Search

The majority of patients exposed to the hepatitis C virus develop chronic infection. The morbidity and mortality associated with chronic hepatitis C (CHC) is a consequence of progressive liver fibrosis, leading to cirrhosis, decompensated liver disease and hepatocellular carcinoma. As fibrosis is the key determinant of prognosis and influences treatment decisions and enrolment in surveillance programs, accurate assessment of fibrosis is crucial in the management of CHC. Currently liver biopsy is the “gold standard” for fibrosis assessment, but has a number of limitations including morbidity and mortality, sampling error and inter/intra-observer variability. The identification of non-invasive biomarkers of fibrosis has expanded rapidly over the last 10 years, providing an attractive alternative to liver biopsy. This article will review non-invasive biomarkers (serum biochemistry, imaging-based and genetic) for the assessment of fibrosis and fibrosis progression in CHC.

Background Currently, no recommendations exist for the endoscopic screening of patients in adulthood, with surgically corrected esophageal atresia (EA), for the development of esophageal cancer. A small number of individual case reports in the literature have raised concern that these cancers pose an increased risk (2 adenocarcinoma and 3 squamous cell carcinoma). Methods St Vincent's hospital has set up an EA clinic to review adult patients previously operated on for correction of EA. These patients underwent clinical review and were offered endoscopic evaluation if they had symptoms of dysphagia or gastroesophageal reflux. Among those patients, 3 have developed esophageal squamous cell carcinoma (SCC). A retrospective review of the EA database from the Royal Children's Hospital (798 patients [309 patients older than 40 years]) was then performed to identify any other cases of esophageal cancer developing in this cohort. One further patient was identified. Results To date, 4 of 309 patients have developed esophageal SCC over the age of 40 years. The cumulative incidence of esophageal SCC in this age group was 50 times that expected in the general population. Conclusions (1) This cluster provides strong evidence that there is a substantial risk of SCC in these adults with surgically repaired EA. (2) We believe that long-term surveillance endoscopy enhanced by advanced imaging techniques is indicated in all adults from the age of 20 years who have had surgical repair of EA.

Background/Aims Endoscopic screening for high-risk gastro-oesophageal varices (GOV) is recommended for compensated cirrhotic patients with transient elastography identifying increasing numbers of patients with cirrhosis without portal hypertension. Using liver stiffness measurement (LSM) ± platelet count, the aim was to develop a simple clinical rule to exclude the presence of high-risk GOV in patients with Child–Pugh A cirrhosis. Methods A retrospective analysis of 71 patients with Child–Pugh A cirrhosis diagnosed by transient elastography (LSM >13.6 kPa) who underwent screening gastroscopy was conducted. A predictive model using LSM ± platelet count was assessed to exclude the presence of high-risk GOV (diameter >5 mm and/or the presence of high-risk stigmata) and validated using a second cohort of 200 patients from two independent centres. Results High-risk GOV were present in 10 (15%) and 16 (8%) of the training and validation cohorts, respectively, which was associated with LSM and Pl count (P

Summary Background The biological mechanism underlying the association between IFNL4/IFNL3 polymorphism and peginterferon/ribavirin (PR) response in HCV-1 is thought to involve differential intrahepatic interferon-stimulated gene expression. HCV-3 is more sensitive to PR, but there are no studies of the association between IFNL4 polymorphism, PR treatment response and liver interferon-stimulated gene expression in HCV-3. Aim We evaluated the association between IFNL4/IFNL3 genotypes, PR treatment outcomes and intrahepatic interferon-stimulated gene expression, according to HCV genotype. Methods HCV-1 and HCV-3 patients who received PR therapy were identified. IFNL3 (rs12979860) and IFNL4 genotype (rs368234815) were determined. A second cohort with stored liver specimens was identified. Expression of ISGs was measured by rt-PCR. Results Two hundred and fifty-nine patients were identified: 55% HCV-1, 45% HCV-3. IFNL4 genotype frequency was TT/TT 44%, TT/ΔG 42% andΔG/ΔG 14%. Linkage disequilibrium with IFNL3 genotype was high (r2 = 0.98). The association between IFNL4 genotype and PR response was attenuated in HCV-3 vs. HCV-1 (HCV-3: SVR 89% vs. 76% vs. 72% for TT/TT vs. TT/ΔG vs. ΔG/ΔG, P = 0.09; HCV-1: SVR: 82% vs. 29% vs. 24%, P

IL28B genotype predicts response to pegylated interferon (peg-IFN)-based therapy in chronic hepatitis C. However, the utility of IL28B genotyping in chronic hepatitis B (CHB) cohorts treated with peg-IFN is unclear. It was investigated whether IL28B genotype is associated with peg-IFN treatment outcomes in a predominantly Asian CHB cohort.This was a retrospective analysis of CHB patients treated with 48 weeks of peg-IFN monotherapy. IL28B genotype (rs12979860) was determined (TaqMan allelic discrimination kit). Baseline hepatitis B virus (HBV)-DNA, alanine aminotransferase, and liver histology were available. The primary end-points were HBV e antigen (HBeAg) seroconversion with HBV-DNA 2000 IU/mL 24 weeks post-therapy (HBeAg-positive patients) and HBV-DNA 2000 IU/mL 24 weeks after peg-IFN (HBeAg-negative patients). The association between IL28B genotype and peg-IFN outcomes was analyzed.IL28B genotype was determined for 96 patients. Eighty-eight percent were Asian, 62% were HBeAg positive, and 13% were METAVIR stage F3-4. Median follow-up time was 39.3 months. The majority of patients carried the CC IL28B genotype (84%). IL28B genotype did not differ according to HBeAg status. The primary end-points were achieved in 27% of HBeAg-positive and 61% of HBeAg-negative patients. There was no association between IL28B genotype and the primary end-point in either group. Furthermore, there was no difference in HBeAg loss alone, HBV surface antigen, alanine aminotransferase normalization, or on-treatment HBV-DNA levels according to IL28B genotype.In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region.

The current standard of care for hepatitis C virus (HCV) infection is pegylated interferon and ribavirin. Unfortunately, treatment cures at best only 40% to 50% of patients infected with genotype 1 HCV, the most common HCV genotype in Western countries. Treatment is also expensive and is often poorly tolerated. Therefore, the identification of patients most likely to benefit from treatment is clinically important. Genome-wide association studies have recently identified genetic variants, most notably IL28B and ITPA, which will enhance the ability of clinicians to personalize antiviral therapy for HCV infection.