Snapshots —Alan Franciscus, Editor-in-Chief

Read about fast rate of fibrosis progression after seroconversion, compassionate use of sofosbuvir for post-transplant, and transplant delisting after being cured of HCV.

Abstract: Liver Fibrosis Progression in Hepatitis C Virus Infection After Seroconversion—A Butt et al.
  Source: JAMA Intern Med.2015;175(2):178-185.  doi:10.1001/jamainternmed.2014.6502

The current study analyzed electronic records from the Veterans Administration between 2002 and 2012.  Among the 610,514 records 1,840 patients were found to be HCV positive, and the HCV negative patients were matched for age, race and sex.  People with HIV, HBV, with less than 24 months of follow-up, liver cancer or cirrhosis were excluded from the analysis.  The HCV patients in the study had an initial HCV negative antibody test, but later tested positive for an HCV antibody test and a positive HCV viral load indicating active HCV infections.  The control group had 2 HCV negative antibody tests indicating HCV negative status.

Fibrosis scarring was found to start early after initial infection—452 patients developed cirrhosis, and 85 patients developed decompensated cirrhosis (end-stage liver disease). 

After 10 years of follow-up—18.4% of the HCV patients developed cirrhosis vs. 6.1% of the patients without hepatitis C.  Nine years after diagnosis of hepatitis C, 1.79% developed decompensated cirrhosis vs. 0.33% in the group without hepatitis C.

One very interesting finding was that white race was associated with a 51% increased risk of developing cirrhosis.
Editorial Comments:  This is the first study (to my knowledge) that has shown a fibrosis progression after initial infection.  It should also wake us up to the need for treatment soon after exposure or immediately after the onset of chronic infection to prevent any damage to the liver.

Abstract: Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C following liver transplantation—X. Forns et al.
  Source: Hepatology.  2014 Dec 29. doi: 10.1002/hep.27681. [Epub ahead of print]

Hepatitis C resides in the liver and blood.  As a consequence, if someone receives a transplant the new liver is always re-infected with the hepatitis C virus.  Due to many factors including the use of immunosuppressant drugs (to prevent rejection of the organ by the body) the virus multiplies out of control.  Many times (but not always) there is severe and quick disease progression.  Unless there is another donated liver available, the person may face death. 

Compassionate use is a program that allows the use of drugs untested in a particular population, i.e., post-transplant patients, which may help save lives when there are no other available options.  In this case sofosbuvir and ribavirin was given for 24 to 48 weeks to people who had severe recurrent HCV disease after a liver transplant.  The patients in the study were expected to live less than a year.  The decision to add pegylated interferon was left up to the judgment of the treating physician.  

At the time of the analysis (January 1, 2014) there were 92 patients assessed, 54 (59%) patients achieved SVR12 (virologic cure).  Those with early recurrent hepatitis C were more likely to achieve SVR12 (73%) than those with cirrhosis (43%).  More than half of the patients who achieved a cure had clinical improvement, more than a fifth were unchanged and only 3% of the patients were worse.  Eighteen percent of patients had serious adverse events (side effects).
Editorial comments:  These results are excellent for patients who are very difficult to treat.  The 73% cure rate of those who were treated early on after recurrent hepatitis C means that everyone with hepatitis C at the time of transplant should be treated as soon as it is safe.  However, we should not have to wait—treat well before the need for a transplant, and no one with hepatitis C should ever have to face this potentially life-threatening (and expensive) transplant procedure again.

Article: Letter from the Frontline: Patient with decompensated hepatitis C virus–related cirrhosis delisted for liver transplantation after successful sofosbuvir-based treatment—I Ruiz et al.
  Source:  Liver Transplantation Volume 21, Issue 3, pages 408–409, March 2015

This was a case study of one patient who was listed for a liver transplant in October 2013. The patient was a 67-year-old woman with HCV genotype 4 and decompensated cirrhosis.  She was treatment experienced (null responder) to pegylated interferon plus ribavirin and had weekly paracentesis (she had to have fluid drained from her abdominal cavity due to ascites), and moderate encephalopathy (brain disorder caused by the build-up of ammonia and toxins in the brain) that required several hospitalizations.

Treatment consisted of sofosbuvir plus ribavirin for 24 weeks.  After 8 weeks, of treatment the woman’s viral load was undetectable.  The treatment was well tolerated.  The patient achieved a cure and her encephalopathy, ascites and liver disease improved to the point that she was taken off the transplant list. 

The authors commented that (to their knowledge) this is a first—a patient with hepatitis C related decompensated cirrhosis was delisted from the transplant list.   
Editorial comment:  In the past interferon and ribavirin was given but was poorly tolerated for people with end-stage liver disease.  In fact, treatment with interferon and ribavirin could lead to more severe disease progression and death. 

The two studies above provide proof that all-oral therapy provides safe and effective treatment.  Now, we just need to provide treatment to everyone with hepatitis C so that no one has to suffer from end-stage liver disease and the need for a liver transplant.