Rising incidence of hepatitis B-related hepatocellular carcinoma in South Australia: 1996-2010.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is likely to be an important driver of increasing hepatocellular carcinoma (HCC) incidence in Australia. However, there is paucity of Australian data on HBV-related HCC incidence or outcomes. AIMS: To determine the incidence rates and survival trends of HBV-related HCC in South Australia (SA) over 15 years. METHODS: A population-based cohort study was performed in HBV patients notified to the SA Communicable Disease Control Branch between 1996 and 2010. The dataset was probabilistically linked with the SA Cancer Registry and death registry. Incidence rate trends and survival were determined for three 5-year time periods (1996-2000, 2001-2006 and 2006-2010). RESULTS: Forty-seven of 3881 notifications with HBV were linked to a HCC record (median (interquartile range) age at diagnosis: 58.9 (13.4) years, 83% males, 8.5% born in Australia, 62% diagnosed between 51-69 years). The overall crude HCC incidence was 111.3/100 000 person-years with an age-standardised HCC incidence of 189.1/100 000 person-years, the rate for men was higher than for women: 241.7 versus 88.6/100 000 person-years. The age-standardised HCC incidence increased over time with an annual percentage increase of 20.8% (95% CI: 10.06-32.54, P = 0.001). Median survival following HCC diagnosis was 12.5 months (95% CI: 3.6-21.4), with a trend towards longer survival during the 2006-2010 time period (21.8 months) compared to the previous two time periods (9.2 and 10.2 months, P = 0.056). CONCLUSION: Both crude and age-standardised incidences of HBV-related HCC increased between 1996 and 2010 in SA. There was a trend to longer survival in the latter time-period.

Prevalence of hepatic osteodystrophy and vitamin D deficiency in cirrhosis.

BACKGROUND: Hepatic osteodystrophy (HO) is a major complication of cirrhosis. However, the prevalence of HO in a general cirrhotic patient population is not well defined as previous studies were in single aetiology or pre-liver transplant patients. AIMS: The aims of this study were to investigate the prevalence of HO and vitamin D deficiency in patients with cirrhosis of mixed aetiology and disease severity and to determine the risk factors for HO. METHODS: This is a single-centre cross-sectional study of all patients newly diagnosed with cirrhosis between September 2009 and December 2012. All patients underwent bone mineral density assessment using dual energy X-ray absorptiometry within 3 months of diagnosis. Demographic and biochemical factors, severity of underlying liver disease, previous fragility fractures, smoking status and alcohol use were collected on diagnosis. Logistic regression analysis was used to assess risk factors for HO. RESULTS: Among the 406 patients (67% males), the median (range) age was 56 years (21-85) and most (84%) were Childs-Pugh A or B with a median (range) model for end-stage liver disease score of 11 (5-40). Alcohol (41%) was the most common underlying aetiology. The prevalence of HO and vitamin D deficiency (≤50 nmol/L) was 56% and 54%, respectively, and previous fragility fractures had occurred in 3%. Increasing age (odds ratio (95% confidence interval): 1.49 per 10 years (1.02-2.18), P = 0.04), excessive alcohol intake (2.34 (1.03-5.32), P = 0.04) and lower body mass index (0.92 per kg/m2 (0.87-0.98), P = 0.009) were independent risk factors for HO. CONCLUSION: There is a high prevalence of HO and vitamin D deficiency in patients with cirrhosis at presentation irrespective of disease severity or underlying aetiology.

Optimisation of hepatocellular carcinoma surveillance in patients with viral hepatitis: a quality improvement study.

BACKGROUND: Surveillance for hepatocellular carcinoma (HCC) with 6-monthly ultrasound is a standard of care for higher-risk patients with viral hepatitis. Adherence to screening guidelines is an important quality indicator in hepatology, but multiple studies have demonstrated poor HCC surveillance practices in real-world settings. AIMS: The aim of this project was to audit and then optimise HCC surveillance of viral hepatitis patients, who fulfilled criteria for screening, associated with a large tertiary hospital. METHODS: Clinical practice improvement principles were utilised. A baseline audit of 22 consecutive viral hepatitis patients was performed. Major barriers preventing adequate surveillance were identified and three interventions to improve adherence to guidelines were introduced. These included: improved doctor education, system redesign and improved patient education. The effects of interventions were measured by serial random audits of patients. A final audit occurred over 3 years after the initial baseline audit. RESULTS: At baseline, 46% and 0% of patients had appropriate surveillance performed during the prior 6 months (one surveillance cycle) and 2 years (four surveillance cycles) respectively. Three years after initiation of these strategies, a final audit revealed 92% (vs 46% at baseline) and 64% (vs 0% at baseline) of patients had appropriate HCC surveillance performed during the preceding 6 months and 2 years intervals respectively (P < 0.001 in each case). CONCLUSIONS: Simple and low-cost interventions can considerably improve the clinical effectiveness of HCC screening programmes in real world settings. Clinical practice improvement principles appear to be a valid methodology for achieving this positive change.

Liver resection and transplantation offer similar 5-year survival for Child-Pugh-Turcotte A HCC-patients with a single nodule up to 5 cm: a multicenter, exploratory analysis.

BACKGROUND AND AIM: The current guideline of the American Association for the Study of Liver Diseases recommends liver resection for Child-Pugh-Turcotte A patients with a single hepatocellular carcinoma, total serum bilirubin ≤ 1 mg/dL and absence of significant portal hypertension. This subset of patients would have a long-term survival comparable to transplantation. The main aim of this study is to evaluate the survival rates in patients with a single nodule ≤ 5 cm following resection. METHODS: Medical records of 105 Child-Pugh-Turcotte A patients who underwent liver resection between 1997 and 2009 were analyzed in 3 countries. RESULTS: One, 3-, and 5-year survival rate was 97%, 83%, and 66%, respectively, and no variable that can be assessed prior to liver resection predicted survival probabilities. CONCLUSIONS: Liver resection offers 5-year survival similar to transplantation for Child-Pugh-Turcotte A patients with hepatocellular carcinoma and a single nodule up to 5 cm, independently of any patient baseline characteristics.

Chronic kidney disease following liver transplantation: a South Australian experience.

The incidence of chronic kidney disease (CKD) and its impact on survival have not been widely studied in the Australian liver transplant (OLT) population. The aims of this study were to evaluate the prevalence of CKD stages at various time points, calculate the cumulative incidence of progression to severe CKD, and study the impact of CKD stages on patient survival and risk factors for severe CKD in a single-center post-OLT population. We studied retrospectively 130 patients who underwent OLT in South Australia with a minimum of 6 months of follow-up from 1992 to 2008. CKD was staged according to Kidney Diseases Outcome Quality Initiative Guidelines. Glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Multiple pre- and post-OLT variables were examined for their association with severe CKD. Log-rank tests and Cox regression analysis were performed to evaluate the survival data. The cumulative incidences of severe CKD (stages 4 and 5) at 2, 5, and 15 years were 3.8%, 12.7%, and 14.8%, respectively. Severe CKD was associated with an increased mortality (hazard ratio 6.5; 95% confidence interval = 2.5-17.0; P < .001). Mild and moderate CKD stages were not associated with increased mortality. Risk factors for severe CKD were: female gender, hepatitis C infection, pre-OLT diabetes, acute renal failure post-OLT, and low 1-year GFR. Mild and moderate CKD are common post-OLT. The development of severe CKD, which can be predicted early in the post-OLT period, is strongly associated with an increased mortality rate.

Heterozygous recipient and donor HFE mutations associated with a hereditary haemochromatosis phenotype after liver transplantation.

We observed the development of phenotypic hereditary haemochromatosis in a non-hereditary haemochromatosis liver transplant recipient, following transplantation with a liver from a C282Y heterozygous donor. No cause for secondary iron overload was identified. Subsequent sequencing of the HFE gene of both donor and recipient revealed a strong candidate for a novel pathogenic HFE mutation. In the recipient, heterozygosity for a single base substitution in exon 1, g.18 G>C, resulting in the substitution of arginine by serine at codon 6 (R6S), was detected. This R6S variation is likely to represent a novel pathogenic missense mutation of the HFE gene. An interaction between R6S heterozygosity in the recipient and C282Y heterozygosity in the donor liver is the most likely explanation for the development of iron overload in this patient. The report suggests that an hepatic defect is required for expression of hereditary haemochromatosis and that the intestinal HFE genotype is not the exclusive determinant of iron status. It also raises the possibility that a hereditary haemochromatosis phenotype may result from transplantation of C282Y heterozygous donor livers into recipients with heterozygous pathogenic HFE mutations. This possibility may have significant implications for the common practice of transplanting C282Y heterozygous livers.

The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis.

BACKGROUND: Small intestinal bacterial overgrowth may contribute to the development of non-alcoholic steatohepatitis, perhaps by increasing intestinal permeability and promoting the absorption of endotoxin or other enteric bacterial products. AIMS: To investigate the prevalence of small intestinal bacterial overgrowth, increased intestinal permeability, elevated endotoxin, and tumour necrosis factor alpha (TNF-alpha) levels in patients with non-alcoholic steatohepatitis and in control subjects. PATIENTS AND METHODS: Twenty two patients with non-alcoholic steatohepatitis and 23 control subjects were studied. Small intestinal bacterial overgrowth was assessed by a combined (14)C-D-xylose and lactulose breath test. Intestinal permeability was assessed by a dual lactulose-rhamnose sugar test. Serum endotoxin levels were determined using the limulus amoebocyte lysate assay and TNF-alpha levels using an ELISA. RESULTS: Small intestinal bacterial overgrowth was present in 50% of patients with non-alcoholic steatosis and 22% of control subjects (p=0.048). Mean TNF-alpha levels in non-alcoholic steatohepatitis patients and control subjects were 14.2 and 7.5 pg/ml, respectively (p=0.001). Intestinal permeability and serum endotoxin levels were similar in the two groups. CONCLUSIONS: Patients with non-alcoholic steatohepatitis have a higher prevalence of small intestinal bacterial overgrowth, as assessed by the (14)C-D-xylose-lactulose breath test, and higher TNF-alpha levels in comparison with control subjects. This is not accompanied by increased intestinal permeability or elevated endotoxin levels.