Coinfection

Severe Liver Fibrosis during Acute HCV Infection in HIV Positive Men Who Have Sex with Men

Over the past several years, there have been increasing reports of outbreaks of acute hepatitis C virus (HCV) infection among HIV positive men who have sex with men (MSM). Acute HCV is the initial 6-month period of newly acquired HCV infection.

In the current study, published in the July 15, 2008 online edition of the Journal of Infectious Diseases, Daniel Fierer from the Mount Sinai School of Medicine in New York City and colleagues evaluated risk factors and liver histopathology of 11 consecutively enrolled HIV positive men with recently acquired HCV infection.

Fierer first reported at the 2007 Conference on Retroviruses and Opportunistic Infections (CROI) in Los Angeles that several HIV positive MSM with acute hepatitis C showed evidence of severe liver fibrosis, which typically develops much later in the course of HCV infection. He followed up with additional similar findings at the 2008 CROI in Boston.

The recently published report extends the data further.

Results

• 11 MSM with asymptomatic, sexually-acquired HIV infection of 11 months to 16 years duration were found during routine medical visits to have elevated transaminase levels, which led to further testing and the clinical diagnosis of acute HCV infection.
• In all these patients, acute hepatitis A virus infection was excluded serologically and acute and chronic HBV infection were included both serologically and by HBV DNA testing.
• 8 patients were completely asymptomatic for liver disease throughout the acute course of infection; patients 3, 8, and 11 experienced transient jaundice.
• 10 patients had recently engaged in unprotected receptive anal intercourse, some with many partners.
• None had experienced ulcerative sexually transmitted infections within the prior year.
• Patients 1, 3, and 6 reported a single recent episode of injecting methamphetamine; 1 remembered sharing injection equipment, but the others had no recollection of doing so.
• Patients 2, 6, and 11 had shared paraphernalia used for snorting drugs on multiple occasions with other MSM.
• Patient 4 had a possible percutaneous exposure.
• 5 men denied any parenteral risk factors or “club drug” use.

Discussion

According to the investigators, immunosuppression increases the progression of fibrosis in HCV-infected patients. “The magnitude of the acceleration is relatively modest if immunosuppression occurs after the chronic phase of HCV infection has been established,” they wrote. 

The authors pointed out that prior study results have indicated that the fibrosis progression rate (FPR) of patients with chronic HCV monoinfection is 0.11 unts per year and that the FPR of patients with chronic HIV-HCV coinfection is <2-fold greater, at 0.15 units per year.

“The majority of HIV-HCV coinfected injection drug users (IDUs) are not expected to develop cirrhosis (stage 4 fibrosis) for 20 years or more,” wrote the researchers. In contrast, they noted, “Patients who acquire HCV infection when they already have defects in cellular immunity are reported to progress to cirrhosis, end-stage liver disease, and death in as few as 3 years.

They continued, “This dire outcome has been observed in transplant recipients, patients with hematological disorders and immunodeficiencies, and patients with preexisting HIV infection.”

Among the 11 consecutive HIV-infected MSM in the study who underwent liver biopsy during the early periods of HCV infection, nine (82%) had stage 2 fibrosis. In contrast, biopsy specimens from immunocompetent patients obtained during the early periods of HCV infection contained no or minimal fibrosis [1].

“[Therefore] the FPR of the HIV-infected MSM with newly acquired HCV infection in our study was far higher than that of immunocompetent patients with acute HCV infection,” wrote the authors.

“Our findings of moderately advanced fibrosis during the initial period of HCV infection are consistent with the rapid clinical progression to end-stage liver disease reported in previous studies of individuals who acquired HCV infection while already infected with HIV or who acquired HIV and HCV infection simultaneously.”

In their conclusion, the researchers stated that their study indicates that high-risk sexual practices and non injection-drug use may play a role in the transmission of HCV to HIV-infected MSM.

In addition, they wrote, “Our findings also demonstrate that HIV-infected men with acute HCV infection have moderately advanced liver disease. The FPR of this population is 5 times greater than that for people who are not immunocompromised at the time when they become HCV infected. Our findings are of particular importance with regard to the recent outbreaks of acute HCV infection in HIV-infected MSM in Europe and the United States” [2].

The authors observed that regular screening of MSM for HCV antibodies “is not currently recommended by U.S. or international HIV care guidelines, and ALT elevations during acute HCV infection are relatively transient and therefore could be easily missed during routine clinical care.” They maintained that many (if not most) cases of acute HCV infection “are not diagnosed, even in areas in which the outbreaks have been recognized.”

In closing, the study authors urge caregivers to initiate more intensive screening of HIV-infected MSM, “given the grave implications of missing the diagnosis of acute HCV infection in these patients.”

Divisions of Infectious Diseases and Liver Diseases, Department of Medicine, and Department of Pathology, Mount Sinai School of Medicine, New York, NY.

8/05/08

Reference

DS Fierer, AJ Uriel, DC Carriero, and others. Liver fibrosis during an outbreak of acute hepatitis C virus infection in HIV-infected men: a prospective cohort study (brief report). Journal of Infectious Diseases. July 15, 2008 [Epub ahead of print].

Other Citations

1. SM Kamal, Turner B, Q He, and others.. Progression of fibrosis in hepatitis C with and without schistosomiasis: correlation with serum markers of fibrosis. Hepatology 43: 771–779. 2006. 

2. M Danta, D Brown, S Bhagani, and others.. Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours. AIDS 21: 983–991. 2007.