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Hepatitis C Research

2003

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  The Efficacy of Daily Interferon Alfa Plus Ribavirin in Treatment-naive Patients with Chronic Hepatitis C
  Interferon Alfa Combined with Ribavirin with and without Amantadine in Nonresponders with Chronic Hepatitis C
  Isis Optimistic About Latest Antisense Compounds
by Deena Beasley
  Impact of High-Dose Interferon Induction and Ribavirin Therapy in Patients With Chronic Hepatitis C Relapsing After or Not Responding to Interferon Monotherapy
  Treatment of Hepatitis B and C Virus Infections in Immune Compromised Individuals
  Taming Hepatitis C: High stakes but low odds
   

 

  The Efficacy of Daily Interferon Alfa Plus Ribavirin in Treatment-naive Patients with Chronic Hepatitis C

A randomized trial at multiple medical centers in Greece was conducted to assess the efficacy of interferon alfa (IFN) daily in combination with ribavirin in 301 naive patients with chronic hepatitis C (CHC).

Patients were randomized to receive ribavirin 1.2 g daily (QD) for 48 weeks with either IFN 5 MU (thrice weekly) TIW for 8 weeks followed by IFN 3 MU TIW for 40 weeks (IFN TIW, n = 154) or IFN 5 MU QD for 8 weeks followed by IFN 3 MU QD for 16 weeks followed by IFN 3 MU TIW for 24 weeks (IFN QD, n = 147).

Treatment discontinuation rates, because of adverse events, were similar in the two arms (14.9% in IFN TIW and 14.3% in IFN QD, P = 0.87).

The proportion of patients with sustained virological response (SVR) was 27.9% for patients treated TIW and 38.8% for those treated QD (P = 0.046). According to logistic regression analysis, patients in the IFN QD arm had 1.7 times higher probability of achieving SVR, than those receiving IFN TIW (P = 0.038).

Low baseline viral load (P = 0.017) and genotype non-1 (P = 0.036) were associated with higher SVR rates.

The authors conclude, “Combination of IFN/ribavirin for 48 weeks is more effective when IFN is administered daily for the first 24 weeks in naive patients with CHC.”

10/08/03

Reference
NC Tassopoulos and others (The Hellenic Viral Hepatitis Research Network).
A randomized trial to assess the efficacy of interferon-alpha daily in combination with ribavirin in the treatment of naive patients with chronic hepatitis C. Journal of Viral Hepatitis 10(5): 383-389. September 2003.

 

  Interferon Alfa Combined with Ribavirin with and without Amantadine in Nonresponders with Chronic Hepatitis C

There are few options for therapy among patients with chronic hepatitis C who are nonresponders to treatment with interferon alfa (IFN-alfa) plus ribavirin. Several studies have explored the addition of amantadine to interferon alfa/ribavirin in the hope of eliciting more sustained virologic responses. Study results have varied.

In this German study, conducted at the Johann Wolfgang Goethe Clinic in Frankfurt, Germany, researchers evaluated the efficacy and safety of interferon-alfa (IFN-alfa)/ribavirin retreatment with or without amantadine sulphate in non-responders with chronic hepatitis C.

Two hundred twenty five consecutive nonresponders to previous antiviral treatment(s) with IFN-alfa alone or in combination with ribavirin or amantadine were treated with IFN-alfa 2b 5 MU daily for 4 weeks, 5 MU tiw for 20 weeks, followed by 3 MU tiw for additional 24 weeks combined with ribavirin 1000-1200 mg/d.

One hundred fifteen of 225 patients were randomized to receive amantadine 100 mg bid for 48 weeks. Treatment was discontinued in patients with detectable serum hepatitis C virus (HCV)-RNA at treatment week 24.

Study Results

An overall sustained virologic response with undetectable serum HCV-RNA levels was observed in 49/225 patients (22%). Patients infected with HCV-genotype non-1 (P<0.001), low viremia (P=0.011) and only one previous antiviral treatment (P=0.032) were more likely to respond to antiviral retreatment.

There was a trend towards higher sustained virologic response rates in patients receiving triple retreatment compared with those treated with IFN-alfa/ribavirin alone (25 versus 18%, P=0.172).

The authors conclude, “The addition of amantadine was well tolerated and led to an improvement of sustained virologic responses compared with retreatment with IFN-alfa/ribavirin alone, in particular in patients with low baseline viremia.”

10/08/03

Reference
G Teuber and others. Randomized, controlled trial with IFN-alpha combined with ribavirin with and without amantadine sulphate in non-responders with chronic hepatitis C.
Journal of Hepatology 39(4): 606-613. October 2003.


www.hivandhepatitis.com


 

 

 
http://www.hcvadvocate.org/news/newsRev/NewsRev-22.html#31

 

Isis Optimistic About Latest Antisense Compounds
by Deena Beasley
 
LOS ANGELES (Reuters) - Isis Pharmaceuticals Inc. on Thursday said early clinical trials of its second generation experimental arthritis and diabetes drugs confirm that they are active against targeted human proteins, paving the way for larger studies.
 
"These trials are evidence that we can produce antisense pharmacology in man," said Dr. Stanley Crooke, the biotechnology company's chief executive.
 
Isis, based in Carlsbad, California, is a pioneer in the field of antisense drugs, which are meant to work at the genetic level to prevent production of disease-causing proteins. It makes the only commercial antisense drug, a treatment for a rare type of eye infection.
 
Despite the promising science, results for most antisense compounds have been underwhelming. Isis itself has abandoned experimental therapies for diseases like HIV and genital warts. In March, the company said Affinitak, an experimental lung cancer drug it is developing with Eli Lilly & Co., failed a late-stage trial.
 
But Crooke maintains that the greater potency, stability, lower cost and better side effect profiles of its latest-generation drug candidates serve to validate the field.
 
"This is the embodiment of our strategy to use a series of second-generation drugs to help guide dose selection and scheduling ... in order to enhance efficacy trials (phase 3)," he said.
 
The improved chemistry is also allowing Isis to develop therapies for chronic conditions like diabetes and cardiovascular disease, as opposed to its earlier efforts against diseases like cancer and hepatitis C.
 
A 20-patient trial of a drug known as Isis 104838, which is designed to block a protein called TNF-alpha, showed that it significantly reduced joint swelling in rheumatoid arthritis patients compared to placebo, according to researchers.
 
The complete trial results are scheduled to be presented at a meeting next month of the American College of Rheumatology in Orlando, Florida.
 
Crooke said results from a second 160-patient study of Isis 104838—this one measuring improvement in arthritis symptoms—will be available later this year.
 
Earlier this week, Isis reported results from an early-stage trial of a drug called Isis 113715, which is designed to enhance insulin's ability to transport glucose, or blood sugar, into cells. The drug is a potential therapy for diabetes and possibly obesity, Crooke said.
 
"At the top two doses, we saw a dramatic increase in glucose tolerance," Crooke said. Isis plans to start a Phase 2 diabetes trial as soon as possible.
 
The drugs are given by injection or infusion, but it is possible to make antisense pills, he said.
 
"We have treated about 150 patients with these second-generation compounds and there have been no meaningful side effects," Crooke said.
 
He said drugs like Isis 104838 would have a competitive advantage over antibody-based therapies that target the same protein—like Amgen Inc.'s Enbrel —because they are safer.
 
"These drugs are not proteins. There is no antibody response so administration is enhanced and efficacy is improved. There would also be a dramatic reduction in cost," Crooke said.
 
Amgen officials were not immediately available for comment.
 
Meanwhile, the company continues to develop several earlier-version antisense drugs, including Affinitak. Lilly is expected to announce results from a second pivotal-stage trial of the lung cancer drug in mid-2004.
 
Isis expects around the same time to have results from a Phase 3 trial of Alicaforsen in Crohn's disease and a Phase 2 study of the same drug in ulcerative colitis, Crooke said.
 
Last week, Genta Inc. and Aventis SA said they would seek approval for experimental skin cancer drug Genasense, even though the antisense compound showed only limited effectiveness in late-stage trials.

 

 

Impact of High-Dose Interferon Induction and Ribavirin Therapy in Patients With Chronic Hepatitis C Relapsing After or Not Responding to Interferon Monotherapy
 
Posted 09/19/2003

Petra Steindl-Munda, Peter Ferenci, Harald Brunner, Karin Nachbaur, Christian Datz, Michael Gschwantler, Harald Hofer, Rudolf Stauber, Franz Hackl, Wolfgang Jessner, Martha Rosenbeiger, Alfred Gangl, Wolfgang Vogel

Abstract and Introduction

Abstract

Background/Aims: Initial high-dose interferon-alpha induction therapy in combination with ribavirin improves sustained response rates in treatment-naïve patients. This prospective, randomized, controlled study tested whether non-responders or relapsers to interferon monotherapy also benefit from induction therapy.
Methods: Patients with chronic hepatitis C who had not responded to (n=75) or relapsed (n=80) after previous interferon therapy were randomized to receive three different interferon doses during the first 14 weeks of therapy (A: 10 MU IntronA®/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; B:5 MU/d for 14 weeks; C: 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. All patients received 1-1.2 g ribavirin/day throughout the whole study.
Results: The rates of viral clearance at any time on treatment were similar in all groups. Sustained response rates were also not different among the groups in interferon nonresponders (A 32%, B 29%, C 31%) and relapsers (A 64%, B 68%, C 71%), respectively, as well as in patients with different genotypes. As expected, sustained response rates were higher in patients with genotype non-1 than in those with genotype 1.
Conclusion: High-dose induction therapy does not improve the outcome of interferon/ribavirin therapy in interferon nonresponders or relapsers.

Introduction

The outcome of antiviral therapy of chronic hepatitis C has improved considerably over the last decade, but the results are still unsatisfactory. Interferon-alpha (IFN) monotherapy has a limited efficacy in naïve patients[1] as well as for re-treatment of nonresponders with higher doses of IFN.[2] Combination of IFN with ribavirin improved response rates considerably in de novo patients,[3, 4] in relapsers after interferon therapy, and in interferon non-responders.[5-9] Nevertheless, the majority of interferon nonresponders fail to respond to standard combination therapy. Therefore, further strategies to improve response rates are needed. One possible approach would be to use high-dose interferon induction therapy in combination with ribavirin. This concept is based on studies of the kinetics of virus clearance[10] and was tested in naïve patients in an Austrian multicenter trial.[11] High-dose interferon induction therapy (with 10 MU interferon-alpha2b/daily for 14 days followed by 10 MU every other day for 12 weeks) increased sustained response rates in genotype 1 patients.[11]

The initial virologic response to interferon is rapid and dose-dependent.[10] Patients infected with IFN-sensitive viral strains clear the virus rapidly from blood and have a high probability to achieve a sustained response.[12] However, patients infected with viral strains that can only be partially suppressed by IFN include nonresponders, partial responders and relapsers to 'standard' IFN therapy. A large proportion of relapsers respond to IFN/ribavirin combination therapy.[5] In contrast, the rate of sustained responders in IFN-nonresponders receiving standard dose interferon/ribavirin combination therapy is unsatisfactory. Even with increasing doses of IFN to 10 MU/TIW, only 8.6% of nonresponders to a 3-month course of 3 MU/TIW IFN monotherapy became sustained responders.[8] Therefore, in this trial the impact of two different induction schedules in combination with ribavirin was compared with standard interferon/ribavirin therapy in nonresponders and relapsers to IFN (using the same protocol as for IFN-naïve patients). In affluent countries this patient group may not exist anymore, since interferon/ribavirin combination therapy is the accepted standard since 1999.[13] However, many patients in Eastern and Central Europe are still treated with interferon monotherapy. Furthermore, the response to daily interferon together with ribavirin may help to design studies using pegylated interferons in this very difficult patient group.

 

Patients Selection

One hundred and fifty-five patients with chronic hepatitis C (age 19-65 years), who were relapsers or nonresponders to previous interferon monotherapy with doses of at least 3 MU/TIW for at least 6 months, were recruited for this study until mid-2000. Relapse was defined as the reappearance of HCV-RNA (by PCR) after stopping successful therapy ( = complete inhibition of viral replication on interferon therapy). Patients were considered as nonresponders, if they had never achieved PCR negativity throughout the previous treatment course. Most of the patients had participated in a previous trial and had received 5 MU interferon/TIW for 9 months or were treated off study with 3 MU/TIW for 52 weeks. All were HCV-RNA positive and had at least 1.5-fold elevated transaminases within the last 6 months prior to therapy, and had histologic evidence (at a biopsy obtained within 1 year prior to treatment) of chronic hepatitis. A recent liver biopsy was not required, but was strongly recommended. To minimize hematologic side effects of therapy, only patients with Hb values of >/=12 (women) or >/=13 (men) g/dl, leukocytes >/=3000/µl and thrombocytes >/=100 000/µl were recruited.

Exclusion Criteria

The following were considered as exclusion criteria: refusal by women of child-bearing age or by sexually active patients to use a safe contraceptive, pregnancy or breast-feeding, cirrhosis with signs of decompensated liver disease (ascites, bleeding varices and spontaneous encephalopathy), coronary heart disease, confirmed co-infection with HIV or HBV, the presence of overt psychiatric disorders, active alcohol or drug abuse, diabetes mellitus requiring medical therapy, autoimmune disorders and any other unstable medical condition not due to liver disease.

Study Design

The protocol of this study was identical to the study in de novo patients.[11] After obtaining a written informed consent, patients were randomized to one of the three treatment groups which received different interferon doses during the first 14 weeks. Randomization was carried out centrally using a computer-derived list of random numbers. At randomization, patients were stratified according to the presence or absence of cirrhosis, and according to their response to previous interferon therapy (relapsers or nonresponders).

Group A (high-dose induction): 10 MU interferon-alpha2b (IntronA®, AESCA-Schering-Plough, Traiskirchen, Austria)/day for 2 weeks, followed by 10 MU every other day for 12 weeks.
Group B (intermediate-dose induction): 5 MU IntronA® daily for 14 weeks.
Group C (standard treatment according to the consensus of the Austrian Society for Gastroenterology and Hepatology:[14] 5 MU IntronA® every other day for 14 weeks.

Thereafter, all patients received 5 MU every other day for a further 6 months. During the whole treatment, all patients received the same amount of ribavirin: 1 g/day (<75 kg body weight) or 1.2 g/d (>/=75 kg). Therapy adjustments were performed according to the changes in hemoglobin, WBC and platelet count at the discretion of the attending physician.

The study protocol was approved by the ethics committees of all participating hospitals.

Measurements

Viral load was determined using the COBAS AMPLICOR HCV MONITOR® test, v2.0 (Roche Diagnostic Systems, Branchburg, NY). Qualitative PCR was determined by the COBAS AMPLICOR® HCV test (Roche Diagnostic Systems, Branchburg, NY). The lower level of 100% detection of HCV-RNA is 500 copies/ml. HCV genotypes were determined by the Line Probe assay (Innogenetics N.V., Zwijnaarde, Belgium).

Statistics

Patients' baseline data and demographic characteristics were compared by either an unpaired Student's t-test or a chi2 test, as appropriate. Primary outcome measures were the rates of virus elimination measured by a qualitative PCR at 2, 14 and 38 weeks of therapy, and 6 months after the end of therapy (week 62). The statistical evaluation strategy was based on the intention-to-treat principle and was in accordance with the relevant EU directives. The efficacy of the three treatment arms was compared by univariate analysis using Fisher's exact test. The prediction of successful therapy based on viral response at various time points was evaluated by the chi2 test.

Results

Characteristics of the Patients

Baseline characteristics of the 75 nonresponders (group A: 22; group B: 24; group C: 29) and 80 relapsers (group A: 28; group B: 28; group C: 24) are shown in Table 1.

Treatment per protocol and follow up was completed by 17, 18 and 21 nonresponders patients and by 23, 23 and 22 relapser patients in groups A, B and C, respectively. Twelve relapsers (group A: 5; group B: 4; group C: 3 = 15%) and 19 nonresponders (group A: 4, group B: 7 and group C: 8 = 25%) stopped therapy prematurely. There was no difference between the different treatment groups. The most frequent reasons for premature termination of therapy were noncompliance (patients did not show up for further examinations) in 18 and wish of patient in seven (because they felt that they could not tolerate the side effects). Only in five patients therapy had to be stopped by the physician because of side effects (depression: 2; symptomatic coronary heart disease: 1; leuko-penia: 1; abscess: 1), and in one because of a breakthrough. Major efforts were undertaken to motivate drop-outs to come to scheduled visits until week 62 ( = end of follow-up). All patients in whom complete follow up data were not available were considered as treatment failures.

Response to therapy was evaluated at four different time points: at day 14 (comparison of 3 different doses), after 14 weeks (comparison of alternate day and daily dosing by administering the same total IFN dose group A vs. B, and of two different doses using the same alternate day dosing regime – group A vs. group C), at the end of treatment (week 38) and at the end of follow-up (week 62). The results are shown in Table 2 and Table 3. At weeks 2, 12 and at the end of treatment and after the end of follow-up (SR) response rates were not different among the three groups (62-64% in genotype 1; 75-88% in genotype non-1 patients). Similarly, no differences were observed in the IFN nonresponders at any time point. Nevertheless, sustained response rates of 29-36% were achieved (15-26% in genotype 1, 40-57% in genotype non-1).

Biochemical response was achieved in all sustained responders in the the groups. At the end of therapy and end of follow-up, two of the nonresponders in the relapser group and five in the nonresponder group showed a biological response only. In the patients who relapsed virologically, two in the relapser group and four in the nonresponder group had sustained normalization of liver enzymes.

Except for genotype, no factors predictive of response in nonresponders were found. The drop-out rate was slightly higher in nonresponders, but neither in nonresponders nor in relapsers there was an effect of dose on the drop-out rate. The side effects were not different among the three groups, although there was a clear trend towards lower WBC and platelet count in patients receiving higher IFN doses.

 

Treatment of Hepatitis B and C Virus Infections in Immune Compromised Individuals
 

This review compares and contrasts the natural history and treatment of hepatitis B and C virus infections in three principal populations of immune compromised individuals.

(1)     Patients co-infected with HIV;

(2)     Patients with liver failure secondary to hepatitis B or C virus infection who undergo liver transplantation; and

(3)     Patients with hepatitis B or C virus infection who undergo anticancer chemotherapy.

Recent Findings

Chronic liver disease resulting from hepatitis B or C virus infection progresses more rapidly in patients co-infected with HIV than in HIV negative patients. Treatment protocols for antiviral therapy are, however, similar to those used in immunocompetent individuals and although few long-term results are available, the efficacy of interferon and ribavirin therapy in hepatitis C virus/HIV infection and lamivudine in HIV/hepatitis B virus infection has been proven in the short-term.

Perhaps the most important consideration is the timing of administering treatments to co-infected patients. For patients with well preserved CD4 counts and hepatitis C virus/HIV co-infection, the hepatitis infection should be treated as early as possible to avoid drug interactions of hepatitis C virus antivirals with antiretroviral therapy.

Response to hepatitis C virus treatment appears better when treatment is administered in the context of preserved immune function.

Conversely, in hepatitis B virus/HIV co-infection, hepatitis B virus antivirals are best administered with anti-retroviral therapy, thus preventing the selection of HIV viral species which may be resistant to the drugs used for hepatitis B virus.

Improved graft and patient survival after liver transplant and with anticancer chemotherapy in hepatitis B virus infected patients has been proven using lamivudine prophylaxis. However, although therapy for hepatitis C virus recurrence after liver transplantation would seem rational, limited success with current treatment protocols has been achieved.

The authors conclude, “Although the prognosis of hepatitis B and C virus infections in the immune compromised may be inferior to that of immunocompetent individuals, such patients should have full evaluation of their viral hepatitis, and antiviral therapy should be considered.”

10/01/03

Reference
GH Haydon and DJ Mutimer.  Hepatitis B and C virus infections in the immune compromised. Current Opinion in Infectious Diseases 16(5): 473-479. October 2003

Taming Hepatitis C: High stakes but low odds

 

By JANE E. BRODY
c.2003 New York Times News Service

 

For once, there is some good news to report about a blood-borne virus that has infected 4 million Americans and 170 million people worldwide.

The disease, hepatitis C, will eventually debilitate the livers of many of its sufferers, but new cases of it have declined 80 percent since the virus was identified in 1988 and blood banks started screening for contaminated donations four years later.

But -- and this is no small but -- the annual death toll from the long-term consequences of this infection is 10,000 a year in the United States, and scientists expect deaths to triple by 2010 before that statistic begins to decline, unless new treatments are developed to eliminate the virus or at least keep its complications at bay indefinitely.

Several such treatments are being studied, and expert hope they will work as well as those that have radically improved the control of HIV infections. If their early promise holds up in clinical trials, most hepatitis C infections may be cured or at least rendered virtually harmless. Current therapies are lengthy, expensive and can cause devastating side effects. Further, they work in only slightly more than half the patients.

Experts have learned enough about the virus and how it is transmitted to alert those at risk of the need to be tested, to take steps that can forestall complications and to prevent transmission to others.

Unlike HIV, the hepatitis C virus is rarely transmitted through sexual contact. Its primary route to a new bloodstream has been through contaminated needles shared by drug users and by blood transfusions. People with hemophilia and others who received blood products before the testing for the virus began may also be infected.

Low rates of transmission affect health care workers exposed to contaminated blood through needle-stick accidents, men who have sex with men and babies born to infected women.

Fatal cases have resulted from organs inadvertently transplanted from a contaminated donor.

Household contacts and sexual partners in monogamous relationships are rarely affected. But people who engage in high-risk sexual behavior with multiple partners and people who have sexually transmitted diseases face increased risk.

Although those receiving tattoos and body piercings in other countries can be at risk, there is as yet no evidence for transmission by those routes in the United States.

A blood test for the virus relies on the presence of antibodies to it, but antibodies may not appear for weeks after the infection. A more sensitive genetic test can detect the presence of the virus itself.

Testing is recommended for people who have had blood transfusions or organ transplants before July 1992 or were treated for clotting problems with blood products made before 1987, those who have been on long-term kidney dialysis and those who have injected street drugs, even once many years ago.

Not everyone infected becomes ill. Some people seem to eliminate the virus, and a chronic infection never develops.

Others who remain chronically infected may be free of symptoms indefinitely.

In most cases, however, as with HIV, the virus can linger in the body for a long time -- even decades -- before symptoms of liver damage appear.

The most serious consequences are severe cirrhosis, a scarring of the liver, liver failure and liver cancer, which have made hepatitis C the leading reason for liver transplants.

Symptoms, when they appear, are usually mild, intermittent and easily attributed to other causes. The symptoms may include fatigue, nausea, poor appetite, muscle and joint pains and mild discomfort or tenderness in the right upper abdomen.

Those who develop cirrhosis or severe liver disease may, in addition to complaining about those symptoms, experience weight loss, itching, dark urine, fluid retention and abdominal swelling.

No vaccine against the virus has been developed, and prospects for one are not promising because there are at least six major genetic types and more than 50 subtypes of the virus. And, it changes rapidly. The possibility of a vaccine depends on finding an exposed part of the virus that remains stable even as its protein coat mutates.

The main goal of treatment is to eradicate the virus to prevent progressive liver disease. Existing therapies are most effective in patients with Genotypes 2 and 3, which represent about 25 percent of patients in the United States. The most common ones, Genotypes 1a and 1b, affect about 75 percent of patients and are the most difficult to treat.

Two main therapies have been developed. One involves injections of interferon, usually long-acting pegylated interferon, which is injected weekly, and the other an oral antiviral drug called ribavirin.

Therapy is most successful when the treatments are used simultaneously. But each can cause serious problems in certain patients. Interferon should not be prescribed for people with serious psychiatric illness, unstable heart disease or poorly controlled diabetes. People with anemias, heart disease, stroke and kidney disease should avoid ribavirin, as should pregnant women.

Patients with the Type 1 virus are treated for 48 weeks; those with Types 2 and 3 do well with 24 weeks. The combination therapy is effective in slightly more than half the cases, in 42 percent of those with Type 1 and 80 percent for those with Types 2 or 3.

The side effects can be quite miserable, at least at the outset. But they subside with time and disappear when the treatment ends. Patients report that the drugs commonly cause flulike symptoms. They can seriously disrupt sleep and create havoc with sexual response and personality.

People tend to become irritable, forgetful and seriously depressed, and they may lose considerable weight. Even when treatment seems to have eliminated the virus, it can sometimes rebound, requiring a second round of therapy.

While some experts recommend that everyone who has chronic hepatitis C infection be treated, others suggest that each patient, in consultation with physicians, carefully weigh the likelihood that the disease will progress and the benefits and risks of therapy, as well as its considerable cost.

In a recent article in The Journal of the American Medical Association, Dr. Joshua A. Salomon and colleagues at the Harvard Center for Population and Development Studies noted that "30 percent to 70 percent of infected individuals may never progress to cirrhosis before dying from other causes."

The authors further pointed out that progression of the infection was highly variable and unpredictable. The probability of developing cirrhosis over 30 years ranges from 13 to 46 percent for men and 1 to 29 percent for women, they stated. Also, the progression of the infection to serious liver disease is less common among patients who are infected when they are young. They seem better able to fend off the virus or keep it under wraps.

With or without treatment, people infected with the virus should take steps to protect their livers from further damage. The steps include avoiding alcohol, getting vaccinated for hepatitis A and consulting physicians before taking any new medicines, including over-the-counter and herbal remedies