An updated assessment of hepatitis delta prevalence among adults in Canada: A meta-analysis.

Foreign-born (FB) persons represent a large proportion of adults with chronic hepatitis B (CHB) in Canada due to higher prevalence rates in countries of birth for FB persons. Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of Canada HDV prevalence. We aim to provide an assessment of CHB and HDV prevalence in Canada using a comprehensive literature review and meta-analysis. A comprehensive literature review of articles reporting HBsAg seroprevalence and anti-HDV prevalence was conducted to calculate country-specific rates and pooled prevalence of CHB and HDV using meta-analyses. Country-specific CHB and HDV rate estimates were combined with number of FB persons in Canada in 2021 from Statistics Canada to estimate total numbers of FB with CHB and HDV, respectively. These estimates were combined with estimates of Canada-born persons with CHB and HDV to yield the total number of persons with CHB and HDV. In 2021, we estimated 0.550 million (M) (95% CI 0.488-0.615) persons with CHB; 0.344 M (95% CI 0.288-0.401) were FB and 0.206 M (95% CI: 0.200-0.214) were Canada-born. The weighted average HDV prevalence among FB persons in Canada was 5.19% (17,848 [95% CI 9611-26,052] persons), among whom 50% emigrated from Asia and 31% from Africa. When combined with estimates of Canada-born persons with HDV, we estimate 35,059 (95% CI: 18,744-52,083) persons with HDV in Canada. In conclusion, we estimate 0.550 M and 35,059 persons living with CHB and HDV, respectively, in Canada in 2021.

Assessment of pathomorphological characteristics of the oral mucosa in patients with HBV, HCV and HIV.

INTRODUCTION: Oral clinical manifestations in HBV HCV and HIV patients indicate a deterioration in general health status. The aim of the study was to assess pathomorphologic features of oral mucosa observed in patients with these diseases. METHODOLOGY: The study was conducted in N1 Dental Clinic of YSMU after M. Heratsi. The total number of patients taking part in the research was 120, including HBV (n = 40), HCV (n = 40) and HIV (n = 40). After biopsy and subsequent histological examination of the oral mucosa, statistical analysis was carried out using Excel 2013 and R software. RESULTS: Pathomorphological examination revealed inflammatory infiltrations in all samples collected from HBV, HCV and HIV patients. These changes included microcirculatory disorders in 98.3% of samples: fibrinous-like deposits lining the surface of erosions and ulcers on the oral mucosa (1.67%), fibrosis of the mucous membrane (70%), dystrophy of squamous epithelium (93.3%) and bone sequestration (3.3%). Comparative analysis of pathomorphological characteristics revealed distinct content of infiltrates: lymphoplasmacytic infiltration in patients with HBV and HCV, while HIV patients showed neutrophils infiltration and lack of plasmocytes. CONCLUSIONS: There are common abnormal morphological changes in the oral mucosa typical of all patients with HBV, HCV and HIV, as well as liver diseases specific to each of them. Inflammation in the patients with HIV indicated impairment of the humoral immune system. Understanding the distinct characteristic of inflammation in the oral cavity could be useful for early differential diagnosis and management of patients with HIV, HBV and HCV.

Unmet needs in occupational health: prevention and management of viral hepatitis in healthcare workers in Ho Chi Minh City, Vietnam: a mixed-methods study.

OBJECTIVES: Vietnam is an endemic area for hepatitis B virus and hepatitis C virus infection (HBV-HCV), yet its largest city, Ho Chi Minh City (HCMC), has no comprehensive policy to educate, screen, treat and protect healthcare workers (HCWs) from viral hepatitis. We conducted a mixed-methods study to document HBV-HCV infection rates, risk factors, local barriers and opportunities for providing education, screening and medical care for HCWs. DESIGN: This mixed-methods study involved an HBV and HCV serological evaluation, knowledge, attitude and practice survey about viral hepatitis and many in-depth interviews. Descriptive statistics and thematic content analysis using inductive and deductive approaches were used. SETTING: HCMC, Vietnam. PARTICIPANTS: HCWs at risk of viral hepatitis exposure at three hospitals in HCMC. RESULTS: Of the 210 invited HCWs, 203 were enrolled. Of the 203 HCWs enrolled, 20 were hepatitis B surface antigen-positive, 1 was anti-hepatitis C antibody (anti-HCV Ab)-positive, 57 were anti-hepatitis B core Ab-positive and 152 had adequate anti-hepatitis B surface Ab (anti-HBs Ab) titre (≥10IU/mL). Only 50% of the infected HCWs reported always using gloves during a clinical activity involving handling of blood or bodily fluid. Approximately 50% of HCWs were still not vaccinated against HBV following 1 year of employment. In-depth interviews revealed two major concerns for most interviewees: the need for financial support for HBV-HCV screening and treatment in HCWs and the need for specific HBV-HCV guidelines to be independently developed. CONCLUSIONS: The high HBV infection rate in HCWs coupled with inadequate preventive occupational practices among the population in HCMC highlight the urgent needs to establish formal policy and rigorous education, screening, vaccination and treatment programmes to protect HCWs from HBV acquisition or to manage those living with chronic HBV in Vietnam.

An Updated Assessment of Chronic Hepatitis B Prevalence Among Foreign-Born Persons Living in the United States.

BACKGROUND AND AIMS: Although prevalence of chronic hepatitis B (CHB) in the USA includes 0.42 million (range, 0.28-0.67) U.S.-born persons, foreign-born (FB) persons contribute a substantially larger number to the burden of CHB in the USA. Over the past decade, patterns of U.S. immigration have changed and many countries have implemented HBV prevention programs. This study aims to estimate the number of FB persons with CHB in the USA by country of origin, updating our 2011 study. APPROACH AND RESULTS: We performed systematic searches for articles published in 2009-2019 reporting HBsAg seroprevalence in emigrants and in-country populations of 117 countries. Data meeting inclusion criteria were combined with data from our 2011 study to calculate pooled prevalence estimates for 99 countries using meta-analyses (total 2,800 surveys involving 112 million subjects). Combining country-specific CHB rate estimates with the number of FB in the USA in 2018, by country of origin from the U.S. Census Bureau, we estimate that the number of FB with CHB in the USA in 2018 was 1.47 million (95% CI, 1.21-1.73), substantially higher than previously reported. The weighted average CHB prevalence for all FB in the USA in 2018 was 3.07%. Approximately 59% of FB with CHB in the USA in 2018 emigrated from Asia, 19% from the Americas, and 15% from Africa. Subgroup analyses found that for many countries, CHB rates are higher in males than females and have declined over the past three decades, but no consistent pattern is observed between emigrant and in-country rates. CONCLUSIONS: Including FB and U.S.-born persons, the total prevalence of CHB in the USA may be as high as 2.4 million.

Assessment of treatment options for patients with hepatitis C virus recombinant form 2k/1b.

AIM: Hepatitis C virus (HCV) intergenotype recombinant form (RF) 2k/1b has been actively circulating in HCV-infected patients, and the prevalence of this RF virus in the Republic of Georgia is one of the highest reported worldwide. The aim of this study was to define the optimal treatment regimen for patients with RF_2k/1b. METHODS: We analyzed the data of 2735 patients who started treatment at the Medical Center Mrcheveli within Georgia's hepatitis C elimination program from May 2015 through December 2019. The patients were treated with sofosbuvir (SOF)-based regimens. For identification of RF_2k/1b variants, refinement of standard (INNO-LiPA) genotyping results for all patient samples assigned the unspecific HCV genotypes (GT) 2a/2c was carried out by sequencing of core and non-structural protein 5B genes. RESULTS: Overall, 444 patients, representing 66% of GT2 and 16% of the total samples, were RF_2k/1b. Treatment of patients with RF_2k/1b with SOF/ledipasvir and SOF/velpatasvir was highly effective and viral cure rates did not differ among genotypes treated with the same regimen: RF_2k/1b, 99% (343/346); GT1, 99% (876/885); GT2, 96% (156/162); and GT3, 99% (545/552). A separate comparison analysis of sustained virologic response rate, treated with SOF plus ribavirin, showed significantly higher sustained virologic response (96%) in patients with confirmed GT2 (by sequencing) compared to unspecified GT2 (by INNO-LiPA) (79%) (P < 0.05). CONCLUSION: Sofosbuvir-based regimens are highly effective for treatment of RF 2k/1b patients, and with availability of new pan-genotypic direct-acting antivirals, genotyping to identify RF 2k/1b patients might not be necessary.

Markov modeling in hepatitis B screening and linkage to care.

BACKGROUND: With up to 240 million people chronically infected with hepatitis B worldwide, including an estimated 2 million in the United States, widespread screening is needed to link the infected to care and decrease the possible consequences of untreated infection, including liver cancer, cirrhosis and death. Screening is currently fraught with challenges in both the developed and developing world. New point-of-care tests may have advantages over standard-of-care tests in terms of cost-effectiveness and linkage to care. Stochastic modeling is applied here for relative utility assessment of point-of-care tests and standard-of-care tests for screening. METHODS: We analyzed effects of point-of-care versus standard-of-care testing using Markov models for disease progression in individual patients. Simulations of large cohorts with distinctly quantified models permitted the assessment of particular screening schemes. The validity of the trends observed is supported by sensitivity analyses for the simulation parameters. RESULTS: Increased utilization of point-of-care screening was shown to decrease hepatitis B-related mortalities and increase life expectancy at low projected expense. CONCLUSIONS: The results suggest that standard-of-care screening should be substituted by point-of-care tests resulting in improved linkage to care and decrease in long-term complications.

Management of hepatitis C virus infection in the Asia-Pacific region: an update.

The Asia-Pacific region has disparate hepatitis C virus (HCV) epidemiology, with prevalence ranging from 0·1% to 4·7%, and a unique genotype distribution. Genotype 1b dominates in east Asia, whereas in south Asia and southeast Asia genotype 3 dominates, and in Indochina (Vietnam, Cambodia, and Laos), genotype 6 is most common. Often, availability of all-oral direct-acting antivirals (DAAs) is delayed because of differing regulatory requirements. Ideally, for genotype 1 infections, sofosbuvir plus ledipasvir, sofosbuvir plus daclatasvir, or ombitasvir, paritaprevir, and ritonavir plus dasabuvir are suitable. Asunaprevir plus daclatasvir is appropriate for compensated genotype 1b HCV if baseline NS5A mutations are absent. For genotype 3 infections, sofosbuvir plus daclatasvir for 24 weeks or sofosbuvir, daclatasvir, and ribavirin for 12 weeks are the optimal oral therapies, particularly for patients with cirrhosis and those who are treatment experienced, whereas sofosbuvir, pegylated interferon, and ribavirin for 12 weeks is an alternative regimen. For genotype 6, sofosbuvir plus pegylated interferon and ribavirin, sofosbuvir plus ledipasvir, or sofosbuvir plus ribavirin for 12 weeks are all suitable. Pegylated interferon plus ribavirin has been replaced by sofosbuvir plus pegylated interferon and ribavirin, and all-oral therapies where available, but cost and affordability remain a major issue because of the absence of universal health coverage. Few patients have been treated because of multiple barriers to accessing care. HCV in the Asia-Pacific region is challenging because of the disparate epidemiology, poor access to all-oral therapy because of availability, cost, or regulatory licensing. Until these problems are addressed, the burden of disease is likely to remain high.

Race/ethnicity-specific disparities in cancer incidence, burden of disease, and overall survival among patients with hepatocellular carcinoma in the United States.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the fastest rising causes of cancer-related deaths in the United States, with disparities observed in cancer incidence and survival between ethnic groups. This report provides updated analyses on race-specific disparities in US HCC trends. METHODS: This large, population-based cohort study was conducted using Surveillance, Epidemiology, and End Results cancer registry data from 2003 to 2011 to investigate race-specific disparities in HCC incidence and survival. Survival was analyzed using Kaplan-Meier methods and multivariate Cox proportional-hazards models. RESULTS: From 2003 to 2011, Asians had the highest HCC incidence, followed by blacks, Hispanics, and non-Hispanic whites. During the same period, Hispanics had the greatest increase in HCC incidence (+35.8%), whereas Asians experienced a 5.5% decrease. Although patients aged ≥65 years had the highest HCC incidence among all racial/ethnic groups, the higher HCC incidence in Asians was observed only for patients ages <50 and ≥65 years, whereas HCC incidence among patients ages 50 to 64 years was similar among Asians, blacks, and Hispanics. The overall 5-year HCC survival rate was highest among Asians (26.1%; 95% confidence interval [CI], 24.5%-27.6%) and lowest among blacks (21.3%; 95% CI, 19.5%-23.1%). On multivariate regression, Asians (hazard ratio, 0.83; 95% CI, 0.79-0.87; P < .001) and blacks (hazard ratio, 0.94; 95% CI, 0.89-0.99; P = .01) had significantly higher survival compared with non-Hispanic whites. CONCLUSIONS: Asians were the only group to demonstrate a declining HCC incidence in the form of a shift from advanced HCC to more localized HCC. These findings most likely reflect improved screening and surveillance efforts for this group. Cancer 2016;122:2512-23. © 2016 American Cancer Society.

Birth cohort-specific disparities in hepatocellular carcinoma stage at diagnosis, treatment, and long-term survival.

BACKGROUND & AIMS: Individuals born between 1945 and 1965 account for nearly 75% of hepatitis C virus (HCV) infections in the United States. As this cohort ages, progressive HCV-related liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) will place a significant burden on the healthcare system. We aim to evaluate birth cohort-specific disparities in HCC stage at diagnosis, treatment rates, and overall survival with a focus on the 1945-1965 birth cohort. METHODS: A population-based retrospective cohort study of adult patients with HCC identified in the Surveillance, Epidemiology, and End Results 2003-2011 registry evaluated birth cohort-specific disparities in the prevalence and outcomes of HCC, including multivariate logistic regression models to evaluate disparities in HCC stage at diagnosis and HCC treatment received. Birth cohort-specific survival was evaluated with Kaplan-Meier methods and multivariate Cox proportional hazard models. RESULTS: The proportion of HCC represented by the 1945-1965 cohort increased by 64% from 2003-2011, and accounted for 57.4% of all HCC in 2011. Compared to patients born after 1965, the 1945-1965 cohort were more likely to have HCC within Milan criteria (OR, 3.66; 95% CI, 3.13-4.28; p<0.001). However, among patients with HCC within Milan criteria, the 1945-1965 cohort had no difference in receipt of surgical treatment, but had higher overall long-term survival (HR, 0.82; 95% CI, 0.69-0.97; p<0.03). CONCLUSIONS: The 1945-1965 birth cohort accounts for the majority of HCC in the United States. Despite earlier HCC stage at diagnosis, no difference in receipt of surgical treatment was observed, but higher overall survival was achieved.

Chronic hepatitis B virus in the Philippines.

Multiple studies have shown a high prevalence of chronic hepatitis B (CHB) infection in the Philippines, not only in high-risk populations but also in the general population. The most recent national study estimated HBsAg seroprevalence to be 16.7%, corresponding to an estimated 7.3 million CHB adults. The factors underlying the high prevalence of CHB and its sequelae include the inadequate use of vaccination for prevention and the lack of treatment for many Filipinos. Because without medical monitoring and treatment of CHB the risk of progression to liver failure and death is 25-30%, the ultimate medical and societal costs will be very high if the Philippines fails to properly address hepatitis B infection. It will be very important to move forward with programs that can help to ensure universal vaccination of newborns, screening and vaccination nationwide, and monitoring and treatment for CHB persons. It will also be crucial to address transmission of HBV in the health-care setting (via contaminated needles and syringes and inadequately sterilized hospital equipment) and via injection drug use and tattooing. Because of the relatively low average per capita income and the lack of coverage by PhilHealth of outpatient visits and medications, there is an urgent need to move forward with a nationally supported program that includes education for both the general public and health-care workers on liver disease and screening for hepatitis viruses, followed by, as appropriate, vaccination or treatment, with expanded government coverage for these for all those who could not otherwise afford it.

A case study of quality improvement methods for complex adaptive systems applied to an academic hepatology program.

Although demands for greater access to hepatology services that are less costly and achieve better outcomes have led to numerous quality improvement initiatives, traditional quality management methods may be inappropriate for hepatology. We empirically tested a model for conducting quality improvement in an academic hepatology program using methods developed to analyze and improve complex adaptive systems. We achieved a 25% increase in volume using 15% more clinical sessions with no change in staff or faculty FTEs, generating a positive margin of 50%. Wait times for next available appointments were reduced from five months to two weeks; unscheduled appointment slots dropped from 7% to less than 1%; "no-show" rates dropped to less than 10%; Press-Ganey scores increased to the 100th percentile. We conclude that framing hepatology as a complex adaptive system may improve our understanding of the complex, interdependent actions required to improve quality of care, patient satisfaction, and cost-effectiveness.

United Network for Organ Sharing regional variations in appeal denial rates with non-standard Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exceptions: support for a national review board.

Although it has been generally recognized that there are inconsistencies among Regional Review Boards in the assignment of points for model for end-stage liver disease (MELD)/pediatric end-stage liver disease (PELD) exception patients with resulting considerable variation in appeal denial rates, data to actually prove this have been limited. We reviewed 6533 MELD/PELD exception applications submitted between 2005 and 2008, calculated the variation in approval/denial rates, and followed these cases through mid-2013 to assess the effects on patient outcomes. We found highly significant regional variations in denial rates for appeals by exception patients and in transplantation rates. The odds of transplant for patients whose appeals are approved is 2.45 times that of patients not approved; that this effect does not vary by region suggests that the variation in transplant rates is driven, at least in part, by the variation in appeal denial rates. Health deterioration or death accounts for more than two-thirds of wait list removals among patients removed for reasons other than transplant. Our findings add to the weight of evidence that a national review board that uses current clinical expertise, peer review literature, and data to consistently assign priority could reduce regional inequities and move toward equitable allocation of organs and compliance with the United States Department of Health & Human Services Final Rule.

Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery.

With recent studies showing increased prevalence of hepatitis delta (HDV) even in the US, Australia, and some countries in Europe, and very high prevalence in endemic regions, HDV infection is far from being a disappearing disease. Although immigrants from endemic countries have been shown to have increased risk, studies have clearly shown that the disease is not solely appearing in traditional high-risk groups. Recent studies provide increasing evidence that sexual transmission may be an important factor in HDV infection spread. Based on the totality of evidence showing increased disease progression and substantially increased risk of cirrhosis in HDV-infected CHB patients, and the current studies showing higher than expected prevalence, it is time to call for HDV screening of all CHB patients. HDV viral load detection and measurement should be considered in all patients whether or not they are anti-HDV-positive. With universal screening of CHB patients for HDV, earlier diagnosis and consideration of treatment would be possible. Current treatment of HDV is IFN-based therapy with or without HBV antivirals, but current research indicates the possibility that prenylation inhibitors, entry inhibitors, HBsAg release inhibitors, or other therapies currently in the pipeline may provide more effective therapy in the future. In addition, universal screening would serve the important public health goal of allowing patients to be educated on their status and on the need for HDV-negative patients to protect themselves against superinfection and for HDV-infected patients to protect against transmission to others. Further studies and global awareness of HDV infection are needed.

The impact of race/ethnicity on the clinical epidemiology of autoimmune hepatitis.

GOALS: To evaluate race/ethnicity-specific variations in autoimmune hepatitis (AIH) with a focus on Asians and Hispanics, the fastest growing populations in the United States. BACKGROUND: AIH is a chronic inflammatory disease in which race/ethnicity-specific variations in clinical epidemiology have been reported. However, earlier studies were small or did not include a comprehensive analysis of Asians and Hispanics, the 2 fastest growing population cohorts in the United States. STUDY: A retrospective study analyzing patient data from 1999 to 2010 in a large tertiary-care community hospital to assess AIH epidemiology among a racially diverse population. RESULTS: One hundred eighty-three patients with AIH were included in the study with 81 patients having "definite" AIH by International Autoimmune Hepatitis Group criteria and 63 were diagnosed with overlap syndromes. Women and whites were the largest cohorts. The average age of diagnosis was similar among all groups. Biopsy-confirmed cirrhosis was present in 34% of AIH patients with Hispanics demonstrating the highest prevalence of cirrhosis (55%). When compared with whites, Asians had higher international normalized ratio (INR) (1.4 U vs. 1.1 U, P<0.01), and Hispanics had lower serum albumin (3.3 g/dL vs. 3.7 g/dL, P<0.001) and platelets (123.8 thousand/mcL vs. 187.5 thousand/mcL, P<0.001) and higher international normalized ratio (1.5 U vs. 1.1 U, P=0.05). Kaplan-Meier survival analysis demonstrated a trend toward worse outcomes among Asians. CONCLUSIONS: Among AIH patients, Hispanics had the highest prevalence of cirrhosis, and Asians had poorer survival outcomes. Race/ethnicity-specific disparities in AIH epidemiology may reflect underlying genetic differences, contributing to variations in disease severity, response to therapy, and overall mortality.

Liver disease in Viet Nam: screening, surveillance, management and education: a 5-year plan and call to action.

Despite a high prevalence of liver disease in Viet Nam, there has been no nationwide approach to the disease and no systematic screening of at-risk individuals. Risk factors include chronic hepatitis B (estimated prevalence of 12%), chronic hepatitis C (at least 2% prevalence), and heavy consumption of alcohol among men. This combination of factors has resulted in liver cancer being the most common cause of cancer death in Viet Nam. There is a general lack of understanding by both the general public and health-care providers about the major risk to health that liver disease represents. We report here the initial steps taken as part of a comprehensive approach to liver disease that will ultimately include nationwide education for health-care providers, health educators, and the public; expansion of nationwide screening for hepatitis B and C followed by hepatitis B virus vaccination or treatment of chronic hepatitis B and/or hepatitis C; education about alcoholic liver disease; long-term surveillance for liver cancer; reduction of infection transmission related to medical, commercial, and personal re-use of contaminated needles, syringes, sharp instruments, razors, and inadequately sterilized medical equipment; and ongoing collection and analysis of data about the prevalence of all forms of liver disease and the results of the expanded screening, vaccination, and treatment programs. We report the beginning results of our pilot hepatitis B screening program. We believe that this comprehensive nationwide approach could substantially reduce the morbidity and mortality from liver disease and greatly lessen the burden in terms of both lives lost and health-care costs.

A clinical assessment of Wilson disease in patients with concurrent liver disease.

GOALS: To investigate variations in clinical epidemiology of Wilson disease in patients with concurrent liver disease and the effect of coexisting disease on current diagnostic algorithms. BACKGROUND: Wilson disease is a rare disorder and few studies exist on diagnosis and natural history. Currently available tools have limited efficacy in complex patients, and the presence of coexisting diseases may further limit their use. More in-depth analyses of Wilson disease among complex patients with concurrent diseases will help improve algorithms for earlier diagnosis and treatment. STUDY: A retrospective cohort study using data from a large tertiary-care center to carry out a clinical assessment of Wilson disease among patients with coexisting liver disease. RESULTS: Forty-two Wilson disease patients were identified; 9 had comorbid liver diseases. The average age of diagnosis was significantly older in patients with concurrent liver disease compared with those without underlying disease (49.1 y vs. 26.8 y, P<0.0001). Patients with concurrent liver disease had more evidence of cirrhosis at presentation (9/9, 100% vs. 15/33, 45.5%), and showed greater mortality (4/8, 50% vs. 4/29, 13.8%, P=0.0222). Without mutation analysis data, a definitive diagnosis of Wilson disease using Leipzig criteria was made in 44% of patients with concurrent liver diseases. CONCLUSIONS: Patients with concurrent liver diseases were diagnosed with Wilson disease at significantly older ages, presented with more liver cirrhosis, and showed greater mortality. Mutation analysis is crucial for definitive diagnosis among complex cohorts and those with intermediate Leipzig scores.

Diagnosis of chronic hepatitis B and the implications of viral variants and mutations.

Chronic infection with the hepatitis B virus (HBV) is a major cause of morbidity and mortality worldwide, necessitating accurate and timely diagnosis of infected patients coupled with optimal treatment strategies. Although the prevalence of HBV infection in the United States is low owing to the implementation of universal vaccination, growing immigration from areas where infection is more endemic means that prevalence is forecast to increase. Healthcare providers must be active in providing low-cost screening (hepatitis B surface antigen identification) and vaccination programs for high-risk communities, such as Asian Americans, with linked specialist referral schemes for patients found to carry the virus. Serologic technologies and improved nucleic acid testing techniques generate important information about the stage of disease, viral load, and disease subtype, including the presence of precore and core promoter variants that provide prognostic indicators and can guide patient management. Serial DNA monitoring is playing the major role in the assessment of therapeutic response and steering treatment approaches. More research is needed to further clarify the significance of HBV variants and their relation to therapeutic agents and strategies.

Cost effectiveness of entecavir versus lamivudine with adefovir salvage in HBeAg-positive chronic hepatitis B.

OBJECTIVE: To evaluate the cost effectiveness of treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with entecavir compared with lamivudine with adefovir salvage, based primarily on the results of a recent 2-year, randomised, multicentre, clinical trial (n = 709). Previous economic analyses have been limited by the lack of comparative clinical data for entecavir and lamivudine beyond 1-year duration and for salvage therapy. METHODS: We conducted a cost-utility analysis using a Markov model from a US-payer perspective over a lifetime time horizon. The hypothetical cohort was 35-year-old patients with HBeAg-positive CHB. We evaluated 2 years of treatment with entecavir 0.5mg/day versus lamivudine 100mg/day, plus addition of adefovir 10mg/day for patients who developed virologic breakthrough due to resistance to either drug. In a scenario analysis, we considered adefovir plus lamivudine combination therapy for treatment-naive patients. Clinical and economic inputs ($US, year 2006 values) were derived from publicly available data, and probabilistic sensitivity analyses were conducted to evaluate uncertainty in the results. RESULTS: The estimated 10-year cumulative incidence of cirrhosis for patients initiated on entecavir was 2.3% lower than for those on lamivudine (20.5% vs 22.8%). The discounted incremental cost per QALY gained was $US7600 in the base-case analysis, and the 95% central range from probabilistic sensitivity analysis was $US2500-$US19 100. Combination therapy for treatment-naive patients led to an increase in costs without improvement in patient outcomes compared with entecavir monotherapy. CONCLUSIONS: Our analysis suggests entecavir improves health outcomes in a cost-effective manner compared with lamivudine with adefovir salvage or combination therapy, and highlights the importance of using evidence-based effectiveness estimates in economic studies of CHB therapies.