Hepatic metallothionein expression in chronic hepatitis C virus infection is IFNL3 genotype-dependent.

The IFNL3 genotype predicts the clearance of hepatitis C virus (HCV), spontaneously and with interferon (IFN)-based therapy. The responder genotype is associated with lower expression of interferon stimulated genes (ISGs) in liver biopsies from chronic hepatitis C patients. However, ISGs represent many interacting molecular pathways, and we hypothesised that the IFNL3 genotype may produce a characteristic pattern of ISG expression explaining the effect of genotype on viral clearance. For the first time, we identified an association between a cluster of ISGs, the metallothioneins (MTs) and IFNL3 genotype. Importantly, MTs were significantly upregulated (in contrast to most other ISGs) in HCV-infected liver biopsies of rs8099917 responders. An association between lower fibrosis scores and higher MT levels was demonstrated underlying clinical relevance of this association. As expected, overall ISGs were significantly downregulated in biopsies from subjects with the IFNL3 rs8099917 responder genotype (P=2.38 × 10(-7)). Peripheral blood analysis revealed paradoxical and not previously described findings with upregulation of ISGs seen in the responder genotype (P=1.00 × 10(-4)). The higher MT expression in responders may contribute to their improved viral clearance and MT-inducing agents may be useful adjuncts to therapy for HCV. Upregulation of immune cell ISGs in responders may also contribute to the IFNL3 genotype effect.

The effectiveness of rifabutin triple therapy for patients with difficult-to-eradicate Helicobacter pylori in clinical practice.

BACKGROUND: Failure of first line and subsequent Helicobacter pylori eradication therapy is a significant problem and alternative treatments are few. AIMS: To evaluate the efficacy of a rifabutin-based triple therapy in clinical practice and determine the optimal strategy for its use. METHODS: Patients referred after first or subsequent treatment failure were prescribed rifabutin triple therapy consisting of standard dose proton pump inhibitor, amoxicillin 1 g and rifabutin 150 mg each b.d. for 10 days. RESULTS: In 67 patients, the main indications for treatment were dyspepsia (55%), peptic ulcer disease (24%) and increased gastric cancer risk (18%). The median number of previous treatments was 2 (range: 1-9). Eradication of Helicobacter pylori was achieved in 76% (48/63) per protocol and 72% (48/67) on an intention-to-treat basis. When used as second line therapy, 95% (18/19) achieved eradication compared with 68% (30/44) when two or more previous treatments had been used (P = 0.03). Outcome was independent of age, ethnicity, gender or indication for treatment. Adverse events were reported in 10%. CONCLUSION: Rifabutin triple therapy is a well tolerated and effective second line therapy in the treatment of persistent Helicobacter pylori; however, its efficacy decreases with increasing number of failed previous therapies.

Twenty-year audit of percutaneous liver biopsy in a major Australian teaching hospital.

BACKGROUND: To examine the changes in indications, patient characteristics, safety and outcomes in consecutive patients undergoing percutaneous core liver biopsies in a major Australian teaching hospital over a period of two decades. METHODS: A retrospective audit was carried out on all percutaneous core liver biopsies from a single institution between 1996 and 2005. This was combined with 10 years of data already reported on for the years 1986-1995 to detect trends in indications and outcomes. RESULTS: Medical records from 1398 patients were included for analysis. Over a 20-year period, the most common indications for liver biopsy were hepatitis C (37.8%), hepatitis B (26.4%) and abnormal liver function tests (22.2%). Twelve major complications (1.0%) were seen; 10 episodes of haemorrhage, 1 bile leak and 1 visceral perforation. Seven of these patients had an abnormal baseline coagulation profile; a significant risk for major haemorrhage (P < 0.001), resulting in three deaths. All deaths occurred in inpatients with major comorbidities. Minor complications occurred in 13.6% of patients, with multiple passes a significant risk factor. Whereas the overall major and minor complication rates were independent of operator experience inadequate specimens were more frequently obtained by the registrar. CONCLUSION: This large series extending over two decades shows that despite advances in biopsy techniques, the rates of both minor and major complications remain significant. Of particular concern are the procedure-related deaths. Identifying factors that may increase risk requires further scrutiny and careful patient selection needs to be undertaken.