DETAILS OF TESTS:
Following is my "normal" configuration which has worked with QEMU for years, until upgrading to qemu-4.2.0-r2:
+alsa (set globally in make.conf, for non-QEMU packages)
+pulseaudio (set globally in make.conf)
+oss (default)
+sdl (set for qemu in package.use so I am not totally reliant on VNC for video)

The guest VM I tested with is emulating es1370 sound.  The guest OS is Windows 10 Pro.

FIRST TEST:
1. Modified qemu-4.2.0-r2.ebuild (as requested in Comment #2)
2. app-emulation/qemu +alsa +pulseaudio +oss +sdl (among others)
3. Configure stage shows --audio-drv-list=pa,sdl,alsa,oss during build
4. QEMU_AUDIO_DRV not set prior to running QEMU.
5. Result was good sound.  No warnings nor errors.  Same behavior as before upgrading to qemu-4.2.0-r2.

Details:
As requested, I modified my qemu-4.2.0-r2.ebuild.  I replaced the relevant "if" block with the equivalent code from qemu-3.1.0-r4.ebuild.  Because it seems irrelevant for the current qemu version, it was necessary to remove the following part from the old ebuild's "if":
&& conf_opts+=( --with-sdlabi=2.0 )

I rebuilt qemu and the configure stage showed the following option being used:
--audio-drv-list=pa,sdl,alsa,oss

QEMU ran with no errors nor warnings.  The sound in my guest was good.  It was not necessary to specify QEMU_AUDIO_DRV=pa.

I shut down the guest and restarted it and saw the same behavior again.



So I ran two more tests using the current/unmodified qemu-4.2.0-r2.ebuild, while also fiddling with the alsa USE flag and the QEMU_AUDIO_DRV variable.

SECOND TEST:
1. Unmodified qemu-4.2.0-r2.ebuild
2. app-emulation/qemu -alsa +pulseaudio +oss +sdl (among others)
3. Configure stage shows --audio-drv-list=oss,sdl,pa, during build (including the extra comma)
4. QEMU_AUDIO_DRV not set prior to running QEMU.
5. Result was working sound, but noticeably scratchy.  QEMU warning about 'adc'.

Details:
I restored the original qemu-4.2.0-r2.ebuild.  I added "app-emulation/qemu -alsa" to my package.use file.  I rebuilt qemu and the configure stage showed:
--audio-drv-list=oss,sdl,pa,
with the extra comma on the end.

I ran my guest without specifying QEMU_AUDIO_DRV=pa.  When starting the guest, I received the following warning:
audio: Failed to create voice `adc'

Sound in the guest worked but was noticeably scratchy.

I shut down the guest and restarted it and saw the same behavior again.


THIRD TEST:
1. Unmodified qemu-4.2.0-r2.ebuild
2. app-emulation/qemu +alsa +pulseaudio +oss +sdl (among others)
3. Configure stage shows --audio-drv-list=oss,sdl,pa, during build.
4. QEMU_AUDIO_DRV=pa set prior to running QEMU.
5. Result was good sound.  No warnings nor errors.

Details:
I ran the SECOND TEST again, but this time I specified QEMU_AUDIO_DRV=pa when starting the guest.

QEMU ran with no errors nor warnings, and sound in my guest was good.

I shut down the guest and restarted it and saw the same behavior again.