Discussion
In many liver diseases such as hepatitis B and autoimmune hepatitis,
when the cause is effectively treated, regression of cirrhosis has been
observed.22-25 In the case of hepatitis C, in the
interferon- era, several studies observed liver fibrosis regression in a
significant number of HCV-infected cirrhotic patients
(30-56%).26,27 With the emergence of DAAs in recent
years, there has been growing evidence of a similar effect of this
pharmaceutical class. To our knowledge, this study is the first
investigation in middle-east region in this regard.
Almost all studies comparing liver fibrosis before and after DAA
treatment, have shown a significant decrease in fibrosis score,
regardless of the baseline characteristics or treatment regimen. In a
study by Tada et al, the effect of dual DAA therapy with daclatasvir and
asunaprevir on liver stiffness of all HCV-infected patients who achieved
SVR (both cirrhotic and non-cirrhotic), was assessed by shear wave
elastography at baseline, EOT, and six months after the EOT and they
reported a significant decrease in the post-treatment LS
values.28 Another Japanese study with the same regimen
and a follow-up period of 72 weeks, indicated a significant, gradual and
steady decline in LS values.29 Another study from
Egypt with sofosbuvir-based therapies also supported the same
results.30 Our findings are in agreement with previous
studies too.
We evaluated the association of demographic factors, HCV
characteristics, any prior treatment experience, as well as, baseline
liver fibrosis status with changes in LS in patients achieving SVR.
Based on our results, higher baseline scores of liver fibrosis was
independently associated with better improvement of LS values after DAA
therapy. Comparing the results of previously published studies
estimating the predictors of LS regression after DAA therapy,
the advanced baseline liver
fibrosis stage was the most pronounced factor.28,31-33Previous studies on Pegylated interferon and ribavirin demonstrated
several factors to be significantly associated with improvement in LS
values, such as baseline fibrosis stage, BMI, age, viral load, and
genotype1.34,35 However, our results as well as
earlier data from Japanese patients indicated that the regression of
liver fibrosis after DAA therapy is more probably influenced by baseline
LS scores.28 Additionally, low platelet, high serum
angiopoietin‐2, low ALT, diabetes, and esophageal varices were of other
proposed factors to have an inverse association with significant LS
reduction.36-38 The effects of these predictive
factors need to be further evaluated in larger populations with longer
follow-up.
The severity of liver steatosis, represented as CAP value, improved in
half of our patients. However, the improvement did not achieve
statistical significance. The observed difference was meaningful when
the analysis was limited to patients with CAP value ≥ 220 dB/m, an
optimal cut-off point associated with hepatic steatosis decline after
HCV eradication suggested by a recently published study from Japan in
which patients with higher baseline CAP value experienced significant
decline six months after HCV eradication.39 These
findings are also supported by two other studies conducted in
Japan.40,41 The higher the baseline CAP value, the
greater the therapeutic effect appears to be. As explained in a study by
Powell et al, this is mostly because of “burn out” phenomenon, in
which hepatic steatosis might already have been replaced by fibrosis.
It seems that lipids play a pivotal role in HCV life
cycle.42 That is why HCV infection might induce
hepatic steatosis. Animal studies have explained that the HCV core
protein inhibits the microsomal triglyceride transfer protein activity
and very low density lipoprotein secretion in
hepatocytes.43 The other molecular mechanism
underlying this phenomenon is that HCV upregulates the secretion of
sterol-regulatory element binding proteins (SREBPs), resulting in
increased uptake of lipoprotein particles by infected
cells.44 These mechanisms support our findings that
HCV eradication could lessen the severity of hepatic steatosis.
Considering the substantial amount of liver steatosis as an independent
risk factor for HCC development, long-term careful monitoring of
patients with post-eradication hepatic steatosis is
crucial.45,46