Benjamin C. Cowie

Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews

BACKGROUND Injecting drug use is an important risk factor for transmission of viral hepatitis, but detailed, transparent estimates of the scale of the issue do not exist. We estimated national, regional, and global prevalence and population size for hepatitis C virus (HCV) and hepatitis B virus (HBV) in injecting drug users (IDUs). METHODS We systematically searched for data for HBV and HCV in IDUs in peer-reviewed databases (Medline, Embase, and PsycINFO), grey literature, conference abstracts, and online resources, and made a widely distributed call for additional data. From 4386 peer-reviewed and 1019 grey literature sources, we reviewed 1125 sources in full. We extracted studies into a customised database and graded them according to their methods. We included serological reports of HCV antibodies (anti-HCV), HBV antibodies (anti-HBc), or HBV surface antigen (HBsAg) in studies of IDUs with more than 40 participants (<100% HIV-positive) and sampling frames that did not exclude participants on the basis of age or sex. With endorsed decision rules, we calculated prevalence estimates with anti-HCV and anti-HBc as proxies for exposure and HBsAg as proxy for current infection. We combined these estimates with IDU population sizes to calculate the number of IDUs with positive HBV or HCV statuses. FINDINGS We located eligible reports with data for prevalence of anti-HCV in IDUs for 77 countries; midpoint prevalence estimates suggested 60-80% of IDUs had anti-HCV in 25 countries and more than 80% of IDUs did so in 12 countries. About 10.0 million (range 6.0-15.2) IDUs worldwide might be anti-HCV positive. China (1.6 million), USA (1.5 million), and Russia (1.3 million) had the largest such populations. We identified eligible HBsAg reports for 59 countries, with midpoint prevalence estimates of 5-10% in 21 countries and more than 10% in ten countries. Worldwide, we estimate 6.4 million IDUs are anti-HBc positive (2.3-9.7 million), and 1.2 million (0.3-2.7 million) are HBsAg positive. INTERPRETATION More IDUs have anti-HCV than HIV infection, and viral hepatitis poses a key challenge to public health. Variation in the coverage and quality of existing research creates uncertainty around estimates. Improved and more complete data and reporting are needed to estimate the scale of the issue, which will inform efforts to prevent and treat HCV and HBV in IDUs. FUNDING WHO and US National Institutes of Health (NIDA R01 DA018609).

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013

BACKGROUND With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS We estimated mortality using natural history models for acute hepatitis infections and GBDs cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING Bill & Melinda Gates Foundation.

The burden of chronic hepatitis B virus infection in Australia, 2011.

Objective: The number of Australians living with chronic hepatitis B (CHB) is thought to be increasing, as are adverse outcomes including cirrhosis and liver cancer, however, robust, up‐to‐date estimates of this burden are limited. Contemporary estimates of the prevalence of CHB in Australia are essential to guide appropriate public health and clinical responses.

Three years' experience of focused cardiovascular ultrasound in the peri-operative period

Ultrasound applications in peri‐operative medicine have become common place in modern anaesthesia practice. Anaesthetists have performed transoesophageal echocardiography in cardiac and selected non‐cardiac surgery for over two decades. We aimed to assess the indications, impact on clinical management and accuracy of focused cardiovascular ultrasound performed by anaesthetists in the peri‐operative period. One hundred and seventy patients over a 3‐year period had a focused transthoracic echocardiogram. Adequate images to answer the clinical question were obtained in 167 out of 170 patients (98%). The undifferentiated systolic murmur was the commonest indication (98 out of 170, 58%). Some degree of aortic stenosis was present in 47 out of 170 (26%) of patients; mitral valve disease (30 out of 170 (18%)) and pulmonary hypertension (25 out of 170 (14%)) were also common. Changes in peri‐operative management occurred in 140 out of 170 (82%) patients and major findings correlated with a formal cardiology transthoracic echocardiogram in 52 out of 57 (92%) patients. Focused cardiovascular ultrasound performed by anaesthetists in the peri‐operative period accurately detects major cardiac pathology and significantly alters peri‐operative management.

Hepatitis B Virus Epidemiology

The epidemiology of hepatitis B virus (HBV) infection is geographically diverse, with population prevalence, age and mode of acquisition, and likelihood of progression to chronic infection mutually interdependent. The burden of chronic HBV infection is increasingly being recognized, with cirrhosis and liver cancer attributable to HBV continuing to increase. The outcomes of chronic HBV infection are affected by a range of factors, including viral genotype, the presence of coinfections with other blood-borne viruses, and the impact of other causes of liver disease. The increased recognition of HBV infection as a leading cause of death globally has resulted in the development of new structures and policies at the international level; immediate attention to implementing these strategies is now required.

The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015

Importance Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. Objective To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes. Design, Settings, and Participants Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. Main Outcomes and Measures Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. Results There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. Conclusions and Relevance Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts.

Liver cancer is the fastest increasing cause of cancer death in Australians.

MJA 197 (9) · 5 November 2012 492 IN REPLY: The letters of Morgan and Fullerton correctly emphasise the importance of palliative care in the management of patients with metastatic melanoma. They also draw attention to the immense cost of new drugs for melanoma, and their limited efficacy in life extension — something I also emphasised.1 Much ignored in this debate is the rapid and dramatic improvement in quality of life experienced by nearly all melanoma patients on BRAF inhibitors,2 an example of where medical oncology and palliative care should, and must, work hand in hand in optimising patient comfort. We strive toward this goal in our multidisciplinary teams. However, it is in the adjuvant setting that the new antimelanoma drugs are likely to show large improvements in survival and where reimbursement of drug costs will become an increasing challenge. Morgan refers to the utility of adjuvant radiation therapy for cerebral metastases and quotes an uncontrolled retrospective series, from which, due to selection bias and other factors, only highly restricted conclusions can be made. Prospective randomised evidence for the benefit of adjuvant whole-brain radiation therapy awaits completion of an ongoing study by the Australia and New Zealand Melanoma Trials Group.

Evaluation of systolic murmurs using transthoracic echocardiography by anaesthetic trainees.

Focused transthoracic echocardiography by anaesthetists in the peri‐operative period has recently been described; the data suggest that the specific skills required can be obtained by non cardiology physicians with limited training. Aortic stenosis is known to increase significantly the peri‐operative risk in non‐cardiac surgery. This study aimed to assess the ability of echocardiography naive trainee anaesthetists to recognise and assess the severity of aortic stenosis after a set amount of training. Five trainees underwent 2 h of didactic and hands‐on teaching in evaluation of the aortic valve, after which they scanned 20 patients each. Their results were compared with those obtained by an experienced cardiac anaesthetist with echocardiography training and qualifications. There was 100% concordance between trainees and the consultant for assessment of clinically significant aortic stenosis, with no cases of misdiagnosis. There was also 90–100% agreement (kappa statistic 0.8–1) between the consultant and each trainee’s assessment of clinically significant aortic stenosis based on a peak aortic velocity > 3 m.sec−1. Anaesthesia trainees can be successfully and rapidly trained to recognise and estimate the severity of aortic stenosis.

The molecular epidemiology of hepatitis B in the Indigenous people of northern Australia

The hepatitis B surface antigen was first described in the blood of an Indigenous Australian man, yet little is known about its molecular epidemiology in this population, in which it is endemic. The study aimed to determine the clinical and molecular epidemiology of hepatitis B virus (HBV) in Indigenous people from northern Australia.

Mortality due to viral hepatitis in the Global Burden of Disease Study 2010: new evidence of an urgent global public health priority demanding action.

The recently published Global Burden of Disease Study 2010 (GBD 2010) contains accurate, contemporary estimates of human morbidity and mortality, with substantial changes in the patterns of illness observed over the last two decades. One of the most significant alterations to these estimates has been the recognition that viral hepatitis is a leading cause of human mortality, with an estimated 1.29 million deaths worldwide in 2010. The global community must act to address emerging health priorities identified by GBD 2010, including the need to provide treatment and care to people living with viral hepatitis, especially in resource-poor settings.