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