It's the most destructive non-nuclear weapon in the USA arsenal and Thursday's blast marked the first time it has been used in conflict.
No civilians were affected by the explosion, the ministry said.
Former Afghan President Hamid Karzai however denounced the use of the weapon. The bomb is guided by satellite to its target.
The U.S. assessment is still in progress, a Pentagon official tells NPR's Tom Bowman, adding that there's a chance the death toll might include results from two other smaller operations against ISIS-K that took place last night.
Addressing the Afghan public, Nicholson said all precautions were taken to prevent civilian casualties.
The commander of US forces in Afghanistan, Gen. John Nicholson, said in a statement Thursday that it was the "right munition" to use to destroy the militants' network of tunnels in the area.
Thursday's strike was not the first time Islamic State fighters have been targeted by heavy American bombardment in Nangarhar, where a USA special forces soldier was killed battling militants a week ago.
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Presidential spokesman Shah Hussain Murtazawi told the BBC that IS commander Siddiq Yar was among those killed.
"They were Arabs, Pakistanis, Chinese and local insurgents coming to buy from shops in the bazaar", said resident Raz Mohammad.
A security official stands guard near the site where the US dropped a GBU-43 Massive Ordnance Air Blast (MOAB) on an Islamic State (IS) militant cave complex in Achin district, Nangarhar province, Afghanistan, April 14.
More than 9m (30 ft) in length, it was first tested in 2003 but had not been deployed in combat before.
"It was the right weapon for the right target, and not in retaliation", the official said. "There will be no sanctuary for terrorists in Afghanistan".
In a message distributed on the instant messaging app Viber, the Taliban said the United States had "no justification" for using such a powerful bomb during combat operations, calling it a "show" by USA forces to persuade the world it is battling the Islamic State.
But Congresswoman Barbara Lee, a Democrat who was the only "no" vote for authorization for use of military force in Afghanistan in 2001, said the move was unprecedented and asked for an explanation.
Nangarhar Provincial Governor Gulab Mangal said IS fighters had used the complex to "kill people and hold important meetings".
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The $16 million, 21,600-pound explosive - officially known as the GBU-43/B Massive Ordnance Air Blast - is capable of leveling an area equivalent to nine New York City blocks. The weapon is carried on a special cradle inside the aircraft from which it is extracted by a parachute.
The review of Afghanistan policy is evidently still underway in the Trump administration, so this tactical choice wouldn't be meant to signal a change in course. There was no immediate comment from IS or other militants regarding the United States bomb attack.
He said civilians would have been "impacted in terms of feeling the tremor" of the weapon.
President Donald Trump called Thursday's operation a "very, very successful mission".
The U.S. government's top watchdog on Afghanistan said earlier this year that the Afghan government controls less than 60 percent of the country.
However, experts say it has struggled to build a wide political base and the indigenous support it expected. He said there has been heavy fighting in the area in recent weeks between Afghan forces and IS militants.
American military officials estimate there are around 600 to 800 Islamic State fighters in Afghanistan, mostly in Nangarhar, but also in the neighboring province of Kunar.
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