Impact of viral hepatitis aetiology on survival outcomes in hepatocellular carcinoma: A large multicentre cohort study.

While HBV and HCV are risk factors for HCC, uncertainty exists as to whether these viral infections have prognostic significance in HCC. Thus, we compared the overall survival of patients with HBV, HCV and nonviral HCC, and evaluated whether the presence of HBV and HCV predicts patient outcomes. We conducted a multicentre study of HCC cases diagnosed at six Melbourne tertiary hospitals between Jan 2000-Dec 2014. Patient demographics, liver disease and tumour characteristics and patient outcomes were obtained from hospital databases, computer records and the Victorian Death Registry. Survival outcomes were compared between HBV, HCV and nonviral hepatitis cases and predictors of survival determined using Cox proportional hazards regression. There were 1436 new HCC cases identified including 776 due to viral hepatitis (HBV 235, HCV 511, HBV-HCV 30) and 660 from nonviral causes. The median survival of HBV, HCV and nonviral HCC patients was 59.1, 28.4 and 20.9 months, respectively (P<.0001). On multivariate analysis, independent risk factors for survival included HCC aetiology, gender, BCLC stage, serum AFP, total number and size of lesions, and serum creatinine and albumin. After adjusting for these and method of detection, HBV remained an independent predictor of improved overall survival when compared to both nonviral (HR 0.60%, 95% CI 0.35-0.98; P=.03) and HCV-related HCC (HR 0.51%, 95% CI 0.30-0.85; P=.01). In this large multicentre study, HBV is independently associated with improved overall survival compared with HCV and nonviral-related HCC. Further studies are needed to determine the underlying factor(s) responsible.

Novel association of achalasia with hereditary sensory and motor neuropathy with sensorineural deafness.

Achalasia is a primary esophageal motility disorder. Unlike diffuse esophageal spasm, it has not previously been described in association with hereditary sensory and motor neuropathy (HSMN). An 18-year-old-male with HSMN with sensorineural deafness presented with a 2-day history of dysphagia to solids and liquids. Achalasia was diagnosed after extensive investigations, and his symptoms resolved with endoscopic and definitive surgical management. His monozygotic twin brother had also been diagnosed with HSMN and suffered from chronic dysphagia, which was also subsequently diagnosed with achalasia. This is the first case to illustrate an association between HSMN with sensorineural deafness and achalasia.

Portal hypertension: pathophysiology, diagnosis and management.

Portal hypertension is an important complication of liver disease. As a result of elevated pressures within the portal vein several complications can arise, including the development of oesophageal and gastric varices, ascites, hepatic encephalopathy as well as complications secondary to circulatory dysfunction, such as hepatorenal syndrome, portopulmonary syndrome and hepatopulmonary syndrome. This review outlines the pathogenesis and diagnosis of portal hypertension and outlines the management of these various important clinical sequelae. The management of oesophageal and gastric varices is particularly important, and both the emergency management together with prophylactic management of this condition are described.

Drug-induced gastrointestinal disorders.

Drug-induced gastrointestinal disorders can mimic conditions, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and, hence, recognition can prevent unnecessary investigations and treatment. While the knowledge and awareness relating to the adverse gastrointestinal effects of some medications, such as non-steroidal anti-inflammatory drugs are well established, other commonly prescribed drugs, such as antipsychotics, antidepressants and metformin are less well understood and warrant further study. This review attempts to integrate recent information regarding adverse drug reactions and place this in a useful clinical context.

Advances in the management of hepatitis C.

Significant advances have recently been made in the management of hepatitis C virus (HCV) with many of the changes now part of routine clinical practice. These include the use of non-invasive methods to assess liver fibrosis, interleukin 28B genotype testing to predict interferon responsiveness and the use of new anti-viral regimens for HCV genotype 1. Two new antiviral agents (boceprevir and telaprevir) have recently become available in Australia. These protease inhibitors are used in combination with pegylated interferon and ribavirin as triple therapy for genotype 1 HCV. This combination increases sustained virological response from approximately 45-50% to 66-75% in treatment naïve patients. However, these new regimens present novel challenges including complicated treatment algorithms based on virological response, numerous drug interactions and additional side effects especially in patients with advanced fibrosis. The protease inhibitors are the first of many antiviral drugs to become available to treat HCV, heralding the arrival of new agents that will offer greater chances of cure with improved safety and tolerability compared with current therapies.

Epidemiology and outcomes of primary sclerosing cholangitis: an Australian multicentre retrospective cohort study.

BACKGROUND AND AIMS: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. METHODS: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. RESULTS: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. CONCLUSION: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.

Hepatitis B virus reactivation following immunosuppressive therapy: guidelines for prevention and management.

It is well known that immunosuppressive drugs or cancer chemotherapy can stimulate replication of hepatitis B virus (HBV) and precipitate severe flares of HBV infection. The risk of this syndrome of 'reactivation hepatitis B' is highest in haematopoietic stem cell or solid organ transplant recipients and in those undergoing chemotherapy for haematological malignancies; however, it has been described following almost any form of immunosuppressive treatment. Fortunately, it can be largely prevented by prophylactic therapy with oral anti-HBV nucleoside/nucleotide analogues. Importantly, chronic HBV infection is usually asymptomatic, and most patients at risk are likely to be unaware that they carry the infection. Thus, the key to avoiding this potentially fatal complication of immunosuppressive treatment is to ensure that all patients at risk of chronic HBV infection are screened for the disease before commencing immunosuppressive treatment or chemotherapy.

Drug-induced gastrointestinal disorders.

Drug-induced gastrointestinal disorders can mimic conditions, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and, hence, recognition can prevent unnecessary investigations and treatment. While the knowledge and awareness relating to the adverse gastrointestinal effects of some medications, such as non-steroidal anti-inflammatory drugs are well established, other commonly prescribed drugs, such as antipsychotics, antidepressants and metformin are less well understood and warrant further study. This review attempts to integrate recent information regarding adverse drug reactions and place this in a useful clinical context.

Review article: vitamin D and inflammatory bowel disease--established concepts and future directions.

BACKGROUND: Understanding of the role of vitamin D in health and disease has increased markedly in the past decade, with its involvement extending well beyond traditional roles in calcium and phosphate homeostasis and musculoskeletal health. This conceptual expansion has been underpinned by identification and exploration of components of this axis including vitamin D-binding protein, key enzymes and receptors in multiple cell types, and a greater recognition of nonclassical autocrine and paracrine effects. Its influence in IBD remains uncertain. AIM: To review the role of vitamin D in bone health, immune regulation and cancer prevention in IBD, and to outline practical issues and limitations of its use. METHODS: An extensive online literature review including PubMed and Medline. RESULTS: In patients with IBD, the vitamin D axis provides an important and often underutilised pathway to preserving bone health. Furthermore, an exciting body of clinical and basic science research demonstrates that these pathways may have an integral part to play in regulation of the immune response in IBD, through effects on the intestinal barrier, antigen presenting cells and adaptive T cells. The possibility of chemoprevention requires further study. The optimal target level of 25-hydroxy vitamin D in patients with IBD is currently uncertain, as is the best therapeutic modality. CONCLUSIONS: Study of vitamin D pathways may result in the development of relatively inexpensive therapeutic options to optimise patient outcomes. Further prospective clinical research is required to address efficacy and long-term safety.

Review article: the pathophysiological roles of the renin-angiotensin system in the gastrointestinal tract.

BACKGROUND: The renin-angiotensin system (RAS) is a homeostatic pathway widely known to regulate cardiovascular and renal physiology; however, little is known about its influence in gastrointestinal tissues. AIM: To elicit the anatomical distribution and physiological significance of the components of the RAS in the gastrointestinal tract. METHODS: An extensive online literature review including Pubmed and Medline. RESULTS: There is evidence for RAS involvement in gastrointestinal physiology and pathophysiology, with all the components required for autonomous regulation identified throughout the gastrointestinal tract. The RAS is implicated in the regulation of glucose, amino acid, fluid and electrolyte absorption and secretion, motility, inflammation, blood flow and possibly malignant disease within the gastrointestinal tract. Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. Given the ready availability of drugs that modify the RAS and their excellent safety profile, an opportunity exists for investigation of their possible therapeutic role in a variety of human gastrointestinal diseases. CONCLUSIONS: The gastrointestinal renin-angiotensin system appears to be intricately involved in a number of physiological processes, and provides a possible target for novel investigative and therapeutic approaches.

Angiotensin converting enzyme 2 (ACE2) activity in fetal calf serum: implications for cell culture research.

Cell culture experiments often employ the use of culture media that contain fetal calf serum (FCS). The angiotensin peptides angiotensin II and angiotensin 1-7 have opposing effects with angiotensin converting enzyme 2 (ACE2) being the enzyme predominantly responsible for generating angiotensin 1-7 from angiotensin II. The effect of FCS on angiotensin peptides has not previously been described. We have shown that FCS has ACE2 enzyme activity capable of degrading angiotensin II and generating angiotensin 1-7. Researchers should be aware that FCS possesses ACE2 activity and that heat-treating FCS to 56 degrees C only partially inhibits this enzyme activity, whereas heat-treating to 70 degrees C completely abolishes ACE2 activity.

Modern management of portal hypertension.

The development of portal hypertension plays a major role in the pathogenesis of many of the complications of chronic liver disease. In developed countries, most patients with portal hypertension have cirrhosis, and, in this condition, portal pressure is elevated as a result of both an increase in hepatic resistance to portal perfusion and increased mesenteric blood flow. Bleeding from oesophageal varices is a major cause of mortality in patients with significant portal hypertension. This review concentrates on the recognition, prevention and acute management of this life threatening complication of cirrhosis.