The sufficient component cause (SCC) model and counterfactual model are two common methods for causal inference, each with their own advantages: the SCC model allows the mechanistic interaction to be detailed, whereas the counterfactual model features a systemic framework for quantifying causal effects. Hence, integrating the SCC and counterfactual models may facilitate the conceptualization of causation. Based on the marginal SCC (mSCC) model, we propose a novel counterfactual mSCC framework that includes the steps of definition, identification, and estimation. We further propose a six‐way effect decomposition for assessing mediation and the mechanistic interaction. The results demonstrate that when all variables are binary, the six‐way decomposition is an extension of four‐way decomposition and that without agonism, the six‐way decomposition is reduced to four‐way decomposition. To illustrate the utility of the proposed decomposition, we apply it to a Taiwanese cohort to examine the mechanism of hepatitis C virus (HCV)‐induced hepatocellular carcinoma (HCC) with liver inflammation measured by alanine aminotransferase (ALT) as a mediator. Among the HCV‐induced HCC cases, 62.27% are not explained by either mediation or interaction in relation to ALT; 9.32% are purely mediated by ALT; 16.53% are caused by the synergistic effect of HCV and ALT; and 9.31% are due to the mediated synergistic effect of HCV and ALT. In summary, we introduce an SCC model framework based on counterfactual theory and detail the required identification assumptions and estimation procedures; we also propose a six‐way effect decomposition to unify mediation and mechanistic interaction analyses.

Outbreaks of acute hemorrhagic conjunctivitis caused by enterovirus 70 and several serotypes of adenovirus have occurred in Taiwan since 1971. In 1980-1981, there was a pandemic of acute hemorrhagic conjunctivitis in southeast Asia caused by coxsackie A24 variant (CA24v); however, this virus did not affect Taiwan. In October 1985, CA24v was isolated for the first time from patients with acute hemorrhagic conjunctivitis in southern Taiwan. The following summer, a large epidemic of acute hemorrhagic conjunctivitis due to CA24v occurred. An epidemiologic investigation of patients seen at one ophthalmology clinic in Taipei City revealed that school-age children were the most likely group to introduce illness into households (p less than 0.001) and that males were more often household index cases than were females (p less than 0.01). Multiple case households tended to be more crowded (3.0 vs. 2.5 persons per bathroom; p less than 0.05) and had illness introduced by younger family members (median age of index case = 10 vs. 17 years; p less than 0.01). It is unknown whether this outbreak is an isolated occurrence or represents another resurgence of CA24v in the area.

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