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.and these are just som e of the things I do for you!
I store the iron reserves you need, as well as a lot of vitam ins and other m inerals.
I m ake bile to help digest your food and help get rid of som e of your dietary cholesterol.
I detoxify poisonous chem icals you give m e, and that includes alcohol, beer, wine and drugs- prescribed and over-the-counter as well as illegal substances. I act as a filter to rem ovealcohol and toxic substances from the blood and convert them to substances that can beexcreted from the body. I rem ove poisons from the air, exhaust, sm oke and chem icals youbreathe. I also process drugs and m edications absorbed from the digestive system , enabling the bodyto use them effectively and ultim ately dispose of them I store energy, like a battery, by stockpiling sugar (carbohydrates, glucose and fat) until youneed it. That stored energy is what keeps you going in the m orning until you eat breakfast.
I m anufacture new proteins that your body needs to stay healthy and grow. I m ake clotting factors that stop the bleeding when you nick yourself shaving or paring anapple.
I help defend you against the "germ warfare" going on in your body all the tim e. I takethose cold germ s, flu bugs and other germ s you encounter, and knock 'em dead - or at leastweaken them . I m anufacture the cholesterol you need to synthesize Vitam in D.
I am the ONLY organ in your body that can com pletely regenerate, even from a sm allportion of healthy liver.
You m ay think your brain or your heart is the m ost im portant part of you but, without ahealthy liver, nothing works right.not your brain, not your heart.nothing! W ARNING:
I can't, and w on't, tell you I'm in trouble until I'm alm ost at the end of m y rope.
and yours.
I am a non-com plainer. Overloading m e with drugs, alcohol and other junk can destroy m e! This m ay be the only warning you will ever get. If you ever have a blood test run and it shows elevated liver enzym es ( shown on the blood test results as ALT and AST), NEVER ignore those results - follow up - find out m ore - be insistent! Learn what those results m ean.educate yourself.be your own best health advocate! W hy is the liver so im portant in nutrition?
85-90% of the blood that leaves the stom ach and intestines carries im portant nutrients to
the liver where they are converted into substances the body can use. The liver perform s
m any unique and im portant m etabolic tasks as it processes carbohydrates, proteins, fats
and m inerals to be used in m aintaining norm al body functions.
Carbohydrates, or sugars, are stored as glycogen in the liver and are released as energy
betw een m eals or when the body's energy dem ands are high. In this way, the liver helps to
regulate the blood sugar level, and to prevent a condition called hypoglycem ia, or low blood
sugar. This enables us to keep an even level of energy throughout the day. W ithout this
balance, we would need to eat constantly to keep up our energy.
Proteins reach the liver in their sim pler form called am ino acids. Once in the liver, they are
either released to the m uscles as energy, stored for later use, or converted to urea for
excretion in the urine. Certain proteins are converted into am m onia, a toxic m etabolic
product, by bacteria in the intestine or during the breakdown of body protein. The am m onia
m ust be broken down by the liver and m ade into urea which is then excreted by the
kidneys. The liver also has the unique ability to convert certain am ino acids into sugar for
quick energy.
Fats cannot be digested without bile, which is m ade in the liver, stored in the gallbladder,
and released as needed into the sm all intestine. Bile (specific bile "acids"), acts som ewhat
like a detergent, breaking apart the fat into tiny droplets so that it can be acted upon by
intestinal enzym es and absorbed. Bile is also essential for the absorption of vitam ins A, D,
E, and K, the fat soluble vitam ins. After digestion, bile acids are reabsorbed by the intestine,
returned to the liver, and recycled as bile once again.
There are health conditions that can effect the function of your liver. Som e of them can beand, in fact, alm ost always are com pletely and utterly silent. Then, one day, you just sort ofdon’t feel very well - you’re fatigued, your appetite is off and when you do eat, it m akes youfeel unwell. Perhaps you have som e m ild discom fort in the upper right quadrant of yourabdom inal cavity or swelling in the abdom inal area. You have diarrhea that doesn’t resolveafter a day or so. Maybe your legs and ankles are swollen. W hen you finally decide you’dbetter see your doctor, tim e can be lost chasing the vague sym ptom s you’re m anifestingbefore the root problem is discovered. That’s when you m ay find out you’re in a lot oftrouble and that you m ay or m ay not be able to be fixed. Som e people don’t find out howdam aged their liver is until they have developed cirrhosis - that’s how quiet and well-behaved your liver can be.
In this discussion, I am only taking on two of the conditions that can affect your liver. There are m any others (see list of references). The two we’ll be focusing on are: Viral Hepatitis - all form s of hepatitis (A, B, C, D, E, & G). A m ore in-depth discussion
of the various form s of hepatitis appears later in these papers, including how it is acquired, how it is diagnosed and how it is treated.
Hem ochrom atosis - an inherited m etabolic disorder in which large am ounts of iron are
transported from the intestine and accum ulate in the liver. A m ore in-depth discussion of hem ochrom atosis appears in a later section of these docum ents including, once again, how it is acquired, diagnosed and treated.
Jaundice, or yellowing of the skin Darkened urine Diarrhea, Chalky-colored, clay-colored or black stools (from bleeding) Elevated liver enzym es - ALT and AST (see text and Appendix 1 for specific liver tests) Elevated bilirubin, depressed album in (blood test results) Increased prothrom bin tim es (blood clotting tim es) Rem em ber, though.you m ay not exhibit all of these sym ptom s and ones you areexperiencing m ay be low key enough that you’ll be tem pted to dism iss them asunim portant.som ething that will pass in a day or two.”I can’t take tim e out to go to thedoctor today! It’ll have to wait.” For m ore inform ation about your liver and the conditions that can affect it, see the referenceindex at the end of this docum ent. There is further inform ation about liver tests and othercautions for those with hem ochrom atosis. It lists reading m aterials and internet resourcesto assist you in becom ing m ore inform ed.
Hepatitis is a non-specific injury or inflam m ation of the liver, which can be caused by m any things. The m ost com m on cause is alcohol consum ption. Viral hepatitis is not abacterial infection and cannot be cured with antibiotics. It is m ost often acquired throughcontact with the blood of an infected person (hepatitis B, C and D), but the ingestion of foodprepared in unsanitary surroundings or contam inated water can result in Hepatitis A or E. Am other can pass som e form s of the virus to her child during childbirth and som e form s arealso transm itted through sexual activity. A m ore detailed description of the various form s ofviral hepatitis and how they’re transm itted follows.
Screening of donated blood for Hepatitis C (HCV) did not begin until 1990 for the HCV antibody and m ore specific testing for HCV RNA began in 2003. Screening for theHepatitis B (HBV) surface antigen (like an antibody) began in the early 1970's with testingfor the core antigen (a m ore definitive test) beginning in 1986. Screening for HIV began in1985. There are different form s of viral hepatitis (A, B, C, D, E, & G). Hepatitis can be acute (noticeable sym ptom s following exposure) or chronic (long term , with or without anacute phase). ARE YOU AT RISK FOR EXPOSURE TO VIRAL HEPATITIS?
Did you ever experim ent with drugs, use needles to inject drugs, share needles with other people who were injecting drugs, or share a straw to inhale cocaine? Have you had unprotected sex with m ultiple partners or had rough sex that resulted in the tearing or abrasion of tissue and bleeding? Are you a m an having sex with other m en? Have you ever had sex with a Have you had any body piercing or tattoos? Were they done in a clean studio (are you sure?) or at a friend’s house? Do you share body piercing jewelry? Have you ever used anyone else’s personal hygiene item s? Have you evershared a toothbrush with anyone, or a razor, a nailfile or cuticle scissors - anything that could possibly have blood cells on it? Did you receive any blood products of any type prior to 1992 Any transfusions, plasm a, clotting factor (platelets)? Have you had an organ transplant? Extended periods of kidney dialysis? Did you ever try to assist anyone who was injured and bleeding when Are you a health professional and have you ever had a needle stick? Have you ever had any kind of m edical treatment, especially injections or blood products, in an underdeveloped country where needles are often reused and only som etim es sterilized? Do you eat a lot of restaurant food and/or food in other countries with perhaps less than sanitary preparation conditions? Currently, viral hepatitis is classified into different types that are identified with a letter.
Usually transm itted because of unsanitary conditions, often food borne or in contam inated water. Quickly becom es acute (sym ptom atic) but usually resolves by itself. See the list of sym ptom s above.
In m ore serious cases, the patient is hospitalized to m anage sym ptom s.
Sharing of drug paraphernalia, contact with contam inated blood, sex, and close household contact. Can be passed to babies during childbirth - vaccination within the first twelve hours after childbirth cuts that risk by 95% . Can rem ain viable outside the body for m any days - perhaps 30 or m ore.
Often does not have an acute phase (especially in children) and can rem ain “dorm ant” for m any years (10-30) while it’s dam aging your liver. Can progress directly to liver cancer without first causing fibrosis (scarring of liver tissue).
A tiny organism - 42 nanom eters - easily able to penetrate and infect cells in your body (a nanom eter is one billionth of a m eter, a m eter is 39"). Atom s, m olecules (and HBV) are m easured in nanom eters with an electron m icroscope.
This virus has been around for over 10,000 years.
Sharing of drug paraphernalia, contact with contaminated blood, som etimes transm itted through sex (especially m en having sex with m en).
Having m ultiple sex partners, however, does increase your risk for infection.
Can be passed to babies during childbirth. Can rem ain viable outside the body for 16 hrs. to four days. Often does not have an acute phase and can rem ain “dorm ant” for m any years while it’s dam aging your liver. HEPATITIS D (HDV)
Hepatitis D is directly linked to active infection with Hepatitis B and is only found in persons with active HBV infection - not all those infected with HBV have HDV, however. Transm itted through needles and sex, although not as easily through sex as HBV. At the tim e of infection, people are m ore likely to have sudden and severe sym ptom s, called fulm inant hepatitis.
Sim ilar to Hepatitis A (HAV) - infection is usually acute but does not becom e chronic. HEV (like HAV) is spread by eating or drinking contam inated food or water. Not com m on in the US, but always be careful if you’re traveling in underdeveloped countries.
Hepatitis B and especially C are ticking tim e bom bs in our national
and international health profiles !
Up until 1990 or so, people were still getting paid to donate blood. Many of them were drug users. Until 1989, Hep C was known as NANB Hepatitis (non-A, non-B Hepatitis). Screening of the blood supply for this virus did not begin until approxim ately 1990. If you received any blood products prior to 1992, It is estim ated that 3% of the world’s population (over 170 m illion people) have chronic Hep C. These num bers are probably low. Since the virus can rem ain undetected and lay dorm ant for so long, m any who acquired this virus in the sixties, seventies, and eighties are only now getting to the point where som ething will start to m anifest in the form of liver problem s. Health officials are expecting an a sharp increase over the next 10-15 years in people W H AT CAN YO U DO ?
Get tested for hepatitis A, B & C and also for hem ochrom atosis.
These are the silent liver killers. Be thorough.test for HIV, too.
The tests to determ ine if you have ever been exposed to hepatitis are sim ple and easy. Blood is drawn and checked for antibodies. If you have antibodies, you have had atleast som e exposure and m ay or m ay not be chronic. You m ay have been exposed andbeen lucky enough to clear the virus without becom ing chronically infected.
If you test positive for Hepatitis A (HAV) antibodies, you m ay rem em ber having som ething like the flu, perhaps with som e yellowing of the eyes or skin. You m ay not haveexperienced those sym ptom s, however, and your body m ay have cleared the virus withoutyou even knowing you had been exposed. Most people exposed to HAV clear the viruswithout assistance.
If you test positive for Hepatitis B or C (HBV, HCV), you will have to have further tests run to see if you are chronically infected or if you cleared those viruses withoutbecom ing chronic. More about those tests in a m om ent.
If you test negative for HAV and HBV it m eans you have
never been exposed and you can be vaccinated!
(Note that the vaccine for HBV is NOT effective approx. 10% of the tim e - it does not “take”) The vaccination is a series of three shots at different intervals. You should have your entire fam ily tested. Since HBV especially is so easily sexually transm itted, the CDCrecom m ends vaccination for anyone who is sexually active. These shots are a routine partof childhood vaccinations.
If you test negative for H epatitis C (HCV), count your blessings -
there is NO VACCINE for HCV.
M ost County Health Departm ents offer free or low -cost testing for anyone w ith
a history of injection drug use. There is also an over-the-counter test kit
available called Hep C Check. Your best choice for testing is your fam ily doctor.
It is very im portant that your doctor test for IgG antibodies for HBV. This is a com pleteantibody that appears if you have been infected and have cleared the virus on your own.
People who have been vaccinated also have this com plete antibody. If you do not have thiscom plete antibody, you do not have viral clearance or im m unity. If you test positive for theantibodies discussed below but negative for the IgG, you have further testing ahead of youand you will need to m ake a decision about the physician you will be seeing. If you wereinitially diagnosed by a General Practitioner (GP) who is knowledgeable about hepatitis, youcan stay with that doctor. You can ask to be referred to a gastroenterologist - a physicianwho is responsible for everything in your digestive tract, beginning to end. A better choicewould be a hepatologist - a liver specialist.
To picture the HBV cell, im agine a core (which contains core antigens) surrounded by a ring of DNA, enclosed within an envelope and then enclosed within a ring of protein cellscalled a surface antigens. As you will see, the structure and behavior of HBV is differentfrom HCV. Testing is also done differently and looks for com ponents specific to HBV -surface antigens and core antigens. First, let’s back up one step. An antibody is a proteinin your blood that recognizes certain com ponents of infecting organism s (like viruses andbacteria). An antigen is a protein or other chem ical com ponent of a virus or bacteria that isrecognized by antibodies. The HBV surface antigen (HBsAg) is readily detectable in theblood and is the m ain test for infection. The HBV core antigen(HBcAg), however, isdetectable in liver cells - if the infection is aggressive, a sm aller version of the core antigencan be found in the blood. This sm aller core antigen is known as BeAntigen (HbeAg). Highlevels of HbeAg core antigens are usually associated with m ore rapid disease progressionand a higher risk of infecting others. HBV can be acute or chronic. Disease progression seem s to be tied to one’s age at the tim e of infection. Those infected in childbirth, infancy or at a young age seem tobecom e chronically infected, but do not necessarily have severe disease early on. A childgiven a vaccination within twelve hours of birth has a reduced infection risk of about 95% !This also allows the m other to safely breast feed her infant. Those infected later in life seemto be m ore at risk for severe liver dam age in the short term , but are also m ore likely to getrid of the virus without m edical treatm ent. Most people infected as adults go through anacute stage. HBV tends to be generally m ore aggressive than HCV in the acute phase, butonly about 5 percent of those infected going on to becom e chronic at a low-key level. Manypeople infected with HBV will end up having to seek treatment. HBV can go straight to livercancer without first causing fibrosis.
HBV has eight different varieties (also known as genotypes, A-H), and there are subtypes (Aa, Ab, som tim es seen also as Aa(A1), Ab(A2), etc.).
Tests should be run to determ ine your viral load and, as is the case with Hepatitis C, you m ay need to have a liver biopsy to determ ine the level of dam age to your liver (if any). At this tim e, a biopsy is the only sure way to determ ine or rule out dam age to the liver. Certainly you should have a com plete blood count test (CBC) including a liver panel to checkyour liver enzym es (AST and ALT), bilirubin, album in, cholesterol, iron levels, diabetesfactors, and AFP (alpha-fetoprotein, a tum or m arker). Your doctor m ay also want you tohave a sonigram to check for tum ors - som e of the sneaky liver cancers do not produceenough AFP to show up on a blood test. FURTHER TESTING FOR H EPATITIS C (HCV)
A CBC (com plete blood count) and com prehensive m etabolic panel should be runwith em phasis on liver enzym es (ALT and AST), bilirubin, album in, triglycerides, thyroid functions, serum iron levels and rheum atoid arthritis m arkers. Alpha-fetoprotein (AFP) should be checked and, again, your doctor m ay want you to have asonigram to check for tum or activity. See Appendix 1 for m ore inform ation onspecific liver panel test results.
You should have a quantitative analysis of how m any copies of the virus you have in your blood. Blood is drawn and the num ber of viral RNA copies in a certain m easure ofblood is assayed. This is called your viral load. A high count, however, is not necessarily anindication of disease severity or a tool to predict disease progression. This test is m ostcritical while you are in treatm ent. It will allow your doctor to determ ine if the treatm ent isworking and if treatm ent should be discontinued due to a lack of reduction in viral load. Literally m illions of RNA copies can be contained in a very sm all am ount of blood.
Your doctor should run a genotyping test. There are six different genetic variations of HCV (called genotypes = genetic types). Each of those genotypes has what are calledsubtypes. Blood will be drawn and sent off to a special lab where they will determ ine if youare a 1a, 2b, 1d, 5c, 3a or whatever the test m ight happen to yield. Overall, includingsubtypes, there are roughly 60 variations. Genotyping is im portant because it determ ineshow long you have to undergo treatment to clear this virus from your system . Genotype 1is the m ost com m on genotype in the U.S., com prising about 85 % of the cases. Approxim ately 10 - 12 % of the rem aining cases are genotype 2 or 3. Genotypes 4, 5 and6 are found m ostly outside the U.S., but som e are found here. If you are a genotype 1 or 4and if it is determ ined that you need to undergo treatm ent, you will have to treat for 48weeks using a com bination of pegylated interferon and an antiviral called ribavirin. Genotypes 1 and 4 are the most difficult to treat. If you have not cleared the virus (see #2regarding viral load testing) by week 12, treatm ent will alm ost certainly be discontinued. This is because of the unpleasant side effects associated with treatm ent - no point in m akingyou that m iserable if the drugs are not working. Unfortunately for those with genotype 1,failure at week 12 is relatively com m on with only about a 50 - 60 % success rate at that 12-week juncture. Even m ore unfortunately for those with genotype 1, relapse after 48 weeksof treatment happens in about 30 - 40 % of cases. Re-treatment is som etim es an optionfor those people. If you clear the virus and rem ain clear in followup tests at six m onths andone year, you have probably achieved what is called a sustained viral response (SVR) andrelapse and retreatm ent should be out of the picture. If you have been diagnosed withgenotype 2 or 3, you should be able to treat (if necessary) for only 24 weeks. Once again,you will be assessed at week twelve. These two genotypes, however, have a good rate ofsuccess with 75-90 % of patients achieving an SVR and a very low relapse rate. You willstill receive followup tests at six m onths and one year. To be safe, testing is advised for allgenotypes for several years following treatm ent.
Last, but certainly not least, you will have a liver biopsy. This is an outpatient procedure done at the hospital. A sm all sam ple of liver tissue will be extracted(approxim ately 1" long by 1/16th” or less in diam eter). Tiny slices taken from this tissuewill be exam ined under a m icroscope to determ ine what dam age, if any, the virus has doneto your liver. This is called staging. You will receive a 2-num ber diagnosis. The firstnum ber is the “grade” of inflam m ation and the second is the “stage” of scarring (fibrosis).
There are four basic stages of fibrosis. In the m ost com m only used staging system , the Knodell system , the dam age to the liver is scored as follows: • 0 = no scarring• 1 = m inim al scarring• 2 = scarring has occurred and extends outside the areas in the liver that contains blood vessels • 3= (bridging fibrosis) scarring that is spreading and connecting to other areas that contain fibrosis • 4=cirrhosis or advanced scarring of the liver If you have m ostly inflam m ation and little scarring, you and your doctor are in charge of your prognosis. Once you have reached the point of cirrhosis, you are in trouble.
The liver is very forgiving, but scarring is usually irreversible. Early diagnosis is critical andcan literally be a life or death m atter. TREATM ENT OF HEPATITIS B (HBV)
There are currently six drugs available to treat chronic HBV: Baraclude (entecavir), Epivir (lam ivudine; 3TC), Intron A (interferon alfa-2b), Hespera (adefovir dipivoxil), Pegasys(interferon alfa-2a) Tyzeka (telbivudine). For m ore inform ation on these drugs, please go to and click on the “Hepatitis B” button at the top of the page. Youcan also go to Google and type in each drug nam e for more inform ation. Both form s ofinterferon m entioned above are also used to treat HCV.
You m ay treat HCV at any stage of fibrosis. This is a decision you need to discuss with your doctor. If you are at or beyond than Stage 2, you should seriously considertreatm ent.
Different genotypes have to treat for different lengths of tim e. Genotype 1, the m ost com m on type in Am erica, treats for 48 weeks but with a caveat - rem em ber we discussedm easuring your viral load. If you are a genotype 1 and you begin treatment and you do notreach a point at week twelve of no detectable virus in your system , your treatm ent will m ostlikely be discontinued. You will be classified as a non-responder. This is not necessarily theend of the world. If you started with the drug m anufactured by Roche, you m ay respondbetter to the interferon produced by Schering-Plough. Also, m any new drugs are currentlybeing tested for this virus and will hopefully be available in the next few years. Genotype 4also treats for 48 weeks. Genotypes 2 and 3 treat for 24 weeks. They are m uch m oreresponsive to treatm ent (especially type 2) and the relapse rate is low. Unfortunately, therelapse rate for type 1 and 4 is fairly high. Sadly, this m eans that you can be “clear” atweek twelve, go through the whole 48-week treatment and then find out at your 6-m onth or1-year followup that the virus has com e back. I say sadly because the side effects of thetwo drugs range from m ildly uncom fortable to downright m iserable. As is the case with anydrug, everyone responds differently. For exam ple, if you and I both have a headache andwe both take two aspirin, we m ight both get rid of the headache, but you m ight have anupset stom ach from the aspirin and I m ight not. There’s just no way to know until you starttreatment - there are no predictors for side effects. These side effects will be item izedshortly.
The drugs used to treat HCV are pegylated interferon and an antiretroviral, ribavirin. These drugs are m anufactured prim arily by Roche and Schering-Plough. There are otherdrugs (protease and polym erase inhibitors) and other form s of interferon being developedby these two com panies and other com panies. W e’ll get to those other options in a bit.
Interferons are a naturally-occurring part of your im m une system . They are proteins produced by the cells of the im m une system in response to challenges by foreignagents such as viruses, bacteria, parasites and tum or cells. Interferons assist the im m uneresponse by inhibiting viral replication within other cells of the body.
Pegylated interferon is a m an-m ade replica of natural interferon and the pegylation process gives the drug a longer life in your system . Shots of pegylated interferon areadm inistered once a week subcutaneously in the abdom en. Before pegylation, shots had tobe taken three tim es a week to m aintain a sufficient level of the drug in your system . The other drug used in treatm ent is called ribavirin and it is an anti-retroviral. Its function is also to inhibit viral reproduction. Ribavirin is a pro-drug, m eaning that it is achem ical precursor for the actual pharm acologically active m olecule. W hen the pro-drug isadm inistered, the body converts it into the desired chem ical. Both drugs are intended toboost your own im m une system in the fight against the virus. These drugs have differentnam es depending on the pharm aceutical com pany of origin. Roche’s drugs arePegIntron/Rebetol, Schering-Plough’s drugs are Pegasys/Copegus.
The side effects of both interferon and ribavirin are well docum ented. Interferon produces flu-like sym ptom s (chills, fever, nausea, headache, aching joints), depression insom e people, fatigue, insom nia, hair thinning or loss, sores in the m outh and throat. Lessfrequent side effects can include hearing loss and retinopathy (dam age to the retina). Ribavirin’s m ost pronounced side effect is hem olytic anem ia. This m ust be carefullym onitored as it m ay worsen pre-existing heart conditions. If you are a wom an, you shouldavoid becom ing pregnant during treatm ent and for at least six m onths after treatm ent isover. Don’t allow a m an in treatm ent to im pregnate you. Ribavirin can cause birth defects. The side effects with this drug com bination can be severe enough to cause people to discontinue treatm ent. One of the m ain functions of your treating physician as you go intotreatm ent (besides m onitoring your progress in com bating the virus) is to m anage sideeffects. As was stated before, however, you won’t know until you get into treatm ent andstart using the drugs. I did have som eone tell m e of two different people who startedtreatm ent on the sam e day. One left the clinic to walk hom e (a distance of three blocks),got about two blocks, called and said, “I don’t think I’m going to m ake it!”. (He did.) Theother person lived out of town, headed out after doing the shot, got about 45 m inutes out,called and said. “You prom ised m e that everyone in this trial would get drugs, that therewere no placebos - I don’t feel anything!”. Both were on the sam e drugs. Your doctor willdo a com plete workup on you - both physical and psychological - prior to treatm ent and willvery carefully monitor you the entire tim e you’re in treatm ent. As with any m edicalsituation, it is im perative that you be totally honest with your doctor. If you are taking orusing any other substances, legal or not, you MUST discuss this with your doctor. I dom ean anything - herbs, pot, alcohol, vitam ins, aspirin - anything! Side effects for m ost people resolve fairly quickly after treatm ent is over. By six m onths, you could very well be feeling 80-95% . By the end of a year, all side effects shouldhave resolved. Once again, however, rem em ber that everyone is different.
Hem ochrom atosis (som etim es seen as “hem achrom atosis”) is an inherited m etabolicdisorder - it is not a disease. It can be acquired, but not from any kind of contact withanother person (m ore about that in a bit). It is most often seen in people of NorthernEuropean, Baltic, Celtic and Scandinavian descent, and also those with Jewish heritage. Approxim ately 10-13 % of the population are carriers for this condition and it is one of them ost under-tested health disorders. Additionally, persons affected by this disorder haveunusually high levels of the protein that binds with iron to keep it in the body - a proteincalled ferritin. Both the m other and father of a child have to be carriers of the altered genefor the disorder to be passed along to their child. As that child m atures, iron begins buildingup in their body. That iron is m ostly stored in the liver and over tim e will com pletelydestroy the liver. Not all children born to “carrier” parents will be equally affected.
The excess iron can also dam age the heart, the pancreas, the joints and the brain. It buildsup slowly and m ay not be apparent in blood tests until som eone is in their fifties or sixties. In wom en, the diagnosis can occur even later because of m enstruation. Iron is carried inthe bloodstream and wom en lose som e blood every m onth, causing the buildup of excessiron in the body to m ove at a slower pace. Som e wom en are not diagnosed until theybecom e m enopausal. Once again, because this is a condition that affects the liver,sym ptom s can be slow to appear, low-key, and subtle. This condition does not necessarilycause cirrhosis, but can cause organ failure - liver, kidney and heart failure are m ostcom m on.
Two sim ple blood tests and one m ore in-depth blood test are needed to check for thiscondition. One tests the level of ferritin protein in your system , one checks your serum ironsaturation percentage and the third checks for the chrom osom al genetic variation thatconfirm s the presence of this condition. If found at an early stage or age, this is a conditionthat is sim ple to treat. The treatment is phlebotom y - blood draws. If you have beendiagnosed with this condition, your doctor will start you on a schedule of blood draws(usually done at a blood bank) and you m ay have a blood draw as often as once a weekuntil all of the excess iron has been depleted from your body tissues and blood stream . Depending on how m uch iron is in your system when this process begins, this can take up toor even over a year. Once your iron levels are under control, you will be on a lifetim eregim en of blood draws, usually at regular intervals like once every two or three m onths. Ifyou do not faithfully adhere to this regim en, iron will once again build up in your body anddam age your organs. If anyone in your fam ily tests positive for this condition, everyoneshould be tested (especially if you’re a parent - have your children tested - early diagnosiscould save their life!) W HAT ARE THE SYM PTOM S?
The sym ptom s are in m any ways the sam e as they are for hepatitis. Certainly you shouldlook at the list for sym ptom s of liver disease that appeared here earlier. Additionally,however, because the iron can also affects other organs in the body, you m ay experience: Mental disorientation, confusion, inability to concentrate Enlarged liver and elevated liver enzym es (ALT and AST) Skin that has a grayish or bronze coloration Peripheral neuropathy (num bness in the extrem ities) This is another condition where the sym ptom s whisper - you have to be aware and you haveto “listen” to your body! Your body will alm ost always tell you when som ething is wrong,but you have to be listening.
Rem em ber that I m entioned that hem ochrom atosis could be acquired instead of inherited. Repeated blood transfusions for thalassem ias ( a condition that affects the production ofhem oglobin) and iron supplem entation for anem ia are the two m ost com m on causes.
Oddly enough, blood that is drawn from a person with iron overload can be used forsom eone else in, say, a surgery setting. A person with a norm al system will sim ply excretethe excess iron. You wouldn’t want iron-rich blood if you needed blood on a regular basis,but one unit or a one-tim e transfusion won’t dam age you.
Please see the Appendix at the end of this paperwork for inform ation on a bacterial infectionthat is particularly voracious in people with hem ochrom atosis - it’s found in raw orundercooked shellfish and can also be found in the sand at the beach.
Living W ith Hepatitis C: A Survivor’s Guide, Gregory T. Everson, M.D.
The Hepatitis Help Book, Misha Ruth Cohen, O.M.D, L.A.C and Robert Gish, M.D.
- Offers the basics plus an Asian perspective for alternative therapies INTERNET RESOURCES - HEPATITIS
Inform ation about all liver conditions, acquired and inherited A com prehensive and easy-to-navigate web site. Covers the basics about all form s of hepatitis, HIV/AIDS, and HIV/Hepatitis co-infection. Staffed by m edical personnel with inform ation geared m ore toward m edical professionals than laypersons. Presents detailed inform ation from all HIV and liver disease related A com prehensive and easy-to-navigate site with lots of inform ation and news Inform ation in 20+ languages. Started by a HCV survivor, Alan Franciscus.
Am erican Association for the Study of Liver Diseases (AASLD European Association for the Study of Liver Diseases (EAS UNOS - United Network of Organ sharing. Donor and transplant inform ation, transplant READING M ATERIALS - HEM OCHROM ATOSIS
Living W ith Hem ochrom atosis, Gregory T. Everson, M.D.
The Iron Disorders Institute Guide to Hem ochrom atosis, m ultiple authors Exposing the Hidden Dangers of Iron, E. D. W einberg, Ph.D.
(If you have trouble accessing this site, their phone # is 888/655-IRON) OTHER RESOURCES
Metabolic Liver Diseases - Mendelian Inheritance in Man - Also look here for m edical literature - free searches for prim ary literature, often with Anything you could ever want to know about your lab test results or about tests the doctorhas ordered for you. o here to look up tests that are going to be run or have already beenrun to see why they were run (what the doctor is looking for) and what those tests tell youand your doctor Appendix 1 - Liver Function Tests
The term “liver function tests” and its abbreviated form , “LFTs,” is a com m only used termthat is applied to a variety of blood tests that assess the general state of the liver and biliarysystem . Routine blood tests can be divided into those tests that are true LFTs, such asserum album in or prothrom bin (a plasm a protein, coagulating factor) tim e, and those teststhat are sim ply m arkers of livers or biliary tract disease, such as the various liver enzym es.
In addition to the usual liver tests obtained on routine autom ated chem istry panels,physicians m ay order m ore specific liver tests, such as viral serologic tests or autoim m unetests that, if positive, can determ ine the specific cause of a liver disease.
There are two general categories of “liver enzym es.” The first group includes the alanineam inotransferase (ALT) and the aspartate am inotransferase (AST), form erly referred to asthe SGPT and the SGOT. These are enzym es that indicate liver cell dam age. The otherfrequently used liver enzym es are the alkaline phosphatase (alk. phos.) and thegam m aglutam yltranspeptidase (GGT) that indicate obstruction to the biliary system , eitherwithin the liver or in the larger bile channels outside the liver.
The ALT and AST are enzym es that are located in liver cells and leak out and m ake theirway into the general circulation when liver cells are injured. The ALT is thought to be a m orespecific indicator of liver inflam m ation, since the AST m ay be elevated in diseases of otherorgans such as the heart or m uscle. In acute liver injury, such as acute viral hepatitis, theALT and AST m ay be elevated to the high 100s or over 1,000 U/L. In chronic hepatitis orcirrhosis, the elevation of these enzym es m ay be m inim al (less than 2-3 tim es norm al) orm oderate (100-300 U/L). Mild or m oderate elevations of ALT or AST are nonspecific andm ay be caused by a wide range of liver diseases. ALT and AST are often used to m onitor thecourse of chronic hepatitis and the response to treatm ents, such as prednisone and interferon.
The alkaline phosphatase and the GGT are elevated in a large num ber of disorders thataffect the drainage of bile, such as gallstone or tum or blocking the com m on bile duct, oralcoholic liver disease or drug-induced hepatitis, blocking the flow of bile in sm aller bilechannels within the liver. The alkaline phosphatase is also found in other organs, such asbone, placenta and intestine. For this reason, the GGT is utilized as a supplem entary test tobe sure that the elevation of alkaline phosphatase is indeed com ing from the liver or thebiliary tract. In contrast to the alkaline phosphatase, the GGT is not elevated in diseases ofthe bone, placenta or intestine. Mild or m oderate elevation of GGT in the presence of anorm al alkaline phosphatase is difficult to interpret and is often caused by changes in theliver cell enzym es induced by alcohol or m edications, but without causing injury to the liver.
Bilirubin is the m ain bile pigm ent in hum ans that, when elevated, causes the yellowdiscoloration of the skin and eyes called jaundice. Bilirubin is form ed prim arily from thebreakdown of substance in red blood cells called “hem e.” It is taken up from bloodprocessed through the liver, and then secreted into the bile by the liver. Norm al individualshave only a sm all am ount of bilirubin circulating in blood (less than 1.2 m g/dL). Som econditions, including liver disease or the destruction of red blood cells, cause increasedlevels of bilirubin in the blood stream. Levels greater than 3 m g/dL are usually noticeable asjaundice. The bilirubin m ay be elevated in m any form s of liver or biliary tract disease, andthus it is also relatively nonspecific. How ever, serum bilirubin is generally considered a true test of liver function (LFT), since it reflects the liver’s ability to take up, process and secretebilirubin into the bile.
Two other com m only used indicators of liver function are the serum album in andprothrom bin tim e. Album in is a m ajor protein form ed by the liver, and chronic liver diseasecauses a decrease in the am ount of album in produced. Therefore, in m ore advanced liverdisease, the level of the serum album in is reduced (less than 3.5 m g/dL). The prothrom bintim e, which is also called protim e or PT, is a test that is used to assess blood clotting. Bloodclotting factors are proteins m ade by the liver. W hen the liver is significantly injured, theseproteins are not norm ally produced. The prothrom bin tim e is also a useful test of liverfunction, since there is a good correlation between abnorm alities in coagulation m easuredby the prothrom bin tim e and the degree of liver dysfunction. Prothrom bin tim e is usuallyexpressed in seconds and com pared to a norm al control patient’s blood.
Finally, specific and specialized tests may be used to m ake a precise diagnosis of the causeof liver disease. Elevations in serum iron, the percent of iron saturated in blood, or the ironstorage protein ferritin m ay indicate the presence of hem ochrom atosis, a liver diseaseassociated with excess iron storage. In another disease involving abnorm al m etabolism ofm etals, W ilson’s disease, there is an accum ulation of copper in the liver, a deficiency ofserum ceruloplasm in and excessive secretion of copper into the urine. Low levels of serumalpha1-antrypsin m ay indicate the presence of lung and/or liver disease in children or adultswith alpha1-antrypsin deficiency. A positive antim itochondrial antibody indicates theunderlying condition of prim ary biliary cirrhosis. Striking elevations of serum globulin,another protein in blood, and the presence of antinuclear antibodies or antism ooth m uscleantibodies are clues to the diagnosis of autoim m une hepatitis. Finally, there are specificblood tests that allow the precise diagnosis of hepatitis A, hepatitis B, hepatitis C andhepatitis D.
For those w ith hem ochrom atosis -
RISKS OF EATING RAW OR UNDERRCOOKED SHELLFISH Advice for persons with liver disease, diabetes, or weakened im m une system s. Did you know ?.
Each year, m illions of Am ericans enjoy eating raw m olluscan shellfish -- especially oysters
and clam s. But if you have a liver disease, diabetes, or a w eak im m une system , raw
oysters or clam s containing the bacteria Vibrio vulnificus can m ake you seriously ill.
Eating only oysters or clam s that have been thoroughly cooked.
Eating raw oysters or clam s only if they are treated and labeled "Processed to reduce Vibrio vulnificus to non-detectable levels." W hat is Vibrio vulnificus?
Vibrio vulnificus is a bacteria that can cause sever illness or death to at-risk people who eatraw oysters or clam s. From 1989 to 2000, the U.S. Food and Drug Adm inistration (FDA)recorded 282 serious illnesses associated with consum ption of raw oysters and clam scontaining the Vibrio vulnificus bacteria. W hile illnesses are infrequent, about half (149)have resulted in death.
W here is it found?
Vibrio vulnificus is found naturally in warm coastal waters, such as the Gulf of Mexico, wherelevels of the bacteria are elevated during the sum m er m onths. Vibrio vulnificus is NOT aresult of pollution, and can be found in waters approved for oyster and clam harvesting.
Vibrio vulnificus does NOT change the appearance, taste, or odor of oysters or clam s.
Are you at risk?
You are at risk of serious illness if you eat raw oysters or clam s and have any of thesehealth conditions: Liver disease (from hepatitis, cirrhosis, alcoholism , or cancer) Iron overload disease (hem ochrom atosis) Cancer (including lym phom a, leukem ia, Hodgkin's disease) Or any illness or m edical treatment that weakens the body's im m une system Unsure of your risk? Ask your doctor.
Healthy people are not at risk of serious infection. How can you avoid infection?
If you at risk, raw or undercooked oysters or clam s containing Vibrio vulnificus can m akeyou sick.
You can also becom e infected if these bacteria enter your body through an open woundwhile swim m ing in ocean water.
To safeguard your health, take these precautions: EAT oysters or clam s that have been THOROUGHLY COOKED -- heat destroys EAT raw oysters or clam s ONLY if they are treated and labeled "Processed to reduce Vibrio vulnificus to non-detectable levels." W hat are the sym ptom s?
Sym ptom s usually occur within 24-48 hours, and m ay include: If you have any of these sym ptom s after eating raw oysters or clam s, seek m edical
attention im m ediately.
For those at risk, infection can lead to death within two days. Early, aggressive antibiotic
treatm ent is the m ost effective therapy.
Vibrio vulnificus rarely affects healthy individuals. W hen it does, sym ptom s are m ild and

Source: http://www.lashgroup.org/hcvdoc.pdf

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Strategies for subtypes—dealing with the diversity ofbreast cancer: highlights of the St Gallen InternationalExpert Consensus on the Primary Therapy of EarlyBreast Cancer 2011A. Goldhirsch1*, W. C. Wood2, A. S. Coates3, R. D. Gelber4, B. Thu¨rlimann5, H.-J. Senn6 & Panelmembers 1International Breast Cancer Study Group, Department of Medicine, European Institute of Oncology, Milan, Italy;


Ce corrigé est proposé par François-Xavier Coudert (ENS Ulm) ; il a été relu parFabrice Maquère (ENS Cachan) et Mickaël Profeta (Professeur en CPGE). Le sujet, divisé en six parties complètement indépendantes, est d’une longueurraisonnable et alterne les questions proches du cours et les questions un peu plus diffi-ciles. À l’intérieur de chaque partie, les questions s’e

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