icon-folder.gif   Conference Reports for NATAP  
  DDW Liver Conference
San Francisco, May 19-22, 2002
Back grey_arrow_rt.gif
HCV /HIV Nonresponders Experience Improved Disease Progression
Maribel Rodriguez-Torres, Jose F. Rodriguez-Orengo, Carlos F. Rios-Bedoya, Elba Alicea-Bonilla, Santurce, PR; Rio Piedras, PR; Ponce, PR
editorial note: This study found an important result. As we know, some patients with HCV or HCV/HIV will not achieve the desired viral load response (undetectable or a clear reduction in viral load). What this study found was that HCV/HIV coinfected patients who do not achieve a viral load response to HCV therapy (nonresponders) were able to achieve an improvement of liver disease. Both fibrosis and inflammation improved despite no response in viral load. These types of benefits have been seen in HCV moninfected patients. This is the first study I know of showing this benefit in HCV/HIV coinfected patients. The study looked at patients with biopsy before and after treatment. This study is small and the results preliminary but they found that (1) the fibrosis progression rate reversed in the patients receiving interferon but not in the patients who did not receive treatment; (2) the study found liver disease activity (necroinflammatory score necroinflammatory progression rate) was reversed. The second biopsy was performed 1.5 years after therapy was stopped suggesting that the benefit can last that long.
This addresses the question --does maintenance therapy help when a patient does not achieve a viral load response? This is a controversial issue. There have been numerous studies that found interferon can improve liver disease and slow or prevent progression of disease and cancer. However, these studies have not conclusively proven that maintenance therapy actually slows or prevents disease progression and achieves clinical benefit. The HALT-C study is being conducted by the NIH to look at this question but results will not be available for several years. Smaller studies are ongoing or in planning stage to look at this question. In the meantime, patients have to make treatment decisions. A patient with cirrhosis who does not achieve a viral load response will have to consider maintenance therapy. The evidence so far accumulated suggests maintenance therapy is helpful. In treating patients, many doctors in fact use maintenace therapy for patients with advanced disease while waiting for more conclusive study results.
Background : HIV/HCV coinfection is associated with higher progression to liver cirrhosis. A significant number of coinfected patients will not achieve SVR with therapy. The effect of INF in the liver histology is unknown.
Methods : We evaluated 28 coinfected patients with pre and post INF Tx. liver biopsies. INF Tx. was given for at least 6 months. Detailed history was assessed: age, gender, risk , alcohol , HIV Tx, and HCV duration. ALT, HIV PCR, HCV PCR, CD4 were also obtained. 23 patients (82%) received INF Tx. Analysis of histology (fibrosis) using Ishak score was performed. Fibrosis score (0-5), necroinflammatory score (0-18), fibrosis progression rate and necroinflamatory progression rate were calculated. Mean duration of INF Tx was 11 Mo (6-22 Mo.). Chi-Square (Fishers p-value) was used for nominal variables. Kruskal Wallis and Mann-Whitney tests were used for continuous variables with the paired biopsies.
Results and Discussion: Most patients were male (83%), with mean age 42.4 years (28-61), HCV Gen 1 (86%), and no significant alcohol ingestion was documented pre and between both biopsies. Most patients (67%), were on HAART. Patient are immunocompetent with a mean CD4 of 473 cells/mm3. The mean HIV PCR is 3.9 log and 33% were HIV PCR non-detectable. Mean HCV PCR was 6.1 log and mean duration HCV disease 18 years (9-42 years). Mean fibrosis score Pre Tx. was 2.79 vs. 3.46 post Tx (p=.02). The necroinflamatory score (NS1) was reduced from the first biopsy with a mean score of 7.96 vs. NS2 of 5.82; (p=0.013). In addition, necroinflamatory progression rate, NPR1 was reversed, between the two biopsies (NPR1) =0.48 vs. NPR2= - 0.59, P=.03). ALT levels did not correlate with activity or fibrosis values at any point. In fact, ALT changes were inversely correlated to necroinflamatory scores at the post Tx. biopsy (P=.04). INF treated vs. non-treated patients analysis show: FPR1 is .146 (N=18) vs .27 (N=5). The FPR2 is .172 and .24 respectively. The difference between the FPR2 and FPR1 is .4685 (N=5) vs -.6468 (N=18) for the IFN treated group. This difference is not significant In conclusion, INF Tx. in coinfected non-responders has a significant beneficial effect in activity. No conclusions can be reached in this population, regarding fibrosis progression, but the data suggests that fibrosis progression can be diminished with IFN Tx. Further follow up of liver histology and additional patients are needed to assess the long-term impact of Treatment.