Jonathan Fawcett

The influence of viral genotypes and rejection episodes on the recurrence of hepatitis C after liver transplantation

AbstractPurpose. The aim of this study was to report the influence of hepatitis C virus (HCV) genotype and rejection episodes on the outcome of orthotopic liver transplantation (OLT), hepatitis recurrence, and progression to graft cirrhosis after OLT. Methods. Fifty-three patients who all had undergone OLT for end-stage liver cirrhosis were selected for this study. Hepatitis C genotype was determined. Recurrent hepatitis and rejection were diagnosed based on elevated liver function tests and a liver biopsy. Results. The patients were followed up for a mean of 51.9 ± 34.3 months. The cumulative survival rate was no different in OLT for hepatitis C and OLT for all other liver diseases. After OLT, serum HCV RNA was detected in 93%. Histological recurrence occurred in 85% of all patients. The 1-, 3-, and 5-year recurrence rates were 48%, 77%, and 85%, respectively. Of the 41 patients with recurrent hepatitis C, 4 (10%) had cirrhosis, 18 (44%) had hepatitis with fibrosis, and 91 (46%) had hepatitis without fibrosis at the end of follow-up. A total of 32% of the patients were infected by HCV genotype 1b and 68% by other HCV genotypes. The recurrence rates were significantly higher in patients infected with genotype 1b than in those with other genotypes (p = 0.04). Twenty of 48 patients (42%) experienced acute rejection. There was a strong association between the number of rejection episodes and the incidence of HCV-related cirrhosis (p < 0.01). Conclusion. Our findings showed the genotype 1b to result in a higher recurrence rate after OLT. On the other hand, rejection episodes were associated with a more rapid progression to graft cirrhosis.

Cyclosporin A pretreatment in a rat model of warm ischaemia/reperfusion injury

BACKGROUND/AIMS These studies investigated the role of apoptosis following ischaemia/reperfusion (I/R) injury to the liver and the effect of pretreatment with Cyclosporin A. METHODS Male Sprague-Dawley rats received 30 min of warm ischaemia followed by a period of reperfusion of 6 h. Rats were given olive oil or Cyclosporin A (30 mg/kg p.o.) the day before surgery. Neutrophil numbers were assessed in haematoxylin-eosin-stained sections of liver. In situ staining of sections using TdT-mediated dUTP-fluorescein nick-end labelling was carried out to determine the extent of apoptosis, followed by electron microscopy. Semi-quantitative polymerase chain reaction (PCR) analysis of the transcript for Fas antigen was performed. RESULTS AND CONCLUSIONS High levels of apoptosis were observed in I/R injury, which were greatly ameliorated in Cyclosporin A-pretreated groups. PCR analysis indicated a reduction in the level of expression of Fas transcript in Cyclosporin A-treated rats. Histological analysis showed a significant increase in the number of neutrophils infiltrating I/R-injured tissue (62 +/- 10.69, n=16), which was markedly reduced by Cyclosporin A pretreatment (16 +/- 7, n=6, P<0.05). These results indicate a role of parenchymal apoptosis in the pathogenesis of I/R injury, which occurs in association with neutrophil infiltration, both of which can be significantly reduced by Cyclosporin A pretreatment.

Cell adhesion molecules and cancer.

Cell adhesion molecules are complex protein and carbohydrate molecules of many different types found on the surfaces of all cells. They are important in many aspects of cell biology including development, differentiation, and motility. These processes are frequently disturbed in cancer and recent work has demonstrated that disturbances in cell adhesion molecule expression are also common in malignancy.

Tumor progression in hepatocellular carcinoma: Relationship with tumor stroma and parenchymal disease

Background: Encapsulation in hepatocellular carcinoma is associated with decreased invasiveness and improved survival in several series. Although active fibrogenesis by myofibroblasts has been demonstrated in the capsule, it is unclear if the capsule results from a general increase in peritumoral fibrosis, or an inherently less invasive tumor phenotype. The relationship between collagen deposition within tumor stroma, presence of cirrhosis and invasiveness also needs clarification.

Effect of hospital and surgeon volume on patient outcomes following treatment of abdominal aortic aneurysms: a systematic review.

OBJECTIVES This systematic review assessed the efficacy of centralisation for the treatment of unruptured and ruptured abdominal aortic aneurysms. Patient outcomes achieved by low and high volume hospitals/surgeons, including morbidity, mortality and length of hospital stay, were used as proxy measures of efficacy. DESIGN Systematic review was designed to identify, assess and report on peer-reviewed articles reporting outcomes from unruptured and ruptured abdominal aortic aneurysms. No language restriction was placed on the databases searched. MATERIALS Only peer-reviewed journals articles were included. METHODS To ensure the contemporary nature of this review, only studies published between January 1997 and June 2007 were sought. Studies were included if they reported on at least one volume type and patient outcome. RESULTS Twenty two studies were included in this review. In the majority of group assessments, the number of studies reporting statistical significance was similar to the number of studies reporting no statistical significance. CONCLUSION The paucity of studies reporting statistically significant results demonstrates that although this evidence exists, its potential to be overstated must also be taken into account when drawing conclusions as to its efficacy for twenty first century healthcare systems.

Outcomes of split versus reduced‐size grafts in pediatric liver transplantation

Background:  Split‐liver transplantation, where two grafts are created from a single donor organ, is a means of overcoming donor organ scarcity. There are few data comparing outcomes of split with reduced‐size liver grafts, which is the most common type of cadaveric graft in pediatric liver transplantation. The aims of the present paper were to compare survival and complication rates between split and reduced‐size cadaveric grafts in pediatric patients receiving a liver transplant in Brisbane.

Poorer survival in patients whose explanted hepatocellular carcinoma (HCC) exceeds Milan or UCSF Criteria. An analysis of liver transplantation in HCC in Australia and New Zealand

BACKGROUND Milan and University of California San Francisco (UCSF) Criteria have been used for selection of patients with hepatocellular carcinoma (HCC) for liver transplantation (LTx). The aims of this study were to analyse the results of LTx for HCC in Australia and New Zealand with emphasis on the effects of discordance between pre-LTx radiological and post-LTx pathological staging. METHODS A total of 186 LTx for HCC carried out between July 1985 and August 2003 were included. Patients were categorized according to the Milan and UCSF Criteria. RESULTS The median follow-up was 6.55 years (range 2.96-20.93 years). Pre-LTx factors associated with better survival include tumour size < or = 5 cm, number of tumours < or = 3, staging within Milan and UCSF Criteria and more recent transplantation (1996-2003). In all, 14 patients had a pre-LTx stage outside the Milan but within the UCSF Criteria. One- and 5-year patient survival rates were, respectively, 88% and 74% within the Milan Criteria, and 87% and 73% within the UCSF Criteria. Vascular invasion, capsular invasion, lymph node invasion and pathological stage outside UCSF Criteria were associated with poor outcome. Of patients within the Milan and UCSF Criteria pre-LTx, 24% and 18%, respectively, were outside the same criteria post-LTx. These patients had poorer survival rates. CONCLUSIONS The use of the UCSF Criteria in this cohort increased the number of patients eligible for LTx without compromising 5-year survival rates. Patients whose explant tumours were outside the Milan or UCSF Criteria had poorer outcomes compared with those whose explants remained within these criteria.

Association Between Ultraviolet Radiation, Skin Sun Sensitivity and Risk of Pancreatic Cancer

BACKGROUND Ecological studies showing an inverse association between pancreatic cancer incidence and mortality and levels of ultraviolet radiation (UVR), suggest that higher levels of sun exposure may reduce risks of pancreatic cancer but there has been only one individual-level study that examined this issue. We aimed to examine the association between pancreatic cancer and markers of exposure to solar UVR, namely skin type, treatment of skin lesions, ambient UVR and time outdoors on work days. METHODS We used data from an Australian case-control study. Location at birth, residential location during adulthood, outdoors work, history of skin lesion treatment and sensitivity of the skin to the sun were obtained by questionnaire. We limited the analyses to Caucasians who answered the questionnaire about UVR (controls=589/711 recruited; cases=496/705 recruited). We used NASAs Total Ozone Mapping Spectrometer to estimate ambient UVR. RESULTS Being born in or living in areas of higher ambient UVR (compared to lower ambient UVR) was associated with about 30-40% lower risk of pancreatic cancer. People with fair skin colour had 47% lower risk of pancreatic cancer than those with dark skin colour (95% CI 0.37-0.75). There was some suggestion of increased risk with increased average number of hours spent outside at work. CONCLUSIONS This study suggests that people with light skin colour or those born or living in areas of high ambient UVR have lower risk of pancreatic cancer. Our analysis supports an association between UVR and pancreatic cancer, possibly mediated through production of vitamin D.

Liver Transplantation for Hepatolithiasis

Hepatolithiasis is frequently encountered in Asia, but is relatively uncommon in Western societies. The improved surgical and stone fragmentation techniques that have evolved over the past decade have reduced the incidence of retained or recurrent stones with a consequent reduction in progressive liver damage and cirrhosis. Nonetheless, disease-related mortality from liver failure, bleeding oesophageal varices and cholangiocarcinoma still exists and a proportion of patients are cirrhotic at their initial presentation. There have been good long-term results following liver transplantation for a variety of cholestatic liver diseases, but transplantation for hepatolithiasis has seldom been reported. This paper reports four patients who underwent successful liver transplantation for hepatolithiasis with secondary biliary cirrhosis.

Acute liver failure in children: A regional experience

Objective: To review the outcome of acute liver failure (ALF) and the effect of liver transplantation in children in Australia.