40%); Sinusoids (blood channels); Cholangioles (bile channels); Lobes: right & left; Segments: eight (1 to VIII)
Functions  Synthetic: secretion of bile; synthesis of liver specific proteins (liver enzymes); synthesis of plasma proteins (all proteins except immunoglobulin’s). Metabolic: detoxification of drugs & toxins; maintain blood glucose; phagocytosis of particulate material and bacteria; store Vitamin A and other fat soluble vitamins
Patterns of liver disease presentation  Incidental/asymptomatic (elevated liver tests or positive HBsAg or anti-HCV); Acute viral hepatitis; Acute hepatic failure; Chronic hepatitis; Cirrhosis; Acute on chronic liver failure (AoCLF);  End Stage Liver Disease (ESLD); Cholestatic liver disease
Causes of liver diseases Hepatitis viruses (A, B, C, D,E); Alcohol; Metabolic syndrome (Non-alcoholic Fatty Liver Disease); Hepatocellular cancer (HCC); Metastatic liver disease (colon, breast, stomach, pancreas, etc); Drugs & toxins; Auto-immune chronic active hepatitis (AICAH); Destructive cholangiopathies (Primary biliary cirrhosis, Sclerosing cholangitis); Genetic diseases (Wilson’s disease & Hemochromatosis); Vascular liver diseases (Budd Chiari syndrome-BCS; Venoocclusive disease-VOD; Extrahepatic portal vein obstruction-EHPVO); Progressive familial intrahepatic cholestasis (PFIC-1; PFIC-2; PFIC-3); Hydatidosis (Hydatid liver cysts); Amebiasis (amebic liver abscess); Schistosomiasis (Schistosomial liver disease); Tuberculosis (granulomatous hepatitis); Malaria (malaria hepatopathy); Dengue (dengue hepatitis) etc.
Investigation to assess liver disease Physical; Routine blood counts; serum chemistry; Elevated liver test patterns may be Hepatocellular, Cholestatic, hemolytic/Gilbert’s syndrome, Infiltrative; Hepatobiliary ultrasound; MRI/MRCP; triple phase CT; ERCP; Liver biopsy 
Staging & scoring of liver disease Child Pugh Score (A, B & C); MELD Score; Metabolic syndrome; Maddrey discriminant function (Alcoholic hepatitis);
Prevention
Management  Vaccination (HBV; HAV & HEV); Safe blood,  needle, pregnancy, sex, food, water, shave, tattoo; Abstinence; Life style modifications; Anti-viral drugs; specific drug treatment for primary causes; Liver transplant

Lastupdate on : Tue, 22 Jan 2013 21:30:00 Makkah time
Lastupdate on : Tue, 22 Jan 2013 18:30:00 GMT
Lastupdate on : Wed, 23 Jan 2013 00:00:00 IST




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