Anthony Rode

Oral vitamin D replacement is effective in chronic liver disease

BACKGROUND & AIMS End-stage chronic liver disease is associated with vitamin D deficiency but the prevalence across a broad-spectrum of liver disease is unknown. This study prospectively examines prevalence of vitamin D deficiency and response to replacement in chronic liver disease. METHODS One hundred and fifty-eight outpatients with chronic liver disease were enrolled. Serum 25-hydroxyvitamin D (25[OH]D) levels were classified as: severely deficient less than 25 nmol/l, deficient 25-54 nmol/l or replete greater than 54 nmol/l. Sixty-five of 158 (41%) had cirrhosis. RESULTS 25[OH]D was suboptimal in 101/158 (64%), including severe deficiency in 24 patients (15%). Vitamin D deficiency occurred in liver disease of all aetiologies, including patients with only mild liver disease. 25[OH]D increased by 60.0% (19.11 ± 13.20 nmol/l) in patients with deficiency after vitamin D replacement and decreased by 25.2% (-18.33 ± 12.02 nmol/l) in non-treated initially replete patients over a median of 4 months. CONCLUSIONS Vitamin D deficiency improves with oral vitamin D supplementation and levels fall without supplementation. Chronic liver disease patients are at very high risk of vitamin D deficiency regardless of etiology or severity.

Hepatic macrophage activation predicts clinical decompensation in chronic liver disease

Hepatic macrophages (Kupffer cells) play important roles in inflammation and portal hypertension in patients with chronic liver disease (CLD).1 We recently showed that plasma soluble CD163 (sCD163), a specific marker for macrophage activation, is produced within and released from the liver with a direct relationship to the portal venous pressure gradient.2 ,3 We hypothesised that: (1) sCD163 is elevated in patients with CLD with previous clinical decompensation; and (2) sCD163 is a marker for CLD progression and clinical deterioration. We measured sCD163 in 52 controls and 116 consecutive patients with CLD (89% cirrhosis) caused by chronic hepatitis C (36%), alcohol (30%), non-alcoholic fatty liver disease (11%), chronic hepatitis B (10%); other liver diseases (12%) accounted for the remainder of the cases. Cirrhosis was diagnosed by consistent examination and radiological findings, or by liver biopsy. All controls had no history or clinical examination signs of CLD, and normal liver function tests. They were followed for a median of …

Vitamin B12 and its binding proteins in hepatocellular carcinoma and chronic liver diseases

Abstract Background. The vitamin B12 (B12)-binding protein haptocorrin (HC) has proven to be a potentially useful biomarker in patients with fibrolamellar hepatocellular carcinoma (HCC). Little is known concerning the level of HC and other B12-related proteins in patients with HCC as compared to patients with other chronic liver diseases (CLDs) and healthy controls. We hypothesized that HC could be a biomarker of HCC. Aims. To investigate levels of HC and B12-related proteins in HCC compared to CLDs and healthy controls. Methods. We investigated two patient populations: A cross-sectional cohort of HCC patients (n = 130), CLD patients (n = 102) and healthy controls (n = 46) and a cohort of 38 HCC patients studied at baseline and 1, 4, and 12 weeks following ablative treatment. Patients were evaluated by standard biochemistry, Child–Pugh-score and Barcelona Clinic Liver Cancer (BCLC) classification. We analyzed total B12 by routine methods and HC, transcobalamin (TC), B12 saturated TC (holoTC), and the soluble cell surface receptor for holoTC (sCD320) by in-house enzyme-linked immunosorbent assay. Results. HC showed higher median (range) levels for both HCC (590 [290–5860]) and CLD patients (620 [310–4010]) compared to controls (460 [250–2020]) (p < 0.01). Total B12, TC, holoTC, and sCD320 showed elevated levels in both HCC and CLD compared to controls. Only holoTC changed following treatment, without a concurrent change in TC. Conclusion. B12 and B12-related proteins (total B12, HC, TC, holoTC, and sCD320) show elevations in both HCC and CLD patients compared to controls, suggesting a relation to CLD in general rather than to primary liver cancer. Thus, HC is not useful as a biomarker for HCC.

Radiofrequency ablation versus resection for the treatment of early stage hepatocellular carcinoma: a multicenter Australian study

Abstract Objectives. It remains unclear whether radiofrequency ablation (RFA) provides comparable outcomes to surgical resection (SR). We, therefore, compared survival outcomes of RFA to SR in patients with early stage and very early stage hepatocellular carcinoma (HCC). Methods. A multicenter retrospective analysis was performed in patients from five academic hospitals with Barcelona Cancer of the Liver Clinic (BCLC) stages 0–A HCC having RFA or SR as primary therapy. Results. From 2000–2010, 146 patients who received treatment with RFA (n = 96) or SR (n = 52) were identified. In BCLC A patients with ≤5 cm HCC, there was a trend of lower overall survival after RFA compared with SR (3- and 5-year survival: 62% and 37% vs. 66% and 62% respectively; p = 0.11). By multivariate analysis, RFA was an independent predictor of poor survival (hazard ratio = 2.26; 95% confidence interval: 1.02–5.03; p = 0.04). In ≤3 cm HCC (n = 109), the 3- and 5-year survivals in RFA and SR groups were 66% and 39%, and 69% and 59%, respectively, with no difference in the median survival (p = 0.41). Local recurrence was significantly higher after RFA compared to SR in HCC ≤5 cm (p = 0.006) with a trend of lower recurrence-free survival (p = 0.06) after RFA in HCC ≤3 cm. There were fewer major complications after RFA (2% vs. 8%). Conclusion. While SR is superior to RFA for the management of early stage BCLC A disease with ≤5 cm HCC, both appear effective as first-line treatment options for Western patients with small ≤3 cm tumors. Although safer than SR, RFA is associated with higher rates of tumor recurrence and local disease progression. Further prospective randomized controlled trials are warranted to compare these two modalities.

Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma.

Abstract Background: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. Methods: In a cohort from Australia, we studied 109 HCC patients, 116 patients with chronic liver disease (CLD), and 52 healthy controls. We examined associations between baseline sCD163 and parameters of HCC severity as well as overall and progression-free survival. In a cohort of 42 Danish HCC patients, we measured sCD163 at baseline and 1, 4 and 12 weeks after ablative treatment. Results: In the Australian cohort, median sCD163 was similarly increased in HCC (5.6[interquartile range 3.5–8.0] mg/L) and CLD (6.1[3.6–9.6] mg/L) patients as compared to controls (2.0[1.5–2.7] mg/L, p < 0.001). sCD163 correlated with Child-Pugh and MELD scores in both HCC and CLD patients. Patients with high sCD163 levels had shorter progression-free survival (p < 0.001), but not overall survival (p = 0.15). In the Danish cohort, patients with HCC progression at 12 weeks had an increase in sCD163. There was no association between sCD163 and HCC size, number, vascular invasion or metastasis in any of the cohorts. Conclusions: We confirmed increased sCD163 levels in CLD and HCC patients associated with Child-Pugh and MELD scores and portal hypertension, but not with HCC size and number, or metastasis. As a novel finding, baseline sCD163 appeared to predict a rapid HCC progression, as sCD163 increased during follow-up in HCC patients who showed progression.

Circulating CD147 predicts mortality in advanced hepatocellular carcinoma

The glycoprotein CD147 has a role in tumor progression, is readily detectable in the circulation, and is abundantly expressed in hepatocellular carcinoma (HCC). Advanced HCC patients are a heterogeneous group with some individuals having dismal survival. The aim of this study was to examine circulating soluble CD147 levels as a prognostic marker in HCC patients.

Gastroenterology training in Australia: a perspective from the coal face

The Royal Australasian College of Physicians is developing curricula for training.