The signs of compensated cirrhosis include a large, hardened liver, small, star-shaped vessels (spider angiomata) on the skin of the upper torso, blotchy redness on the palms (palmar erythema), whitened nails, thin silky hair, loss of body hair, prominent veins on the abdomen (abdominal collateral veins), irregular or absent menstruation in pre-menopausal women, and small testes and enlarged, sometimes painful breasts (gynecomastia) in men. The signs of decompensated cirrhosis include all the above except that the liver may be shrunken and there may be swelling of the legs (edema), accumulation of fluid in the abdomen (ascites), bleeding from veins in the esophagus (varices), and mental confusion (hepatic encephalopathy).

Most chronic liver disease damages the liver over time by forming scar in the liver that replaces normal liver tissue. When there is enough scar, we call this cirrhosis. Cirrhosis is an advanced form of scarring or liver damage. However, even a cirrhotic or badly scarred liver can often still perform all the functions that a liver needs to do and in fact, it often continue to perform these functions quite well even for decades. This is because we are all given excess liver capacity which allows the liver to function well even if a significant amount of the liver is damaged. When a liver is diseased or cirrhotic but is still functioning well we say this is compensated liver disease.

This is a critical distinction because many people with hepatitis C will have cirrhosis but have no signs of liver failure. We call this compensated cirrhosis. Many of these people will be stable for years and many will be candidates for therapy. They typically do not have to be considered for liver transplant unless the liver starts to fail or their disease “decompensates”. Signs of decompensated liver disease include jaundice, marked fluid retention in the abdomen (ascites), episodic confusion or a specific type of gastro-intestinal bleeding.

I do want to say that when the liver starts to fail with chronic liver disease, it almost never happens suddenly, unless some one is drinking heavily or gets another insult to the liver like hepatitis A. People with chronic liver disease often feel they will feel fine one day and then be close to death the next and this is not the way things work. In fact, typically, liver specialists can start to see signs of liver failure in tests months or years before the patients themselves notice them.

This response is being provided for general informational purposes only and should not be considered medical advice or consultation. Always check with your personal physician when you have a question pertaining to your health.

http://www.medhelp.org/perl6/hepatitis/messages/30083a.html

Cirrhosis--A Liver Problem
 

What is cirrhosis?

If the liver is damaged, scars can form. When the liver has a lot of scar tissue, blood will not easily flow through it. Cirrhosis is the name for a scarred liver. (Say this: sir-oh-sis.) Cirrhosis keeps the liver from working the way it should. A liver with cirrhosis can't make enough of some proteins your body needs. It can't remove enough harmful toxins (poisons) from your blood. It can't help your blood to clot normally.

What causes cirrhosis?

Cirrhosis is most often caused by heavy use of alcohol or by an infection (usually with the hepatitis B or hepatitis C virus). Some medicines and chemicals can hurt the liver. Diseases that weaken the immune system and some inherited diseases can damage the liver.

What problems can cirrhosis cause?

a.. People with cirrhosis bruise easily because their blood does not clot the right way. When these people have a cut, it may bleed for a long time.

b.. Blood vessels around the esophagus (in the throat) and the intestines can stretch and become thin. If these blood vessels burst open, the result is a dangerous amount of bleeding.

c.. Because the liver is not working right, toxins build up in the blood. They can hurt your brain. People with cirrhosis are also more likely to get liver cancer.

d.. If the cirrhosis is so bad that the liver stops working, the only treatment is a liver transplant.

e.. Cirrhosis can cause death. According to the American Liver Foundation, cirrhosis is the 8th leading cause of death in the United States.

Can any of these problems be prevented?

If you have cirrhosis, it may be possible to avoid, or at least slow down, many of the problems caused by cirrhosis. Here are some things you can do to feel better for a longer time:

a.. Don't drink any amount of alcohol of any kind.

b.. Ask your doctor about getting important vaccines, like hepatitis A vaccine, hepatitis B vaccine, pneumococcal vaccine (to help prevent pneumonia) and influenza vaccine (to help prevent the flu). Hepatitis A infection is very dangerous for people with liver damage.

c.. Tell your doctor about every medicine, vitamin and herbal remedy you are taking. Many medicines and herbal remedies are dangerous to people with cirrhosis.

d.. Follow a low-fat, "heart-smart" diet. Foods that are low in fat, oil, and salt are good for your liver and your heart.

e.. Work with your doctor to set up a health care routine. In addition to your regular doctor visits, you will need tests at least once a year to check your liver and your risk for bleeding problems.

Some Medicines, Vitamins and Herbal Remedies That May Be Harmful to Patients with Cirrhosis*

Over-the-counter medicines Ibuprofen (brand names: Advil, Motrin), ketoprofen (brand name: Orudis KT), naproxen (brand name: Aleve) Acetaminophen (brand name: Tylenol)Ý

Prescription medicines

Some antidepressants

Diabetes medicines like rosiglitazone (brand name: Avandia), pioglitazone (brand name: Actos) and troglitazone (brand name: Rezulin)

Estrogens

Cholesterol-lowering medicines like atorvastatin (brand name:
Lipitor) and simvastatin (brand name: Zocor)

Some muscle relaxants

Rofecoxib (brand name: Vioxx) and celecoxib (brand name:Celebrex)
Oral medicines for fungus infections, like fluconazole (brand name: Diflucan), itraconazole (brand name: Sporanox) and ketoconazole (brand name: Nizoral)

Prescription ketoprofen (brand name: Orudis), naproxen (brand name: Anaprox), ibuprofen (brand names: Advil, Motrin), rofecoxib (brand name: Vioxx) and celecoxib (brand name: Celebrex)

Vitamins

Niacin (also called nicotinic acid; brand name: Nicolar)
Vitamin A (in doses higher than 25,000 IU per day)

Herbal products
Amanita mushrooms
Chaparral
Comfrey
Germander
Pennyroyal oil
Senna fruit extracts

* -- Not all of the dangerous medicines and herbal remedies are included in this list. Ask your doctor for more information about every medicine and herbal product you use.

Ý -- Acetaminophen in a dosage of 500 mg four times daily (2,000 mg per day) is safe; higher doses can harm the liver

Where can I get more information about chronic liver disease and cirrhosis?

For more information, you can contact the following groups:

Hepatitis Information Network
Web address: http://www.hepnet.com

National Digestive Diseases Information Clearinghouse
2 Information Way
Bethesda, MD 20892-3570
Telephone: 1-800-891-5389
Web address: http://www.niddk.nih.gov/health/digest/nddic.htm

American Liver Foundation
75 Maiden Lane, Suite 603
New York, NY 10038
Telephone: 1-800-465-4837
Web address: www.liverfoundation.org

United Network for Organ Sharing
1100 Boulders Parkway, Suite 500
P.O. Box 13770
Richmond, VA 23225-8770
Telephone: 1-888-TXINFO1 (1-888-894-6361)
This handout provides a general overview on this topic and may not apply to everyone. To find out if this handout applies to you and to get more information on this subject, talk to your family doctor.

Copyright © 2001 by the American Academy of Family Physicians.

Treatment of Chronic Hepatitis C in Decompensated Cirrhotics

Gregory T. Everson, M.D. University of Colorado School of Medicine, Denver, CO

May 20 2002 

There are two main reasons to treat patients with decompensated cirrhosis.  First, effective treatment could clear the virus prior to transplantation and avoid post-transplant recurrence of hepatitis C. Second, viral eradication may halt disease progression and possibly avoid the need for transplantation.

 Currently, hepatitis C is the leading indication for liver transplantation in the United States and the proportion of patients with end stage liver disease due to hepatitis C is increasing. Many studies

have demonstrated that patients who are HCV RNA positive prior to transplant will experience post-transplant recurrence of infection and many of these may require retransplantation due to progressive  hepatitis and cirrhosis. Post-transplant treatment of recurrent hepatitis C is problematic   due to effects of immunosuppression and intolerance to side effects of interferon-based  treatment. For these reasons, pre-transplant treatment and viral eradication is potentially the   most effective strategy in limiting the impact of post-transplant recurrence of hepatitis C.

Combination therapy with standard interferons plus ribavirin in clinically stable populations without advanced liver disease clears hepatitis C RNA in 50% to 60% on treatment, and clearance is sustained    in approximately 40%. Results with peginterferon plus ribavirin are even more encouraging with on-treatment clearance rates of 70 to 80% and sustained viral clearance of approximately 55%.

Most studies, but not all, have indicated that rates of viral clearance are lower in cirrhotic patients, due, in part, to dose reductions and side effects of treatment. Nonetheless, many cirrhotic patients experience both on-treatment and sustained response. Those that clear virus may experience reduction or abolition of liver inflammation, arrest of disease progression, and even resolution of fibrosis. The published experience has mainly focused on compensated cirrhotics as interferon-based    treatment has generally been considered to be contraindicated in those with clinical evidence   of advanced liver disease.

Colorado Experience

The expanding numbers of patients with hepatitis C on the waiting list coupled with the problems of post transplant recurrence of disease, stimulated us to consider treatment of decompensated cirrhotics. Our treatment protocol was dubbed LADR (low-accelerating dose regimen) to indicated initiation of therapy at half doses of IFN and ribavirin followed by dose increases based upon patient tolerance. G-CSF and erythropoietin analogue, were used to treat cytopenias. Efficacy was defined by   clearance of HCV RNA and tolerance was assessed by occurrence of side effects, adjustments in dose of interferon and ribavirin, frequency of dropouts from treatment, and use of G-CSF or erythropoeitin to correct cytopenias.

Our initial group of 86 candidates for treatment was male-predominant with 50% reporting significant   past alcohol use or abuse. The population was enriched in hepatitis C genotype 1 and 86% had either biopsy-proven or obvious clinical signs of cirrhosis. The remaining 14% had bridging fibrosis on biopsy or other features suggesting advanced disease (spider telangiectasia (a vascular lesion formed by dilatation of a group of small blood vessels), thrombocytopenia). Sixty three percent   had experienced clinical decompensation with either variceal hemorrhage, ascites, spontaneous bacterial peritonitis, or encephalopathy. Two-thirds of patients who had upper endoscopy, had esophageal varices.

Treatment was difficult in this patient population. There were 21 dropouts, mainly for side effects of    fatigue, neuropsychiatric symptoms, or cytopenias. The rate of serious inter-current illness was what one might expect in this population. 28% required G-CSF and only 1 required erythropoeitin.

Eleven of the 86 patients elected not to enroll in the trial. Of the remaining 75, 21 dropped from treatment due to side effects, 29 were nonresponders. 25 cleared RNA on treatment. Of the 25 on-treatment responders, 12 relapsed. RNA was positive by 3 months in all who relapsed. The other 13 remain RNA negative but 4 were still on treatment and 3 others were followed for less than 6 months post-treatment. Overall, the on-treatment rate of clearance of RNA was 29% for all eligible patients, 33% for enrolled patients, and 46% for those who enrolled and did not drop from treatment. Responders and nonresponders were similar in terms of age, gender distribution, % with obvious cirrhosis, or frequency of clinical decompensation.

In this initial experience, two factors seemed to be most important in determining response. Nonresponders were enriched in genotype 1 and a lower percentage of responders were able to achieve full doses of treatment for at least 3 months. The effect of dose on response was observed primarily in genotype 1.

Of the 57 patients with genotype 1, 23 never achieved full dose for at least 3 months. Only 2 of these   23 patients cleared RNA on treatment and neither sustained this response. The only sustained   responses in patients with genotype 1 occurred in those who were able to take at least 6 months of full dose treatment. In contrast to patients with genotype 1, those with other genotypes cleared RNA more frequently and there was less dependency upon dose. In fact, 2 sustained responders, who were treated for 12 months, never received full dose therapy for over 3 months.

Outcome in LADR Patients who were Transplanted.

Twenty six patients treated by LADR underwent transplantation. Six were sustained responders prior to transplantation and none have experienced post-transplant recurrence. Seven had on-treatment response but relapsed prior to transplant. One was retreated, became HCV RNA negative, was transplanted, and remains HCV RNA negative for one year post-transplant. The other 6 relapsers were   not retreated, underwent transplant, and all recurred. All thirteen

non responders have post-transplant recurrence of hepatitis C.

Implications for Living Donor Liver Transplantation.

Twenty eight patients infected with HCV have received LDLT (living donor liver

transplantation) at our center between 8/97 - 4/2001.  Fourteen received no treatment and remained    HCV positive pre- and post-transplant. Two of the remaining twelve were non responders    to interferon monotherapy and recurred post-transplant. The 12 remaining patients received either standard combination therapy or LADR. Four of the 12 were complete responders on-     treatment (33%) and remain free of HCV 6 months or more post-transplant.

Summary

HCV RNA can be cleared in at least 33% of cirrhotics with advanced liver disease using the LADR protocol. Best response is achieved in non-1 genotypes and in genotype 1 patients able to take full dose treatment for at least 3 months. Relapse, after discontinuation of treatment, is more frequent in this group of patients but retreatment of relapse prior to transplantation may clear virus and prevent post-transplant recurrence. Those who experience sustained response will not relapse post-transplant. LADR treatment may be well-suited for application in the setting of LDL T where the timing of transplantation in relation to treatment can be fixed. Treatment is difficult in this population, dropouts are common, serious complications can occur, and G-CSF or erythropoeitin may be needed.

Conclusions

LADR may be warranted in decompensated cirrhotics, but genotype 1 patients who become RNA negative should be maintained on treatment until time of transplantation. In addition, if treatment is   withdrawn in a responder, HCV RNA should be monitored for relapse and consideration of reinstitution of therapy. We also speculate that clearance or suppression of hepatitis C RNA will slow disease progression, improves hepatic function, and possibly reduces the need for transplantation.