years or decades, people with chronic
hepatitis C can develop advanced liver disease including
cirrhosis and liver
cancer. Cirrhosis is characterized by blockage of the flow
of blood through the heavily scarred liver, leading to symptoms
such as bleeding varicose veins in the stomach and esophagus,
abdominal fluid accumulation, and cognitive impairment due to
new study adds to the evidence showing that sustained response
to interferon-based antiviral
therapy can improve liver health and prevent development or
worsening of cirrhosis and its associated conditions, in this
case esophageal varices. None of the 34 participants (out of
an initial group of more than 200) who were treated for hepatitis
C and achieved SVR developed new varices, compared with 32%
of untreated patients and 39% of those who underwent treatment
but did not achieve sustained response.
varices are enlarged veins in the lower esophagus.
They're often due to obstructed blood flow through
the portal vein, which carries blood from the intestine
and spleen to the liver.
following is the text of a media advisory from Wiley-Blackwell,
publisher of Hepatology, describing the study and it's
Therapy Impacts Esophageal Varices in HCV-Induced Cirrhosis
Shows Sustained Virologic Response Prevents EV
Italian researchers have discovered that antiviral treatment
and sustained virologic response (SVR) prevents esophageal varices
in patients with compensated hepatitis C (HCV)-induced cirrhosis,
indicating that endoscopic surveillance can be safely delayed
or avoided in these patients. Full findings are published in
the June issue of Hepatology, a journal of the American
Association for the Study of Liver Diseases (AASLD).
According to the National Digestive Diseases Information Clearinghouse
(NDDIC), an estimated 4.1 million Americans have antibody to
HCV (anti-HCV), indicating ongoing or previous infection with
the virus. Researchers estimate that at least 20% of patients
with chronic HCV develop cirrhosis. Progression of cirrhosis
leads to portal hypertension, which can result in esophageal
varices (EV) and other complications.
EVs are abnormally enlarged veins in the esophagus that occur
when portal hypertension obstructs normal blood flow to the
liver, causing blood to back up into the esophageal vessels.
Esophageal varices can rupture which can be life-threatening.
The onset of EV marks a crucial turning point in the outcome
of cirrhosis. The research team led by Savino Burno, MD, set
out to determine whether antiviral treatment resulting in SVR
could prevent this condition.
The study, spanning from January 1989 to December 1992, evaluated
218 patients less than 70 years of age with compensated Child-Pugh
class A cirrhosis who presented at three referral centers in
Milan and tested positive for serum anti-HCV. Only subjects
who agreed to undergo upper endoscopy at the time of enrolment
and who were found to be EV-free were included. All 218 subjects
had regular follow up with surveillance ultrasound for hepatocellular
carcinoma (HCC) every six months and endoscopy every three years
to identify de novo varices.
The standard antiviral regimens of recombinant alpha IFN monotherapy
or combination with both IFN and ribavirin were administered,
regardless HCV genotype, for at least six months and for an
additional six-month period in patients who achieved a complete
biochemical response. Combination therapy with IFN or pegylated
IFN and ribavirin was administered in agreement with guidelines.
SVR was defined as undetectable serum HCV RNA (< 50 IU/mL)
six months after stopping therapy.
The primary endpoints were development of de novo varies or
HCC. Of the 218 patients, 149 (68%) received HCV therapy and
34 (23%) achieved SVR and no EVs. During the follow-up of median
11.4 years, de novo EVs were detected equally among untreated
and treated patients who did not achieve SVR. Sixty-seven patients,
7 of whom achieved SVR, developed HCC.
"Our study provides an accurate estimate of the 10-year
cumulative incidence of EV in this population of patients,"
stated Dr. Bruno. "A major finding of our study, of great
importance in clinical practice, is that the achievement of
SVR abolishes the development of EV in the long-term. The reliability
of our result is guaranteed by the ample length of observation
among this group of patients. In routine clinical practice,
serial surveillance by EGD can be safely delayed or avoided
in SVR patients, sparing a significant amount of useless invasive
and costly procedures."
The Milan study is the largest study with the longest follow-up
to date that addresses the impact of SVR on the development
of esophageal varices. In his editorial also published in Hepatology
this month, Dr. Richard Sterling concurs, "If these results
are confirmed, it may not be necessary to subject patients with
HCV-induced cirrhosis to the expense and risks of repeated endoscopies."
He further points out that the current study is the first to
demonstrate a pharmacologic treatment to reduce (or in this
case, eliminate) the development of varices. However, Dr. Sterling
cautions, "Before we get too excited, we must remember
that current treatment to achieve SVR in those with cirrhosis
is difficult and there are often increased side effects, more
cytopenias, and lower response rates than those without cirrhosis.
Therefore, given the cost, both in dollars and resources, the
increased side effects, and decreased response rates of HCV
therapy, it remains to be determined if the "bang is worth
the buck" in this select group of patients."
Investigator affiliations: Department of Internal Medicine,
A.O. Fatebenefratelli e Oftalmico, Milan, Italy; Department
of Internal Medicine, A.O. S. Paolo, Italy; A.O. Sondrio, Italy;
Endoscopy Unit, A.O. S. Gerardo, Monza, Italy; Gastroenterology
and Gastrointestinal Endoscopy Unit, Ospedale Policlinico, Milan,
Italy; Department of Medical Sciences, University of Milan,
Milan, Italy; Gastroenterology and Hepatology Unit, University
of Palermo, Palermo, Italy; Division of Epidemiology and Biostatistics,
European Institute of Oncology, Milan, Italy.
Bruno, A Crosignani, C Facciotto, and others. Sustained virologic
response prevents the development of esophageal varices in compensated,
Child-Pugh class A hepatitis C virus-induced cirrhosis. A 12-year
prospective follow-up study. Hepatology 51(6): 2069-2076
Sterling. Long-term effects of sustained virologic response
on the development of esophageal varices in compensated cirrhosis:
"is the bang worth the buck?" Hepatology 51(6):
1891-1893. June 2010.
Wiley-Blackwell. Antiviral Therapy Impacts Esophageal Varices
in HCV-Induced Cirrhosis. Press release. May 25, 2010.