By Liz Highleyman

Several prior studies have indicated that HIV positive individuals with chronic hepatitis C virus (HCV) tend to experience more rapid liver disease progression than HIV negative people with hepatitis C. Furthermore, people with HIV are less likely to experience spontaneous HCV clearance without treatment, and therefore are more likely to develop chronic liver disease.

Two studies presented at the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008) in San Francisco looked at outcomes in HIV positive patients with acute HCV.

New York City Outbreak

Recent outbreaks of apparently sexually transmitted HCV among HIV positive men who have sex with men (MSM) provide an opportunity to study acute hepatitis C. People with HIV are advised to be screened for HCV, and those on HAART should receive regular liver function tests to monitor for antiretroviral toxicity, which can reveal HCV infection at its earliest stages. Patients identified and treated with interferon-based therapy at this stage are more likely to experience sustained response than those with chronic HCV infection.

Researchers at Mount Sinai School of Medicine analyzed factors influencing spontaneous clearance of acute HCV in HIV positive individuals, as well as response to treatment. As background, they noted that recent data suggest sexual exposure to HCV might be associated with greater likelihood of spontaneous clearance.

Hepatitis C Virus

The investigators prospectively enrolled 22 HIV positive MSM infected during an ongoing outbreak of acute HCV in New York City (2005-2008); 1 patient had 2 episodes of acute HCV. All had recent-onset ALT elevation and dramatic fluctuations in HCV RNA and/or HCV antibody seroconversion. The median age was about 42 years, 45% were Caucasian, 41% were Hispanic, and 14% were African-American. Most (70%) were on HAART, 43% had undetectable HIV RNA, and the median CD4 count was about 500 cells/mm3. All were infected with HCV genotype 1. Most men had sexual activity as the sole identified risk factor for HCV infection, but 5 reported injection drug use.

This research team has previously reported that liver disease progression may be particularly rapid and severe in HIV positive MSM with acute HCV.

Results

• 11 of 23 acute HCV episodes (48%) were symptomatic.

• 4 of 23 episodes (17%) resulted in spontaneous clearance, defined as HCV RNA persistently < 600 IU/ml for > 6 months post-diagnosis.

• Spontaneous clearance was not associated with sexual exposure to HCV.

• 16 men with persistent detectable HCV started treatment with pegylated interferon plus ribavirin:

• 50% (7 of 14 with available follow-up data) achieved rapid virological response (RVR; HCV RNA < 600 IU/mL) at week 4 of treatment.

• 93% (13 of 14 with available data) achieved early virological response (EVR) at week 12.

• 70% (7 of 10 with available data) achieved sustained virological response (SVR) 24 weeks after completing treatment.

• No significant differences with respect to clinical or virological factors were identified between patients with and without spontaneous HCV clearance, although there was a trend toward higher peak ALT levels in patients who developed chronic infection.

• Among 14 patients who underwent liver biopsies (median 4.3 months after first ALT increase), 12 (86%) had stage F2 (moderate) fibrosis and 1 each had stage F1 (mild) and stage F0 (absent) fibrosis.

• 3 of 4 patients who ultimately experienced spontaneous clearance nevertheless had stage F2 fibrosis.

• There were no correlations between treatment outcomes or spontaneous clearance and degree of fibrosis.

The investigators noted that "Moderately advanced liver fibrosis was seen during the acute phase and in the early chronic phase in almost every patient evaluated suggesting far more rapid fibrosis progression than previously reported in patients with HIV infection, even in those who eventually had spontaneous clearance."

"It is therefore crucial to detect and treat acute HCV infections during the acute phase to take advantage of the higher cure rate (70%) and prevent further progression of the already moderately advanced liver disease," they continued. "We therefore recommend that HIV-infected MSM be considered a risk group for HCV infection and that at least yearly screening for HCV antibody be performed in addition to quarterly surveillance of [liver function tests]."

After treatment, 1 individual who achieved SVR became acutely infected a second time following a relapse in injection drug use. The researchers were able to confirm reinfection rather than relapse because he had HCV genotype 1b the first time and 1a the second time.

"The occurrence of a second episode of acute HCV in one subject underscores the need for continuing surveillance and better strategies to modify high risk behavior in this population," they stated.

Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY; Infectious Diseases, Mount Sinai School of Medicine, New York, NY; Pathology, Mount Sinai School of Medicine, New York, NY.

Factors Predicting Spontaneous Clearance

In a related study, investigators analyzed the natural history and treatment outcomes of acute HCV infection in 30 HIV positive and 32 HIV negative individuals seen between 2000 and 2008 at Mount Sinai, the University of Pennsylvania, the Philadelphia Veterans Affairs (VA) Medical Center, and the Brooklyn VA Medical Center.

Most were white or Hispanic men with a median age of 41 years, but the HIV negative group included more women (31% vs 3%). HCV risk factors included injection drug use, high-risk sexual activity, and exposure via healthcare procedures.

Results

• HCV genotype 1 was most prevalent overall (76%), with subtype 1a being more common among the coinfected patients (67% vs 16%) and subtype 1b being more common among those with HCV alone (38% vs 10%).

• The HIV positive and HIV negative groups had similar peak ALT values and maximum HCV RNA levels.

• Spontaneous HCV clearance occurred with similar frequency in both groups (19% HIV negative vs 13% HIV positive; P = 0.73).

• 16 HIV negative and 18 HIV positive patients started interferon-based therapy (16 and 10, respectively, had sustained response data available).

• SVR rates were similar in both groups, 69% for HIV negative patients and 60% for coinfected patients (P = 0.69).

Based on these results, the investigators concluded, "In our cohort, natural and therapeutic HCV clearance occurred with similar frequencies regardless of established HIV coinfection, suggesting that HIV-associated CD4 T-cell dysfunction does not necessarily prevent HCV clearance."

"These findings strongly support the need to identify and treat acute hepatitis C early in HIV-infected patients," they added. "Work is ongoing to examine the relevant host-virus interactions in these patients."

University of Pennsylvania, Philadelphia, PA; Philadelphia VAMC, Philadelphia, PA; Pennsylvania Hospital, Philadelphia, PA; Brooklyn VAMC, Brooklyn, NY; Mount Sinai Medical Center, New York, NY.

11/18/08

References

AJ Uriel, DS Fierer, DC Carriero, and others. An On-going Outbreak of Acute HCV in HIV-infected Men in New York City: Rates of Spontaneous Clearance and Treatment Responses. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 503.

LM Jones, AJ Uriel, DE Kaplan, and others. Natural History and Treatment Outcome of Acute Hepatitis C with and without HIV Co-infection in a North American Cohort. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 1838.