Hepatitis C Treatment and Management
Lifestyle-related choices that help your liver are covered in the section Living with coinfection.
One approach to managing hepatitis C (HCV) is to decide first what your priority is. Clearing the virus is the most important goal for many people but not for everyone. In some cases, treatment may be more likely to improve the condition of your liver than to clear the virus. In other cases, treatment may not be necessary right away, or ever.
For some people, deciding whether to start HCV treatment is an easy decision. For most, it isn't. There are a lot of factors to be considered.
This section focuses on conventional HCV treatment with the current standard of care, which is a combination of pegylated interferon and ribavirin.
Lifestyle-related choices that help your liver are covered later in the section "Living with coinfection".
Treatment guidelines generally agree about when to treat hepatitis C (HCV), and who to treat.
Regardless of HIV status, for all HIV-positive people this is when the benefits of therapy outweigh the risk. Sometimes treatment is recommended for people with coinfection earlier than HIV-negative people.
Hepatitis C treatment is a combination of two drugs, pegylated interferon (PEG interferon) and ribavirin (RBV).
Interferon is a man-made version of a chemical made by the human body that works against HCV in two ways. It works directly against the virus. It also stimulates the immune system to fight viruses. "Pegylated' means that a small molecule has been attached to interferon to keep it in the body longer. This means you only need to inject once a week, and makes it more effective at treating HCV.
There are two types of PEG interferon:
Different formulations have been studied differently in patients with different severity of disease. They have not been compared directly, and so it is difficult to know whether one may be better than another in different circumstances.
Ribavirin is a nucleoside analogue, from the same family as many HIV drugs, but it does not work against HIV.
On its own, ribavirin is not effective against hepatitis C. It needs to be used with PEG interferon.
Ribavirin is given as pills or capsules, twice daily. It is usually dosed by body weight and by HCV genotype. Brand names for ribavirin include Copegus, Rebetrol and Ribasphere.
In HIV-positive people, treatment for hetatitis C is currently recommended for at least a year, for all genotypes, although recently, researchers have looked at tailoring treatment according to individual response.
Some doctors are treating coinfected people with genotypes 2 and 3 for less time if they have an early response to treatment (see Evaluating response to HCV treatment).
Some doctors treat people with genotype 1 and 4 for longer than a year. In particular, people with HIV/ HCV coinfection may require a longer course of treatment, especially people with genotype 1.
Curing hepatitis C
The primary goal is usually to get rid of the hepatitis C infection.
In hepatitis C, a sustained virological response, or SVR, means that a person does not have HCV in his/her blood six months after the end of treatment. Most people who have had an SVR stay free of HCV, although there are less long-term results in HIV-positive people. Although some recent research has found very low levels of hepatitis C in the blood and liver tissue of some people with a sustained virological response, this may not have any significant effect on liver health.
Most people who have had an SVR stay free of HCV, although there are less long-term results in HIV-positive people.
Although some recent research has found very low levels of HCV in the blood and liver tissue of some people with a sustained virological response, this may not have any significant effect on liver health.
Improving liver health
A secondary goal of HCV treatment is to improve liver health by reducing inflammation, and, sometimes, reversing fibrosis.
This even happens in people who do not get an SVR, although only in about half the number of cases.
For some people, the condition of the liver may worsen after HCV treatment, particularly among people who did not clear the virus. It is not clear why this happens.
Use of full or reduced dose pegylated interferon as a maintenance therapy in people who did not clear their hepatitis C with treatment, did not reduce the risk for liver disease progression. Therefore, maintenance therapy is no longer recommended for people with hepatitis C, regardless of their HIV status.
SVR reduces the risk of liver cirrhosis, liver cancer and liver failure for HIV negative and HIV positive people.
For HIV-positive people, there may be an additional benefit from HCV treatment in reducing the risk of liver-related side effects from HIV drugs.
Generally, HIV treatment should be started first if CD4 count is less than 200 cells/mm3, and probably started first if it is between 200-350 cells/mm3.
People with serious liver damage may need HCV treatment even when their CD4 count is lower than this.
HIV treatment may be started at higher CD4 counts if the CD4 count is falling, and HCV treatment will be used soon.
If HCV treatment is needed, people on a stable HIV regimen should be treated, even if their CD4 cell count is under 200 cells/mm3.
Older studies, that used standard interferon to treat HCV, reported that it was less effective for people with low CD4 counts. However, in a small group of people studied so far, PEG interferon plus ribavirin works at both high and low CD4 counts.
It is best not to start treatment for both HIV and HCV at the same time. This is because side effects from both treatments make this too difficult.
Even if you are on HIV treatment, interferon can cause your CD4 count to drop. However, your CD4 'percentage' usually remains the same, or may even increase. This shows that the drop in the count is unlikely to reflect a real change in your immune system.
To support this, the three major HCV treatment trials in HIV-positive people did not find more opportunistic infections among people with low CD4 counts (under 200 cells/mm3).
After HCV treatment is ended, the CD4 cell count usually returns to the pre-treatment level within a few months.
In someone whose CD4 count is already strong (above 500 cells/mm3) there is no need to use HIV treatment before HCV treatment.
The most important aspects of HIV treatment are just as relevant for people who also have hepatitis C (HCV), including choice of treatment, adherence, side effects and resistance.
The main differences in HIV treatment for someone who also has HCV relate to:
Some drugs are less "liver-friendly" than others. It is not clear though whether small increases in liver enzymes increase the risk of clinical disease. Caution is clearly important. HIV drugs should be selected carefully, and liver enzyme levels monitored regularly.
Some side effects occur more frequently in people with HCV coinfection, including lipodystrophy (fat accumulation or fat loss) and abnormal blood fat and insulin levels.
HCV increases the risk of developing diabetes and this risk is higher in HIV-positive people. Use of HIV protease inhibitors and nucleoside analogues, especially d4T (stavudine, Zerit), has been linked with an increased risk for high blood sugar and diabetes.
However, this risk should never be used as a factor to withhold HIV treatment.
Clearly, many factors are involved with response to treatment.
The information in the table below is a snapshot of response rates from trials of PEG interferon plus ribavirin.
Table 4: Response rates to treatment
Week 24, 48 or 72
Week 48, 72 or 96
Hepatitis C (HCV) treatment has traditionally been withheld from injecting drug users, even though current treatment guidelines recommend that treatment decisions be made on a case-by-case basis.
Fortunately, this has begun to change. Experience in HIV treatment confirms that it is possible for drug users to adhere to anti-retroviral therapy, and response rates from clinical trials of HCV treatment in IDUs are similar to those reported in non-users.
Depression and other mental health diagnoses are much more common among people with HCV, people with HIV, and drug users than the general population. Many of these conditions are treatable.
People with a history of depression are more likely to develop depression during HCV treatment. Depression can also happen to people who have not been depressed in the past. If you are concerned about the psychiatric side effects of HCV treatment, but want to treat your hepatitis C, consider support from mental health care services.
Some people can manage HCV treatment while they are using drugs; others have found that stopping or cutting down on drug use has helped them to prepare for, and stay on HCV treatment. This could be from a self-help programme, counselling, drug treatment, or heroin substitution, methadone maintenance, naltrexone implants, or using buprenorphine. Increasing the dose of methadone has helped people manage side effects of HCV treatment.
If you are still injecting drugs, ask your doctor or local syringe exchange programme for information on safer injection to lower your risk of HCV reinfection (and other infections).
Many people fear that they will relapse to active drug use, because the symptoms of interferon are very similar to opiod withdrawal.
The risk of relapse is lower when side effects are promptly and effectively treated and when counselling and support from peers and medical and mental health providers is available.
Some people are concerned about self-injecting PEG interferon. If possible, injections can be given once weekly by a nurse to avoid triggering a relapse to injection drug use.
With greater access to treatment, the number of people who did not clear the virus during treatment is also increasing.
Strategies for retreating hepatitis C (HCV), including treatment with a different formulation of interferon, called consensus interferon, or a higher dose of PEG interferon and/or ribavirin and a longer course of treatment have yielded disappointing results.
If you did not respond to treatment with the older non-peglated formulations of interferon, which was much less effective, you should consider retreating with pegylated interferon.
Some of the new oral hepatitis C drugs are being studied in people who were unsuccessfully treated for hepatitis C. Based on the experience with HIV, it may be better to wait until there is more than one new HCV drug to add to a regimen that didn't work before.
A damaged liver can still function, but people who have developed cirrhosis are at risk for liver failure and other serious, life-threatening complications.
People with compensated cirrhosis should be screened for liver cancer, and monitored regularly for decreasing liver function and varices. These are stretched and bursting veins resulting from liver scarring that obstructs the flow of blood through the portal vein and increases blood pressure. Drugs called beta-blockers can help to prevent varices. Variceal bleeding is managed with medication and surgery.
Changing your diet can help to manage some of the complications of cirrhosis. Cutting down on salt, eating many small light meals per day with protein from vegetables and dairy products rather than meat can help address nutritional imbalances. A nutritionist and your doctor can help you plan a healthy diet.
Hepatic decompensation (decompensated cirrhosis) occurs when the liver cannot compensate for damage, and liver function has deteriorated. After hepatic decompensation, a liver transplant is necessary.
In people with decompensated liver disease, a liver transplant is the final option.
This is a major operation, and success rates vary. It is also complicated by a scarcity of donor organs that are available for transplant.
For many years, transplant services actively avoided liver transplants in HIV-positive people. This was due to several factors including discrimination from some surgeons, who did not want to operate on HIV-positive people.
The poor long-term life expectancy for HIV-positive people before combination therapy meant that a donor organ would provide fewer years of additional life than it might to a person without HIV or other medical conditions. There were also concerns about using drugs to suppress the immune system that are an essential part of a transplant, in HIV-positive people.
The effectiveness of HIV drugs has changed this. HIV is no longer an exclusion criteria for a liver transplant.
Centres in the UK, Spain, France and the United States have transplanted livers into HIV-positive people. Some centres have reported no significant difference in survival according to HIV status.
However, medical management remains complex, due to drug interactions between drugs used to suppress the immune system after the transplant and protease inhibitors, the risk of graft rejection, HCV reinfecting the new liver, and difficulty in tolerating HIV and HCV treatment after the transplant.
Only a few transplant centres in the UK have reported liver transplants in people with coinfection, and referral to one of these centres is essential. The success is largely limited by recurrent HCV infection in the new liver.
HCV infection progresses more rapidly in people with HIV coinfection, and their survival after hepatic decompensation is shorter that that of people with HCV alone. Some specialists suggest that people with coinfection should be referred to a transplant list at an earlier stage of disease than people with HCV monoinfection.
This article was provided by HIV i-Base. It is a part of the publication Hepatitis C for People Living With HIV. Visit HIV i-Base's website to find out more about their activities, publications and services.