On The Sides

With the combo came a combination of side effects that have left many hepatitis patients suffering long after their treatment is through.

By: Brian J. Todd

Niccolo Machiavelli would be proud. The only treatment for a deadly disease is a pair of drugs that will often make patients feel worse than the disease itself. Furthermore, the treatment is effective only half the time — at best — and patients complain the side effects can last long after the yearlong drug treatment is completed. It is a scenario that has hepatitis patients asking every day, “Does the end justify the means?”

“Classically, most patients on (interferon and ribavirin) treatment get flu-like symptoms,” says Dr. Michael Ader, of Riverside Gastroenterologists in Bronx, N.Y. “For most patients, the first one or two shots are the worst.”

To Ader, the end — turning a hepatitis C patient into a sustained viral nonresponder — certainly justifies the means. But ask any hepatitis C patient who is contemplating interferon treatment, and he or she will tell you that the specter of long-lasting side effects is one of the biggest roadblocks to recovery.

Side Effects To Watch

Part of the problem with the standard combination therapy is that the two drugs involved, ribavirin and inter-feron — either regular interferon or even the new pegylated interferon — both have side effects that create their own unique problems.

According to Schering-Plough, the manufacturer, the side effects from Peg-Intron injections — the new standard interferon — are numerous. Mental health problems, including irritability, depression and hostility as well as the potential for suicide, are part of the Peg-Intron package. Other side effects include low blood pressure, fast heart rate and, on rare occasions, heart attacks. Peg-Intron can lower one’s white blood cell count, which leads to lower immunity; it also can lower a patient’s platelet count, which can interfere with clotting; and it can damage internal organs, which may lead to abdominal pain.

The side effects of Rebetol, according to Schering-Plough, include a lowering of the red blood cell count, a prelude to anemia and fatigue. “Anemia associated with therapy may exacerbate symptoms of coronary disease or deteriorate cardiac function,” Schering states on its Web site.

And, of course, everyone on treatment watches for the well-documented flu-like symptoms that, according to Schering-Plough, are some of the most common side effects associated with their ribavirin pills: nausea, lack of appetite, fever, chills and joint and muscle aches.

But these are just some of the more common side effects associated with treatment. Many more — some well- known like thyroid problems and others such as sarcoidosis, a lung ailment — exist.

Long-Term Effects

When Niki Rogers, a nurse from Arden, N.C., began treatment in March 2000, she certainly understood the possibility of side effects, but the degree to which her condition deteriorated came as a shock.

“I had really bad sides,” Rogers said, “and it got worse as time went on. I had all the usual ones that everyone has: fatigue, nausea — I lost 25 pounds. I had problems with my hemoglobin. I could not walk and speak at the same time; I was so out of breath.”

Her doctor reduced her medication to compensate for the low hemoglobin, she said, but her condition did not get better. Only later when her family physician noticed lumps under her skin was Rogers diagnosed with sarcoidosis — a condition where substances collect in the lungs causing shortness of breath and in some cases death.

While her other side effects ended quickly after she stopped her treatment in February 2001, Rogers said the sarcoidosis lingered until October, eight months later. “Everything else went away quickly. I was very pleased with how fast I felt better. Two months after treatment I remodeled two bathrooms.”

Or Smooth Sailing

But not everyone feels the pain of treatment. In fact, Dan Lubin said he never felt so good as when he started treatment in the middle of October 2001. Now more than half way through treatment, Lubin knows he is fortunate.

“I know I’m in a small and lucky category,” Lubin of Bronx, N.Y, said. “A lot of people have these immune responses that shock their central nervous systems. I’ve had none of that. In fact, things have cleared up for me.”

Lubin said he can credit a lot of his success to Dr. Ader, his gastroenterologist, who gives him no-nonsense advice and talked him into giving up drinking. A healthier lifestyle, Lubin said, has contributed greatly to his well being and his lack of side effects and clearing up some of the symptoms of his hepatitis C, such as occasional liver pain and diarrhea.

“I had minor muscle aches, no joint aches, and my liver pain went away pretty quickly,” Lubin said of his initial Peg-Intron shot. “The first time was the worst time.”

One more piece of advice Ader gave Lubin may have helped as well. “He said, ‘Let’s get you on treatment as early as we can justify,’” Lubin said of Ader’s advice. “‘If you wait, it’ll be a rough ride.’”

All Pain, No Memory

Bill Atwell can empathize with Rogers’ battle against side effects rather than Lubin’s easy run through treatment. After starting the Rebetron combo therapy in August 2000, Atwell said he was hit with a cocktail of aches, pains and odd conditions.

“I had muscle and joint aches, nausea, fatigue, brain fog, a lot of cognitive dysfunction,” Atwell said. “I’d walk into a room and forget why.”

He lost 40 pounds in the first two months of treatment before taking steps to help his body battle the side effects. “I found out I required a lot more water than I thought,” he said. “I made sure to try to sleep more. Before all this happened I used to get five hours of sleep a night.” He also started watching what he put in his mouth, realizing that his old habit of eating junk food and snacks was not helping his body cope.

When Atwell ended his year of treatment in August 2001, he, like Rogers, was surprised to see that his side effects lingered. “It took a couple of months before I felt 100 percent,” he said. “And I never really responded to therapy. I still have my hepatitis side effects, but my medication sides are finally gone.”

What Caused That?

While side effects in general are fairly well understood, Dr. Ader said the phenomenon of side effects lasting far beyond the end of treatment is rare. “I haven’t seen that happen very much,” he said. “And I don’t know if that is psychological or if there are any permanent changes in the body. I don’t understand it.”

One possible cause of some patients’ extended side effects, he said, could be a placebo-like effect. Dr. Ader noted that in many studies, patients taking a placebo acquired many of the same side effects as the patients taking the drug in the test.

He also said a patient’s attitude going into treatment makes all the difference toward how smoothly their treatment goes. In his own practice — because of how long it takes to get all the tests back, and due to insurance companies often needing to preauthorize medications — he will often see a patient three or four times before they actually take their first interferon injection. “This gives them a lot of opportunities to back out before they get started,” he said, “so if they do start, they’re generally pretty committed.”

Mary Van Bronkhorst, a physician assistant at Harborview Medical Center in Seattle, said emotions and mental outlook almost certainly play a part in ongoing depression that some patients feel after the treatment has ended.

“Fatigue is the biggest, and one that doesn’t seem to get better as they go on in treatment,” Van Bronkhorst said of side effects she sees in her patients each week. “The initial side effects — fever, nausea, diarrhea — seem to get better in the first three or four weeks of treatment. But (fatigue) generally resolves promptly after treatment.”

Of a larger concern, she said, is the depression she sees her patients battle when they take a year of their lives to commit to treatment. “If the patient has depression that did not resolve itself, or the patient did not respond to treatment,” she said, “then you could expect that the symptoms would persist.

“I think people go through a sort of grief process for time lost,” Van Bronkhorst said. “Sometimes patients get better and they feel more energy initially, then they go through a sadness on the time — the year of their lives — wasted on treatment.” Considering how interferon treatment changes a patient’s life for the time they are taking the drug, she said, it is understandable that patients might feel some personal loss. “But it is hard to separate that out from the depression created by the medications themselves.”

Altered Mental States

While Karin Button did face a mood altering side effect when she started treatment with standard interferon and ribavirin, it was not depression that changed her personality.

“The interferon was very tolerable,” the 56-year-old from Lahaina, Hawaii, said, “but the ribavirin was another story.  It made me extremely anxious, almost to the point of panic attacks. I tried reducing the dosage, but it didn’t help.” Button was saved from her panic attacks because the clinical trial in which she was taking part allowed her to switch to Pegasys monotherapy after four weeks of treatment.

Before treatment, Button said her biggest symptom due to hepatitis was stomach aches she suffered from for about four years — starting even before her diagnosis in May 1999. Once she started the Pegasys treatment, Button said, she still had side effects, but they were much more manageable.

“The biggest problems I had with the interferon were headaches and general aches and pains, but it was nothing I couldn’t deal with,” she said. “I did become very irritable too, which tended to make me not want to socialize much, and at times I did find it difficult to sleep without some help.”

Her side effects that began when she started treatment lingered for six to eight months after she finished her 48 weeks. “The headaches went first then slowly the aches and pains,” she said. Through it all, an effective side effect management program helped her cope with treatment.

A Little Helper

“I did have meds for side effects,” she said, “but tried not to take them unless necessary. The only thing I took daily was Zoloft. I had Xanax for anxiety, Tylenol III for pain and Ambien for sleep.”

She also credits her doctors for being understanding about how the medications can change a patient’s life during treatment. “My regular Kaiser doctor didn’t know much about hep C,” Button said, “so he listened to what I had to say. My Stanford doctors (where her clinical trial was being administered) knew how treatment affected people and were really great.”

But for the people who don’t believe that side effects can linger long after the treatment ends, Lucinda Porter, a registered nurse working with the Hepatology Team at Stanford University Medical Center in Palo Alto, Calif., said she has experienced it firsthand.

“I saw it with the monotherapy, which didn’t make any sense,” Porter said, referring to the claim patients make that their side effects linger. “Then I felt it with the monotherapy,” she said, referring to her own treatment. “I saw it with Rebetron, and I see it with the Peg.”

While Porter admits her observations are anecdotal at best, she said the biggest issue concerning side effects isn’t whether they linger or not, but how bad they will be and whether that should affect a decision to seek treatment.

“Most patients do postpone treatment because the reports of the side effects are there,” she said, adding, “Most patients later say ‘I imagined that it would be worse than it actually was.’”

Porter, like so many others, said there is most certainly a mental aspect to dealing with the side effects and treatment in general. “We have to get treatment, and a positive attitude helps,” she said. “It is not an insurance policy. But it sure makes our days go by better.” hep

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Brian J. Todd is managing editor of Hepatitis