HBsAg loss may not mean what the trials assume, and lactulose cut falls in cirrhosis

The edition in brief

Combining intrahepatic HBsAg immunostaining, quantitative serum HBsAg and droplet digital PCR of HBV DNA and RNA in liver biopsies, investigators separated patients whose surface antigen came predominantly from covalently closed circular DNA from those in whom it came from integrated HBV DNA. The two were indistinguishable: all three envelope proteins were present in both, relative abundance of L and S did not differ, intrahepatic burden correlated with serum levels in both, and every established staining pattern occurred in both groups. Serum HBsAg therefore cannot report cccDNA burden or transcriptional activity, and its use as the functional-cure endpoint warrants re-evaluation. LiveSMART randomised 230 adults with cirrhosis and portal hypertension but no prior overt hepatic encephalopathy across four US centres in a two-stage sequential design: lactulose or enhanced usual care for 12 weeks, then TeleTai-Chi or exercise education. Lactulose followed by TeleTai-Chi reduced injurious falls (4% vs 12%) and non-injurious falls (19% vs 32%) against usual care, with a win ratio of 2.7 (95% CI 1.3 to 5.5). Lactulose users had fewer injurious falls than non-users (3.5% vs 8.5%), win ratio 2.3 (1.3 to 4.0), with no excess of overt encephalopathy. In 3,743 patients with cholangiocarcinoma, those with pre-existing chronic liver disease presented at earlier stage, had curative surgery more often (60% vs 48%) and lived longer (median 12.2 vs 11.1 months). A Swedish register study of 124,387 patients with inflammatory bowel disease found the largest absolute excess of colorectal cancer in those with two or more affected first-degree relatives.