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HIV and Hepatitis.com Coverage of the
61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010)
October 29 - November 2, 2010, Boston, MA
Rapid Liver Disease Progression among HIV Positive Men with Acute Hepatitis C Coinfection

 
SUMMARY: People who already have HIV when they become infected with hepatitis C virus (HCV) may experience very rapid liver disease progression, researchers from Mt. Sinai Medical Center reported at the American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) held recently in Boston. A detailed review of 4 coinfected patients with persistent HCV viral load revealed progression to decompensated cirrhosis over relatively short periods of time, resulting in persistent symptoms, liver transplantation, or liver-related death.
 

By Liz Highleyman

Since the early 2000s, clinicians in the U.K. and Europe have reported clusters of apparently sexually transmitted acute HCV infection among HIV positive gay and bisexual men, with similar cases later seen in the U.S. and Australia. A considerable body of evidence indicates that HIV/HCV coinfected people tend to experience more rapid liver disease progression than individuals with HCV alone, especially if they have low CD4 cell counts.

But a subset of coinfected patients -- those with are already HIV positive when they contract HCV -- may experience very aggressive liver disease progression. Daniel Fierer and colleagues from Mt. Sinai in New York City first reported unexpectedly advanced liver disease in a cohort of HIV positive men with short-term HCV infection at the 2007 Conference on Retroviruses and Opportunistic Infection, and later in the September 1, 2008 Journal of Infectious Diseases.

Since then, Fierer's group has continued to describe disease progression in this cohort, on the basis of liver biopsy findings. Other groups, primarily in Europe, have not observed similar rapid progression, but they typically use the non-invasive transient elastometry or Fibroscan method rather than biopsy, which may underestimate liver damage.

At the recent AASLD meeting Fierer and colleagues presented a poster describing 4 cases of rapid liver disease progression in detail. These HIV positive men were initially diagnosed with new HCV infection, defined as ALT elevation with detectable plasma HCV vial load; all had HCV genotype 1a. They went on to experience HCV antibody seroconversion and developed chronic or persistent infection. Three were members of the Mt. Sinai cohort of 14 coinfected patients with persistent detectable HCV for at least 2 years, suggesting that "this phenomenon is not rare," the researchers said. The fourth man was from San Diego.

Patients' ages ranged from 39 to 54 years. CD4 cell counts were 53, 200, 381, and 442 cells/mm3. None of the men reported heavy alcohol use, which can contribute to rapid liver damage.

Most HIV patients diagnosed with acute hepatitis C at Mt. Sinai undergo treatment with pegylated interferon plus ribavirin and achieve sustained virological response, or a cure. Of the 4 cases described here, however, 2 refused treatment, 1 did not tolerate therapy and stopped after 1 dose, and 1 experienced treatment failure. In the real world acute HCV infection is typically not detected during the acute stage, so these cases may reflect what usually happens when HCV infection occurs on top of HIV.

Fibrosis was staged according to the Scheuer system, with 0 indicating absent fibrosis and 4 indicating cirrhosis. Three of the described patients had stage 3 fibrosis when first biopsied and progressed to stage 4 by the second biopsy; the remaining man had stage 2 fibrosis at first biopsy and did not receive a second test. All 4 men progressed to decompensated cirrhosis within 14 months to 6.5 years after ALT elevation was first detected; among HCV monoinfected individuals, in contrast, this degree of liver disease progression typically takes decades.

Decompensation means the liver can no longer carry out its normal functions. Impaired blood flow through the increasingly damaged organ can cause portal hypertension, or increased pressure in the portal vein, leading to symptoms such as bleeding varicose veins in the esophagus and ascites, or accumulation of fluid in the abdomen.

None of the 4 men had nodular regenerative hyperplasia or hepatoportal sclerosis (2 other possible causes of portal hypertension in the absent of significant fibrosis); 2 had mild-to-moderate steatohepatitis, or fat accumulation in the liver along with inflammation. The researchers said the patients did not have pathology suggesting liver toxicity from antiretroviral drugs such as stavudine (d4T, Zerit) or didanosine (ddI, Videx). Serial imaging showed progression from mildly abnormal livers to small nodular livers in all patients.

The 4 patients continued to experience rapid clinical disease progression after developing decompensated cirrhosis. One man underwent liver transplantation 2 years after initial HCV diagnosis, another was still alive but with persistent ascites after 6.5 years, and 2 died of liver failure at 2.75 and 7 years.

These 4 cases show that "early onset fibrosis after HCV infection of HIV-infected men is not benign, does not spontaneously resolve, and can quickly progress to cirrhosis, liver failure, and death," the researchers concluded.

Progression may be more rapid in people with AIDS (CD4 cell count < 200 cells/mm3), "but even those with well-controlled HIV infection progress far more rapidly than expected," they added. "It is therefore essential to identify, treat, and cure all HIV-infected men with new HCV infection to prevent these dire outcomes."

Investigator affiliations: Departments of Medicine and Pathology, Mount Sinai School of Medicine, New York, NY; Weill Cornell Medical College, New York, NY; St. Vincent's Medical Center, New York, NY; University of California, San Diego, CA; VA Medical Center, San Diego, CA.

11/9/10

Reference
D Fierer, D Dieterich, MI Fiel, and others. Rapid Progression to Decompensated Cirrhosis and Death in HIV-infected Men with Newly-acquired HCV Infection. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 879.


 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



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