The steel industry has changed radically over the last two decades, as large, integrated companies such as Bethlehem Steel once conducted operations from mining at one end of the process to shipping at the other have greatly downsized, or in some cases shut down altogether.

(A) as large, integrated companies such as Bethlehem Steel

(B) as large, integrated companies, such as Bethlehem Steel, that

(C) with large, integrated companies, such as Bethlehem Steel, that

(D) while large, integrated companies, such as Bethlehem Steel, that

(E) and large, integrated companies such as Bethlehem Steel

The steel industry has changed radically over the last two decades, (C) as large, integrated companies such as Bethlehem Steel once conducted operations from mining at one end of the process to shipping at the other have greatly downsized, or in some cases shut down altogether.

Explanation:

In this case, the whole second sentence after the first comma represents a clear example of how important the change of steel industry has been in the last twenty years. By using the conjunction "as", a connection between a cause and a result is produced: The steel industry changed radically over the last two decades (cause) = integrated companies such as Bethlehem Steel have greatly downsized, or in some cases shut down altogether (result).