Looking to the Future -HCV Treatment 0WionsBY LUCINDA PORTER, R.N.

a f a a a a t a a f * r i t * r f a a r a ] r t a a r f a a a r a r a f a f t a a t r f f a l a a a t a a a a l a t a a a a a a a

he standard of treatment for hepatitis C infection (FICV) is interferon,mostment

What new

The Cunent Stnndard of CareIfyour doctor suggests treatrnent foryour HCV infection, most likely itwill be in the form of Rebeuon, acombination of Inuon-A (alpha inter-feron, specifi cilly alfa-2b) and Rebetol (rib-avirin). The two drugsare used together andare commonly referredto as t'combination ther-^Pyj'

When interferon isused alone, it may bereferred to as interferonmonotherapy. Althoughthere are a number oftypes of interferon,alpha interferon is thestandard form of inter-feron used for HCVinfection. Sometimesthese are referred to bytheir product names,Infergen, Intron-d andRoferon.

Your doctor will eval-uate your suiability forcombination therapy orinterferon monotherapy.Interferon-based thera -

py is recommended forpatients with elevatedserum liver enz,rmes and

the presence of HCV RNA in theblood, usually measured by a poly-merase chain reaction @CR) test.

Patients with mild liver diseasemay never have any progression of

their liver disease and may not needtreatrnent. However, this same groupof people is more likely to respond totreatrnent.

Since it is impossible to accuratelypredict the future, manyphysicians recommendtreating HCV infectionin all patiena who donot have any reasonstreatrnent would be dan-gerous, i.e., contraindica-tions. This is especiallytrue if the infection isacute (recendy acquired).In general, it is acceptedthat the potential bene-fits of the treatrnent ofchronic hepatitis C out-weigh the potential risks.

Presendy, treatrnent ofchronic HCV infectionis not recommended forthose individuals withnormal liver enzymes.Studies reveal that therate of disease progres-sion is slower in thisgroup of patients. Also, ithas not been provenwhether treatrnent iseffective for this groupof individuals.

How do you and your

likely in combination with ribavirin. But are there any other treat-options for chronic HCV infection? What are the fallback options?treatnents are on the horizon?

Moy[une 2000 Hepatitis 19

phpician deter-mine if Rebetron orinterferonmonotherapy isright for you? First,review the con-traindications totreafinent (see sidebar). Do you haveany condition that

will need to be closely monitoredwhile you undergo theraPy? Ifso,

how will you be monitored?What are some of the otler factors

that you might want to considerbefore entering treatrnent? Is this a

particularly stressfirl dme in your life?

Are you actively drinking alcohol,abusing drugs, or engaging in behav-

ior that may put you at risk for viral

re-infection? Have you just started a

new job or found yourself with a

major responsibility that requires a

lot ofattention? Ifso, tell your doc-

tor.The cost of treaunent maY be an

issue for you. Do you have medicalinsurance, and if so, does it cover the

entire cost of treatrnent? According

to t Nns York Tirnes article, the cost

of a year of Rebeuon treatrnent can

be as much as $17,200. For those

with no insurance and extreme finan-

cial hardship, pharmaceutical compa-

nies offer financial assistance pro-

grams (see sidebar).Your doctor has probablY men-

tioned that interferon is self-adminis-

tered by injection. This technique is

fairly easy to learn. However, do you

have any special concerns that need

to be addressed regarding this, suchas poor eyesighg impaired hand coor-

dination, or a needle Phobia?Some people who are in recovery

from injection drug use are uncom-forable with self-injection. If so, dis-

cuss this with your doctor or nurse.

None of these concerns should Pre-vent you from attempting treatrnent.

There are solutions for these and

other issues that may arise.What are the side effects of

Rebetron and interferon monothera-py? Your doctor will probably discuss

potential adverse events with you.Between this discussion and the listprovided in the package insert, it is

enough to discourage anyone from

trying treatrnent. If you have anYconcerns, talk to your doctor or

nurse.The most common side effects are

the initial flu-like symptoms that gen-

erally accompany the first few injec-tions. These usually diminish in

intensity but can come and go

throughout the treatrnent.Patients complain about fatigue,

muscle and joint aches, headaches,rashes, irritability, and decreased abil-

ity to concentrate. Some people suffer

from depression and others exPeri-ence hair loss.

There are a number of other side

effects, such asthyroid disor-ders, so it isimportant to beaware of these.However, the pos-sibility of experi-encing side effecais usually notenough to prevent Peo-ple from consider-ing treatrnent.Some people arehardly botheredbv side effects. Ingeneral, most peopleare able to tolerate the treatrnent.

Current treatrnent options do not

guerantee elimination of the virus.Rebeuon offers a higher success rate

than interferon alone. Overall, the

chances ofresponding to a Year of

treafinent using standard doses of

Rebetron are approximately 40 per-

cent. These success rates mayincrease or decrease dePending on

your genotype or "strain" ofvirus.

Those with genotype t have nearlY

a 30 percent probability ofresponse,while those with genotypes 2 or 3have about a 65 percent likelihood ofresponse. Unfornrnately, the majorityof Americans infected with HCVhave genotype 1, while the remaining20 percent to 30 percent have themore favorable genotypes 2 or 3.Genotypes 4, 5, and 6 are rare in the

United Sates.These figures drop significandY

when sandard doses of interferonmonotherapy are used for one year.

Some patients express discourage-ment with these percentages, wantingbetter odds for their effort at treat-

ment. However, there are alternativeways to interpret these statistics. fuDr. Dennis Israelski, Chief ofInfectious Diseases and AIDSMedicine, San Mateo CountY Health

Center & associate clinical professor,

Stanford University Medical Centerin Palo Alto, Calif., said, "If I told my

AIDS patients that I could offer them

a drug that had a 40 percent chanceof eliminating their virus with a year

of treaunent, they would be ecstatic."Furthermore, recent data suggess

that even if treatrnent does not com-

pletely eradicate the virus, there may

be some benefit to the liver.

Options Available forNonres@nderc or Rela4sercWhat if you have already tried interfer-

on monotherapy or Rebetron and the

results were not what you hoPed for?

Dr. Emmet Keeffe, professor of medi-

cine and medical director of the Liver

Ti'ansplant Program at Stanford Univer-sity Medical Center in Palo Alto, Calif.,

suggests several potential approaches for

Rebetron nonresponders."There are several options includ-

ing deferral of further therapy over

the next several years Pending the

developrnent of future non-interferontreatrnents, particularly if liver biopsy

or noninvasive data suggest the pres-

20 Hepatitis MoylJune 2000

e etherapvor F

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hepatitis C a Icure? The answer

Glis anyone's guess, ,"=T_.:.T.-:ry QJ-(I)

it a good

[Tn""e ORebetron Warning labels

Rebetrcn must not be used by:.Women who are or might

become pngnant' Patients with autoimmune

hepatitis. Anyone who is hypersensitive to

either interfenon or ribavirin. Patients with hemoglobinopathies. Patients with a history of unstable

cardiac disease

Womings:Use extreme caution before andwhile undergoing combination ther-apy if there is a history or develop-ment of the following. Anemia. Any cardiac abnormalities. Any pulmonary abnormalities. Psychiatric problems. Caution in patients with creatinine

clearance of <50m1/min. Diabetes mellitus. Eye problems. Thyroid problems

Precnutions:Exacerbations of autoimmune prob-lems have been repofted. Safety andefficacy have not been established inthose with organ transplants,decompensated HCV infection, orthose who are co-infected withHBV or HIV

For information about interferonmonotherapy, consult your physi-cian, pharmacist, and/or appropriatepackage insert.

ence of mild disease."Tivo, pegylated interferon plus

ribavirin therapy flater in 2000 whenavailablel, if preliminary data showpromise of a reasonable rate of sus-tained responses in prior Rebetronnonresponders.

"Three, a furttrer course of inter-feron using an induction regimen[i.e., daily, high-dose therapy for l-2months] and an alternative interferon,such as consensus interferon [interfer-on alfacon-l].

"And, finally, if advanced disease ispresent on liver biopsy, long-terminterferon monotherapy (3-5 years ormore) to suppress inflammation andhopefully slow the progression offibrosis and development of liver can-cer [this approach is currendy underinvestigation by the National Instituteof Health (MFI)1."

Regarding Rebetron (or interferon)relapsers, Dr. Keeffe points out, "they

have more promise of a sustainedresponse with additional interferon-based therapy." These individualshave already demonstrated a responseto treatrnent, indicated by loss ofvirus and normalization of ALIs dur-ing therapy.

"Their best options are pegylatedinterferon plus ribavirin when avail-able, and possibly a longer course oftherapy if tolerable. If mild disease ispresent and interferon plus ribavirinwas poorly tolerated, waiting forfuture non-interferon therapies is alsoa very reasonable option," said Dr.Keeffe.

Whfrt Trefrtments are on theHorizon?The answer to that depends on yourdefinition of treatrnent. Some of thedrugs being tested are designed toprevent the formation of fibrosis inthe liver; others specifically try totlrwart the hepatitis C virus. Thereare drugs being developed that targetspecific parts of HC{ as well as

drugs to enhance patients'immuneresponse.

At the most recent meeting of theAmerican fusociation for the Study ofLiver Diseases, there were a stagger-ing number of presentations. Thenext drug will most likely be pegylat-ed interferon. This is basically a long-acting interferon that will require aonce or rwice weekly injection ratherthan the current regimen of threetimes a week. This will likely be usedin combination with ribavirin.

In the future, there may be clinicaltrials using HCV helicase inhibitors,HCV protease inhibitors, HCV repli-case inhibitors, ribozymes, cytokines,and much more. What does all thismean? It means maintain an opti-mistic oudook. And, in the interim,make sure your status is monitored byyour doctor.

In considering all of these options,what do you hope will be the out-come? Most of us would answer withone word - "cure." A patient recendysaid to me that he was not sure whyhe bothered with treatrnent if it wasnot going to cure him.

I was surprised by this remark.Although the word "cure" is not com-monly used, it is known that over 90percent of those who have a sustainedresponse after six months of treat-ment will continue to maintain thatresponse.

Furthermore, the liver shows sig-nificant signs of improvement forthose who demonstrate a sustainedresponse. This is based on interferonmonotherapy data from the past 10years.

In the meantime, how many yearshave to pass before we start callingthe sustained response to antiviral

Ffrwrrjal n enWans

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MoylJune 2000 Hepatitis 2 |