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Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiological studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the US.

An increase in the number of cases of hepatocellular carcinoma has occurred in the United States over the past two decades. The age-specific incidence of this cancer has progressively shifted toward younger people.

SUMMARY Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole exome sequencing and DNA copy number analyses, and 196 HCC also by DNA methylation, RNA, miRNA, and proteomic expression. DNA sequencing and mutation analysis identified significantly mutated genes including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or down-regulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.

Objective To update the findings of the 2005 systematic review of population-based studies assessing the epidemiology of gastro-oesophageal reflux disease (GERD). Design PubMed and Embase were screened for new references using the original search strings. Studies were required to be population-based, to include ≥200 individuals, to have response rates ≥50% and recall periods <12 months. GERD was defined as heartburn and/or regurgitation on at least 1 day a week, or according to the Montreal definition, or diagnosed by a clinician. Temporal and geographic trends in disease prevalence were examined using a Poisson regression model. Results 16 studies of GERD epidemiology published since the original review were found to be suitable for inclusion (15 reporting prevalence and one reporting incidence), and were added to the 13 prevalence and two incidence studies found previously. The range of GERD prevalence estimates was 18.1%–27.8% in North America, 8.8%–25.9% in Europe, 2.5%–7.8% in East Asia, 8.7%–33.1% in the Middle East, 11.6% in Australia and 23.0% in South America. Incidence per 1000 person-years was approximately 5 in the overall UK and US populations, and 0.84 in paediatric patients aged 1– 17 years in the UK. Evidence suggests an increase in GERD prevalence since 1995 (p<0.0001), particularly in North America and East Asia. Conclusions GERD is prevalent worldwide, and disease burden may be increasing. Prevalence estimates show considerable geographic variation, but only East Asia shows estimates consistently lower than 10%.

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The incidence rates of cholangiocarcinoma (CC) vary greatly among different areas of the world, and this variation is related to distribution of risk factors. Intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) have different epidemiological features. Recent data show that the incidence and mortality rates of ICC have been increasing in several areas around the world. On the other hand, the incidence and mortality rates of ECC have been decreasing. For example, in the United States, the age-adjusted incidence rates of ICC increased by 165% from 0.32 per 100,000 in 1975 to 1979 to 0.85 per 100,000 in 1995 to 1999, whereas ECC declined by 14%. In the meantime, there has been very little improvement in long-term survival, which remains dismal (3.5%). Men are affected 1.5 times more than women are, and Asians are affected almost 2 times more than whites and blacks. There are few well-established risk factors for CC, including primary sclerosing cholangitis, liver fluke infestations, hepatolithiasis, Thorotrast exposure, and choledochal cysts. None of these risk factors can explain the recent increasing trends of ICC in the United States. Some data, however, point to a potential role for chronic liver disease, hepatitis C, and probably hepatitis B infections in the development of ICC.