icon-folder.gif   Conference Reports for NATAP  
 
  AASLD (American Association for the Study of Liver Diseases)
 
Nov 2-5, 2002, Boston, MA
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Treating Patients with Decompensated Cirrhosis: 20% sustained response rate
 
Reported by Jules Levin
 
  Greg Everson (University of Colorado at Denver, Section of Hepatology) reported at the AASLD liver conference in November 2002 on treating patients with chronic hepatitis C and decompensated liver cirrhosis with what he calls LADR: low accelerating dose regimen.
 
Everson said there are two main reasons to treat patients with decompensated liver cirrhosis:
 
--to stop or reverse disease progression
 
--to prevent post-transplant recurrence of hepatitis C
 
The aims of this study are to determine the effectiveness of interferon alfa-2b plus ribavirin in patients with advanced liver disease-(1) to see the percent of patients with HCV-RNA negative viral load, (2) to define factors predictive of clearance of HCV-RNA, (3) to determine the rate of recurrence of HCV in liver transplant recipients.
 
Here is the summary by Everson and the data results from the study are below. Clerance of HCV RNA occurred in 40% by the end of treatment and 20% had a sustained viral response. SVR was more common in genotype non-1 and for patients able to achieve a full dose for >6 months. Response in the short-term did not affect rate of transplantation, HCC (cancer), and death. But the most important finding in this study was that no patient with HCV RNA clearance who underwent transplant experienced post-transplant relapse (recurrence of HCV RNA). There were 28% dropouts by patients; 8% experienced complications; GCSF was required in 28% and EPO in 4% of patients. Everson concluded treatment of early to moderately decompensated cirrhotics with non-1 genotype is effective. Response in genotype 1 patients is linked to ability to achieve adequate dose and duration of treatment. Additional strategies are needed for genotype 1. Liver transplant recipients may achieve greatest benefit due to reduction in risk of post-transplant recurrence. LADR may be particularly suited for LDLT where determination of time of transplantation is possible. Everson went on to say that he thought effectiveness, particularly for genotype 1 patients, could be improved by use of pegylated interferon, althoigh cytopenias may be a problem. The long-term effect of clearance of HCV RNA will be to reduce disease progression; and improve hepatic function which might avoid liver transplant, For those who have liver transplant he thinks this approach of LADR can prolong survival after transplantation.
 
102 patients were enrolled--
 
age: 37 to 71 yrs
EtOH: 50%
Genotype 1: 77%
Biopsy proven or clinical cirrhosis: 87%
Bridging fibrosis (stage 3): 13%
Platelet count <50K: baseline 5%, on treatment 36%
 
COMPLICATIONS
 
Variceal hemorrhage: 22%
Ascites: 45%
SBP: 6%
Encepholopathy: 37%
Patients with 1 or more complications: 66%
66% of patients with EGD (38/59) had varices
CHILDS-TURCOTTE-PUGH CLASS
 
The mean CTP score was 7.12.0. About 50% were Class A, Class B 30%, Class C 20%.
 
LADR PROTOCOL
 
--initially: IFN-a-2b 1.5 MU 3x/week plus ribavirin 600 mg/day
--2 weeks: increase IFN-2b to 3 MU 3x/week
--4 weeks: increase ribavirin by 200 mg/day, weekly
--CBC and Biochemistry q 2 weeks
--HCV RNA q 3 months
GOAL: 3 MU IFN with 1.0 to 1.2 g/day RBV
 
RESULTS
 
--6 patients dropped out of study very early
--40 patients had negative viral load at the end-of-treatment
--56 were non-responders
--of the 40 pts who were HCV-RNA negative 21 had an SVR (sustained viral response) and 19 had a relapse
--of the 56 non-responders 38 were virologic non-responders, 16 were discontinued from treatment due to adverse events, and 2 had a liver transplant early on in the treatment.
 
Definition of SVR: classic definition--HCV-RNA negative with 6 months or more post-treatment follow-up, but this includes 3 patients who were on treatment at the time of liver transplant; one of these 3 patients was an individual who stopped treatment early in the course, was RNA negative, relapsed and was put back on treatment, and then was transplanted.
 
Rate of Clearance of RNA
 
--End of Treatment Response: 40/102 (39%) or 40/96 (42%)
 
--Sustained Response: 21/102 (21%) or 21/96 (22%)
 
Characteristics of Responders
which includes end-of treatment responders, ie SVRs and relapsers
 
Decompensation did not appear to be a factor as 64% of responders were decompensated vs 56% of non-responders. Similarly, the Childs-Pugh distribution was similar between sustained responders, non-responders and relapsers. Suggesting that patients having more advanced liver disease could respond as well.
 
Everson reported the two key factors he found to be important were genotype and the ability to achieve a full dose by 6 months on treatment. Genotype 1 patients were less likely to respond: 52% of responders were genotype 1 vs 88% of the non-responders were genotype 1. The ability to achieve full dose was important, particularly in genotype 1 patients. Patients who were able to achieve a full dose for >month 6 were more likely to respond and perhaps also for those who could achieve this for 3-6 months: 48% of responders got to full dose while only 30% of non-responders were able to achieve a full dose. 28% of responders had an inadequate dose while 52% of non-responders had an inadequate dose.
 
 
 
  COMPLICATIONS and USE of GROWTH FACTOR
 
--4 patients experienced encepholopathy. 3 of these patients experienced encepholopathy in the setting of infection: staph skin abscess with septicemia, E coli sepsis, multilobar pneumonia requiring mechanical ventilation.
 
--3 patients suffered gastrointestinal bleeding: 2 for varisces and 1 for Mallory-Weiss.
 
--no patient died while on treatment. 1 death occurred about 3 weeks after discontinuing treatment for side effects.
 
Growth factors: GCSF used in 28% and erythropoetin (EPO, Procrit) in 4%.
 
RESULTS OF FOLLOW-UP (Short Term), relative to treatment response
 
In the short term this intervention did not affect rates of transplant, liver cancer (HCC), or death as reflected in this table.
 
 
 
  RESULTS WITH LIVER TRANSPLANTATION
 
The important benefits of this intervention is to those who ultimately undergo liver transplantation. Of the 32 patients that had liver tranplantation. All 22 patients who were HCV RNA positive before liver transplantation remained HCV RNA positive after the transplant, about 70% had post-transplant HCV recurrence after transplant.
 
10 patients who were HCV RNA negative before transplant and remained HCV RNA negative post transplant. 9 of these 10 patients have been followed for for greater than 6 months and all remain RNA negative. The one patient who did not achieve the 6 month follow-up being negative died early post-transplant from complications of the transplant.