Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

Patients with chronic hepatitis C virus (HCV) infection are often asymptomatic with few clinical signs of liver disease. Recognition of the presence of fibrosis or cirrhosis is difficult without liver biopsy, but with the availability of effective treatments, such as interferon, and the potential for progression to hepatoma in some cases, an accurate measure of the stage of disease is important. Serum hyaluronic acid (HA) has been identified as a potential marker of fibrosis or cirrhosis in other settings. In a prospective study in 130 chronic HCV carriers therefore, serum HA concentrations were compared with conventional liver function tests (including alanine aminotransferase (ALT), a-glutathione-S transferase (GST) and serum HCV RNA in order to determine which identified the stage of liver fibrosis as assessed by liver biopsy most accurately. The median HA concentrations according to the stage of fibrosis 0, 1 & 2, 3 and 4 & 5 were 17 g l-1 (range 5-37), 17 g l-1 (5-80), 30 g l-1 (10-105) and 350 g l-1 (20-800) respectively. The median HA concentration in stage 4 & 5 was significantly greater than in stages 0, 1 & 2 or 3. Serum HA concentration rose with age, but even when adjusted for age the median HA at stage 4 & 5 was greater than all other groups (95% CI of difference between the medians exceeded 0). Thus, serum HA gave a sensitivity and specificity for stage 4 & 5 fibrosis of 85% and 88% respectively, exceeding those for ALT or GST. In contrast, serum ALT or GST levels were not correlated with the stage of fibrosis although ALT was significantly greater in the cirrhotic group when compared to the group with no fibrosis (stage 0). There was no correlation between serum HA and either the grade of inflammatory changes or serum HCV RNA. These results suggest that serum hyaluronic acid is a useful marker of liver fibrosis in patients with chronic HCV infection. It could therefore be used to monitor patients at risk of progressive fibrosis, in controlled clinical trials, as a measure of response to antifibrotic therapy and in those in whom liver biopsy is difficult or contraindicated.

Aims-To study the inter-relation between hepatic fibrosis and other histological features of chronic hepatitis C virus (HCV) infection. Methods-Liver biopsy specimens from 200 consecutive patients with chronic HCV infection were graded and staged separately for necro-inflammatory activity and for fibrosis. The interaction between fibrosis and other histological features was evaluated by univariate and multivariate analysis, followed by hierarchical log linear modelling.

Many clinicians appear to be concerned about the potential hepatotoxicity of the opiate antagonist naltrexone (NTX) and this may be one reason why it is not used more widely in treating both heroin and alcohol abusers. Some much-quoted early studies noted abnormalities in liver function tests (LFTs) in very obese patients taking high doses, although there was no evidence of clinically significant liver dysfunction. These concerns may be reinforced by advice in the UK product information sheet to perform LFTs before and during treatment, by high infection rates with hepatitis C virus (HCV) among injecting heroin addicts and by the frequency of abnormal LFTs in alcohol abusers. We describe a heroin abuser in whom clinical and laboratory manifestations of acute hepatitis B and C appeared a few days after the insertion of a subcutaneous naltrexone implant. A decision was made not to remove the implant but the hepatitis resolved completely and uneventfully well within the normal time-scale. A review of the literature indicates that even when given at much higher doses than are needed for treating heroin or alcohol abusers, there is no evidence that NTX causes clinically significant liver disease or exacerbates, even at high doses, serious pre-existing liver disease. During the past decade, NTX has been shown to be safe and effective in the treatment of pruritus associated with severe jaundice caused by severe and sometimes life-threatening cirrhosis and other liver diseases. Its safety, even in these extreme conditions, is particularly reassuring. We suggest that it may be more appropriate and economical to advise patients to report promptly any suspected side effects than to perform regular LFTs, which may be misleading.