National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Mechanistic study of interaction between IL-22 and HCV core protein in the development of hepatocellular carcinoma among liver transplant recipients.

BACKGROUND: Hepatitis C virus (HCV) infects more than 170 million people worldwide that represents a major threat to global public health. Several viruses including HCV have developed mechanisms against the cellular responses essentially "hijacking" the antiviral responses generated against it. Interleukin 22 activated JAK-STAT pathways are responsible for several functions including liver regeneration, antiviral responses and cell cycle regulation. OBJECTIVES: Present study aims to un-reveal the speculated role of HCV core protein in perturbing IL-22 mediated JAK-STAT pathway. Principally investigating through interaction with IL-22 and SOCS-3 proteins. PATIENTS AND METHODOLOGY: Total 36 liver transplant patients were enrolled in the study. Out of which 24 were found HCV + ve. Immunohistochemistry (IHC) based qualitative expression analysis of IL-22, SOCS-3 and HCV core protein was carried out. Microscopy was performed for detection and visualization of immunostained liver tissues and biopsies. RESULTS: Hepatic expression of IL-22, HCV core protein and SOCS-3 showed that SOCS-3 expression levels were considerably high compared to HCV core and IL-22 protein. IL-22's moderate to high expression was found in 70% of the liver transplant patient sample. Total 87% patients showed moderate to high SOCS-3 expression. However, the overall expression of HCV core was stronger in 87% of cirrhotic patients and 14% in HCC patients. Suggesting the presence of HCV core protein clearly impacted the IL-22 mediated cellular signaling (JAK-STAT pathway leading towards hepatocarcinogenesis. CONCLUSION: HCV core and IL-22 and SOCS-3 molecules are found to be correlated statistically under this study. Concluded from this study that HCV core protein plays a potential role in diverging the hepatocytes from normal to carcinogenic. One cell signaling path cannot decide, the direct role of a single viral protein in developing viral induced hepatocarcinogenesis. Interpreting the complex network of cell signaling involved in HCC development is impractical to study under single study. That is why step by step unmasking the interactive role of few molecules under single study is the ideal way to resolve the impact of viral proteins on cell signaling. SOCS-3 is mediator for dysregulating IL-22 mediated liver regenerative pathway. Moreover, SOCS-3 and STAT-3 molecules are proposed to be a potential therapeutic target for managing HCC progression.

Purinoceptor expression in hepatocellular virus (HCV)-induced and non-HCV hepatocellular carcinoma: an insight into the proviral role of the P2X4 receptor.

The basic idea behind this study was to discover the association and prevalence of purinoceptors in hepatitis C virus (HCV) and non-HCV hepatocellular carcinoma (HCC). Immunohistochemistry was performed to study the expression of P2X4 and P2X7 receptors on ex-planted liver tissue samples that were collected from HCC patients. Antibodies specific for the P2X4 and P2X7 receptors were used to target the specific receptors and secondary antibody was used with 3,3'-diaminobenzidine (DAB) detection system to visualize the color change in case of any positive expression There was a substantial increase in P2X4 receptor expression in HCV induced HCC as compared to non-HCV HCC. Surprisingly, there was no increase in the P2X7 receptor expression in both HCV HCC and non-HCV HCC. We conclude that P2X4 receptor expression was significant in the presence of HCV HCC. This may confirms the potential role of P2X4 receptor in the presence of virus in liver pathology. However insignificant expression of P2X7 receptor may avert our attention towards understanding the role of this receptor in pro-inflammatory and immune responses.