Editorial: microbial translocation and immune activation profiling during treatment of chronic HCV

The hypothesis that microbial translocation (MT) is a key mechanism of systemic immune activation and a potential pathway leading to disease progression, was originally proposed by Brenchley et  al in 20061 in a study about the HIV pathogenesis. In recent years, accumulating evidence confirmed the key role of MT and immune activation in HIV disease.2, 3

Regarding chronic hepatitis C virus (HCV) infection, the link between chronic inflammation and liver fibrosis and MT remains poorly known. Specifically, data regarding the role of MT in patients with chronic hepatitis or cirrhosis related to HCV infection, either during or after HCV clearance, are still lacking. Lattanzi et  al have used an elegant approach to uncover an important link between direct-acting antiviral (DAA) treatment and its impact on MT and immune activation.4 The objective of the study was to evaluate the MT and immune activation changes during treatment of chronic HCV in a cohort of patients with advanced fibrosis (F3-F4) (Group ≥F3) and patients with HCV recurrence after liver transplantation (LT) and fibrosis ≥F2 (Group LT + ≥F2). In order to understand correctly the markers trend, a cohort of healthy individuals was included. The authors studied different MT markers such as LPS, LPB, sCD14, and I-FABP; in order to explore the immune activation profile, also T-cell activation markers such as CD38+HLADR+expression on CD4+ and CD8+ T cells were studied.

The markers’ profiling was ensured, thanks to four measurement time points: before the start of treatment, at first month, at the end of treatment, and at 12 weeks after the end of treatment. At baseline, MT markers were significantly higher in HCV-infected patients than in healthy subjects; moreover, sCD14 levels in both groups significantly correlated with I-FABP (r = 0.342; P = 0.01) and LBP (r = 0.430; P = 0.001).

Moreover, DAA treatments seemed to induce a significant decrease in studied markers; specifically, a significant decrease in CD38 + HLADR + expression on T lymphocytes in patients in Group ≥ F3 was reported.

Interestingly, no correlation was found between sCD14 and liver stiffness (kPa) (P = 0.876) and these results were similar to those of Sacchi et al suggesting that MT markers were increased in HIV/HCV coinfection, although they were not correlated with the extent of fibrosis.5 However, these findings contradicted the results of Sandler et  al, who found that sCD14 plasma levels were associated with cirrhosis and could predict progression to end-stage liver disease.6

Moreover, an association of MT and fibrosis was not found also in case of portal hypertension (the presence of oesophageal varices in 41% of patients) in the Lattanzi's study.4 The authors inferred that it was due to the mild degree of portal hypertension in the cohort, of which only 15% had varices ≥ F2.

Anyway, despite MT markers and T-cell activation were increased in hepatitis C patients with liver fibrosis and decrease during DAA treatment, their correlation to liver fibrosis remains to be established.