Institute of Liver & Biliary Sciences

Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer globally, third most common cause of cancer-related death, and most common primary liver malignancy.While nodular well-defined HCC remains the classical phenotype, presentations with infiltrative phenotype, very large HCC, and complications as tumor rupture provide immense diagnostic and therapeutic challenges.Infiltrative HCC is difficult to distinguish against the background cirrhotic liver.They are ill defined on imaging, have poor vascularity, and aggressive biol. behavior.Vascular invasion, metastasis, and poor response to loco-regional, as well as systemic therapy, leads to dismal prognosis.Very large HCCs have a relatively better prognosis than infiltrative HCC and mandate multimodal therapies to downstage for a curative response including liver transplant.Improvement in interventional radiol. techniques, emerging evidence with systemic therapies including immunotherapy, and better understanding of tumor biol. have opened newer avenues in the management of such complex cases.HCC rupture is a catastrophic moment in the natural history of HCC which has an exponential increase in mortality.Clin. presentation of pain abdomen, hypotension/syncope, new onset, or sudden increase in ascites mandates a strong suspicion of rupture.Presence of hemoperitoneum on diagnostic tap and contrast extravasation in a computed tomog./magnetic resonance imaging are the diagnostic hallmarks.Emergency surgical intervention, locoregional therapies in the form of bland embolisation, or chemoembolisation forms the management cornerstone.The long-term survival and liver transplant as a curative therapy still needs more data as fear of tumor spread is a possibility.This review summarises the clin. challenges with this advance HCC and provides an algorithmic approach for management.

Hepatitis B virus (HBV) is a major cause of acute and chronic liver disease and represents a major public health problem worldwide.Current antiviral therapies with nucleos(t)ide analogs can effectively suppressing viremia but are not curative, and have little or no impact upon the HBV cccDNA minichromosome or the portions of integrated HBV DNA.Several alternative therapeutic strategies targeted at viral components and life cycle are under intense investigation.This article highlights the reasons for considering HBx as a therapeutic target as this may allow targeting of both virus and disease.Recent studies focused at HBx have led to the identification of several new pharmacol. agents and development of some novel therapeutic approaches that now deserve to be taken to the next level for better management of hepatitis B.Besides, new therapies could be combined with other established therapies, to provide a functional cure from hepatitis B infection.

India has a high incidence of gallstones, which can cause chronic inflammation and increase the risk of gallbladder cancer. Understanding the age and composition of gallstones can provide insights into their formation and growth. This study used radiocarbon dating (¹⁴C dating), Fourier transform infrared (FTIR) spectroscopy, and metagenome analysis to explore the natural history, deposition rate, and microbial/chemical composition of gallstones.

In this pilot study, 3 cholesterol gallstones were chosen with different tissue histopathologies (normal, metaplasia, and dysplasia), and respective layers were analyzed for ¹⁴C bomb-pulse dating and FTIR for age and chemical composition, respectively. The core of each gallstone was subjected to scanning electron microscopy and further to 16S rRNA sequencing for microbial analysis.

The ¹⁴C data indicated that the largest stone with dysplastic epithelium formed over 6 years, whereas stones with metaplasia and normal pathology took 13 and 12 years to develop, respectively. Furthermore, the largest stone was dormant for 6 years before the individual experienced acute pain, whereas the other 2 stones laid dormant for 7 and 18 years. FTIR analysis revealed that all 3 gallstones were primarily composed of cholesterol. In addition, calcium oxalate, calcium carbonate, and calcium bilirubinate were present in stones with underlying dysplasia. The 16S rRNA analysis revealed an increased abundance of Corynebacterium sp. in stones associated with metaplasia and dysplasia. Moreover, pathogenic Klebsiella and Escherichia coli species were abundant in calcium oxalate-rich gallstones with underlying dysplasia.

Overall, the pilot study established the feasibility of ¹⁴C bomb pulse for evaluating the timeline of gallstone formation. In addition, ¹⁴C dating combined with FTIR/metagenome analysis helped in understanding the natural history of gallstone-associated disease.