HCV /HIV Nonresponders Experience Improved Disease Progression
study abstract: IMPACT OF INF TREATMENT IN THE LIVER ACTIVITY AND FIBROSIS IN
COINFECTED HCV/HIV THAT ARE NON-RESPONDERS PATIENTS.
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.