Mohamed I.F. Shariff

Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide and, owing to changes in the prevalence of the two major risk factors, hepatitis B virus and hepatitis C virus, its overall incidence remains alarmingly high in the developing world and is steadily rising across most of the developed world. Early diagnosis remains the key to effective treatment and there have been recent advances in both the diagnosis and therapy of HCC, which have made important impacts on the disease. This review outlines the epidemiological trends, risk factors, diagnostic developments and novel therapeutics for HCC, both in the developing and developed world.

Urinary Metabolic Biomarkers of Hepatocellular Carcinoma in an Egyptian Population: A Validation Study

The advent of metabonomics has seen a proliferation of biofluid profiling studies of patients with hepatocellular carcinoma. The majority of these studies have been conducted in single indigenous populations making the widespread applicability of candidate metabolite biomarkers difficult. Presented here is a urinary proton nuclear magnetic resonance spectroscopy study of mainly hepatitis C virus infected Egyptian patients with hepatocellular carcinoma, which corroborates findings of a previous study from our group of mainly hepatitis B-infected Nigerian patients with hepatocellular carcinoma. Using multivariate statistical analysis, in the form of orthogonal signal-corrected partial least squared discriminant analysis, the sensitivity and specificity of the technique for distinguishing patients with tumors from healthy controls and patients with cirrhosis was 100%/94% and 81%/71%, respectively. Discriminatory metabolites included glycine, trimethylamine-N-oxide, hippurate, citrate, creatinine, creatine, and carnitine. This metabolic profile bears similarity to profiles identified in the Nigerian cohort of subjects indicative of tumor effects on physiology, energy production, and aberrant chromosomal methylation. This is the first study to identify similarly altered urine metabolic profiles of hepatocellular carcinoma in two etiologically and ethnically distinct populations, suggesting that altered metabolism as a result of tumorogenesis is independent of these two factors.

Characterization of urinary biomarkers of hepatocellular carcinoma using magnetic resonance spectroscopy in a Nigerian population.

Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy worldwide. Current serum diagnostic biomarkers, such as alpha-fetoprotein, are expensive and insensitive in early tumor diagnosis. Urinary biomarkers differentiating HCC from chronic liver disease would be practical and widely applicable. Using an 11.7T nuclear magnetic resonance system, urine was analyzed from three well-matched subject groups, collected at Jos University Teaching Hospital (JUTH), Nigeria. Multivariate factor analyses were performed using principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). All patients were of Nigerian descent: 18 hepatitis B surface antigen (HBsAg)-positive patients with HCC, 10 HBsAg positive patients with cirrhosis, and 15 HBsAg negative healthy Nigerian controls. HCC patients were distinguished from healthy controls, and from the cirrhosis cohort, with sensitivity/specificity of 100%/93% and 89.5%/88.9%, respectively. Metabolites that most strongly contributed to the multivariate models were creatinine, carnitine, creatine and acetone. Urinary (1)H MRS with multivariate statistical analysis was able to differentiate patients with HCC from normal subjects and patients with cirrhosis. Creatinine, carnitine, creatine and acetone were identified as the most influential metabolites. These findings have identified candidate urinary HCC biomarkers which have potential to be developed as simple urinary screening tests for the clinic.

Hepatocellular carcinoma: diagnostics and screening

Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy and the third most common cause of cancer-related death worldwide. Incidence remains highest in the developing world and is steadily increasing across the developed world. The majority of HCC occurs on a background of cirrhosis, principally caused by two major risk factors, chronic hepatitis B and hepatitis C infection. Current diagnostic modalities, of ultrasound and α-fetoprotein, are expensive and lack sensitivity in tumour detection. Early diagnosis is integral to improved survival rates and there have been recent advances in technology that have enabled early identification of the process of hepatocarcinogenesis. This review outlines the epidemiological trends and risk factors for HCC; diagnostic techniques and current guidelines for screening and surveillance; and newer methods of screening.

Biofluid metabonomics using (1)H NMR spectroscopy: the road to biomarker discovery in gastroenterology and hepatology.

Metabolic profiling or ‘metabonomics’ is an investigatory method that allows metabolic changes associated with the presence of an underlying pathological process to be investigated. Various biofluids can be utilized in the process but urine, serum and fecal extract are most pertinent to the investigation of gastrointestinal and hepatological disease. Nuclear magnetic resonance spectroscopy-based metabonomic research has the potential to generate novel noninvasive diagnostic tests, based on biomarkers of disease, which are simple and cost effective yet retain high sensitivity and specificity characteristics. The process involves a number of key steps, including sample collection, data acquisition, chemometric techniques and, finally, validation. This technique-driven review aims to demystify the metabonomics pathway, while also illustrating the potential of this technique with recent examples of its application in hepato–gastroenterological disease.

Hepatocellular carcinoma: Review of disease and tumor biomarkers

Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburgs phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest.

The palliation of cholangiocarcinoma.

Purpose of reviewCholangiocarcinoma is the second most common primary liver tumour, worldwide. Its incidence and mortality are rising, the cause of which is unclear. Cholangiocarcinoma usually presents late, with obstructive jaundice, malaise, weight loss and discomfort. For most patients, complete surgical resection, the only potential cure, is not possible. Survival length and palliation of symptoms become paramount and often this centres on restoration of bile flow to relieve jaundice and improve general well being. There are now multiple options to achieve this goal and emerging evidence supports certain methods over others. Recent findingsFor advanced cholangiocarcinoma, endoscopic biliary stenting has become an established treatment. Recent evidence supports the use of metal stents over plastic to improve survival and stent patency. Locoregional therapies, such as radiofrequency ablation, transarterial chemoembolisation and radiotherapy have shown promise in preliminary studies. Landmark studies have established the use of cisplatin and gemcitabine as first-line chemotherapy in advanced cholangiocarcinoma. SummaryThe rise in incidence of advanced cholangiocarcinoma, has necessitated the development of novel therapies to optimize palliation. This article discusses the current options for palliation of cholangiocarcinoma, including stenting, locoregional therapy, surgery, endoscopic ultrasound and palliative chemotherapy.