Summary : This figure presents two line plots showing the typical serologic courses of acute and chronic hepatitis B virus (HBV) infection, comparing the progression and recovery of serologic markers over time. line plot: # Panel A: Typical serologic course of acute HBV infection to recovery ## Title & Axes : • Title: "A. Typical serologic course of acute HBV infection to recovery" • X-axis: "Weeks after exposure" (tick labels: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 52, 100) • Y-axis: "Relative concentration" (no explicit tick labels) • Additional timeline annotations: "HBV DNA", "Symptoms", "HBeAG", "Anti-HBe" (horizontal arrows above plot) ## Data Points : • HBsAg (solid line): Rises sharply after exposure, peaks around 8–12 weeks, then declines and disappears by ~24–28 weeks. • Total anti-HBc (dashed line): Rises after exposure, peaks around 16–20 weeks, remains elevated beyond 100 weeks. • IgM anti-HBc (dotted line): Rises after exposure, peaks around 12–16 weeks, declines and disappears by ~28–32 weeks. • Anti-HBs (long dashed line): Appears after ~24–28 weeks, rises and remains elevated beyond 100 weeks. ## Design Encodings : • HBsAg: solid purple line • Total anti-HBc: dashed purple line • IgM anti-HBc: dotted purple line • Anti-HBs: long dashed purple line • All lines plotted against the same axes; no log scale or error bars. ## Distribution & Trends : • HBsAg and IgM anti-HBc both show transient peaks and then decline. • Total anti-HBc and anti-HBs persist long-term after recovery. # Panel B: Typical serologic course of progression to chronic HBV infection ## Title & Axes : • Title: "B. Typical serologic course of progression to chronic HBV infection" • X-axis: "Weeks after exposure" (tick labels: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 52), then "Years" (break in axis) • Y-axis: "Relative concentration" (no explicit tick labels) • Additional timeline annotations: "HBV DNA", "Acute (6 months)", "Chronic (years)", "HBeAG", "Anti-HBe" (horizontal arrows above plot) ## Data Points : • HBsAg (solid line): Rises after exposure, remains persistently elevated for years. • Total anti-HBc (dashed line): Rises after exposure, remains persistently elevated for years. • IgM anti-HBc (dotted line): Rises after exposure, peaks around 12–16 weeks, declines and disappears by ~28–32 weeks. ## Design Encodings : • HBsAg: solid purple line • Total anti-HBc: dashed purple line • IgM anti-HBc: dotted purple line • All lines plotted against the same axes; no log scale or error bars. ## Distribution & Trends : • HBsAg and total anti-HBc remain persistently elevated in chronic infection. • IgM anti-HBc is transient and disappears after the acute phase. # Analysis : • In acute HBV infection (Panel A), HBsAg and IgM anti-HBc are transient, while total anti-HBc and anti-HBs persist after recovery, indicating resolution and immunity. • In chronic HBV infection (Panel B), HBsAg and total anti-HBc remain persistently elevated for years, while IgM anti-HBc is only present during the acute phase, indicating ongoing infection without resolution. • The presence and duration of serologic markers distinguish acute recovery from progression to chronic infection.

This pathophysiology diagram illustrates the mechanisms underlying undetectable Hepatitis B surface antigen (HBsAg) in patients who are HBeAg-positive and anti-HBs-positive. The diagram is divided into two primary pathways: the formation of Circulating Immune Complexes (CICs) and the emergence of HBsAg mutants. In the CIC pathway, HBsAg particles are shown in circulation bound by Y-shaped anti-HBs antibodies; this 'masking' of epitopes renders the antigen undetectable by standard assays. A lower panel demonstrates that chemical dissociation or specialized assays (e.g., Lumipulse HBsAg-HQ) can unmask these antigens, making them detectable. The second pathway shows 'Immune escape-associated HBsAg mutants' arising from antibody selective pressure. These are depicted as spheres, filaments (together termed subviral particles or SVPs), and complete virions with altered surface epitopes (marked by purple stars). Both CIC formation and mutant emergence contribute to the diagnostic challenge of occult Hepatitis B infection (OBI). This diagram is intended for intermediate to advanced medical education regarding HBV serology, diagnostic pitfalls, and immune escape mechanisms.

This pathophysiology diagram illustrates the differential immune responses to Hepatitis B core antigen (HBcAg) and surface antigen (HBsAg) in the context of chronic HBV infection. The diagram depicts a liver releasing HBV virions, nucleocapsids, and soluble antigens. The immune response is divided into two distinct pathways: the HBcAg-specific pathway and the HBsAg-specific pathway. In the HBcAg pathway, classical memory B cells differentiate into HBcAg-specific plasma cells, characterized by high expression of CD99, IL6R, CXCR3, and TGFB1, alongside low CD24. These cells actively secrete anti-HBc IgG and stimulate HBcAg-specific T cells, leading to a robust immune response. Conversely, the HBsAg pathway shows HBsAg-specific B cells exhibiting an atypical memory (AtM) phenotype. These cells produce anti-HBs IgM but are associated with HBsAg-specific T cells in a state of immune tolerance, characterized by reduced cytokine production. The visual highlights how high levels of surface antigens contribute to B-cell dysfunction and T-cell exhaustion compared to the more activated core-antigen response.