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Hepatocellular carcinoma incidence post direct-acting antivirals in hepatitis C-related advanced fibrosis/cirrhosis patients in Australia

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Hepatobiliary & Pancreatic Diseases International 2020年第6期19卷 541-546页

作者： Patrick P Y Chan Miriam T Levy nicholas shackel Scott A Davison Emilia Prakoso Department of Gastroenterology and Hepatology Liverpool HospitalElizabeth StreetLiverpoolNSW 2170Australia South Western Clinical School University of New South WalesLiverpoolNSW 2170Australia Central Clinical School-The Faculty of Medicine and Health University of SydneyNSW 2050Australia

Background:Despite efficacy in HCV eradication,direct-acting antiviral(DAA)therapy has raised controversies around their impact on hepatocellular carcinoma(HCC)*** we reported the first Australian data on HCC incidence in DAA-treated HCV patients with advanced fibrosis/***:We conducted a retrospective single center study of DAA-treated HCV patients with advanced fibrosis/cirrhosis from April 2015 to December *** with prior HCC were included if they had complete response to HCC ***:Among 138 patients who completed DAA therapy,133(96.4%)achieved sustained virologic response(median follow-up 23.8 months).Ten had prior HCC and 5/10(50.0%)developed recurrence,while de novo HCC developed in 7/128(5.5%).Median time from DAA to HCC diagnosis was 34 weeks in recurrent HCC *** novo 52 weeks(P=0.159).In patients with prior HCC,those with recurrence(***)had shorter median time between last HCC treatment and DAA(12 vs.164 weeks,P<0.001).On bivariate analysis,failed sustained virologic response at 12 weeks(SVR12)(P=0.011),platelets(P=0.005),model for end-stage liver disease(MELD)score(P=0.029),alpha fetoprotein(AFP)(P=0.013),and prior HCC(P<0.001)were associated with HCC *** multivariate analysis,significant factors were prior HCC(OR=4.80;95%CI:1.47–48.50;P=0.010),failed SVR12(OR=2.83;95%CI:1.71–16.30;P=0.016)and platelets(OR=0.97;95%CI:0.95–0.99;P=0.009).Conclusions:Our study demonstrates a high incidence of recurrent HCC in HCV patients with advanced fibrosis/cirrhosis treated with *** associated with HCC development post-DAA were more advanced liver disease,failed SVR12 and prior HCC,with higher rates of recurrence in those who started DAA earlier.

关键词： Direct-acting antiviral Cirrhosis Hepatitis-C virus Hepatocellular carcinoma Recurrence

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Cirrhotic portal hypertension: From pathophysiology to novel therapeutics

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World Journal of Gastroenterology 2020年第40期26卷 6111-6140页

作者： Lakmie S Gunarathne Harinda Rajapaksha nicholas shackel Peter W Angus Chandana B Herath Department of Medicine Melbourne Medical SchoolThe University of MelbourneHeidelbergVIC 3084Australia School of Molecular Science College of ScienceHealth and EngineeringLa Trobe UniversityBundooraVIC 3086Australia ANZAC Research Institute ConcordNSW 2139Australia Department of Gastroenterology Austin HealthHeidelbergVIC 3084Australia South Western Sydney Clinical School Faculty of MedicineUniversity of New South WalesIngham Institute for Applied Medical Research1 Campbell StreetLiverpoolNSW 2170Australia

Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these *** statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This rev

关键词： Portal hypertension Cirrhosis Intrahepatic vascular resistance Hyperdynamic circulatory state Splanchnic vasodilatation Portal blood flow Non-selective betablockers Alternate renin angiotensin system

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Serum 25-hydroxyvitamin D deficiency and hepatic encephalopathy in chronic liver disease

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World Journal of Hepatology 2017年第10期9卷 510-518页

作者： Helen Vidot Alison Potter Robert Cheng Margaret Allman-Farinelli nicholas shackel Department Nutrition and Dietetics Royal Prince Alfred Hospital Centenary Institute University of Sydney Royal Prince Alfred Hospital School of Life and Environmental Sciences University of Sydney Faculty of Medicine University of Sydney South Western Sydney Clinical School University of New South Wales

To investigate the relationship between 25-hydroxyvitamin D (25-OHD) deficiency and hepatic encephalopathy (HE) in patients with chronic liver disease (CLD). METHODSA retrospective analysis of the results of 392 adult patients with chronic liver disease who were assessed for liver transplantation between 2006 and 2010 was undertaken. HE, severity of CLD, nutritional status and 25-OHD were analysed in patients assessed for liver transplantation between 2006 and 2010. Patients who presented with acute, fulminant or subacute disease, with a primary diagnosis of liver cancer, were assessed for re-transplantation or who did not have a 25-OHD measurement were excluded from the analysis. RESULTSOne hundred and sixty-five patients were included in this analysis. The mean age of all patients was 53 ± 8 years. Moderate to severe 25-OHD deficiency was identified in 49 patients of whom 36 had grade 2-3 HE compared with 13 patients who were not encephalopathic (P ≤ 0.0001). Mild 25-OHD deficiency was not associated with HE. There was a significant correlation between the severity of 25-OHD deficiency and the severity of liver disease (r = 0.39, P ≤ 0.0001) and disease severity and the presence of HE (P ≤ 0.0001). Importantly, individuals with 25-OHD deficiency were more likely to have a diagnosis of overt HE (OHE) at a significantly lower model for end stage liver disease (MELD) score than individuals without OHE (P ≤ 0.0001). This significant difference was observed with MELD scores from 10 to 38. CONCLUSION25-OHD deficiency was observed in the majority of patients with CLD and for the first time was found to be significantly worse in patients with OHE.

关键词： Vitamin D Chronic liver disease Hepatic encephalopathy Model For End Stage Liver Disease Dementia Malnutrition Cognitive function

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Patients with non-viral liver disease have a greater tumor burden and less curative treatment options when diagnosed with hepatocellular carcinoma

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World Journal of Gastroenterology 2017年第15期23卷 2763-2770页

作者： Waled Mohsen Marcia Rodov Emilia Prakoso Barbara Charlton David G Bowen David J Koorey nicholas A shackel Geoffrey W McCaughan Simone I Strasser AW Morrow Gastroenterology and Liver Centre Royal Prince Alfred Hospital

AIM To assess the impact of underlying liver disease etiology on the presenting features and outcomes in a large cohort of patients with hepatocellular carcinoma(HCC). METHODS A prospective database of all patients with HCC was established from 1998 to March 2012. One thousand and seventy-eight patients were categorized into three groups, based on the etiology of their liver disease: hepatitis B virus(HBV), hepatitis C virus(HCV) and non-viral liver disease(NVLD). Overall survival was determined by Kaplan Meier analysis to time of death or last *** HCC patients with HCV(85%) were more likely to be diagnosed as part of a surveillance program, compared to HBV or NVLD(both 71%)(P < 0.001). Patients with NVLD were more likely to receive best supportive care(29%) compared to those with HBV(21%) or HCV(20%)(P < 0.02). Twelve percent of NVLD and 13% of HBV patients underwent liver transplantation compared to 21% of HCV patients(P = 0.001). Median survival from presentation was lowest in NVLD(1.7 years) when compared to HBV(2.8 years) and HCV(2.6 years)(P < 0.05). In multivariate analysis, independent predictors of survival included Child Turcotte Pugh score, size of dominant lesion, absence of vascular invasion, and management with surgical resection or liver transplantation. Patient age and the etiology of the underlying liver disease were not independent predictors of survival CONCLUSION Patients with NVLD and HCC were less likely to be enrolled in a HCC surveillance program and are less likely to have curative therapies such as liver resection and transplantation after diagnosis with HCC, when compared to patients with Hepatitis B and Hepatitis C.

关键词： Hepatitis B Hepatitis C Hepatocellular carcinoma Surveillance Therapy Nonalcoholic fatty liver disease Survival

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