A majority of people
with chronic hepatitis C and advanced fibrosis or cirrhosis showed improvement
in liver health following treatment, according to study findings presented last week at the 2015 AASLD Liver Meeting in San
Francisco, USA. However, the researchers identified few demographic,
laboratory or disease-related factors that could predict who would experience fibrosis
regression and who would have worsening liver damage.
Over years or
decades, chronic hepatitis C virus (HCV) infection can lead to advanced liver
disease including cirrhosis, liver cancer and liver failure requiring a
Prior studies have
shown that treatment with interferon-based therapy for hepatitis C, as well as
tenofovir (Viread) for hepatitis B,
can lead to some reversal of fibrosis and reduced risk of hepatocellular carcinoma and liver-related
death. Direct-acting antiviral agents used in interferon-free
regimens can now cure upwards of 90% of people with hepatitis C, but it is not
yet known how treatment response will be reflected in long-term clinical
A protein made in the liver, needed to maintain a balance of the fluids in the body. In a blood test, lower than normal levels of albumin and total protein may indicate liver damage or disease. If there is not enough albumin, fluid may accumulate in the abdomen (ascites).
A non-invasive test, used instead of a biopsy, to measure the stiffness
or elasticity of the liver using an ultrasound probe.
Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.
Stretched veins which may burst and cause severe bleeding; a complication of cirrhosis.
Ana Maria Crissien of the
Scripps Clinic in La Jolla, California, and colleagues looked at the
association between sustained virological response at 12 weeks post-treatment
(SVR12) – recognised as a cure – and regression of advanced fibrosis or cirrhosis as
determined by FibroScan elastography
imaging. Long-term follow-up will assess changes in the risk of hepatocellular
carcinoma and the need for ongoing liver cancer screening.
Liver biopsy has traditionally been considered the
'gold standard' for determining the extent of liver fibrosis, but clinicians
are increasingly using less expensive non-invasive imaging methods and
biomarker indexes. Elastography uses shear waves to assess liver elasticity or 'stiffness'.
Higher liver stiffness scores (measured in kiloPascals or kPa) are associated
with more advanced liver damage; a score below 6.0 kPa suggests absence of
fibrosis while a score above 14.0 kPa indicates cirrhosis.
The researchers conducted a retrospective chart review
of data from people with chronic hepatitis C and advanced fibrosis or cirrhosis
(according to clinical features, FibroScan
or biopsies) who achieved sustained
virological response to treatment. This was followed by prospective FibroScan and clinical assessments at
six-month intervals after SVR.
Of the 224 patients at Scripps who were eligible for the
study, the present analysis included 100 people, of whom 35 had advanced
fibrosis and 65 had cirrhosis at baseline. Of the remainder, 110 were still
awaiting analysis, three declined to participate and 11 were excluded (one due
to transplantation and 10 due to additional causes of liver disease such as
hepatitis B or heavy alcohol use).
About 65% of patients in the present analysis were
men, most were white and the mean age was about 59 years. Most had HCV
genotypes 1a or 1b. The most commonly used treatment was the first-generation
HCV protease inhibitor telaprevir (Incivo
or Incivek) plus pegylated
interferon/ribavirin, followed by sofosbuvir (Sovaldi) plus simeprevir (Olysio),
pegylated interferon/ribavirin alone, sofosbuvir/ledipasvir (Harvoni), and sofosbuvir plus pegylated
interferon/ribavirin; overall, 45% used regimens containing sofosbuvir
Among the 35 participants who had advanced fibrosis at
baseline, 69% demonstrated improvement according to FibroScan, 14% remained unchanged and 17% worsened to cirrhosis. Among
the 65 people with cirrhosis at baseline, 55% showed improvement and 45%
remained unchanged. Taken together, 60% improved, 34% had no change and 6%
Median time to improvement was 2.5 years for people
with advanced fibrosis and 3.0 years for those with cirrhosis at baseline,
indicating that those with less severe liver injury improved faster.
The researchers identified few factors that predicted
fibrosis improvement or worsening. There were no significant associations with
patient sex, age, race/ethnicity, obesity, most medical conditions or most
complications of cirrhosis. However, diabetes and varices (enlarged veins in
the stomach or oesophagus) were associated with a lower likelihood of fibrosis
Most laboratory tests including albumin and platelet counts
showed no association with changes in fibrosis. Fibrosis improvement was
significantly associated with changes in ALT and AST liver enzyme levels and APRI
(AST-to-platelet ratio index) scores, but patient numbers were small and the
clinical relevance of this is unclear.
In a sub-analysis of six people with HCV genotype 3 –
which is associated with more aggressive liver disease – all but one (83%)
showed improvement by at least one fibrosis stage. Among the five people who
had developed hepatocellular carcinoma by the end of follow-up, two had
improved fibrosis, two remained unchanged and one worsened.
In summary, this study showed an
"overall 60% improvement in subjects with baseline cirrhosis or advanced
fibrosis after achieving SVR based on FibroScan,"
the researchers concluded, suggesting that APRI might be used to predict
regression in people with advanced fibrosis.