Treatment of chronic hepatitis C virus infection in the United States: some remaining obstacles.

Hepatitis C infection is an important problem in inner city neighbourhoods, which suffer from multiple health disparities. Important factors in this population include alcoholism and substance abuse, mental illness and homelessness, which may be combined with mistrust, poor health literacy, limited access to healthcare and outright discrimination. Systemic barriers to effective care include a lack of capacity to provide comprehensive care, insufficient insurance coverage, poor coordination among caregivers and between caregivers and hospitals, as well as third party payers. These barriers affect real world treatment effectiveness as opposed to treatment efficacy, the latter reflecting the world of clinical trials. The components of effectiveness include efficacious medications, appropriate diagnosis and evaluation, recommendation for therapy, access to therapy, acceptance of the diagnosis and its implications by the patient and adherence to the recommended therapy. Very little attention has been given to assisting the patient to accept the diagnosis and adhere to therapy, i.e. care coordination. For this reason, care coordination is an area in which greater availability could lead to greater acceptance/adherence and greater treatment effectiveness.

Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected men.

BACKGROUND: There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal. METHODS: We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men. Men who were treated prior to the availability of, or ineligible for, telaprevir were the comparator group. The primary endpoint was SVR12, defined as an HCV viral load <5 IU/mL at least 12 weeks after completing treatment. RESULTS: In the telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the comparator group. Among men with SVR, median time to undetectable viral load was week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53% had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in the telaprevir group received ≤12 weeks of treatment and there were no relapses after treatment. The overall safety profile was similar to that known for telaprevir-based regimens. CONCLUSIONS: Incorporating telaprevir into treatment of acute genotype 1 HCV in HIV-infected men halved the treatment duration and increased the SVR rate. Larger studies should be done to confirm these findings. Clinicians should be alert to detect acute HCV infection of HIV-infected men to take advantage of this effective therapy and decrease further transmission in this epidemic.

Hepatitis B therapies and antiviral resistance detection and management.

Hepatitis B virus (HBV) infection is an important health problem and a major cause of chronic hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Durable viral suppression has been documented to lower the risk of hepatocellular carcinoma and disease progression. Treatment of chronic HBV infection remains a major clinical challenge because long-term use with approved oral antiviral agents is associated with drug resistance. Antiviral resistance can result in poor clinical outcomes; therefore first-line therapy with the most potent agent(s) is recommended to lower the risk. Early detection of resistance is paramount to possibly reduce the risk of liver-related morbidity and mortality. It is important that clinicians monitor for therapeutic efficacy and resistance, so as to optimize the management of chronic HBV.

Liver fibrosis during an outbreak of acute hepatitis C virus infection in HIV-infected men: a prospective cohort study.

Outbreaks of acute hepatitis C virus (HCV) infection are occurring in HIV-infected men who have sex with men. We evaluated risk factors and liver histopathology in 11 consecutively enrolled men with newly acquired HCV infection that was diagnosed on the basis of antibody seroconversion, new elevations in alanine aminotransferase level, and wide fluctuations in HCV RNA level. Ten patients reported unprotected anal intercourse, and 7 reported "club-drug" use, including methamphetamine. Liver biopsy showed moderately advanced fibrosis (Scheuer stage 2) in 9 patients (82%). No cause of liver damage other than acute HCV infection was identified. The specific pathways leading to periportal fibrosis in HIV-infected men with newly acquired HCV infection require investigation.

Treatment of acute hepatitis C in an HIV-positive man with pegylated interferon and ribavirin for 24 weeks.

An epidemic of acute hepatitis C is emerging among HIV-infected men who have sex with men (MSM), with a growing number of cases reported in the MSM population in the United States and Europe. We report a case of a 47-year-old HIV-infected MSM who sexually contracted acute hepatitis C and was treated with pegylated interferon and ribavirin for 24 weeks. After 4 weeks of therapy, the patient's HCV RNA level became undetectable and remained undetectable 1 year after the 24-week treatment course.

Effect of switching to tenofovir with emtricitabine in patients with chronic hepatitis B failing to respond to an adefovir-containing regimen.

BACKGROUND: In patients with chronic hepatitis B, long-term use of lamivudine is limited by resistance mutations. Adefovir dipivoxil has a very low rate of resistance, but there have been recent reports describing resistance mutations. Tenofovir disoproxil fumarate and emtricitabine show potent activity against wild-type and lamivudine-resistant hepatitis B virus. METHODS: We describe a series of seven HIV-seronegative patients who failed to achieve undetectable hepatitis B viral DNA on adefovir. No lamivudine resistance testing was performed. The antiviral regimen was changed to tenofovir (300 mg daily) and emtricitabine (200 mg daily). Variables collected included levels of hepatitis B viral DNA by polymerase chain reaction, alanine and aspartate aminotransferase, hepatitis B e antigen and hepatitis B e antibody. RESULTS: The median hepatitis B viral DNA level while on adefovir was 430,000 copies/ml with a median fall in hepatitis B viral DNA levels of 2.0 log10 copies/ml. Patients were on adefovir for a median period of 10 months before a change in regimen to tenofovir and emtricitabine. This regimen change resulted in a median fall in hepatitis B viral DNA levels of 3.0 log10 copies/ml (range, 2-4) after a median treatment duration of 23 months (range, 14-28). All patients (100%) had achieved undetectable hepatitis B viral DNA levels following combination therapy. Anti-hepatitis B e seroconversion occurred in one patient. No change in serum creatinine was observed during therapy, and no significant adverse events were reported. CONCLUSIONS: In patients failing to respond to adefovir monotherapy or an adefovir-containing regimen for chronic hepatitis B virus, a combination of tenofovir and emtricitabine resulted in undetectable hepatitis B viral DNA levels without any renal toxicity. Tenofovir, in combination with emtricitabine, may be an alternative treatment for those with detectable hepatitis B viral DNA on adefovir.