William Kemp

Irreversible electroporation for unresectable hepatocellular carcinoma: initial experience and review of safety and outcomes.

The aims of this study were to evaluate the safety, feasibility and tumour response of irreversible electroporation, a non-thermal ablation technique, for the treatment of unresectable hepatocellular carcinoma. The endpoints were safety and local treatment efficacy. Patients with unresectable tumours and tumours not amenable for radiofrequency ablation because of their vicinity to organs vulnerable to thermal damage such as the bowel or because they were close to large blood vessels that would limit efficacy of ablation due to the heat sink effect were treated with irreversible electroporation using percutaneous ultrasound and/or computed tomography guided electrode placement between November 2008 and December 2009. Early, late, minor and major complications were recorded. Tumour response was determined on triphasic helical computed tomography follow-up at one month, then every three months post-procedure. Eleven patients received IRE therapy to 18 HCC lesions (Mean diameter 2.44 ± 0.99 cm; range 1.0–6.1 cm) with five patients having more than one treated HCC. Mean follow-up was 18 months (range 14–24 months). Six patients required repeat treatments for local residual or recurrent disease; two of these also had IRE for distant intrahepatic recurrence. No serious complications were observed despite seven lesions lying adjacent to important structures or organs. Four patients developed transient urinary retention and seven developed transient local post-procedure pain. After IRE therapy, 13 (72%) lesions were completely ablated with 93% success for lesions <3 cm (13/14). The local recurrence-free period was 18 ± 4 months and the distance recurrence free period was 14 ± 6 months. These preliminary results suggest that IRE is a safe and feasible technique for local ablation of HCC, particularly for lesions less than 3 cm. No major complications were encountered during this study even for tumours close to essential structures or organs.

Survival in hepatocellular carcinoma : Impact of screening and etiology of liver disease

Background and Aims:  As the merits of screening at‐risk populations for hepatocellular carcinoma (HCC) remain unclear, we compared the clinico‐pathologic features and survival of patients with cirrhosis and HCC detected by screening (Group A) to that in non‐screened cases (Group B).

Impact of heart failure and changes to volume status on liver stiffness: non‐invasive assessment using transient elastography

The impact of cardiac dysfunction on the liver is known as cardiac hepatopathy. In certain instances this can result in significant hepatic fibrosis or cirrhosis. The validity of non‐invasive tools to assess hepatic fibrosis, such as FibroScan® which measures liver stiffness (LSM), has not been established in this setting. We examined the impact of cardiac dysfunction on LSM using FibroScan® and the influence of volume changes on LSM.

Chronic urotensin-II infusion induces diastolic dysfunction and enhances collagen production in rats.

The vasoactive peptide urotensin-II (U-II) is likely to play a key causal role in cardiac remodeling that ultimately leads to heart failure. Its contribution, specifically to the development of diastolic dysfunction and the downstream intracellular signaling, however, remains unresolved. This study interrogates the effect of chronic U-II infusion in normal rats on cardiac structure and function. The contribution of Rho kinase (ROCK) signaling to these pathophysiological changes is evaluated in cell culture studies. Chronic high-dose U-II infusion over 4 wk significantly impaired diastolic function in rats on echocardiography-derived Doppler indexes, including E-wave deceleration time (vehicle 56.7 +/- 3.3 ms, U-II 118.0 +/- 21.5 ms; P < 0.01) and mitral valve annulus peak early/late diastolic tissue velocity (vehicle 2.01 +/- 0.19 ms, U-II 1.04 +/- 0.25 ms; P < 0.01). A lower dose of U-II infusion (1 nmol.kg(-1).h(-1)) yielded comparable changes. Diastolic dysfunction was accompanied by molecular [significant increases in procollagen-alpha(1)(I) gene expression on real-time PCR] and morphological (increases in total collagen, P < 0.05, and collagen type-I protein deposition, P < 0.001) evidence of left ventricular (LV) fibrosis following high-dose U-II infusion. The ROCK inhibitor GSK-576371 (10(-7) to 10(-5) M) elicited concentration-dependent inhibition of U-II (10(-7) M)-stimulated cardiac fibroblast collagen synthesis and cardiac myocyte protein synthesis. Chronic U-II infusion causes diastolic dysfunction, caused by fibrosis of the LV. The in vitro data suggest that this may be in part occurring via a ROCK-dependent pathway.

Hepatocellular carcinoma in an Australian tertiary referral hospital 1975–2002: Change in epidemiology and clinical presentation

Aim:  We compared the epidemiology and clinical features of hepatocellular carcinoma (HCC) cases diagnosed between 1975 and 2002.

Liver stiffness plus platelet count can be used to exclude high-risk oesophageal varices.

Endoscopic screening for high‐risk gastro‐oesophageal varices (GOV) is recommended for compensated cirrhotic patients with transient elastography identifying increasing numbers of patients with cirrhosis without portal hypertension. Using liver stiffness measurement (LSM) ± platelet count, the aim was to develop a simple clinical rule to exclude the presence of high‐risk GOV in patients with Child–Pugh A cirrhosis.

Urotensin II: a novel vasoactive mediator linked to chronic liver disease and portal hypertension.

Background/Aims: Urotensin II (UII) is recognised as the most potent human vasoconstrictor; however, its role in chronic liver disease (CLD) is unknown.

Norfloxacin treatment for clinically significant portal hypertension: results of a randomised double-blind placebo-controlled crossover trial.

Background: While selective intestinal decontamination (SID) can alter the hyperdynamic circulatory state of cirrhosis, the impact of SID on portal pressure remains unclear especially in the setting of clinically significant portal hypertension.

Novel population-based study finding higher than reported hepatocellular carcinoma incidence suggests an updated approach is needed

Hepatocellular carcinoma (HCC) incidence is rising rapidly in many developed countries. Primary epidemiological data have invariably been derived from cancer registries that are heterogeneous in data quality and registration methodology; many registries have not adopted current clinical diagnostic criteria for HCC and still rely on histology for classification. We performed the first population‐based study in Australia using current diagnostic criteria, hypothesizing that HCC incidence may be higher than reported. Incident cases of HCC (defined by American Association for the Study of Liver Diseases diagnostic criteria or histology) were prospectively identified over a 12‐month period (2012‐2013) from the population of Melbourne, Australia. Cases were captured from multiple sources: admissions to any of Melbournes seven tertiary hospitals; attendances at outpatients; and radiology, pathology, and pharmacy services. Our cohort was compared to the Victorian Cancer Registry (VCR) cohort (mandatory notified cases) for the same population and period, and incidence rates were compared for both cohorts. There were 272 incident cases (79% male; median age: 65 years) identified. Cirrhosis was present in 83% of patients, with hepatitis C virus infection (41%), alcohol (39%), and hepatitis B virus infection (22%) the commonest etiologies present. Age‐standardized HCC incidence (per 100,000, Australian Standard Population) was 10.3 (95% confidence interval [CI]: 9.0‐11.7) for males and 2.3 (95% CI: 1.8 to 3.0) for females. The VCR reported significantly lower rates of HCC: 5.3 (95% CI: 4.4 to 6.4) and 1.0 (95% CI: 0.7 to 1.5) per 100,000 males and females respectively (P < 0.0001). Conclusions: HCC incidence in Melbourne is 2‐fold higher than reported by cancer registry data owing to under‐reporting of clinical diagnoses. Adoption of current diagnostic criteria and additional capture sources will improve registry completeness. Chronic viral hepatitis and alcohol remain leading causes of cirrhosis and HCC. (Hepatology 2016;63:1205–1212)

Utility of transient elastography in the non‐invasive evaluation of cystic fibrosis liver disease

Liver disease frequently complicates cystic fibrosis (CF), with CF liver disease (CFLD) a leading cause of death. Liver biopsy is rarely performed because of the patchy nature of the disease. Transient elastography can reliably stage liver fibrosis via liver stiffness measurement (LSM).