Chronic hepatitis B in 2014: Great therapeutic progress, large diagnostic deficit

Table 1 Subjects with high risk for HBV infection who should be screened irrespective of symptoms and alanine aminotransferase values[1-5]

All individuals born in areas with high and intermediate HBV prevalence (> 2 % HBsAg positivity) including immigrants and adopted children

Further subjects who belong to a high risk group and should generally be screened

Individuals with elevated ALT/AST or others signs of liver disease

Household and sexual contacts of HBsAg-positive persons

Persons who have ever injected drugs

Persons with multiple sexual partners or history of sexually transmitted disease

Men who have sex with men

Inmates of correctional facilities and jails

Individuals infected with HCV or HIV

Patients undergoing renal dialysis

Patients undergoing chemotherapy or immunosuppressive therapy

All pregnant women

HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; ALT: Alanine aminotransferase.

Table 2 Vaccination recommendations for risk groups[1,35,70]

i.v., drug users

Potential household and sexual contacts with HBV infected people

Subjects frequently requiring blood products, dialysis patients

Patients with organ transplantation

People who are in prisons and correctional facilities for a longer time

People with multiple sexual partners and men who have sex with men

Health-care workers with frequent blood contact

Travellers who are go to highly endemic regions often or for longer time intervals

Clients and staff at institutions for the developmentally disabled

Persons with a history of sexually transmitted infection (STI)

Person without immunoprotection who undergo chemotherapy or immunosuppressive therapy

HBV: Hepatitis B virus.

Table 3 Indication for treatment in European Association for the Study of the Liver, Asian Pacific Association for the Study of the Liver, and American Association for the Study of Liver Diseases guidelines[3-5]

EASL

Indication similar for both HBeAg-positive and HBeAg-negative patients

Consider therapy if HBV-DNA is > 2000 IU/mL, ALT is > ULN and there is moderate to severe active necroinflammation and/or at least moderate fibrosis on liver biopsy

Consider biopsy and therapy separately in immunotolerant patients: HBeAg-positive patients < 30 yr with persistently normal ALT and high HBV-DNA, without evidence of liver disease and family history of HCC or cirrhosis, do not require liver biopsy or therapy. Follow-up is mandatory

Consider biopsy or therapy in patients > 30 yr and/or with a family history of HCC or cirrhosis

HBeAg-negative patients with persistently normal ALT and HBV-DNA of 2000-20000 IU/mL and without evidence of liver disease do not require liver biopsy or therapy. Follow-up is mandatory

Patients with ALT > 2 times ULN and HBV-DNA >20000 IU/ml may start treatment without biopsy

Therapy indicated in compensated cirrhosis and detectable HBV-DNA even if ALT is normal

Patients with decompensated cirrhosis and any detectable HBV-DNA require urgent therapy

APASL

HBeAg positive: consider therapy if ALT >2 times ULN and HBV DNA > 20000 IU/mL

HBeAg-negative: consider therapy if ALT > 2 times ULN and HBV DNA > 2000 IU/mL

Consider therapy in advanced fibrosis or cirrhosis with any ALT level

Therapy in all patients with decompensated cirrhosis independent of HBV-DNA

Therapy in compensated cirrhosis if HBV-DNA is > 2000 IU/mL

In the absence of cirrhosis/severe fibrosis patients with persistently normal or minimally elevated ALT should not be treated irrespective of the height of HBV-DNA. Follow-up is mandatory

AASLD

HBeAg-positive: consider therapy if ALT >2 times ULN with moderate/severe hepatitis on biopsy and HBV-DNA > 20000 IU/mL

In general no therapy if ALT is persistently normal or minimally elevated (< 2 times ULN); consider biopsy in patients with fluctuating /minimally elevated ALT especially in those > 40 yr; consider therapy if there is moderate or severe necroinflammation or significant fibrosis on biopsy

HBeAg-negative: consider therapy if HBV-DNA > 20000 IU/mL and ALT > 2 times ULN

Consider biopsy if HBV-DNA is 2000-20000 IU/mL and ALT is borderline normal or minimally elevated. Consider therapy if there is moderate/severe inflammation or significant fibrosis on biopsy

HBV: Hepatitis B virus; EASL: European Association for the Study of the Liver; APASL: Asian-Pacific Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases; ALT: Alanine aminotransferase.

Table 4 Surveillance of hepatocellular carcinoma in subjects with chronic hepatitis B virus infection[3-5,31,255-266]

Surveillance all patients with cirrhosis and severe fibrosis

Including those treated with NUC

Surveillance in individuals with increased HCC risk, even without cirrhosis or severe fibrosis

High HBV-DNA

Males

Age > 40-50 yr (in particular in Asia and Africa)

Long duration of infection

Significant inflammation

Co-infection with HIV, HCV and HDV

Co-morbidities (e.g., diabetes mellitus, high alcohol consumption, NASH/NAFDL)

For surveillance: Ultrasound done every 6 mo by a skilled physician

Determination of AFP (in combination with ultrasound) still recommended by APASL[257], but not by EASL and AASLD guidelines[255-256]

AFP is less useful than ultrasound for surveillance of HCC

HCC: Hepatocellular cancer; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; HDV: Hepatitis D virus; AFP: Alpha fetal protein.