1 log HCV Viral Load Reduction May Improve Liver

Report from Dallas Liver Meeting, 50th Annual AASLD Meeting (American Association for Study of Liver Diseases), Nov 5-9

Report Nine from Dallas - 1 log HCV Viral Load Reduction May Improve Liver
Jules Levin, NATAP

In light of recent internet talks about the utility of maintenance therapy for HCV, this following report should be of interest. Table at end of article shows improved histology by log viral load reductions.

HCV Viral Load Reductions of1 log or Greater or Reducing Viral Load to Below 1000 copies/ml Shows Histologic Improvement. Achieving Sustained Virologic Response May Not Be Necessary to Improve Liver. And Continued Maintenance Therapy May be Beneficial

summary: The following study finds that liver condition (histology) can improve even if a person does not experience a sustained virologic response. This study finds individuals with 1 log or greater decline in HCV viral load due to IFN or IFN/RBV experience an improvement in the condition of their liver. The improvement increases with each 1 log greater reduction. So individuals with 2 log reduction experience more improvement than those seeing 1 log reduction. 25-33% of patients in this study who did not experience virologic sustained response but had above 1 log reduction in HCV RNA had an improved histology observed. As well, fibrosis did not improve for those with <1 log unit drop in HCV-RNA level but did improve in those pts whose HCV-RNA level had fallen to <1,000 copies/ml by the EOT.

The authors said monitoring HCV viral load and histology during therapy may identify those who would benefit from maintenance therapy.

A DECLINE IN HCV-RNA LEVEL DURING INTERFERON OR INTERFERON/RIBAVIRIN THERAPY IN PATIENTS WITH VIROLOGIC NON-RESPONSE IS ASSOCIATED WITH AN IMPROVEMENT IN HEPATIC HISTOLOGY
abstract 567

Mitchell L Shiffman, Med Coll of Virginia Commonwealth Univ, Richmond, VA; Karen L Lindsay, Univ of Southern CA, Los Angeles, CA; Joann Harvey, Janice K Albrecht, Schering-Plough Res Institute, Kenilworth, N

Interferon (IFN) with or without ribavirin (RBV) is the primary therapy for treatment of chronic HCV. Sustained virologic response (SVR) to these therapies is associated with an improvement in hepatic histology. Histologic improvement has also been recognized in many pts with virologic non-response (VNR). The goals of this study were to determine if histologic improvement in pts with VNR was associated with a decline in HCV-RNA level and if these changes occurred in both IFN and IFN/RBV treated pts. Methods: Data were obtained from the recent IFN vs IFN/RBV US and international registration trials (Schering-Plough) in which pts with chronic HCV were treated with either IFN-a-2b alone (3 mU TIW) or IFN-a-2b plus RBV (1000-1200 mg daily) for 24 or 48 wks and then followed for an additional 24 wks (EOF). HCV-RNA level was assessed by quantitative PCR (NGI: lower limit 100 copies/ml). Liver biopsy (LBX) was performed at baseline and at EOF (24 wks off treatment). Paired LBX were scored in blinded fashion according to criteria of Knodell (HAI) and reported as a hepatic inflammation score (HIS: the sum of PMN + lobular + portal inflammation) and fibrosis (FI).

Results: Paired LBX were available from 1040 pts. At baseline, those pts treated with IFN and IFN/RBV were well matched for age (42 yrs), sex (66% male), race (92% Caucasian), genotype (66% type 1), HCV-RNA level (2.5 x 106 copies/ml) and HAI (7.12). Of 432 pts treated with IFN 68 (16%) had SVR and 100 (23%) relapsed (REL). Changes in HIS and FI in these pts were -4.87 and -0.19 for SVR and -0.37 and 0.11 for REL (negative value=improvement in LBX between baseline and EOF). Of 608 pts treated with IFN/RBV, 289 (48%) had SVR and 122 (20%) REL. Changes in HIS and FI were -4.46 and -0.24 for SVR; -1.77 and 0.02 for REL. For pts with VNR a stepwise decline in HIS was observed for each log drop in HCV-RNA level from baseline to EOT (TABLE). A similar stepwise decline in HIS was observed when data were grouped according to the absolute EOT HCV-RNA level from 1,000,000 to <10,000 copies/ml. FI score increased by a mean of 0.08 in pts with <1 log unit drop in HCV-RNA level but declined by -0.07 in those pts whose HCV-RNA level had fallen to <1,000 copies/ml by the EOT. These changes were observed in pts treated with either IFN or IFN/RBV.

Conclusions: 25-33% of pts with VNR have a 1 log unit drop in HCV-RNA level during IFN or IFN/RBV therapy. An improvement in hepatic histology can be observed in these pts. This improvement appears to be a function of the decline in HCV-RNA titer and occurs in pts treated with either IFN or IFN/RBV. Monitoring HCV-RNA levels and assessing histologic change during therapy could identify that subgroup of pts with VNR experiencing histologic improvement in whom maintenance IFN therapy may be of benefit. (Supported by the Schering-Plough Research Institute).

Although not clearly identified it appears the numbers below represent the decline in hepatic inflammation score (HIS: the sum of PMN + lobular + portal inflammation) as discussed in body of abstract above.