Focus on Hepatitis B and C risk based screening

Posted on April 18, 2015

Real-life clinical relevance of hepatitis screening in Germany: enhancing risk based screening strategies in primary care settings

Effective screening programs are needed to identify HBsAg and anti-HCV positive patients. Population based anti-HCV screening of all adults born between 1945 and 1965 is recommended in the US. For hepatitis B, US-guidelines recommend screening of adults at high risk of infection such as immigrants from regions with a HBV prevalence >2%, HIV positive persons, intravenous (IV) drug users, men who have sex with men, or members of a household containing a person with HBV infection. German hepatitis B and C treatment guidelines recommend HBsAg and anti-HCV screening in several pre-defined risk scenarios. Results of a prospective study to explore the real-life clinical relevance of hepatitis screening in Germany were recently published in Journal of Hepatology (Wolffram I et al. J Hepatol. 2015 Jan 21. pii: S0168-8278(15)00017-3).

Hepatitis screening between January 2012 and June 2013 occurred as part of a preventive medical examination named ‘‘Check-Up 35+’’, which is routinely offered in primary care private practices in Germany to patients at least 35 years of age. Within 16 months, 21,008 patients were prospectively recruited for the study by 51 primary care private practices. The high number of individuals recruited shows that inclusion of hepatitis screening in the ‘‘Check-Up 35+’’ procedure was embraced by primary care physicians and became part of their daily routine.

  • Mean age of the study participants was 57.5 years with a range between 7 and 107 years. 56% (n = 11,766) of the study cohort was female, and women tended to be 1.2 years older than men.
  • Immigration was reported by 2740 (13.9%) individuals. Most frequently reported regions were Eastern Europe and the former Soviet Union (51.8%), the Mediterranean area (29.9%), and Asia (14.2%)
  • Sexual risk factors were under-reported in this study: only 0.5% of the study cohort reported homosexual intercourse (n = 100/19,565) or promiscuity (n = 107/19,511)

HBsAg prevalence was 0.52% (n = 110), a higher disease burden than recently described by the national health care authority (0.3%). HBsAg positive patients were significantly younger (52.3 vs. 57.5 years; P = 3 x 10-5) and contained more males (56% vs. 44%; P = 0.03) than the remaining population.

  • Five HBsAg positive participants were younger than 35 years: 1 of these 5 participants was already aware of the HBV infection
  • Only 15% of HBsAg positive patients knew of their HBV infection
    • Rate of newly diagnosed infections was significantly higher in HBsAg positive than in anti-HCV positive/HCV-RNA negative and in anti-HCV positive/HCV-RNA positive patients of whom 35% were aware of the infection (P = 0.0005).
  • Elevated ALT values were observed in 22% of HBsAg positive patients compared with 13% of HBsAg negative cases.
  • HBV-DNA was positive in 65/109 cases of whom 18 had elevated ALT values
  • A viral load >2000 IU/ml – the threshold above which antiviral treatment is indicated according to German hepatitis B guidelines – was observed in 16/109 (15%) patients (male: n = 9; female: n = 7) of whom 44% (n = 7/16) presented with elevated ALT values.
  • Based on stepwise logistic regression, the following risk factors were associated with HBsAg positivity:
    • Immigration: odds ratio 4.4 [95% CI 2.9, 6.7]. Male immigrants had a 2.1% HBsAg prevalence and 80% were unaware of the infection.
    • Infection in household: odds ratio 2.5 [95% CI 1.2, 4.5]
    • Male gender: odds ratio 1.6 [95% CI 1.1, 2.4]

Anti-HCV prevalence was 0.95% (n = 199), a higher disease burden than recently described by the national health care authority (0.3%). Anti-HCV positive patients were significantly younger (54.8 vs. 57.5 years; P = 0.02) and slightly more often male (46% vs. 44%; P = 0.6) than the remaining population.

  • Five anti-HCV positive cases were younger than 35 years: 2 of these 5 individuals were already aware of the HCV infection
  • 35% of the 199 anti-HCV positive patients already knew of their HCV infection
  • Elevated ALT values were observed in 35% of anti-HCV positive patients
  • HCV-RNA was positive in 43% of the cases (n = 85/197; male n = 45; female n = 40).
  • HCV-RNA prevalence in the total study cohort was 0.43%
  • 65% of the HCV-RNA positive patients presented with elevated ALT values (n = 55/85)
  • HCV infection was already known by 41/85 (48%) HCV-RNA positive individuals
  • Based on stepwise logistic regression, the following risk factors were associated with anti-HCV positivity:
    • IV drug abuse: odds ratio 384 [95% CI 233, 644]
    • Blood transfusion before 1992: odds ratio 5.3 [95% CI 3.5, 7.9]
    • Immigration: odds ratio 2.4 [95% CI 1.5, 3.6].

The CDC recommends anti-HCV screening of US American baby boomers born between 1945 and 1965, but this recommendation could not be transferred to the German study population. Cases born between 1945 and 1965 comprised 46.2% of the study population, but represented 41% of anti-HCV positive patients only. The German baby boomer generation was born between 1955 and 1969, but an increased anti-HCV prevalence could not be detected in this age group either.

The study authors did note that the age distribution of the study cohort is not representative of the general population, as people over the age of 75 were not adequately represented. Alarmingly, the ‘‘true’’ HBV and HCV prevalence in Germany may be even higher than reported in this study, because the ‘‘Check-Up 35+’’ evaluation is probably not frequently applied in relevant risk groups like patients with ongoing drug abuse.

The screening program employed by this study was able to newly diagnose 85% of HBsAg and 65% of anti-HCV positive cases. Interestingly, elevated ALT values, which are frequently used as a screening trigger for hepatitis B and C infections, were present in only 22% and 35% of HBsAg and anti-HCV positive patients, respectively. Screening all immigrants resulted in the highest prevalence of unknown HBsAg positive patients (1.4%) and identified 30% of all undiagnosed HBsAg positive individuals. The authors noted that while sexual risk behavior was not associated with hepatitis B, promiscuity and homosexual intercourse were under-reported in the study. Authors also noted that by far the most important risk factor for hepatitis C is IV drug abuse, and they recommend that guideline-defined risk scenarios should be focused on elevated ALT values and drug abuse, blood transfusion before 1992, and immigration.

At present, an estimated 160,000 individuals with chronic HCV infection are living in Germany, with 4000 HCV-RNA positive individuals newly diagnosed per year. However, the treatment rate is 4.7%. National strategies to tackle chronic HCV infection have only been implemented in a few European countries like France and are not yet established in Germany. The authors conclude the following: “Our analysis is the largest prospective HBsAg and anti-HCV screening approach performed in a primary care physician’s setting so far. Inclusion of an ALT, HBsAg, and anti-HCV screening in the ‘‘Check-Up 35+’’ evaluation was accompanied by high acceptance in the clinical routine. Screening strategies based on national guidelines offer the opportunity to identify the majority of previously unknown infections and may become an important tool to reduce the burden of chronic hepatitis B and C in the future.”

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