News

Both Chinese herbal medicine (CHM) and Western medicine (WM) can lead to drug-induced liver injury (DILI), but with different clinical characteristics, say researchers. 

Overall, 1,985 DILI cases were retrospectively collected from 96,857 patients hospitalised because of liver dysfunction in Beijing’s 302 Military Hospital between January 2009 and January 2014.

In the DILI patients, CHM was implicated in 563 cases, 870 cases were caused by WM. In the remaining patients, accounting for 27.8% of the cohort, the combination of WM and CHM was blamed. Polygonum multiflorum was the major implicated CHM.

The cases caused by CHM were more female (51% versus 71%) and positive rechallenge (6.1% versus 8.9%), a much greater proportion of hepatocellular injury (62.2% versus 88.5%), and a higher mortality (2.8% versus 4.8%). However, no differences in the rates of chronic DILI and ALF were found (12.9% versus 12.4%; 7.6% versus 7.6%, respectively).

Based on Roussel Uclaf Causality Assessment Method, 75.6% of cases caused by CHM were classified as probable and only 16.6% as highly probable, significantly different from WM (38.4% and 60.3%).

Reference

Comparison between Chinese herbal medicine and western medicine-induced liver injury of 1985 patients. Zhu Y, Niu M, Chen J et al. J Gastroenterol Hepatol. 2016 Feb 20 [Epub ahead of print]

A real time study in the Netherlands found that adherence to ribavirin during PEG-interferon containing therapy in chronic HCV was high.

In this randomized controlled trial at the University Medical Centre of Utrecht, 35 patients (the intervention group) received a medication dispenser that monitored ribavirin intake real-time during 24 weeks of PEG-interferon/ribavirin±boceprevir or telaprevir. Thirty-seven patients in a control group received standard-of-care. Adherence was also measured by pill count.

Median adherence by pill count was 96% with 30 (94%) of patients exhibiting 80% adherence. Perfect adherence (i.e. 100%) was similar in intervention and control groups: 22 (85%) versus 15 (75%). Adherences by real-time medication monitoring and by pill count did not correlate. No predictors of poor adherence could be identified.

Ribavirin trough levels after eight weeks (median: 2.4mg/L versus 2.7mg/L) and 24 weeks (median: 3.0mg/L versus 3.0mg/L), and virological responses did not differ between the intervention and control groups.

Reference

Adherence to ribavirin in chronic hepatitis C patients on antiviral treatment: results from a randomized controlled trial using real-time medication monitoring. van Vlerken LG, Lieveld FI, van Meer S et al. Clin Res Hepatol Gastroenterol. 2016 Feb 8 [Epub ahead of print]

Two studies have found diabetes, smoking, alcohol and HBV to be among the main risk factors for hepatocellular carcinoma (HCC) and its mortality.

Researchers from the National Taiwan University College of Medicine followed up 51,164 participants. They were aged 44 to 94, did not have chronic HBV or HCV, and were enrolled from nationwide health screening units (1) . Between 1998 and 2008 there were 253 deaths from HCC. A history of diabetes was associated with deaths from HCC for both total participants (adjusted hazard ratio 2.97 ) and ever smokers with current or past smoking habits (hazard ratio 1.92).

Both never smokers (hazard ratio 0.46) and quitters (hazard ratio 0.62) had a lower adjusted risk of HCC deaths compared with current smokers. Among all ever smokers with current or past smoking habits, as compared with diabetic smokers, only quitters without diabetes had a lower adjusted risk of HCC deaths (hazard ratio 0.37). However, quitters with diabetes had a similar risk of deaths from HCC when compared with smokers with diabetes.

The researchers concluded that clinicians should promote diabetes and smoking prevention in order to reduce subsequent HCC mortality, even in adults without chronic viral hepatitis.

Another study, from China, concluded HBV and alcohol intake were still the major risk factors for HCC (2).

Researchers at Xiamen University conducted a case-control study of 314 HCC cases and 346 controls was conducted in Xiamen, which is an epidemic area in China for both HBV and HCC. Face-to-face interviews were conducted and enzyme-linked immunosorbent assay kits were used to determine the status of serological markers of HBV infection.

As expected, HBV and alcohol intake remained the major risk factors of HCC. Liver disease history and passive smoking are also associated with elevated HCC risk. Indoor air pollution and pesticide exposure were newly identified as risk factors. The researchers suggested alcohol prevention should be promoted and that the consumption of fruit and tea intake could significantly lower the HCC risk .

References

1) The relationship of diabetes and smoking status to hepatocellular carcinoma mortality. Chiang CH, Lu CW, Han HC et al. Medicine (Baltimore). 2016 Feb;95(6):e2699

2) The epidemiological investigation on the risk factors of hepatocellular carcinoma: a case-control study in Southeast China. Niu J, Lin Y, Guo Z et al. Medicine (Baltimore). 2016 Feb;95(6):e2758 

Novel benzothiazepinecarboxamide (BTC) inhibitors that interfere with early and late steps of the HCV viral life cycle have been identified.

Upon screening synthetic small molecule libraries with the infectious HCV cell culture system, researchers at the Korean Pasteur Institute identified a BTC scaffold that inhibits HCV. A structure-activity relationship (SAR) study with BTCs was performed, and modifications that led to nanomolar antiviral activity and improved the selective index (CC50/EC50) by more than 1,000-fold were identified. In addition, a pharmacophore modeling study determined that the tricyclic core and positive charge on the piperidine moiety were essential for antiviral activity.

Furthermore, the researchers demonstrated that BTC interferes with HCV glycoprotein E1/E2-mediated viral entry and the generation of infectious virions by using HCV pseudoparticle and cell culture supernatant transfer assays, respectively. BTC showed potent antiviral activity against HCV genotype 2 but was less potent against a genotype 1/2 chimeric virus, which expressed the structural proteins of HCV genotype 1.

Reference

Benzothiazepinecarboxamides: Novel hepatitis C virus inhibitors that interfere with viral entry and the generation of infectious virions. Kim HY, Kong S, Oh S et al. Antiviral Res. 2016 Feb 2 [Epub ahead of print]

Entecavir in children and adolescents with chronic HBV is safe and shows clinical benefits in short-term biochemical and virologic responses, a new study concluded.

In the study, at the National Taiwan University Hospital, group one comprised nine treatment-naïve patients (median aged 12.2 years) who had been HBeAg seropositive for more than six months, and had alanine aminotransferase (ALT) of more than two times the upper limit of normal value (30 IU/L). They received entecavir at a dose of 0.015 mg/kg/d, with a maximal dose of 0.5 mg daily, for at least 52 weeks. Another 27 untreated chronic HBV patients matched for age, sex, ALT levels, and HBeAg status were recruited as the control group.

The entecavir-treated patients achieved rapid ALT normalisation (all before eight months of treatment) compared with the control group and had a greater chance of achieving undetectable HBV DNA levels at Week 52 after treatment (55.6% versus 11.1%).

The cumulative incidence rates of HBeAg seroconversion were similarly high in both groups (entecavir group 44% at one year and 78% at two years; control group 37% and 63%, respectively). The entecavir group also had a trend of better complete response than the control group (22.2% versus 0%). None of the entecavir-treated patients reported significant adverse effects.

Reference

Entecavir treatment in children and adolescents with chronic hepatitis B virus infection. Chang KC, Wu JF, Hsu HY et al. Pediatr Neonatol. 2015 Dec 23 [Epub ahead of print]