Letter: factors determining liver fibrosis – more to come (2015)

Jiang and colleagues (published in July 2015) reported a large scale population study from the National Health and Nutrition Examination Survey 1999–2010 which showed that low-fasting triglyceride levels were consistently associated with elevated liver fibrosis indices.1 They adopted the five commonly used, well-validated non-invasive indices of liver fibrosis, namely Fibrosis 4 Score (FIB4), NAFLD Fibrosis Score (NFS), AST-Platelet Ration Index, AST/ALT ratio and BARD score. Whether this observation poses implication on patient prognosis is yet to be defined.2 Apart from important clinical parameters, host genetic factor would be another major area which attracts much attention and research interest. One of the genetic variant under hot discussion recently is sodium–taurocholate cotransporting polypeptide (NTCP), which is encoded by SLC10A1 and a cellular receptor for hepatitis B virus (HBV) in human infection.3 The p.Ser267Phe variant of SLC10A1 (rs2296651) was recently found to be associated with healthy status (with or without evidence of previous exposure to HBV) and lower incidence of acute-on-chronic liver failure in patients with chronic hepatitis B (CHB).4 On the other hand, the role of SLC10A1 variants on the severity and progression of liver fibrosis in CHB patients has not been established in this cross-sectional study.5 We previously reported a cohort of 361 CHB patients with inactive disease, which was defined as negative hepatitis B e antigen (HBeAg), HBV DNA <20 000 IU/mL, normal alanine aminotransferase (ALT) and without advanced fibrosis based on liver stiffness measurement (LSM) by transient elastography.6 Their mean age was 48 ± 11 years, 51% were males, ALT was 28 ± 11 IU/L, HBV DNA was 2.7 ± 1.0 log IU/mL and LSM was 5.4 ± 1.5 kPa. Around 342 patients remained treatment-naïve at an interval of 44 ± 7 months and were genotyped for SLC10A1. The prevalence of wild-type homozygotes (CC) and heterozygotes (CT) was 79.8% and 20.2% respectively. The prevalence of the protective allele (T) was much higher than that (8.1%) reported by Peng et al.5 Patients with the heterozygous SLC10A1 genotype were more likely to have insignificant fibrosis at baseline (LSM ≤5.0 kPa) than the homozygotes (89.9% vs. 62.3%, P < 0.001). They tended to have a lower risk of fibrosis progression during follow-up (1.4% vs. 3.7%), though it did not reach statistical significance because of the small number of events (P = 0.352; Table 1). On the other hand, LSM remained lower in the heterozygotes than the homozygotes at follow-up visit (5.5 ± 3.5 kPa vs. 6.6 ± 3.1 kPa; P < 0.001). Interestingly, there seemed to be an interaction between SLC10A1 variant and HBV genotypes. Patients of heterozygous SLC10A1 genotype were more likely to be infected by genotype B HBV, when compared to those of wild-type homozygotes (72.7% vs. 51.9%, P = 0.028). It is well known that genotype C HBV is associated with more advanced liver fibrosis7 and hepatocellular carcinoma.8 Whether NTCP has differential affinity to HBV of different genotypes remain to be defined. Declaration of personal interests: Grace Wong has served as an advisory committee member for Otsuka and Gilead. She has also served as a speaker for Abbvie, Bristol-Myers Squibb, Echosens, Furui, Gilead, Otsuka and Roche. Pete Tse has no competing interests. Henry Chan is a consultant for Abbott, Bristol-Myers Squibb, Furui, Gilead, Merck, Novartis and Roche, has received honorarium for lecture for Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Gilead, Glaxo-Smith-Kline, Merck, Novartis and Roche, and has received an unrestricted grant from Roche for hepatitis B research. Vincent Wong has served as an advisory committee member for Abbvie, Roche, Novartis, Gilead and Otsuka. He has also served as a speaker for Abbvie, Bristol-Myers Squibb, Roche, Novartis, Abbott Diagnostics and Echosens. Declaration of funding interests: None.