Let $D$ be an open set of a Stein manifold $X$ of dimension $n$ such that $H^k(D,𝒪)=0$ for $2\le k\le n-1$. We prove that $D$ is Stein if and only if every topologically trivial holomorphic line bundle $L$ on $D$ is associated to some Cartier divisor $𝔡$ on $D$.