Hepatitis C for Primary Care Physicians
Hepatitis C is treated to lower the risk of progression to end-stage liver disease or hepatocellular carcinoma. The goal of treatment is a sustained decrease in hepatitis C viral RNA (called the sustained virological response [SVR]), which is defined as no detectable hepatitis C viral RNA 24 months after treatment. Studies have found that SVR is linked with a 30% to 50% decrease in all-cause mortality.
The treatment regimen depends on the genotype of the virus. For genotype 1, the most common type in the United States, patients are treated with triple therapy, which includes pegylated interferon-α, ribavirin, and either boceprevir and telaprevir, which are direct-acting protease inhibitors. The addition of the direct-acting protease inhibitors significantly increases the likelihood of successful treatment as determined by SVR in patients infected with genotype 1 and shortens the duration of treatment for some patients. While the 2 agents have equal efficacy, telaprevir has a simpler dosing schedule and for that reason is discussed in detail here (Table 4 and Figure 2). Patients with genotypes 2 to 6 are treated with pegylated interferon and ribavirin at a dosage of 800 mg daily for 24 weeks.
(Enlarge Image)
Figure 2.
Treatment of chronic hepatitis C genotype 1 with telaprevir-based therapy. Dual therapy, peginterferon + ribavirin; HCV, hepatitis C virus; RNA, ribonucleic acid; triple therapy, telaprevir + peginterferon + ribavirin (see Table 4 for dosing).
Both protease inhibitors have multiple drug interactions and should be checked against all of a patient's current medications. Anemia is a frequent complication of treatment, occurring in as many as 49% of patients treated with protease inhibitors, and it may be treated by reducing the dose of ribavirin. Other common side effects of treatment include rash, pruritus, nausea, and diarrhea.
The treatment of hepatitis C is rapidly evolving, with >40 drugs in development, including interferon and ribavirin analogs, vaccines, immunomodulators, and direct-acting antiviral drugs. As the treatment of hepatitis C continues to evolve, primary care physicians may also have a more active role in the treatment of hepatitis C, and some locations are already doing so with the assistance of telemedicine.
Patients who are not immune to hepatitis A or B should receive vaccination. Patients with cirrhosis should also be offered pneumococcal vaccination and annual inactivated influenza vaccination.
All patients with chronic hepatitis C should be advised to abstain from drinking alcohol to decrease the risk of cirrhosis, and referral to treatment facilities should be provided. Alcohol significantly increases the risk of the development of cirrhosis in patients with hepatitis C, with an odds ratio of 147.2 (95% confidence interval [CI], 42.1–514.3) for heavy drinkers (eg, >175 g per day averaged over the lifetime). Even moderate drinking can increase the risk for progression to cirrhosis in some patients. Intravenous drug abusers should be referred for appropriate addiction treatment. Obesity is a risk factor for progression of liver disease because of the development of nonalcoholic steatohepatitis syndrome, so assistance with weight loss should be provided to obese patients.
Patients should be counseled about behaviors to reduce the risk of transmission, including avoiding the donation of blood and plasma. The risk of transmission of hepatitis C by sexual activity in monogamous heterosexual couples is low (approximately 0.07% per year; 95% CI, 0.01–0.13%), and condom use is not necessary in these couples. Sexual transmission may occur at a higher rate in men who have sex with men, especially those infected with HIV. Patients should be counseled to avoid sharing toothbrushes, razors, and other items that may be contaminated with blood.
Chronic hepatitis C infection should not be considered a contraindication to treatment with HMG-coenzyme A reductase inhibitors (statins) and may even be an option for the treatment of hepatitis C in the future. Statins should be avoided if there is evidence of hepatic failure, such as jaundice or increased bilirubin level. Patients with elevated serum aminotransferase levels (>3times baseline or >5 times the upper limits of normal) should not be taking statins, although they could be started if levels fall.
Treatment of pain in patients with cirrhosis can be particularly problematic. Many providers avoid using acetaminophen in patients with chronic liver disease because of the potential for hepatotoxicity. However, at therapeutic doses of <4 g/day, acetaminophen is generally considered safe, although some experts recommend a lower dose of 2 g/day. Nonsteroidal anti-inflammatories should be avoided in patients with cirrhosis because of the potential for hepatorenal syndrome or gastrointestinal bleeding. Because of impairment in drug metabolism, the use of opioids should be minimized since they can precipitate hepatic encephalopathy. If opioids are necessary for adequate analgesia, the minimum effective dose should be used and longer intervals between administrations should be considered.
Primary care physicians may also be asked to manage depression induced by treatment with interferon-α. In general, treatment with selective serotonin reuptake inhibitors can be initiated as soon as patients begin to manifest symptoms of depression. Several small trials have investigated the use of selective serotonin reuptake inhibitors for the prevention of depression, with mixed results. Therefore, current data support waiting for symptoms to develop rather than using pretreatment.
Patients who have both hepatitis C and cirrhosis are at increased risk of developing hepatocellular carcinoma and should be offered screening by annual or semiannual ultrasound. α-Fetoprotein levels alone should not be used for screening unless ultrasound is unavailable. Current guidelines also recommend continued screening for patients who have been successfully treated for hepatitis C and patients who have evidence of bridging fibrosis on liver biopsy, although the data of efficacy lag behind the recommendation.
Treatment
Hepatitis C is treated to lower the risk of progression to end-stage liver disease or hepatocellular carcinoma. The goal of treatment is a sustained decrease in hepatitis C viral RNA (called the sustained virological response [SVR]), which is defined as no detectable hepatitis C viral RNA 24 months after treatment. Studies have found that SVR is linked with a 30% to 50% decrease in all-cause mortality.
The treatment regimen depends on the genotype of the virus. For genotype 1, the most common type in the United States, patients are treated with triple therapy, which includes pegylated interferon-α, ribavirin, and either boceprevir and telaprevir, which are direct-acting protease inhibitors. The addition of the direct-acting protease inhibitors significantly increases the likelihood of successful treatment as determined by SVR in patients infected with genotype 1 and shortens the duration of treatment for some patients. While the 2 agents have equal efficacy, telaprevir has a simpler dosing schedule and for that reason is discussed in detail here (Table 4 and Figure 2). Patients with genotypes 2 to 6 are treated with pegylated interferon and ribavirin at a dosage of 800 mg daily for 24 weeks.
(Enlarge Image)
Figure 2.
Treatment of chronic hepatitis C genotype 1 with telaprevir-based therapy. Dual therapy, peginterferon + ribavirin; HCV, hepatitis C virus; RNA, ribonucleic acid; triple therapy, telaprevir + peginterferon + ribavirin (see Table 4 for dosing).
Both protease inhibitors have multiple drug interactions and should be checked against all of a patient's current medications. Anemia is a frequent complication of treatment, occurring in as many as 49% of patients treated with protease inhibitors, and it may be treated by reducing the dose of ribavirin. Other common side effects of treatment include rash, pruritus, nausea, and diarrhea.
The treatment of hepatitis C is rapidly evolving, with >40 drugs in development, including interferon and ribavirin analogs, vaccines, immunomodulators, and direct-acting antiviral drugs. As the treatment of hepatitis C continues to evolve, primary care physicians may also have a more active role in the treatment of hepatitis C, and some locations are already doing so with the assistance of telemedicine.
Primary Care for Patients With Chronic Hepatitis C
Patients who are not immune to hepatitis A or B should receive vaccination. Patients with cirrhosis should also be offered pneumococcal vaccination and annual inactivated influenza vaccination.
All patients with chronic hepatitis C should be advised to abstain from drinking alcohol to decrease the risk of cirrhosis, and referral to treatment facilities should be provided. Alcohol significantly increases the risk of the development of cirrhosis in patients with hepatitis C, with an odds ratio of 147.2 (95% confidence interval [CI], 42.1–514.3) for heavy drinkers (eg, >175 g per day averaged over the lifetime). Even moderate drinking can increase the risk for progression to cirrhosis in some patients. Intravenous drug abusers should be referred for appropriate addiction treatment. Obesity is a risk factor for progression of liver disease because of the development of nonalcoholic steatohepatitis syndrome, so assistance with weight loss should be provided to obese patients.
Patients should be counseled about behaviors to reduce the risk of transmission, including avoiding the donation of blood and plasma. The risk of transmission of hepatitis C by sexual activity in monogamous heterosexual couples is low (approximately 0.07% per year; 95% CI, 0.01–0.13%), and condom use is not necessary in these couples. Sexual transmission may occur at a higher rate in men who have sex with men, especially those infected with HIV. Patients should be counseled to avoid sharing toothbrushes, razors, and other items that may be contaminated with blood.
Chronic hepatitis C infection should not be considered a contraindication to treatment with HMG-coenzyme A reductase inhibitors (statins) and may even be an option for the treatment of hepatitis C in the future. Statins should be avoided if there is evidence of hepatic failure, such as jaundice or increased bilirubin level. Patients with elevated serum aminotransferase levels (>3times baseline or >5 times the upper limits of normal) should not be taking statins, although they could be started if levels fall.
Treatment of pain in patients with cirrhosis can be particularly problematic. Many providers avoid using acetaminophen in patients with chronic liver disease because of the potential for hepatotoxicity. However, at therapeutic doses of <4 g/day, acetaminophen is generally considered safe, although some experts recommend a lower dose of 2 g/day. Nonsteroidal anti-inflammatories should be avoided in patients with cirrhosis because of the potential for hepatorenal syndrome or gastrointestinal bleeding. Because of impairment in drug metabolism, the use of opioids should be minimized since they can precipitate hepatic encephalopathy. If opioids are necessary for adequate analgesia, the minimum effective dose should be used and longer intervals between administrations should be considered.
Primary care physicians may also be asked to manage depression induced by treatment with interferon-α. In general, treatment with selective serotonin reuptake inhibitors can be initiated as soon as patients begin to manifest symptoms of depression. Several small trials have investigated the use of selective serotonin reuptake inhibitors for the prevention of depression, with mixed results. Therefore, current data support waiting for symptoms to develop rather than using pretreatment.
Patients who have both hepatitis C and cirrhosis are at increased risk of developing hepatocellular carcinoma and should be offered screening by annual or semiannual ultrasound. α-Fetoprotein levels alone should not be used for screening unless ultrasound is unavailable. Current guidelines also recommend continued screening for patients who have been successfully treated for hepatitis C and patients who have evidence of bridging fibrosis on liver biopsy, although the data of efficacy lag behind the recommendation.
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