Hepatitis C

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HEPATITIS C
Hepatitis C is a type of hepatitis - a liver disease - caused by the hepatitis C virus (HCV). It usually spreads through contact with infected blood. It can also spread through sex with an infected person and from mother to baby during childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. A blood test can tell if you have it. Usually, hepatitis C does not get better by itself. The infection can last a lifetime and may lead to scarring of the liver or liver cancer (Cirrhosis). Medicines sometimes help, but side effects can be a problem. Serious cases may need a liver transplant. There is no vaccine for HCV.

HEPATITIS C VIRUS
Hepatitis C virus (HCV) is a small (55-65 nm in size), enveloped, positive-sense singlestranded RNA virus of the family Flaviviridae. Hepatitis C virus is the cause of hepatitis C in humans. The hepatitis C virus particle consists of a core of genetic material (RNA), surrounded by an icosahedral protective shell of protein, and further encased in a lipid (fatty) envelope of cellular origin. Two viral envelope glycoprotein, E1 and E2, are embedded in the lipid envelope. Hepatitis C virus has a positive sense single-stranded RNA genome. The genome consists of a single open reading frame that is 9600 nucleotide bases long. This single open reading frame is translated to produce a single protein product, which is then further processed to produce smaller active proteins. At the 5' and 3' ends of the RNA are the UTR that are not translated into proteins but are important to translation and replication of the viral RNA. The 5' UTR has a ribosome binding site (IRES -Internal ribosome entry site) that starts the translation of a very long protein containing about 3,000 amino acids. This large pre-protein is later cut by cellular and viral proteases into the 10 smaller proteins that allow viral replication within the host cell, or assemble into the mature viral particles. Structural proteins made by the hepatitis C virus include Core protein, E1 and E2; nonstructural proteins include NS2, NS3, NS4, NS4A, NS4B,NS5, NS5A, and NS5B.

GENOTYPES
Based on genetic differences between HCV isolates, the hepatitis C virus species is classified into six genotypes (1-6) with several subtypes within each genotype (represented by letters). Subtypes are further broken down into quasi species based on their genetic diversity. The preponderance and distribution of HCV genotypes varies globally. For example, in North America, genotype 1a predominates followed by 1b, 2a, 2b, and 3a. In Europe, genotype 1b is predominant followed by 2a, 2b, 2c, and 3a. Genotypes 4 and 5 are found almost exclusively in Africa. Genotype is clinically important in determining potential response to interferon-based therapy and the required duration of such therapy. Genotypes 1 and 4 are less responsive to interferon-based treatment than are the other genotypes (2, 3, 5 and 6). Duration of standard interferon-based therapy for genotypes 1 and 4 is 48 weeks, whereas treatment for genotypes 2 and 3 is completed in 24 weeks.

Infection with one genotype does not confer immunity against others, and concurrent infection with two strains is possible. In most of these cases, one of the strains removes the other from the host in a short time. This finding opens the door to replace strains non-responsive to medication with others easier to treat.

SYMPTOMS
Many people who are infected with hepatitis C do not have symptoms. If the infection has been present for many years, the liver may be permanently scarred, a condition called cirrhosis. In many cases, there may be no symptoms of the disease until cirrhosis has developed.             The following symptoms could occur with hepatitis C infection: Abdominal pain (right upper abdomen) Ascites Bleeding varices (dilated veins in the esophagus) Dark urine Fatigue Generalized itching Jaundice Loss of appetite Low-grade fever Nausea Pale or clay-colored stools Vomiting

DIAGNOSIS

Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin(direct and indirect) and others. Liver transaminases (AST/ALT (SGOT/SGPT)) are not liver function tests but are biomarkers of liver injury in a patient with some degree of intact liver function. Most liver diseases cause only mild symptoms initially, but it is vital that these diseases be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance. This testing is performed by a medical technologist on a patient's serum or plasma sample obtained by phlebotomy. Some tests are associated with functionality (e.g., albumin); some with cellular integrity (e.g., transaminase) and some with conditions linked to the biliary tract (gamma-glutamyl transferase and alkaline phosphatase). Several biochemical tests are useful in the evaluation and management of patients with hepatic dysfunction. These tests can be used to (1) Detect the presence of liver disease. (2) Distinguish among different types of liver disorders. (3) Gauge the extent of known liver damage.

(4) Follow the response to treatment. Some or all of these measurements are also carried out (usually about twice a year for routine cases) on those individuals taking certain medications- anticonvulsants are a notable example- in order to ensure that the medications are not damaging the person's liver.

ALBUMIN (Alb)
Albumin is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total protein; the remaining fraction is called globulin (including the immunoglobulins). Albumin levels are decreased in chronic liver disease, such as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the urine. Poor nutrition or states of impaired protein catabolism, such as in Ménétrier's disease, may also lead to hypoalbuminaemia. The halflife of albumin is approximately 20 days. Albumin is not considered to be an especially useful marker of liver synthetic function; coagulation factors are much more sensitive. Reference range 3.5 to 5.5 g/dL

ALANINE TRANSAMINASE (ALT)
Alanine transaminase (ALT), also called Serum Glutamic Pyruvate Transaminase (SGPT) or Alanine aminotransferase (ALAT) is an enzyme present in hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme into the blood, where it is measured. ALT rises dramatically in acute liver damage, such as viral hepatitis or paracetamol (acetaminophen) overdose. Elevations are often measured in multiples of the upper limit of normal (ULN). Reference range 9 to 40 IU/L

ASPARTATE TRANSAMINASE (AST)
Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic Reference range

Transaminase (SGOT) or aspartate aminotransferase (ASAT) is similar to ALT 10 to 35 IU/L in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage, but is also present in red blood cells, and cardiac and skeletal muscle and is therefore not specific to the liver. The ratio of AST to ALT is sometimes useful in differentiating between causes of liver damage.[2][3] Elevated AST levels are not specific for liver damage, and AST has also been used as a cardiac marker.

ALKALINE PHOSPHATASE (ALP)
Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. ALP levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver. ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled) and elderly patients withPaget's disease. Reference range 30 to 120 IU/L

TOTAL BILIRUBIN (TBIL)
Bilirubin is a breakdown product of haem (a part of haemoglobin in red blood cells). The liver is responsible for clearing the blood of bilirubin. It does this by the following mechanism: bilirubin is taken up into hepatocytes, conjugated (modified to make it water-soluble), and secreted into the bile, which is excreted into the intestine. Increased total bilirubin causes jaundice, and can signal a number of problems:  1. Prehepatic: Increased bilirubin production. This can be due to a number of causes, including hemolytic anemias and internal hemorrhage.  2. Hepatic: Problems with the liver, which are reflected as deficiencies in bilirubin metabolism (e.g. reduced hepatocyte uptake, impaired conjugation of bilirubin, and reduced hepatocyte secretion of bilirubin). Some examples would be cirrhosis and viral hepatitis.  3. Posthepatic: Obstruction of the bile ducts, reflected as deficiencies in bilirubin excretion. (Obstruction can be located either within the liver or in the bile duct). Reference range 0.2–1.2 mg/dL

DIRECT BILIRUBIN (Conjugated Bilirubin)
The diagnosis is narrowed down further by looking at the levels of direct bilirubin.  If direct (i.e. conjugated) bilirubin is normal, then the problem is an excess of unconjugated bilirubin, and the location of the problem is upstream of bilirubin excretion. Hemolysis, viral hepatitis, or cirrhosis can be suspected.  If direct bilirubin is elevated, then the liver is conjugating bilirubin normally, but is not able to excrete it. Bile duct obstruction by gallstones or cancer should be suspected. Reference range 0.1–0.4 mg/dL

GAMMA GLUTAMYL TRANSPEPTIDASE (GGT)
Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, Gamma glutamyl transpeptidase (GGT) may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. (GGT is raised in chronic alcohol toxicity). Reference range 0 to 42 IU/L

5' NUCLEOTIDASE (5'NTD)
5' nucleotidase is another test specific for cholestasis or damage to the intra or extrahepatic biliary system, and in some laboratories, is used as a substitute for GGT for ascertaining whether an elevated ALP is of biliary or extra-biliary origin.

COAGULATION TEST (e.g. INR)
The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal. If the INR is increased, it means it is taking longer than usual for blood to clot. The INR will only be increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired; it is not a sensitive measure of liver function. It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the deficient factors) as they could bleed excessively.

SERUM GLUCOSE (BG, Glu)
The liver's ability to produce glucose (gluconeogenesis) is usually the last function to be lost in the setting of fulminant liver failure.

LACTATE DEHYDROGENASE (LDH)
Lactate dehydrogenase is an enzyme found in many body tissues, including the liver. Elevated levels of LDH may indicate liver damage.

HEPATITIS C ANTIBODY
When hepatitis C viruses infect your liver cells (hepatocytes), your immune system responds by using special hepatitis C antibodies to mark the viruses as dangerous intruders. They won't attach to any other viruses or bacteria that might be in your body because they're only for hepatitis C viruses (other viruses or bacteria require different antibodies). Because antibodies are specific to a certain virus or bacterium, doctors can use the presence of the hepatitis C antibody (also called HCAb or anti-HCV) to tell if you've been infected with hepatitis C virus (HCV). Meet ELISA and RIBA. These are the names of two types of tests that detect antibodies in your blood. To determine if hepatitis C antibodies (HCAb or anti-HCV) are in your blood, doctors use a screening test called ELISA, which stands for Enzyme-Linked ImmunoSorbent Assay. There are many different ELISA tests, so doctors must use one specifically for hepatitis C. The ELISA test will search the blood sample for the hepatitis C antibody. If any are found, this means that you might have HCV infection. The ELISA test is very sensitive and picks up approximately 95% of people who have antibodies as positive. However, it's so sensitive that sometimes it over-identifies antibodies in your blood as geared towards hepatitis C even sometimes when they're not. This degree of sensitivity has its advantages. For instance, when the ELISA test is negative, you can feel very confident that you are hepatitis C free. However, if the ELISA test is positive, there is a small possibility that the result could be incorrect. This is called a "false-positive" result. False-positives are most likely considered in people who lack the risk factors for hepatitis C. When the ELISA test is weakly positive or when doctors think the test result doesn't match what they see clinically, a second test may be used to verify the original results. This test may be the RIBA test or another test, called HCV RNA, that directly measures the virus. The RIBA test (which stands for Recombinant ImmunoBlot Assay) uses a different approach to finding hepatitis C antibodies in your blood. If this test is positive, you probably have been infected with hepatitis C. It's important to realize that antibody tests usually can't distinguish between past or current infection. Doctors must use clinical information (such as medical history, signs and symptoms) or other tests to determine active or past infection.

HEPATITIS C RNA
This powerful test allows doctors to see, among other things, how you are responding to treatment. It uses PCR technology (polymerase chain reaction) to detect the virus. While it's also used to establish current infection, it's mostly used to determine viral load. Your hepatitis C viral load is an estimate of how much HCV is in your blood. Since your viral load should decrease after a successful course of treatment, by monitoring the levels of HCV in your blood, doctors can accurately determine how you're responding to the treatment. If your viral load doesn't decrease, they may need to change your therapy. Hepatitis C Virus Genotyping Hepatitis C viruses are not all the same. Certainly, they are all identified as hepatitis C viruses and they all can cause acute and chronic hepatitis C, but they're not exactly genetically alike. They have slightly different variations in their genes and are grouped by these variations into different genotypes. Genotypes are important because hepatitis C viruses with certain genetic variations are harder to treat successfully and usually require a different treatment approach. Other hepatitis C viruses are much easier to treat because they respond well to shorter treatment schedules. Doctors determine your HCV genotype by using a laboratory test called RT-PCR, which stands for reverse transcription polymerase chain reaction. This test analyzes the genetic material of the virus to determine its sequence. Based on its sequence, technicians can determine the virus' genotype. All blood testing requires a certain level of training and equipment, but RT-PCR requires relatively more. Because of this, it's an expensive test (it usually costs more than $100 to perform). However, it's worth the cost. Knowing your genotype can significantly reduce the duration of your treatment.

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