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“The only thing necessary for these diseases to the triumph is for good people and governments to do nothing.”



Exploring the Liver

For Patients

Aging Begins at 30

Ian Maclean Smith, M.D.
Emeritus Professor
Department of Internal Medicine
University of Iowa Hospitals and Clinics

Creation Date: February 2001
Last Revision Date: February 2001
Peer Review Status: Internally Peer Reviewed

It is rumored that Paul Ehrlich did a liver biopsy in 1883, but it was still in medically "prehistoric times" (1946) when I was assigned to do a liver biopsy. I did all the things we know now to be contraindications. I took several minutes, used a large needle and did it in a patient who had liver cancer. It was tragic. The patient died. He was well on his way to death from cancer spread to his liver. I changed his exitus from days to a few hours. Autopsy showed that I went straight through a cancer nodule with a sizeable vessel in the center. Liver biopsy was then a major procedure and is now an outpatient procedure of great usefulness to the patient.

Menghini introduced modern liver biopsy in 1958. He used a new very thin suction needle. His article was entitled "One-second needle biopsy of the liver" in the journal Gastroenterology. This through-the-skin biopsy method makes it possible to get tissue via the laparoscope (intra-abdominal telescope), or from the inside of the liver via a guided catheter threaded through the jugular vein, or through the skin with added accuracy using ultrasound or MRI guidance. A recent article from Harvard in the New England Journal of Medicine retraces these liver biopsy historical steps that I have lived through. As always, good treatment depends on accurate diagnosis. One delivers to the pathologist a piece of tissue between half and one inch in length and about a tenth of an inch in diameter. The liver is made up of cell systems with a main circulation central artery and vein and a special liver (portal) vein. These vessel systems are called triads and one expects to get 6 to 8 of them in the biopsy. With this and multiple stains and techniques the pathologist can give a diagnosis, including the stage of the disease, possible management and information on the likely future course of the disease. Diagnosis is made in about 90% of biopsies.

I remember Charles; a prominent 30-year-old lawyer in town who had abnormal blood tests indicating possible hemachromatosis (a hereditary problem with the over-absorption of iron) which had saturated his liver with iron and caused liver scarring. If untreated this would kill him in about 10 years. His biopsy told the whole story and he is still alive and well with treatment, about 40 years later. Two situations are quite common. First a 55-year-old woman who is apparently well but on routine screening has abnormal liver function blood tests. The answer on liver biopsy was sarcoidosis, a disease of unknown cause but with effective treatment. Less common is an older man, perhaps 68, with normal liver function tests but a past history of damage to the liver by alcohol or hepatitis, and he is now failing for no obvious reason. George was a Newfoundland fisherman of 70 who hadn't drunk for 10 years. His biopsy showed well-established cirrhosis but he had no evidence of varicosities at the bottom of his esophagus that might bleed and no evidence of liver cancer. As it happened, his cirrhosis was only moderate and he did well on standard treatment.



After the biopsy the patient needs watching within 30-minute reach of the hospital for 24 hours, and should spend several hours before that under direct observation. Complications requiring hospital observation occur in about 2%, mainly local pain and fainting. In complicated illness, rare deaths from liver biopsy do still occur (about 1 in 11,000 patients) often with cancers like my patient years ago. As with most procedures, fewer complications occur the more procedures the doctor does each year. The breakaway point seems to be 50 procedures or more yearly. One does not do the procedure on someone with a bleeding tendency, or an uncooperative patient or someone with sheep derived worm cysts (echinococcal cysts), hemophiliacs or patients with fluid or infection in the abdomen. It should be done only with caution in the very obese.

Many years ago I remember telling my fellow medical student, Struan, "Isn't it remarkable how big the liver is and how little we know about it!" Little did I realize how wonderful the progress in understanding it would be in my lifetime.

For Patients

Aging Begins at 30

Jaundice Isn't Simple Any More

Ian Maclean Smith, M.D.
Emeritus Professor
Department of Internal Medicine
University of Iowa Hospitals and Clinics

Creation Date: 1994
Last Revision Date: 1994
Peer Review Status: Internally Peer Reviewed

Elizabeth visited her grandchildren in Arkansas. They developed jaundice and so did she - 28 days later when she returned home. She had nausea, vomiting, fatigue, fever, cold-like symptoms, and aches all over, followed a week later, when she was beginning to feel better, by jaundice. At that time, she had dark urine and clay colored stools. She was tender under her right ribs where I could feel her liver. Five years later she is totally well without complications.

We used to say someone with yellow eyes and skin was jaundiced (from jaune, yellow) and leave it at that. Later we called it infectious hepatitis (liver inflammation) and serum- or syringe-transmitted hepatitis. Now we have five or more hepatitis types: A (epidemic or infectious, which Elizabeth had), B (serum), C (blood transfusion, needle, and community acquired, formerly called Non A, Non B), D or delta agent (piggyback infection on top of B, primarily in mainline drug addicts or hemophiliacs), and E (water borne in India, Africa, and Central America). These types of hepatitis, A through E, are caused by five different families of viruses, called HAV, HBV, etc., from picorna virus (for dwarf RNA virus) to hepadna virus (for DNA virus of the liver). There has been an explosion of knowledge in this field in the past decade, leading to improved prevention and, we hope, in the near future to carefully targeted treatment. The name hepatitis is better than jaundice as with better tests we have found that not all infected patients become jaundiced. Another form of hepatitis is chemical hepatitis caused by alcohol, some anesthetics, nitrofurantoin, isoniazid, and other drugs. Copper build up Wilson's disease is inherited. There are no viruses involved in these varieties.

Hepatitis was recorded first in the 500 to 380 B.C.E. period in the Talmud and by Hippocrates, probably type A, with 10-year cycles of increased prevalence. Since then, it has plagued the armies of Rome, Napoleon, World Wars I and II, Korea, Viet Nam, and Desert Storm. Viral hepatitis became reportable in the U.S. in 1952 and as type A or B, or non-specified, in 1965.

Hepatitis A or HAV is spread by the oral and stool route. It is acquired by exposure to another case in 40%, by day care in 20%, by travel where food handling is unsaniitary and by food (often shellfish) in 5% each. It can be prevented in contacts of patients by intramuscular injection of immune serum globulin in amounts of half to 2 milliliters, according to weight. There are rarely any complications.

Hepatitis B is a big problem and there are estimated to be several billion cases worldwide. The first breakthrough was a Nobel Prize winning discovery by Dr. Baruch Blumberg, a geneticist. He found that when serum from a hemophiliac patient containing hepatitis B was mixed with the serum of a hepatitis B carrier, a visible line was formed that could be used as a test virus. The carrier happened to be an Australian aborigine, so this antigen was called Australia Antigen or Hepatitis Associated Antigen and now is called hepatitis B surface antigen designated HbsAg. The signs and symptoms are similar to HAV infection, but time from contact case to jaundice is 2-6 months. About 10% of hepatitis B and 60% of C patients go on to chronic disease called chronic active hepatitis. They maintain a carrier state so that their blood is infectious. There are about 300 million chronic carriers worldwide. This is why, along with the risk of AIDS, we now use universal precautions using rubber or plastic gloves in hospitals and in nursing homes (where 1% of patients are hepatitis B carriers and 2% hepatitis C carriers). A single needle stick with known hepatitis B positive blood transmits the disease in about 20% because there are 10 trillion disease particles per milliliter of blood, compared to 10 to 100 bacterial particles in blood poisoning patients' blood.

People at high risk of developing HBV infection are spouses of patients, nurses, physicians, dentists, IV drug addicts, recipients of blood or blood products, hemodialysis patients, homosexuals, persons with multiple sex partners, and persons in crowded institutions such as mental hospitals and prisons.

Hepatitis B is acquired by personal contact in 15%, homosexual activity in 12%, heterosexual activity in 20%, drug use in 24%, and hemodialysis in 1%. Jaundice occurs in 50%. Less than a third need hospitalization and 2% of these die. Twenty per cent of infants from infected mothers develop hepatitis and, if untreated, 90% become chronic carriers. A special hepatitis B immune serum globulin, along with vaccination, is used to protect these children. Hepatitis B immunization is now included in universal childhood vaccination schedules.



About 20% of chronically infected patients later die of liver cirrhosis or of liver cancer.

Hepatitis D is a defective or incomplete virus which cannot exist alone and infects people who already have hepatitis B and increases its severity. It is confined to persons exposed frequently to blood and blood products, primarily drug addicts and hemophiliacs.

All contents copyright © 1992-2003 the Author(s) and The University of Iowa. All rights reserved.

For Patients

Liver Disease: Frequently Asked Questions

Douglas R. LaBrecque, M.D., Professor of Internal Medicine
University of Iowa Hospitals and Clinics

Creation Date: May 2001
Last Revision Date: May 2001
Peer Review Status: Internally Peer Reviewed

Moderator: Dr. LaBrecque is associated with University of Iowa Health Care, where he is a hepatologist, a professor, and Director of Liver Services in the Department of Internal Medicine.

What are some of the symptoms of liver disease?

The most important thing to recognize about liver disease is that up to 50 percent of individuals with underlying liver disease have no symptoms. The most common symptoms are very non-specific and they include fatigue or excessive tiredness, lack of drive, occasionally itching. Signs of liver disease that are more prominent are jaundice or yellowing of the eyes and skin, dark urine, very pale or light colored stool or bowel movements, bleeding from the GI tract, mental confusion, and retention of fluids in the abdomen or belly.

What quantity of alcohol usage should be seen as being a risk to the liver?

First, it should be understood that alcohol is a poison. Any amount of alcohol can produce damage to the liver. In an otherwise healthy person with no underlying liver problems, the general rule of thumb is different for men and women. Men metabolize and are able to clear alcohol more efficiently than women due to body size, body fat and certain enzymes. Because of this the maximum "safe" daily intake of alcohol for a woman is 1 - 2 drink per day; for the male it is 3 - 4 over a 24-hour period. It is also important to recognize the body and the liver in particular does not distinguish between different forms of alcohol. Beer and wine are not "safer" than whiskey or spirits. One drink is defined as one shot (1 and 1/4 ounces) of whiskey or spirits, one four-ounce can of wine or one 12-ounce can of beer. If an individual has an underlying liver condition such as hepatitis B or C, or prior damage from alcohol or other diseases, the liver is very sensitive to any amount of alcohol. In those conditions, the only safe dose of alcohol is zero.

Can liver damage be reversed?

The liver is a unique organ. It is the only organ in the body that is able to regenerate... that is completely repair the damage. With most organs, such as the heart, the damaged tissue is replaced with scar, like on the skin. The liver, however, is able to replace damaged tissue with new cells. An extreme example is a patient who suffers an overdose from Tylenol. In this example up to 50 - 60 percent of the liver cells may be killed within 3 - 4 days. However, if no other complications arise, the patient's liver will repair completely, and a liver biopsy after 30 days will appear completely normal with no signs of damage and no scar. However, the long-term complications of liver disease occur when regeneration is either incomplete or prevented by progressive development of scar tissue within the liver. This occurs when the damaging agent such as a virus, a drug, alcohol, etc., continues to attack the liver and prevents complete regeneration. Once scar tissue has developed it is very difficult to reverse that process. Severe scarring of the liver is the condition known as cirrhosis. The development of cirrhosis indicates late stage liver disease and is usually followed by the onset of complications.

How necessary is it to inform employers about Hepatitis C Virus status?

Hepatitis C virus-positive patients face a number of difficulties due to the unfortunate stigma that is attached to this carrier status. Transmission or passing of this virus to others requires that they be exposed to the Hepatitis C Virus positive individual's blood or bodily fluid. In most occupations this is not a risk and can be avoided by common sense. In situations where there is a risk of exposure due to trauma, due to use of needles or knives or other situations of this sort, it is probably best and most appropriate to let the employer know. In most situations including the health care field, this is not a reason to not employ the individuals. Local laws may vary and this needs to be checked locally. If one does inadvertently expose one to blood or bodily fluid, there would be a moral obligation to let the other individual know.

I know alcoholism damages the liver, what other toxic substances are there that will do damage?

The most common agent is probably acetaminophen (Tylenol although it is contained in many OTC medications). It probably remains the safest medication for fevers, aches and pains, but only taken in small recommended amounts. Large amounts, greater than those recommended, can result in liver damage or failure. Acetaminophen overdose is a common reason for considering a transplant. A more serious problem, however, occurs in patients who drink alcohol on a daily basis, particularly more than 2 drinks, in those situations, normal doses of Tylenol 3 - 4 times a day can produce severe liver damage. The same problem can occur in patients with the other liver diseases such as viral hepatitis. Additionally more common toxins tend to be those that are inhaled, such as cleaning solvents, aerosolized paints, thinners, etc. Again, these are more dangerous if there is a preexisting underlying liver condition.

What causes hepatitis?

Hepatitis is a generic term. It indicates inflammation and damage to liver cells. This damage can be caused by drugs, toxins, alcohol, inherited diseases, certain metabolic diseases and viruses. Commonly, however, hepatitis refers to viral hepatitis. There are a wide variety of viruses that can cause hepatitis, but again most commonly the term refers to the viruses designated A, B, C, D, E, and G. In the United States, the most common causes are hepatitis A, B, and C. There are over 4 million chronic carriers of hepatitis C in the US. And almost one and a half million carriers of hepatitis D. Almost 15,000 individuals die from viral hepatitis in the U.S. Hepatitis C is the commonest reason for liver transplant in the U.S.

My 5 year-old son has severe ADHD and OCD. He can't take Ritalin and etc., so his psychiatrist has him on Tenex. Can this drug damage his liver?

This is outside the realm of my expertise.

I have a husband who drinks everyday. How long can he go on drinking and have it effect his liver?

The largest risk factor for liver disease from alcohol is the amount and the length of time the individual has been drinking. Males often develop complications that appear to be on a gender basis as well. Each individual is entirely different. Complication can develop after 5 - 10 years, more commonly it takes 20 - 30 years. Many individuals appear to never develop end stage liver disease from alcohol. This is impossible to predict ahead of time. And many other factors such as other diseases, hepatitis C, exposure to other toxins, as well as the individual's own genetic make-up play a role.

I took Rezulin and Lipitor. Also, my liver enzymes are up to 68.

Rezulin was removed from the market because a small number of patients developed serious liver damage. It does not produce chronic problems and should not produce abnormal enzymes once the drug is discontinued. Lipitor can produce liver enzyme abnormalities in a small number of patients. This is something that should be reviewed with your primary care physician. Especially if the enzymes were previously normal.

How important are hepatitis vaccines?

There are vaccines to prevent hepatitis A and B. Hepatitis B is a disease that could be completely eradicated with universal vaccination. It is now one part of the newborn vaccination series. Attempts are ongoing to vaccinate all children by the time they reach junior high age. Adults who are in high-risk occupations such as the health care field or carry out high-risk activities, such as IV drug use and multiple sexual partners should also be vaccinated. Hepatitis A vaccine is recommended in a number of child-care settings and should be discussed with your pediatrician. Adults or children traveling to areas of the world where hepatitis A is very common, including all underdeveloped or poorly developed countries, should be vaccinated before they go. Any individual with underlying chronic liver disease that is not due to hepatitis B, particular those with hepatitis C or cirrhosis should be vaccinated against both Hepatitis A and Hepatitis B, unless they are already immune.

What are the symptoms of liver damage caused by Rezulin?

The symptoms are the same as they are for any other hepatitis.

Is hepatitis C caused only by an exchange of bodily fluid?

The majority of patients with hepatitis C are found to have a risk factor such as needle exposure, blood exposure, tattooing, body piercing or sexual exposure which would allow for an exchange of blood or bodily fluids. Depending on the study, a small percentage of patients, ranging from 5 to 30 percent have no identifiable risk factor. Presumably, they acquired the disease through inadvertent exposure. Up to 50 percent of patients with hepatitis C have no symptoms. A larger percentage do not know they are carrying the virus. There are many opportunities for inadvertent exposure such as sharing a razor, sharing a toothbrush, sharing scissor for cutting hair or manicure tools, etc.

All contents copyright © 1992-2003 the Author(s) and The University of Iowa. All rights reserved.