The current study revealed higher serum I-FABP level detected in the HCV/HIV co-infected patients than HCV mono-infected patients. Previous studies noticed the same results [6&16]. This could be explained by the additive effect of both viruses on intestinal mucosal damage. This also was explained by mucosal CD + 4 T cell depletion due to HIV infection or may be due to more liver disease progression in co-infected patients [6, 16&17].
In our HCV mono-infected group, the serum I-FABP level was higher than the reference range of the kits but not significantly higher than healthy control participants. Our results agree with previous similar study by Wurcel where mean I-FABP level was 294 pg/ml and 386 pg/ml in HCV patients and control group, respectively and the difference was not statistically significant [16]. In contrary, Reid et al. found significant elevation of the serum I-FABP level in HCV mono-infected patients compared with control group. This may be explained by the difference in the study population, as the latter study included, cirrhotic patients and we excluded cirrhotic patients in our study as elevated I-FABP level may be related to enterocytes damage and microbial translocation that is known to occur in liver cirrhosis [18].
In our exploratory analysis, baseline FIB4 score was positively correlated with the post-treatment serum I-FABP levels in HCV/HIV co-infected patients. This positive correlation suggests a relationship between increased I-FABP and increased liver disease severity. Similar results were confirmed by previous studies Wurcel and French et al., [16&17].
Another potential explanation for the observed statistical correlation between I-FABP in HCV/HIV co-infection and FIB4 score is the effect of anti-retroviral therapy (ART) on the liver in this group. Recent ART-related clinical syndromes such as NAFLD and non-cirrhotic portal hypertension have increased in patients on ART and observational studies propose long-term ART-related hepatic injury [19].
Significant improvement of the elevation of serum transaminases and improvement of platelet count in HCV/HIV co-infected patients after HCV eradication that was noted in our study is in concordance with the study by Brochado-Kith et al., who concluded that at the end of follow-up after all-oral DAA therapy, HCV/HIV-coinfected patients exhibited a significant decrease (q-value < 0.05) in AST and ALT and substantial increase in plateletscount was observed [20].
Regarding improvement of hepatic fibrosis in HCV/HIV co-infected patients after HCV treatment with DAAs, the significant improvement in the FIB4 and APRI scores could be explained by the amelioration of HCV-induced necro-inflammation and fibrosis [21&22&23]. However, this improvement was not reflected on the results of transient Elastography and steatosis measured by CAP. This may be due to confounding effects of ART that may induce hepatic steatosis that consequently affects stiffness and steatosis measurements.
I-FABP level was significantly higher after HCV treatment in HCV/HIV co-infected patients. This may imply that HCV eradication on the liver has potential advantages on the liver (improvement in platelets count, albumin, serum transaminases levels and hepatic fibrosis), but the enterocyte permeability may persist or even worsen after HCV eradication. Studies have found that despite achieving SVR in HCV infected patients monocyte activation (part of systemic inflammation caused by bacterial translocation) may persist [24&25].
Our results are contrary to Medrano et al who found no significant change in I-FABP after HCV treatment (p value = 0.29). This difference may be due to choosing patients with advanced cirrhosis (LSM ≥ 25 kPa, or HVPG ≥ 10 mmHg, or CTP ≥ 7, or prior history of liver decompensation) which may affect baseline I-FABP level in contrast to our patients who were non cirrhotic [8].