The prognosis and management of inactive HBV carriers

Abstract

Patients with chronic hepatitis B virus (HBV) infection lacking the serum hepatitis B e antigen (HBeAg) and with antibodies against HBeAg (anti-HBe), are the prevalent subgroup of HBV carriers worldwide. The prognosis of these patients is different from inactive carriers (ICs), who are characterized by persistently normal serum alanine aminotransferase (ALT) and low (<2000 IU/ml) serum HBV DNA levels, a serological profile that may also be intermittently observed in patients with HBeAgnegative chronic hepatitis. This is why a confirmed diagnosis of IC requires quarterly ALT and HBV DNA measurements for at least 1 year, while a single-point detection of combined HBsAg <1000 IU/ml and HBV DNA <2000 IU/ml has a robust predictive value for the diagnosis of IC. Characteristically, ICs have minimal or no histological lesions of the liver corresponding to liver stiffness values on Fibroscan of <5 kPa. Antiviral treatment is not indicated in ICs since the prognosis for the progression of liver disease is favourable if there are no cofactors of liver damage such as alcohol abuse, excess weight or co-infection with the hepatitis C virus or delta virus. Moreover, spontaneous HBsAg loss frequently occurs (1-1.9% per year) in these patients while the development of hepatocellular carcinoma (HCC) is rare, at least in Caucasian patients. However, an emerging issue reinforcing the need for clinical surveillance of ICs is the risk of HBV reactivation in patients who undergo immunosuppressive therapy without receiving appropriate antiviral prophylaxis. After diagnosis, management of ICs includes monitoring of ALT and HBV DNA every 12 months with periodic measurement of serum HBsAg levels to identify viral clearance.

Clinical features of HBsAg seroclearance in hepatitis B virus carriers in South Korea: A retrospective longitudinal study

“…The natural course of HBV infection is associated with immunological changes that occur in three phases: tolerance, eradication, and recovery[3]. These phases are classified based on the serum aminotransferase level, hepatitis B e antigen (HBeAg) and HBV DNA titers, which represent hepatitis and viral replication, respectively[4,5]. Recovery is defined as ceasing of the self-replicating activity of the HBV genome and its transition to a non-replicating state.…”

“…Recovery is defined as ceasing of the self-replicating activity of the HBV genome and its transition to a non-replicating state. In general, a serum HBV DNA level of below 2000 IU/mL is considered to indicate an inactive hepatitis B surface antigen (HBsAg) carrier state[3,5-7]. Once the HBV genome is inactivated, it remains inert throughout life, HBeAg becomes negative, and HBsAg is cleared in approximately 40% of patients after 25 years of follow-up[3].…”

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“…However, recent studies showed that ALT-adapted cut-offs do not influence TE diagnostic performance [186] and that the only variable associated with overestimation of F4 stage in CHB is moderate/severe necro-inflammatory activity without any direct correlation with transaminase level [187]. Interestingly, a Young's modulus of < 5 kPa in patients with normal ALT and low serum HBV DNA levels (< 2000 IU/ml) characterize inactive HBV carriers [188,189]. TE can be used to rule out significant fibrosis and cirrhosis in HBV inactive carriers, which is the best indication for TE in HBV.…”

“…TE is useful in inactive HBV carriers to rule out fibrosis (LoE 2, GOR B) [188,189]. Strong consensus (18/0/0, 100 %) Point shear wave elastography (pSWE)…”

New horizon for radical cure of chronic hepatitis B virus infection

“…Transition of immuneactive patients to an inactive state with low HBVDNA replication by the direct stimulation of HBVspecific Tcells or removal of immunosuppressive factors, may be sufficient to inhibit progression to cirrhosis or HCC. Inactive HBV carriers may not require specific treatment, because spontaneous HBsAg develops at a rate of 1% to 1.9%/year in these patients, making the development of HCC rare [82] . Therefore, an inactive HBV carrier may be regarded as in a state of functional cure (Table 1).…”