Chronic hepatitis B virus infection and the risk of hepatocellular carcinoma by age and country of origin in people living in Sweden: A national register study.

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), and surveillance is recommended for patients without cirrhosis when risk exceeds an incidence rate (IR) of 0.2%. Populations in Asia and sub-Saharan Africa have been associated with HCC at younger ages, but the risk after immigration to Western countries should be investigated. The aim of this study was to study HCC by age and country of origin in people with chronic HBV infection in Sweden. Through national registers, residents with chronic HBV diagnosis (1990-2015) were identified with information on country of origin, immigration/emigration, death, coinfections, antiviral therapy, and HCC. Observation time started at HBV diagnosis, and IR and hazard ratios for HCC were calculated by sex, age, and region of origin. Among 16,410 individuals (47% women), the origin and observation time (person years) were as follows: Western Europe, 2316 (25,415); Eastern Europe, 2349 (26,237); Middle East/North Africa, 4402 (47,320); sub-Saharan Africa, 3677 (30,565); Asia, 3537 (35,358); and other, 129 (1277). There were 232 individuals with HCC (82% in men). The IR increased with age and exceeded 0.2% for Asian men from age group 40-49 years (IR, 0.63; 95% confidence interval, 0.39-1.00), for men of other origins from age group 50-59 years, and for women aged ≥60 years originating from Eastern Europe, Asia, and Middle East/North Africa. After exclusion of patients with cirrhosis or HBV treatment, the IR still exceeded 0.2% in Asian men aged 40-49 years. This study demonstrates that HBV-infected men of Asian origin should be recommended HCC surveillance at younger ages, but there is a need for further studies of HCC incidence in African-born men without cirrhosis living in the Western world.

Anti-HCV prevalence and risk factor-based screening for hepatitis C in pregnant women and their partners in Sweden.

BACKGROUND: The hepatitis C virus (HCV) prevalence in Sweden is estimated to be <0.5%, but unclear in pregnant women. The dominating route of transmission is drug use (DU), blood transfusions constituted a risk before 1992. The aim was to examine the anti-HCV prevalence and risk factors for HCV among pregnant women and their partners to evaluate screening strategies. METHODS: Pregnant women and partners in Örebro County and in southern Stockholm were offered HCV-screening when visiting an antenatal clinic in 2013-2016, and completed a questionnaire concerning the country of birth, knowledge of HCV-status and HCV risk factors. RESULTS: In Örebro 2,827 pregnant women and 707 partners, and in Stockholm 1,281 pregnant women and 320 partners participated. Anti-HCV was positive in 34 (0.7%) (25 pregnant women) and the associated risk factors were DU (n = 27), partner with HCV (n = 24) and not born in Sweden (n = 8). HCV RNA was positive in 23 (0.4%), 4 previously unknown and 10 who had been lost to follow-up. The most effective risk factor-based screening model for pregnant women included DU, blood transfusions, born in high prevalence country, partner with HCV, resulting in 538 (13%) pregnant women tested with 96% sensitivity, 87% specificity. CONCLUSIONS: In this study of expecting parents in two Swedish regions, the anti-HCV prevalence was 0.7% and 0.4% were viraemic, of which about 60% were previously unknown or lost to follow-up. Awaiting more studies, including cost-benefit analysis evaluating universal screening, we recommend this improved risk factor-based screening model to identify HCV-infected individuals who need follow-up and therapy.

Hepatitis C Virus Infection and the Temporal Trends in the Risk of Liver Cancer: A National Register-Based Cohort Study in Sweden.

BACKGROUND: In many countries, including Sweden, the birth cohorts with the highest prevalence of hepatitis C virus (HCV) infection have now reached the ages with high risk of primary liver cancer (PLC). The aims of this study were to investigate the temporal trends in PLC incidence and the relative risks of PLC among people diagnosed with HCV infection between 1990 and 2015. METHODS: The HCV cohort (n = 52,853) was compared with a matched non-HCV comparison cohort (n = 523,649). Both the national Cancer Register (CR) and Cause of Death Register (DR) were used for follow-up. The crude and age-standardized PLC incidence rates were calculated. The relative risk was estimated as standardized incidence ratios (SIR) and as HRs using stratified Cox hazards regression. RESULTS: There were 1,609 with PLC diagnosis in the HCV cohort; the annual number increased continuously with the crude incidence rate reaching 4.56 per 1,000 person-years in 2013 while remaining low and stable in the comparison cohort. In the HCV cohort, the age-standardized PLC incidence rates per 1,000 person-years remained relatively constant at 2.64 [95% confidence interval (CI), 1.54-3.75] in 2000 and 3.31 (2.51-4.12) in 2014. The highest SIR was 73 (65.9-79.5) among those infected for 35 to 40 years; and the highest HR was 65.9 (55.9-77.6) for men and 62.2 (31.9-121.1) for women. CONCLUSIONS: There was a considerable increase in PLC incidence over time and an extremely high relative risk in the population with HCV infection for more than 35 years. IMPACT: The national HCV-associated PLC incidence should be monitored in future studies to evaluate the effect of direct-acting antiviral (DAA) treatment.

Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients.

OBJECTIVES: Curing of hepatitis C virus (HCV) infection primarily aims to prevent severe liver complications. Our objectives were to investigate the long-term presence and impact of occult HCV infection (OCI) and to study the outcomes in terms of liver disease after virological cure. PATIENTS AND METHODS: A total of 97 patients with achieved sustained virological response (SVR) during 1990-2005 were followed either by a clinical follow-up (FU) visit with blood sampling and liver elastography (n=54) or through national registries for outcomes (n=43). To diagnose OCI among patients with SVR, a highly sensitive method was used to detect HCV-RNA traces in whole blood. The FU duration was a median of 10.5 years, with samples up to 21.5 years after the end of treatment (EOT). RESULTS: The majority of patients [52 (96%)] were HCV-RNA negative at FU, and regression of fibrosis was statistically significant. OCI was found in two (4%) of them at 8 and 9 years after EOT. These patients had F1 and F2 fibrosis before treatment and F2 at FU, but no other abnormal findings. Three previously noncirrhotic men were diagnosed with hepatocellular carcinoma 8-11 years after EOT. CONCLUSION: Occult infection could be detected many years after the achievement of SVR but was not associated with serious liver disease. The majority had persistent viral eradication and regression of fibrosis after SVR. However, an increased risk of hepatocellular carcinoma may persist in the long term after SVR even in noncirrhotic patients. Further studies with FU after direct-acting antiviral therapy and on the long-term impact after cure are needed.