Grading system for cirrhosis: the Child-Pugh score
 

Child class: A= 5 - 6, B= 7 - 9, C= > 9

http://www.unos.org/resources/MeldPeldCalculator.asp?index=98

Staging Cirrhosis

Hepatitis has 4 stages.  Stage 4 Hepatitis = Cirrhosis.

Then,

There's 3 stages to Cirrhosis:
Stage A ("compensated"; not too sick)
Stage B (beginning to decompensate; complications beginning to appear)
Stage C ("decompensated"; end stage)

Doctors use something called a CTP Score, to see what Stage of cirrhosis that a person is in.

The CTP Score is based on FIVE QUESTIONS.
You receive a point value (score) for each of the answers.

Here's how it works:

1. Total Serum Bilirubin
.....if Bilirubin is <2 mg/dl: score 1 point
.....if Bilirubin is 2-3 mg/dl: score 2 points
.....if Bilirubin is >3 mg/dl: score 3 points

2. Serum Albumin
.....if Albumin is >3.5 g/dl: score 1 point
.....if Albumin is 2.8 to 3.5 g/dl: score 2 points
.....if Albumin is <2.8 g/dl: score 3 points

3. INR
.....if INR is <1.70: score 1 point
.....if INR is 1.71 to 2.20: score 2 points
.....if INR is >2.20: score 3 points

4. Ascites
.....No Ascites: score 1 point
.....Ascites controlled medically: score 2 points
.....Ascites poorly controlled: score 3 points

5. Encephalopathy
.....No Encephalopathy: score 1 point
.....Encephalopathy controlled medically: score 2 points
.....Encephalopathy poorly controlled: score 3 points

 

1. Total your score.
   
   Sum total score gives grades of:
   5 to 6 points = Stage A Cirrhosis
   7 to 9 points = Stage B Cirrhosis
   10 to 15 points = Stage C Cirrhosis

   A person has to be at least Stage B or Stage C, in order to get referred for an "Evaluation" for a chance at the liver transplant waiting list.  (Stage A Cirrhosis is not sick enough to think about a referral for an evaluation).

   iCTP scores and MELD scores are two completely different things.

   MELD scores are use for allocation of donor livers

   Also see our Transplants section for Meld-calculator

    

2. Interpretation
   1. Child Class A: 5 to 6 points
      1. Life expectancy: 15 to 20 years
      2. Abdominal surgery peri-operative mortality: 10%
   2. Child Class B: 7 to 9 points
      1. Indicated for liver transplantation evaluation
      2. Abdominal surgery peri-operative mortality: 30%
   3. Child Class C: 10 to 15 points
      1. Life expectancy: 1 to 3 years
      2. Abdominal surgery peri-operative mortality: 82%

PS- There's more examples of these scorecards at 112.1 (you can scroll through about a dozen of them there)

 Thank you Imkindly, please visit her wonderful support forum :

blood type;

the number of other patients listed within the local area;

the illness level of the other patients waiting in the local area; and

the number of organs available in the local area or Region.

Only the patient’s transplant center team can decide when (or if) it is appropriate for a patient to be placed on the waiting list. While the MELD or PELD score determines a patient’s immediate need for a transplant, there are many other factors involved in the decision to list a patient for a liver transplant. The patient’s center will still need to make the final decision about putting you on the list. Please speak to your doctor about your specific medical circumstances and your MELD or PELD score.

There are several documents describing the MELD/PELD system on the UNOS website (www.unos.org). You can also request a brochure about MELD/PELD by calling 1-888-894-6361

http://www.unos.org/SharedContentDocuments/Revised_MELDPELD_2003.pdf

Long-term management of cirrhosis

Appropriate supportive care is both critical and difficult

Adil Habib, MD; Wendy M. Bond, RN; Douglas M. Heuman, MD

VOL 109 / NO 3 / MARCH 2001 / POSTGRADUATE MEDICINE

CME learning objectives

• To understand the various diagnostic tools for detecting liver disease, assessing its etiology, guiding therapy, and establishing prognosis
• To become familiar with the major areas to address in comprehensive management of the cirrhotic patient, as summarized by the mnemonic PORTAL VEIN
• To learn the importance of preventive measures, including nutrition, immunization, and cancer screening, in care of the cirrhotic patient

The authors disclose no financial interests in this article.

This page is best viewed with a browser that supports tables.

Preview: In the United States, about 26,000 of the 3 million people who have chronic liver disease die each year because of hepatic cirrhosis. Liver transplantation offers the best hope of survival for many of these patients, but the number of patients awaiting transplant far exceeds the number of organs available. What can the primary care physician do to slow the course of liver disease and improve both quality and length of life for these patients? In this article, which concludes a four-article presentation on cirrhosis from Virginia Commonwealth University that began in our February issue, Dr Habib, Ms Bond, and Dr Heuman provide a comprehensive guide to day-to-day management.
Habib A, Bond WM, Heuman DM. Long-term management of cirrhosis:appropriate supportive care is both critical and difficult. Postgrad Med 2001;109(3):101-13

Despite therapeutic advances, both life expectancy and quality of life in patients with advanced cirrhosis remain poor. These patients often experience debilitating fatigue and pruritus, disfiguring ascites, disabling encephalopathy, and catastrophic variceal hemorrhage. Anorexia and malnutrition are common. Liver function may decompensate abruptly after infection, trauma, or surgery. Even otherwise stable and healthy patients who have cirrhosis have a high risk of hepatocellular carcinoma, which is often fatal.

In the past, medical management of cirrhosis was largely palliative. The increase of cadaveric liver transplantation over the past two decades has changed the face of hepatology, offering cirrhotic patients the possibility of a new life. Unfortunately, transplant lists are lengthening rapidly, but the availability of organs is increasing very little (figure 1: not shown). As a consequence, many potentially curable patients are spending years on the transplant list, and the number who die while waiting is rising rapidly.

In this environment, the pretransplant care of the patient who has cirrhosis is increasingly critical and difficult. Best results are obtained with a systematic and comprehensive approach. Liver disease should be identified early, its severity assessed, its cause defined, and its treatment established, where possible.

Substance abuse problems should be identified and addressed. Decisions regarding the possibility of transplantation should be made early enough to permit thorough medical and psychosocial evaluation. Complications such as varices, ascites, and encephalopathy should be treated, and measures should be taken to prevent catastrophic complications, such as hemorrhage and sepsis. Attention should be directed to immunization, nutrition, and general healthcare. Finally, efforts should be made to detect hepatocellular carcinoma early in its course, when cure is feasible.

In our practice, we use a 10-point program for comprehensive management of the patient with cirrhosis, for which we have coined the mnemonic PORTAL VEIN (table 1). In this article, we discuss the rationale for this approach and the clinical data that support each component.

Determining the prognosis

The early symptoms of liver disease, primarily fatigue and pruritus, are nonspecific. Physical findings such as scleral icterus, spider angiomata, palmar erythema, dilated abdominal veins, and splenomegaly generally indicate relatively advanced cirrhosis with portal hypertension. More severe or advanced liver disease may present with jaundice or onset of complications, including hepatic encephalopathy, ascites, or variceal hemorrhage.

Many cases of chronic liver disease are detected by abnormalities noted on routine blood tests while the patient is still asymptomatic. Tests of liver enzymes, including aspartate aminotransferase (AST, formerly SGOT), alanine aminotransferase (ALT, formerly SGPT), and alkaline phosphatase are useful because they identify the presence of liver injury and detect enzyme patterns that may provide clues to diagnosis.

Predominant elevation of the transaminases is indicative of necroinflammatory processes, such as hepatitis or ischemia. Predominant elevation of the alkaline phosphatase suggests biliary obstructive or infiltrative processes, such as pancreatic cancer, primary biliary cirrhosis, hepatic metastases, or sarcoidosis. However, enzyme studies provide little information about the functional integrity of the liver and should not be referred to as "liver function tests."

Three laboratory parameters are routinely used to assess liver function. These include serum bilirubin, serum albumin, and plasma prothrombin time. The prothrombin time is a particularly useful indicator because it is strongly dependent on the level of factor VII, which is produced only in the liver and has a short half-life of about 6 hours.

These parameters are commonly combined with clinical estimates of the presence and severity of two cirrhotic complications, encephalopathy and ascites, to determine the Child-Turcotte-Pugh (CTP) score (table 2), a useful index of the clinical severity of liver disease. Because the CTP score is clearly linked to prognosis, it is a major determinant in assigning priority to patients for liver transplantation.

Liver biopsy is often useful in providing clues to the cause of liver disease and assessing both its stage (degree of fibrosis) and grade (extent of ongoing necrosis and inflammation). The latter features are often estimated semiquantitatively, using the numeric scoring system developed by Knodell and associates (1). A gastroenterologist usually can obtain a biopsy specimen by percutaneous puncture. This technique can be performed as an outpatient procedure using local anesthesia and ultrasound guidance and is associated with an acceptably low risk if hemostatic function is normal (2).

Alternatively, biopsy may be obtained by a radiologist via transjugular catheterization of the hepatic vein or by a surgeon via laparoscopy. Biopsy is most helpful in patients with clinically mild to moderate liver disease, because it can detect early cirrhosis at a time when complications are absent and liver function is normal. In patients with advanced disease, clinical and laboratory evaluation usually permits a reliable clinical diagnosis of cirrhosis. Biopsy often is not necessary in these patients and may be precluded by thrombocytopenia and coagulopathy.

Discovering the origin

Cirrhosis is the common end stage in a number of chronic progressive liver diseases. Effective therapy can completely arrest progression of liver injury in many of the most common forms of chronic liver disease. Such treatable conditions include alcoholic liver disease, hepatitis B and C, autoimmune hepatitis, and hemochromatosis, as well as rare disorders, such as Wilson's disease.

Successful treatment of the underlying cause may permit substantial functional recovery, even in the setting of advanced cirrhosis. Table 3 lists some common treatable causes of liver disease, the various tests used to establish these diagnoses, and some of the therapies currently available for managing these disorders.

Many patients with chronic liver disease use a variety of herbal medicines that are readily available in health food stores and on the Internet. In recent surveys of Americans with hepatitis C, more than one third of those surveyed were taking herbal preparations, particularly milk thistle. In vitro and clinical trials have shown that the active ingredient in milk thistle (Silybum marianum) protects nonspecifically against oxidative liver injury and reduces liver inflammation (3). Milk thistle appears to be a harmless agent. However, no clinically significant benefits have yet been proven, and the amount of active ingredient in the available preparations varies widely. Other, more exotic and complex herbal preparations can be hepatotoxic, and patients should be cautioned not to use them.

Managing alcoholism and drug abuse

Substance abuse complicates care of many patients with liver disease. In our population of military veterans with cirrhosis referred for liver transplantation, alcoholism is the sole identifiable cause of liver disease in about 25% and is a major contributor to liver injury in an additional 25% to 50%. Alcohol use, even in moderation, can aggravate other causes of liver injury. In hepatitis C, heavy alcohol use increases the likelihood of progression to cirrhosis by 15-fold (4).

Intravenous or intranasal drug abuse is a major source of infections with hepatitis B, C, and D in the United States. Ongoing addiction is associated with ongoing liver injury, risk of reinfection with hepatitis viruses, and poor compliance with medical therapies. Patients with uncontrolled alcohol or drug addiction often have difficulty handling the rigors of transplantation and post-transplantation immunosuppression. Therefore, active substance abuse is a high-level contraindication to liver transplantation in most programs. For these reasons, we strongly encourage patients with significant liver disease to abstain completely from use of illicit drugs and alcohol. Formal programs for detoxification, counseling, support, and monitoring are invaluable and essential.

Recovered substance abusers may be considered for liver transplantation if they have demonstrated abstinence from drugs and alcohol for more than 6 months, provided that careful psychological assessment indicates a high likelihood of sustained abstinence and they remain abstinent while on the transplant waiting list.

Identifying candidates for transplantation

Once a patient has been identified as having cirrhosis or having a chronic liver disease that is likely to progress to cirrhosis, the possibility of liver transplantation should be considered. Even with carefully selected patients, cadaver liver transplantation is associated with mortality of 10% to 20% at 1 year and 20% to 50% at 5 years. Given the expense involved (on the order of $300,000 in the first year alone [5]) and the scarcity of donor organs, transplantation currently cannot be justified unless there is a high probability of a good long-term outcome.

It is helpful to separate patients into three categories at an early stage of evaluation: (1) those for whom referral for transplantation is appropriate at this time; (2) those for whom transplantation may be appropriate in the future if liver disease progresses or if certain complicating issues can be addressed; and (3) those for whom transplantation is not appropriate.

Several basic questions need to be answered as part of triage. Among these are the following:

• Is the prognosis of the patient's liver disease poor enough to justify the risks of transplantation?
• Are there any psychological, social, or medical problems that would adversely affect the outcome of transplantation? If so, can they be corrected?
• Is transplantation a realistic option? That is, does the patient have the intellectual, psychological, financial, and social resources required to face a difficult surgery and a lifetime of immunosuppression?

The prognosis of patients with uncomplicated cirrhosis and normal or near-normal liver function is relatively good. In contrast, once complications of ascites, variceal hemorrhage, or encephalopathy have occurred, median survival is less than 5 years. Under current rules of the United Network for Organ Sharing, patients generally may not be listed for transplantation until they have reached CTP class B cirrhosis. Thus the onset of a complication or the deterioration of liver function that changes a patient's status to CTP class B serves as a good indicator that the time has arrived for transplant referral. If referral is delayed beyond this point and the patient becomes severely decompensated and debilitated, pretransplant mortality worsens and the cost and difficulty of the transplant procedure increase.

Transplant evaluation consists largely of a search for contraindications. A thorough history is taken and physical examination performed. Cardiac, pulmonary, renal, and neurologic parameters are assessed, and patients are monitored for alcohol and illicit drug use. Screening tests are performed to exclude concurrent infections (eg, HIV, syphilis, tuberculosis) or common cancers (eg, breast, cervix, colon, lung, prostate). Most important, careful psychosocial evaluation and monitoring of compliance are required to assure that patients have the will, stamina, and support they need to make it through the ordeal.

Controlling fluid retention

Ascites is the most common of the major complications of cirrhosis. Contributing factors include increased hydrostatic pressures in hepatic sinusoids and intestinal capillaries secondary to portal hypertension, decreased plasma oncotic pressure secondary to impaired albumin synthesis, and both local and systemic hemodynamic derangements (eg, vasodilation, decreased systemic arterial pressure) leading to activation of the renin-angiotensin axis and renal sodium retention.

Diagnostic paracentesis should be performed at onset of ascites. Cirrhotic ascites typically is transudative, with a low albumin concentration (usually <1 g/dL) and a serum-ascitic fluid albumin gradient exceeding 1.1 g/dL (6). Any evidence of clinical deterioration associated with ascites should prompt a repeat paracentesis to look for evidence of spontaneous bacterial peritonitis. An ascitic fluid granulocyte count greater than 250/mm³ is suggestive of peritonitis; counts greater than 500/mm³ are essentially diagnostic (7).

Ascites is initially managed with dietary salt restriction. Therapy should include a distal tubular agent, such as spironolactone (Aldactone) in doses ranging from 100 to 400 mg daily. A loop diuretic, such as furosemide (Lasix), may be added in doses of 40 to 160 mg daily. Weight should be monitored, and electrolytes should be checked regularly for signs of azotemia, hyperkalemia, and hyponatremia. Nonsteroidal anti-inflammatory drugs aggravate renal salt retention and should be avoided (8).

Ascites is considered refractory if it persists despite increases in diuretic therapy to the maximum tolerable dosage (usually limited by azotemia and hyponatremia). Patients with refractory ascites have more advanced liver disease and a poor prognosis (1-year mortality, about 75%) and should be assigned high priority for liver transplantation (9). Malnutrition with resulting aggravation of hypoalbuminemia often plays a role in refractory ascites and should be managed aggressively.

Removal of refractory ascites through repeated large-volume paracentesis may be necessary for patient comfort. Contrary to earlier teaching, large-volume paracentesis is safe and rarely precipitates hepatorenal syndrome, particularly if intravenous albumin is given concurrently (10). If repeated large-volume paracentesis is impractical, use of peritoneovenous shunt or transjugular intrahepatic portosystemic shunt (TIPS) may be considered.

Maintaining nutrition and general health

Patients who have cirrhosis are often malnourished for any of a number of reasons (eg, ongoing ethanol use, chronic nausea, anorexia, fat malabsorption, meal-induced abdominal discomfort, dietary protein restriction). Malnutrition can lead to proximal muscle wasting, hypoalbuminemia with worsening of ascites, neutropenia with decreased resistance to bacterial infections, and weak cough with predisposition to pneumonia. Weakened connective tissue may predispose to variceal hemorrhage, umbilical hernia, and other complications. Malnutrition also increases surgical risk and prolongs recovery after liver transplantation surgery.

Because of these concerns, adequacy of the diet should be a major focus, particularly when liver transplantation is anticipated. Aside from sodium restriction in patients with ascites, we try to not restrict the diet of patients with cirrhosis, even in the setting of hepatic encephalopathy. Routine supplementation with thiamine, folate, calcium, and a therapeutic multivitamin is appropriate. Some authorities recommend avoiding supplemental iron because excess absorption may contribute to liver injury. Formal nutritional support (enteral or parenteral) may be needed in severely malnourished patients if surgery is required or if profound hypoalbuminemia is contributing to refractory ascites.

General health in patients with cirrhosis should not be neglected. For example, dental care is important to correct periodontal disease that may lead to abscesses. Diabetes mellitus occurs with increased frequency in patients with hepatitis C or hemochromatosis, and complications of diabetes may add to the risk of liver transplantation. Many patients who have cirrhosis smoke cigarettes, which increases the risk for atherosclerotic disease and chronic lung disease, lung cancer, and squamous cell cancers of the head, neck, and esophagus. Ongoing tobacco use is a relative contraindication to liver transplantation, and patients should be strongly encouraged to quit smoking.

Certain classes of medications have the potential to aggravate complications of cirrhosis and are best avoided or used with caution. These include aminoglycosides, which increase nephrotoxicity; angiotensin-converting enzyme inhibitors, which can cause hypotension; nonsteroidal anti-inflammatory drugs, which promote renal sodium retention; and sedative and narcotic agents, which precipitate hepatic encephalopathy. Drugs that are eliminated by the liver must be used in low doses in patients who have cirrhosis. This is particularly true of drugs that undergo high first-pass hepatic clearance, because portosystemic shunting greatly increases their bioavailability. Potentially hepatotoxic medications present a difficult problem. Although patients with cirrhosis are probably no more susceptible to hepatotoxicity than other people, the early signs of hepatotoxicity can be difficult to identify. The consequences of hepatotoxicity superimposed on cirrhosis can be devastating.

Preventing variceal hemorrhage

When portal pressure exceeds systemic pressure by more than 12 mm Hg, leading to portal hypertension, the venous collaterals that connect the portal and systemic circulations may become massively dilated and form varices. Varices may occur in many places. However, those in the esophagus and proximal stomach are particularly likely to rupture and bleed. Bleeding risk increases with wall tension, which is a function of both variceal size and portal pressure. As varices weaken, they acquire characteristic stigmata, such as hematocystic spots or red wales, that can be recognized endoscopically and are important predictors of hemorrhage (11). Risk of bleeding also increases as CTP scores rise. Recurrence can be anticipated within 1 to 2 years in at least two thirds of patients who have had variceal bleeding (12).

Patients who are at modest risk of variceal hemorrhage may be managed with propranolol hydrochloride (Inderal), nadolol (Corgard), or other nonselective beta blockers. When administered at doses that produce a 25% reduction in resting heart rate, these drugs produce a modest decrease in portal pressure and reduce the likelihood of bleeding (13). Patients who have already bled should be managed more aggressively with endoscopic band ligation or sclerotherapy. In general, banding is preferred to sclerotherapy because the efficacy is similar and the rate of complications is lower (14). Prophylactic banding also may be considered for patients who have not previously bled if the endoscopic appearance of the varices and clinical status of the patient indicate a high risk of hemorrhage (15), although this remains controversial. Patients in whom banding and beta blockers fail may require TIPS or portosystemic shunt surgery to prevent variceal rebleeding (16,17).

Managing mental status changes

Hepatic encephalopathy is a neuropsychiatric syndrome manifested by symptoms ranging from subtle personality changes to coma. It is caused by a variety of circulating neurotoxins whose hepatic clearance is impaired in cirrhosis because of decreased hepatocellular mass and portosystemic shunting of blood. Many of these neurotoxins are thought to be amines derived from degradation of dietary protein by colonic bacteria. Ammonia is one such toxin, and elevation of the arterial ammonia level supports a diagnosis of hepatic encephalopathy, although ammonia levels do not necessarily correlate with the degree of impairment (18). Hepatic encephalopathy must be distinguished from other neurologic problems that are common in patients with cirrhosis, including organic brain syndrome with dementia, epilepsy, and subdural hematoma.

Early manifestations of hepatic encephalopathy include episodes of forgetfulness, daytime somnolence with nighttime insomnia, and subtle behavioral changes. Asterixis, a flapping tremor caused by paroxysmal relaxation of sustained skeletal muscle contraction, is a frequent and characteristic finding.

In the cirrhotic patient who has encephalopathy, a wide variety of clinical events can lead to deterioration of mental status. These include acid-base and electrolyte disturbances, dehydration, constipation, infections, gastrointestinal tract bleeding, use of sedative medications, and treatment noncompliance. Treatment of encephalopathy consists of first seeking out and correcting these abnormalities. Additional therapy is directed at reduction of circulating neurotoxins via mechanical cleansing of the colon and acidification of the colonic lumen. This effect is achieved by oral administration of lactulose, a nonabsorbable carbohydrate, in doses adjusted to produce two to four loose stools per day.

Two major changes in management of hepatic encephalopathy have evolved over recent years. First, long-term, aggressive dietary protein restriction is no longer advocated as a general measure. Protein-deficient diets in cirrhosis lead to malnutrition, with worsening of ascites and edema, lethargy and muscle weakness, and increased susceptibility to pneumonia and other infections. The majority of patients with cirrhosis can tolerate at least 1 to 1.5 g of dietary protein per kilogram of body weight per day, especially if vegetable sources of protein are substituted for meat. Rarely, a patient's encephalopathy is exacerbated even by this minimum requirement for daily protein intake, and specialized nutritional supplements enriched with branched-chain amino acids may be needed. Second, oral neomycin sulfate is no longer favored for long-term suppression of intestinal bacterial flora. Although it is effective, its oral absorption occasionally may be sufficient to produce ototoxicity or nephrotoxicity. Metronidazole (Flagyl, Protostat) in doses up to 1 g per day appears to be equally effective (19) and is well tolerated in the absence of alcohol abuse. However, use of higher doses may lead to peripheral neuropathy.

Preventing infection

Immunization is often neglected in adults with cirrhosis. Our experience has encouraged us to routinely immunize for hepatitis A and B, pneumococcus, and influenza. Of these, the most important is probably hepatitis A vaccination. In a large prospective study of 432 patients with chronic hepatitis C (20), 17 patients (4%) acquired hepatitis A over a 7-year period. Fulminant hepatic failure developed in 7 (41%) of these 17 patients, and 6 died. Current hepatitis A vaccines are less effective in patients with cirrhosis than in healthy persons (first-dose seroconversion rates of 74% and 94%, respectively), but after three doses, more than 90% of patients who have cirrhosis have evidence of protective antibody.

Bacterial infections are of particular concern in patients with cirrhosis because they are poorly tolerated. The hemodynamic derangement of cirrhosis resembles that produced by endotoxin (21), and bacteremia can greatly exacerbate this state, producing hypotension, progressive prerenal azotemia with hepatorenal syndrome, deterioration of mental status, and increased portal hypertension with risk of variceal rupture. Factors that predispose to bacterial infection include malnutrition with impaired cell-mediated immunity, decreased integrity of the bowel wall leading to bacterial translocation, and impaired phagocytic activity of the hepatic and splenic reticuloendothelial system resulting from portal hypertension.

Many bacterial infections in patients with cirrhosis are hospital-acquired, and patients hospitalized for acute variceal hemorrhage or ascites are at particularly high risk of secondary infection. The most common bacterial diseases are urinary tract infections, pneumonia, and spontaneous bacterial peritonitis.

Numerous studies demonstrate that the risk of serious bacterial infections can be reduced through antibiotic prophylaxis, either long term in patients with refractory ascites (22) or short term in patients hospitalized with variceal hemorrhage (23). The best-studied prophylactic regimens are once-daily administration of 400 mg norfloxacin (Noroxin) or trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra). Once-weekly administration of 750 mg of ciprofloxacin (Cipro) also is effective (24).Protection of the airway to prevent aspiration, via nasotracheal intubation if needed, is also a key measure in managing variceal hemorrhage.

One additional consideration in potential liver transplant recipients is cytomegalovirus (CMV) infection. CMV is a frequent cause of posttransplantation liver injury and may contribute to allograft rejection, secondary bacterial and fungal infections, and death. Patients who are CMV-negative may become infected through contaminated blood products. To avoid this, all potential transplant recipients should be tested for IgG and IgM antibodies to detect previous exposure to CMV. In those patients who are still seronegative, risk of infection can be reduced by using only CMV-negative blood products in transfusion therapy.

Screening for cancer

Cirrhosis is associated with a markedly increased risk of hepatocellular carcinoma. If the cause of the liver disease is viral hepatitis B or C, hemochromatosis, or ethanol use, the incidence of hepatocellular carcinoma is about 2% to 4% per year. Advanced lesions (stage III or greater in the American Liver Tumor Study Group classification) have a poor prognosis.

No medical therapy is of proven benefit in management of hepatocellular carcinoma, and compromise of liver function often limits surgical treatment options. In particular, the presence of portal hypertension portends a high risk of decompensation after attempted hepatic resection. However, in those patients with early-stage hepatocellular carcinoma who are candidates for radical curative liver resection or total hepatectomy and liver transplantation, prolonged survival can be achieved in 50% to 80%. For this reason, frequent screening for hepatocellular cancers may be justified in patients who are candidates for resection or transplantation.

The product alpha-fetoprotein (AFP) is a tumor marker produced by hepatic and embryonal neoplasms. In the United States, abnormal levels of this fetoprotein are found in about two thirds of patients with hepatocellular carcinoma (25). Low-grade elevations are common in cirrhosis related to hepatocyte regeneration and are relatively nonspecific. Marked elevations or progressive increases of AFP are much more specific but, unfortunately, are associated with cancer stages that are more advanced. Imaging studies complement AFP measurement in screening for hepatocellular carcinoma. Ultrasound has been widely used in combination with AFP testing and is relatively inexpensive, but its sensitivity for detecting early mass lesions is only about 60%, compared with about 80% for contrast computed tomography (CT) or magnetic resonance imaging (MRI).

At present, screening for hepatocellular carcinoma is of unproved benefit, and various strategies have not been compared critically (26). We screen patients on our transplant waiting list for AFP at 3- to 6-month intervals and with an imaging procedure at 6- to 12-month intervals (typically alternating ultrasound with MRI or CT). A similar protocol is reasonable for otherwise healthy patients with compensated cirrhosis who are potential transplant candidates but who are not yet sufficiently ill to be placed on the waiting list. When nodules are identified, CT-guided biopsy is used to confirm the presence of hepatocellular carcinoma. Even if no nodule can be identified, continued progressive increase in AFP to levels higher than 500 ng/mL strongly indicates the presence of carcinoma. Such patients should be reassessed at frequent intervals and should undergo hepatic transplant evaluation without delay.

Patients with early stage I or II cancer who have no evidence of portal hypertension may undergo resection with acceptable morbidity and a 50% likelihood of long-term disease-free survival (27). Those who have portal hypertension may be listed for hepatic transplantation if no contraindications are found. Transplantation in patients with early-stage hepatocellular carcinoma offers the possibility of excellent long-term survival (about 75%) (27). However, with waiting times often exceeding 1 year, illness progresses beyond stage II in a substantial number of patients awaiting transplantation (27); when this occurs, patients are removed from the transplant list because their prognosis is then considered unacceptable.

A variety of treatments, such as chemoablation or chemoembolization, may be used to partially destroy the primary tumor and restrict its growth and spread while awaiting transplantation. However, the long-term benefit of these treatments is unproved. Other liver malignancies in cirrhotic patients, including metastases and cholangiocarcinoma, rarely are curable, even by radical resection, and usually are considered contraindications to transplantation.

Summary

Orthotopic liver transplantation has emerged as an important treatment option for patients with advanced liver disease. However, each year the number of new cases of cirrhosis exceeds the number of livers available for transplantation by a factor of 5 to 10. This translates into long waiting lists and restrictive criteria for selecting transplant recipients. Until advances in surgical technique or biotechnology increase the availability of organs for transplantation, the majority of patients with advanced liver disease will have to be managed medically for years--perhaps indefinitely.

Early consultation with a liver transplant center can be helpful. The transplant hepatologist and surgeon can help with triage decisions, guide workup, provide advice about patient care, optimize the timing of transplantation, offer specialized diagnostic and therapeutic options, and help the treating physician stay abreast of the continuous changes in this complex field. In the final analysis, however, it is often the skill and diligence of the primary care physician in diagnosing liver disease, identifying and treating correctable causes, optimizing the patient's health and nutrition, and anticipating and preventing catastrophic complications that determine whether the patient lives or dies.

References

1. Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1(5):431-5
2. Lindor KD, Bru C, Jorgensen RA, et al. The role of ultrasonography and automatic-needle biopsy in outpatient percutaneous liver biopsy. Hepatology 1996;23(5):1079-83
3. Flora K, Hahn M, Rosen H, et al. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998;93(2):139-43
4. Corrao G, Arico S. Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis. Hepatology 1998;27(4):914-9
5. Evans RW, Kitzmann DJ. Contracting for services: liver transplantation in the era of mismanaged care. Clin Liver Dis 1997;1:287-303
6. Runyon BA, Montano AA, Akriviadis EA, et al. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Intern Med 1992;117(3):215-20
7. Hoefs JC, Runyon BA. Spontaneous bacterial peritonitis. Dis Mon 1985;31(9):1-48
8. Runyon BA. Management of adult patients with ascites caused by cirrhosis. Hepatology 1998;27(1):264-72
9. Runyon BA. Refractory ascites. Semin Liver Dis 1993;13(4):343-51
10. Quintero E, Gines P, Arroyo V, et al. Paracentesis versus diuretics in the treatment of cirrhotics with tense ascites. Lancet 1985;1(8429):611-2
11. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices: a prospective multicenter study. The North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. N Engl J Med 1988;319(15):983-9
12. D'Amico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review. Hepatology 1995;22(1):332-54
13. Bernard B, Lebrec D, Mathurin P, et al. Propranolol and sclerotherapy in the prevention of gastrointestinal rebleeding in patients with cirrhosis: a meta-analysis. J Hepatol 1997;26(2):312-24
14. Laine L, el-Newihi HM, Migikovsky B, et al. Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices. Ann Intern Med 1993;119(1):1-7
15. Sarin SK, Lamba GS, Kumar M, et al. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. N Engl J Med 1999;340(13):988-93
16. Luca A, D'Amico G, La Galla R, et al. TIPS for prevention of recurrent bleeding in patients with cirrhosis: meta-analysis of randomized clinical trials. Radiology 1999;212(2):411-21
17. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol 1997;92(7):1081-91
18. Mullen KD, Dasarathy S. Hepatic encephalopathy. In: Schiff ER, Sorrell MF, Maddrey WC, eds. Schiff's diseases of the liver. Philadelphia: Lippincott-Raven, 1999:545-81
19. Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut 1982;23(1):1-7
20. Vento S, Garofano T, Renzini C, et al. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med 1998;338(5):286-90
21. Navasa M, Feu F, Garcia-Pagan JC, et al. Hemodynamic and humoral changes after liver transplantation in patients with cirrhosis. Hepatology 1993;17(3):355-60
22. Bernard B, Grange JD, Khac EN, et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with ascites: a meta-analysis. Digestion 1998;59 (Suppl 2):54-7
23. Bernard B, Grange JD, Khac EN, et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology 1999;29(6):1655-61
24. Gines P, Arroyo V, Rodes J. Pathophysiology, complications and treatment of ascites. Clin Liver Dis 1997;1:129-55
25. Gregory JJ Jr, Finlay JL. Alphafetoprotein and beta-human chorionic gonadotropin: their clinical significance as tumour markers. Drugs 1999;57(4):463-7
26. Chalasani N, Said A, Ness R, et al. Screening for hepatocellular carcinoma in patients with cirrhosis in the United States: results of a national survey. Am J Gastroenterol 1999;94(8):2224-9
27. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 1999;30(6):1434-40

For a helpful guide to electronic and print resources on cirrhosis for physicians and patients, see the Resource Guide in this issue.

Adil Habib, MD, Wendy M. Bond, RN, and Douglas M. Heuman, MD
Dr Habib is senior fellow in gastroenterology, Ms Bond is liver transplant coordinator, and Dr Heuman is professor of medicine, Virginia Commonwealth University School of Medicine, and director of hepatology, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia. Correspondence: Douglas M. Heuman, MD, PO Box 980711, Richmond, VA 23298-0711. E-mail: Douglas.Heuman@med.va.gov.

http://www.postgradmed.com/issues/2001/03_01/habib.htm

WHAT LIFESTYLE FACTORS CAN HELP MANAGE CIRRHOSIS?

A healthy lifestyle is particularly important for people with cirrhosis.

Dietary Factors

Healthy Foods. Because important antioxidant vitamins are depleted in the cirrhotic liver, cirrhosis patients should maintain a diet rich in fresh fruits, vegetables, and whole grains.

Antioxidant Supplements. There is some preliminary laboratory evidence that various antioxidant supplements including vitamin E, selenium, and S-adenosylmethionine (SAMe) may help protect against liver damage and cirrhosis. Supplements, however, are not recommended for people with liver disease except with the advice of a physician. Some vitamins, such as vitamins D and A, are metabolized in the liver and can be toxic.

Iron Restrictions. Elevated iron levels have been associated with cirrhosis from many causes. Patients should avoid iron-rich foods, such as red meats, liver, and iron-fortified cereals and should avoid cooking with iron-coated cookware and utensils.

Supplemental Nutritional Products. Supplemental nutritional beverages may be helpful, particularly for patients with both alcoholism and cirrhosis. In one study, patients with both alcoholism and cirrhosis drank Ensure every day as a supplement to their regular diet. After six months they showed significant improvement in many signs of overall health compared to those who didn't consume the beverage.

Vitamin B1 (Thiamine). Thiamine binds to iron and helps reduce iron load in the liver. One small study suggested it may be helpful for patients with chronic hepatitis B. It is not known if it has any benefit for cirrhosis. Pork is high in the vitamin, but more healthful sources include dried fortified cereals, oatmeal, corn, nuts, cauliflower, sunflower seeds and vitamin pills.

Omega-3 Fatty Acids. Some research suggests that supplements of omega-3 fatty acids (found in fish oil and evening primrose oil) may help protect the diseased liver.

Protein and Soy. High-quality dietary protein may be especially helpful for patients with ascites and for repairing muscle mass, but excessive protein loads may trigger encephalopathy. Protein solutions have been devised that provide beneficial amino acids without including those that increase this risk. There is no limit on vegetable proteins, such as those from soy.

Salt Restriction. Restricting salt consumption to less than 2,000 mg a day is particularly important for patients with ascites. The less salt the better.

Zinc. In some studies, taking zinc supplements have lowered ammonia levels in some patients who were zinc-deficient, a common problem in cirrhosis. Zinc replacement may reduce frequency and severity of muscle cramps and may even help protect against encephalopathy.

Limiting Fluids

Fluid restriction is not usually necessary, but patients with severe ascites should discuss limiting fluid with their physicians.

Exercise

Exercise increases the risk for portal pressure and variceal bleeding. One study reported that taking a beta-blocker may reduce this risk, although patients should discuss this with their physician.

Preventing Influenza and Infections

Infections can have a severe impact on the liver. Although most respiratory infections generally affect only the lungs, one small study suggested influenza may directly affect the liver in patients with cirrhosis and exacerbate the disease process. Researchers in the study advise annual flu shots for people with cirrhosis. Furthermore, they advise that patients who get the flu be treated immediately with rimantadine, but not a similar treatment called amantadine.

Treating Chronic Fatigue

A 2000 study of 15 patients with chronic liver disease concluded that methylphenidate (Ritalin) improves chronic fatigue symptoms in patients with cirrhosis and chronic hepatitis. All patients reported some improvement in fatigue, and no side effects were severe enough to warrant withdrawal from the study. The researchers recommended that treatment for chronic fatigue in patients with liver disease combine methylphenidate with physical therapy and nutritional counseling. Results of the study need to be confirmed in a randomized prospective trial.

Alternative Remedies

Among the natural substances being investigated for liver disease are ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), SAMe, and silymarin (found in milk thistle). Two natural substances that may have some benefits for people with cirrhosis are discussed in the following paragraphs:

Silymarin. A 2001 review analyzed studies on 10 herbal remedies used for liver disease. None showed any benefits except silymarin. Furthermore, an analysis of five studies on cirrhosis patients reported an association between silymarin and a 7% reduced mortality rates from liver-related diseases. Known side effects from silymarin include rare reports of gastrointestinal problems and allergic skin rashes.

S-adenosylmethionine (SAMe) . S-adenosylmethionine (SAMe) is a chemical found in all parts of the body, which declines with age. It has been investigated for years in Europe for arthritis, depression, and liver disease. Some preliminary studies suggest it may provide some protection against liver damage and scarring and may improve survival rates in alcoholic patients with cirrhosis. It is very expensive, however, and as with all unregulated products, long-term side effects, drug interactions, and other factors are not fully known.

It should be strongly noted that herbal remedies are not necessarily harmless simply because they are natural (or marketed as natural), and their quality is not regulated except in clinical studies. [ See Box Warnings on Alternative and So-Called Natural Remedies.]

Warnings on Alternative and So-Called Natural Remedies

It should be strongly noted that alternative or natural remedies are not regulated and their quality is not publicly controlled. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. Even if studies report positive benefits from herbal remedies, the compounds used in such studies are, in most cases, not what are being marketed to the public.

There have been a number of reported cases of serious and even lethal side effects from herbal products. In addition, some so-called natural remedies were found to contain standard prescription medication.

The following warnings are of particular importance for people with liver disease:

• Kava kava (an herb used for anxiety and tension) can be toxic to the liver and cause severe hepatitis and even liver failure if taken excessively.
  
   
• Black licorice (not the red candy) can increase blood pressure and may be harmful in people with hypertension.

The following website is building a database of natural remedy brands that it tests and rates. Not all are available yet. http://www.ConsumerLab.com/

The Food and Drug Administration has a program called MEDWATCH for people to report adverse reactions to untested substances, such as herbal remedies and vitamins (call 800-332-1088).

http://www.reutershealth.com/wellconnected/doc75.html

Maintaining nutrition and general health

Patients who have cirrhosis are often malnourished for any of a number of reasons (eg, ongoing ethanol use, chronic nausea, anorexia, fat malabsorption, meal-induced abdominal discomfort, dietary protein restriction).

Malnutrition can lead to proximal muscle wasting, hypoalbuminemia with worsening of ascites, neutropenia with decreased resistance to bacterial infections, and weak cough with predisposition to pneumonia. Weakened connective tissue may predispose to variceal hemorrhage, umbilical hernia, and other complications. Malnutrition also increases surgical risk and prolongs recovery after liver transplantation surgery.

Because of these concerns, adequacy of the diet should be a major focus, particularly when liver transplantation is anticipated. Aside from sodium restriction in patients with ascites, we try to not restrict the diet of patients with cirrhosis, even in the setting of hepatic encephalopathy. Routine supplementation with thiamine, folate, calcium, and a therapeutic multivitamin is appropriate. Some authorities recommend avoiding supplemental iron because excess absorption may contribute to liver injury. Formal nutritional support (enteral or parenteral) may be needed in severely malnourished patients if surgery is required or if profound hypoalbuminemia is contributing to refractory ascites.

General health in patients with cirrhosis should not be neglected. For example, dental care is important to correct periodontal disease that may lead to abscesses. Diabetes mellitus occurs with increased frequency in patients with hepatitis C or hemochromatosis, and complications of diabetes may add to the risk of liver transplantation. Many patients who have cirrhosis smoke cigarettes, which increases the risk for atherosclerotic disease and chronic lung disease, lung cancer, and squamous cell cancers of the head, neck, and esophagus. Ongoing tobacco use is a relative contraindication to liver transplantation, and patients should be strongly encouraged to quit smoking.

Certain classes of medications have the potential to aggravate complications of cirrhosis and are best avoided or used with caution. These include aminoglycosides, which increase nephrotoxicity; angiotensin-converting enzyme inhibitors, which can cause hypotension; nonsteroidal anti-inflammatory drugs, which promote renal sodium retention; and sedative and narcotic agents, which precipitate hepatic encephalopathy. Drugs that are eliminated by the liver must be used in low doses in patients who have cirrhosis. This is particularly true of drugs that undergo high first-pass hepatic clearance, because portosystemic shunting greatly increases their bioavailability. Potentially hepatotoxic medications present a difficult problem. Although patients with cirrhosis are probably no more susceptible to hepatotoxicity than other people, the early signs of hepatotoxicity can be difficult to identify. The consequences of hepatotoxicity superimposed on cirrhosis can be devastating.