Complications
Heightened immune response to hepatitis B virus (HBV) resulting in massive immune-mediated lysis of infected hepatocytes is thought to be the cause of fulminant hepatitis associated with acute hepatitis B infection.[22]
It occurs in <1% (around 0.1% to 0.5%) of cases of acute HBV. Co-infection with hepatitis C or D virus increases the risk of developing fulminant hepatitis.[166][167]
Referral for liver transplantation is essential to prevent morbidity and mortality.
Cirrhosis occurs in about 20% of patients with chronic hepatitis B virus (HBV) and is thought to be due to ongoing immune attack of infected cells in the liver, resulting in development of fibrosis and regenerative nodules.[23]
Risk factors associated with progression to cirrhosis include co-infection (with hepatitis C or D, and/or HIV), older age, high levels of HBV DNA, and habitual alcohol intake.[154]
Treatment can be initiated in most patients with chronic HBV and cirrhosis.
The incidence of hepatitis B virus (HBV)-related hepatocellular cancer (HCC) has increased and accounts for 50% of all HCC worldwide.[155] HBV and hepatitis D dual infection may increase the risk of HCC compared to HBV monoinfection.[156]
Screening for HCC should be started as suggested by the recommended guidelines.[2]
HCC associated with hepatitis B is thought to result from chronic inflammation and cellular regeneration.[22] Cirrhosis seems to be the greatest risk factor for developing HCC, although 30% to 50% of HBV-related HCC occurs without cirrhosis.[157] Male sex, older age, diabetes mellitus, co-infection with hepatitis D, co-infection with hepatitis C, core promoter mutation, family history of HCC, presence of hepatitis B surface antigen, and high levels of HBV DNA are risk factors for the development of HCC.[158][159][160][161][162]
Liver transplantation can be considered in the early stages, with small HCC without any evidence of metastasis. Non-curative therapies, such as transarterial chemo-embolisation (TACE), transarterial radio-embolisation (TARE), and systemic chemotherapy/immunotherapy, aim to slow tumour progression and consequently prolong survival.
Hepatitis B virus (HBV)-related glomerulonephritis is not a common complication of HBV infection, and the cause of glomerulonephritis in HBV infection is controversial.
The optimal therapy is also not well defined. One systematic review and meta-analysis evaluating safety and efficacy of interferon and lamivudine in HBV-infected patients with glomerulonephritis reported remission of nephritic syndrome with clearance of HBV replication, suggesting a causal role of HBV in the development of glomerulonephritis.[168]
Reactivation is emerging as an important cause of morbidity and mortality in patients who have current or prior exposure to hepatitis B virus (HBV) infection, particularly in those who require immunosuppressive or biological therapies (including chemotherapy or immunotherapies), people with hepatitis C or D infection who are receiving antiviral treatment, and patients with HIV infection.[163][164] HBsAg-positive patients with HCC are at intermediate or high-risk of HBV reactivation, depending on the type of therapy used to treat HCC.[165]
Defined as a loss of HBV immune control in hepatitis B surface antigen (HBsAg)‐positive/antibody to hepatitis B core antigen (anti‐HBc)-positive, or HBsAg‐negative/anti‐HBc-positive patients receiving immunosuppressive therapy for a concomitant medical condition. Diagnostic criteria include: (a) a rise in HBV DNA compared to baseline (or an absolute level of HBV DNA when a baseline is unavailable); and (b) reverse seroconversion (seroreversion) from HBsAg-negative to HBsAg-positive for HBsAg‐negative/anti‐HBc-positive patients. Following reactivation, a hepatitis flare (indicated by an increase in alanine aminotransferase [ALT] levels) can occur.[2]
Onset is variable; it can be up to 2 weeks after starting immunosuppressive therapy, or up to a year after ceasing immunosuppressive therapy. The risk of reactivation depends on multiple factors including host factors (e.g., older age, male sex, cirrhosis), virological factors (e.g., hepatitis B e antigen status, HBV DNA level), and the type and degree of immunosuppressive therapy.[163]
Screening for HBsAg and anti-HBc (total or IgG) is recommended in patients before starting any immunosuppressive, cytotoxic, or immunomodulatory therapy.[2]
Antiviral prophylaxis is required in patients who are at high risk of reactivation (HBsAg-positive/anti-HBc-positive) before they start immunosuppressive therapy. Lower-risk patients (HBsAg-negative/anti-HBc-positive) can be monitored (ALT levels, HBV DNA, and HBsAg) for reactivation and started on prophylaxis if needed. Prophylaxis should be started as soon as possible, continued during immunosuppressive therapy, and for at least 6 to 12 months after cessation of immunosuppressive therapy, depending on the type of therapy.[2]
Virological breakthrough, defined as a >1 log10 (10-fold) increase in serum hepatitis B virus DNA from nadir after initial virological response, can be related to antiviral resistance mutations or medication non-adherence. Consider drug resistance testing, and either switching to another antiviral drug with a high barrier to resistance (e.g., tenofovir disoproxil or tenofovir alafenamide), or adding a second antiviral with a complementary resistance profile.[2][64]
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