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Hepatocellular carcinoma (HCC) is one of the most common cancers around the globe and third most fatal malignancy. Chronic liver disorders such as chronic hepatitis and liver cirrhosis often lead to the development of HCC. Accumulation of genetic and epigenetic alterations are involved in the development of HCC. Genetic research sparked by recent developments in next generation sequencing has identified the frequency of genetic alterations that occur in HCC and has led to the identification of genetic hotspots. Emerging evidence suggests that epigenetic aberrations are strongly associated with the initiation and development of HCC. Various important genes encoding tumor suppressors including P16, RASSF1A, DLC-1, RUNX3 and SOCS-1 are targets of epigenetic dysregulation during the development of HCC. The present review discusses the importance of epigenetic regulations including DNA methylation, histone modification and microRNA mediated regulation of gene expression during tumorigenesis and their use as disease biomarkers. Furthermore, these epigenetic alterations have been discussed in relationship with promising therapeutic perspectives for HCC and related cancers.

BackgroundChronic kidney disease (CKD) is being increasingly recognized as a leading public health problem. However, there are limited data available with respect to prevalence of CKD in Pakistan, a developing South Asian country. The study presents the baseline findings of prevalence and risk factors for adult kidney disease in a Pakistani community cohort.MethodsA total of 667 households were enrolled between March 2010 and August 2011 including 461 adults, aged 15 and older. Mild kidney disease was defined as estimated Glomerular Filtration Rate (eGFR) ≥60 ml/min with microalbuminuria ≥ 30 mg/dl and moderate kidney disease was defined as eGFR <60 ml/min (with or without microalbuminuria).ResultsThe overall prevalence of kidney disease was 16.6% with 8.6% participants having mild kidney disease and 8% having moderate kidney disease. Age was significantly associated with kidney disease (p < 0.0001). The frequency of diabetes, hypertension and smoking differed significantly among the three groups, i.e., no kidney disease, mild kidney disease and moderate kidney disease.ConclusionOur study results suggest that the burden of kidney disease in this population is found considerable and comparable to neighboring developing countries. We believe that these results have critical implications on health and economics of these countries and due to the epidemic of diabetes, hypertension, cardiovascular disease, smoking and association with worsening poverty, further rapid growth is expected. There is an urgent need for early recognition and prevention strategies based on risk factors and disease trends determined through longitudinal research.

BackgroundThe demographic transition in South Asia coupled with unplanned urbanization and lifestyle changes are increasing the burden of non-communicable disease (NCD) where infectious diseases are still highly prevalent. The true magnitude and impact of this double burden of disease, although predicted to be immense, is largely unknown due to the absence of recent, population-based longitudinal data. The present study was designed as a unique ‘Framingham-like’ Pakistan cohort with the objective of measuring the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection in a multi-ethnic, middle to low income population of Karachi, Pakistan.MethodsWe selected two administrative areas from a private charitable hospital’s catchment population for enrolment of a random selection of cohort households in Karachi, Pakistan. A baseline survey measured the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection.ResultsSix hundred and sixty-seven households were enrolled between March 2010 and August 2011. A majority of households lived in permanent structures (85%) with access to basic utilities (77%) and sanitation facilities (98%) but limited access to clean drinking water (68%). Households had high ownership of communication technologies in the form of cable television (69%) and mobile phones (83%). Risk factors for NCD, such as tobacco use (45%), overweight (20%), abdominal obesity (53%), hypertension (18%), diabetes (8%) and pre-diabetes (40%) were high. At the same time, infectious diseases such as hepatitis B (24%) and hepatitis C (8%) were prevalent in this population.ConclusionOur findings highlight the need to monitor risk factors and disease trends through longitudinal research in high-burden transition communities in the context of rapid urbanization and changing lifestyles. They also demonstrate the urgency of public health intervention programs tailored for these transition communities.

Objectives To compare the outcomes and safety of a rapid access chest pain clinic (RACPC) in Australia with those of a general cardiology clinic. Design Prospective comparison of the outcomes for patients attending an RACPC and those of historical controls. Setting Royal Hobart Hospital cardiology outpatient department. Participants 1914 patients referred for outpatient evaluation of new onset chest pain (1479 patients seen in the RACPC, 435 patients previously seen in the general cardiology clinic). Main outcome measures Service outcomes (review times, number of clinic reviews); adverse events (unplanned emergency department re‐attendances at 30 days and 12 months; major adverse cardiovascular events at 12 months, including unplanned revascularisation, acute coronary syndrome, stroke, cardiac death). Results Median time to review was shorter for RACPC than for usual care patients (12 days [IQR, 8–15 days] v 45 days [IQR, 27–89 days]). All patients seen in the RACPC received a diagnosis at the first clinic visit, but only 139 patients in the usual care group (32.0%). There were fewer unplanned emergency department re‐attendances for patients in the RACPC group at 30 days (1.6% v 4.4%) and 12 months (5.7% v 12.9%) than in the control group. Major adverse cardiovascular events were less frequent among patients evaluated in the RACPC (0.2% v 1.4%). Conclusions Patients were evaluated more efficiently in the RACPC than in a traditional cardiology clinic, and their subsequent rates of emergency department re‐attendances and adverse cardiovascular events were lower.