13
) Non-Alcoholic Steatohepatitis NASH ( ) ( . ) Non- Alcoholic Fatty Liver Disease NAFLD ( ) ( . NASH ) ( : 1 ) ( 2 . ) ( ) ( . 3 4 ) ( . 5 HBs HCV HCV- RNA . B HBsAg . (Non-Alcoholic Steatohepatitis) . . . . . . . . . : E C . . 1383 : 21 - 110 : : * : : : E-mail: [email protected] 1. macrovesicular fatty changes 2. Mallory bodies 3. random 4. desialylated 5. HBsAg 110 / / 2 / 1383

6-Dr Daryani-2 (Nash) - IAGH · 31. propylthiouracil (PTU) 32. selenium 33. cholines 34. betaine ... Sem Liver Disease 2001; 21: 17-26. 4. Clouston AD, Powell EE. Interaction of non-alcoholic

  • Upload
    dangnga

  • View
    216

  • Download
    3

Embed Size (px)

Citation preview

�����

�������� ��� ������ ���� )Non-Alcoholic Steatohepatitis

��NASH ( ��� �� ��� ������ ��!" �#��#�#�#$# %#�&� '���

*#+#��� ��,� -�.� ����� ��� /� �0�� 1����$ /� 2���3� 4��5���

6,� 4��5 ����+7 8�97 /� �:;�� <4#�#�� 6#� ��#= #3� )� ( . �� #+#�#+#?

'�@���A�� /� %�B C� /� ��A�5 ����� ��� ��� ������ '.DE #�� 6#E

��� F�G .DE '�@���A�� ����� )Non-Alcoholic Fatty Liver Disease

�� NAFLD ( �7 H.�7�� .��0 )� ( .

�����

I��JNASH K����� ��/ '� ���L7 �� )� ( :

� �����/���E�7 ���G 1����$1 F�#@#��� �� H��A .�.0 � N���7

) ��D� � �� F�� '�O3 �� ( '����7 P��,� -�.� �� ��2 �#� � /��D�3 <

/���� .

� 4��� 6Q?R7 4��5 ����+7 8�97 P.S ) /� ��J��T"�U" P�#V

� -���7 �� /�� �� �����U"�W" -��/ �� /�� �� P�V ( )� ( . .#�#�X

/� H��#Y#�#�� � ��? Z�0 ��3�V H��0 6� �[��� \�;�7 ���

.]��7 ���@��7/^ �3��9 -�_ 6��A� 3 ����� ��,� ����� '��� �

����� ���Y���� 6�������� 4 -�_ �� ���� )� ( .

� -��� �Y]7 ���̂ -� 5HBs ���̂ �� < '��� .; HCV � �#� HCV-RNA .

��� ��YS *+��� �� -���A��B 6�0`V �� 6= HBsAg �#@#�^

H.0 �Y]7a ��7�b�� .��D� .��0 6�0�`V ��]E .

استئاتوهپاتيت غيرالكلي

(Non-Alcoholic Steatohepatitis)

������ ����� � �� �����∗

����� ���� ���� ��

���� �� ���� ���� ��

������ �� �!" ��#� ��

� <�]�A_ P�7� -�����A�� <c���V d�� <����� -��@ ��0be P��S H�[J���

� -��@ �f0be P��S H�[J��� <�]�A_ P�7� -�����A�� <c���V d�� <�[J �ge

خالصه

����� ��� �� �� �� � �� �������� ������������������ �� !"��� #�$% &� '� (��� ����� ������ �� �) �*�� ��*�� ��� ������+� '�,) '�����

�%���* .�% -�/% 0�1 �,) 2�3������� '��� �� 4�56��% ���7� �89��� �� ��*���: . ;�� &� ���:< ����� !���� �� '����� ;�� ���� ����% =��>?�

�% �6� �� < �� ���@�� (�A� '�������� .�� '����� ;���% (��� �%��������� �B�1 !'� B ����� (���� C��* ��D�% �E� �� ��* F����E� &� ��� ��<

�*�� �� �� ;���8�� �� �%��% .��� ����� 0�1 �,) &� ��G� H���8% �� �8�� I���% F�%� �� �� '����� ;�� ��� . &������� &� F����+� &� �J�D !'3�����9 ��

���* (��� ��� ;��% &��� �� (��� .������ !��� &� �*�� '�,) '�G������ ��E� '�,) ;%>% '�G������ !'����� ;�� �B���?� 4�56� �� !���� ;%>% '��

���* �� ���� ;�����@ '�G������ '�,) 2������% '�G������ . K�8�� ���� � �� �%�� '�G*� ����� ��� '����� ;�� '��� ��/B �%�� �L�M N�M ��

�%���* .'������ N�� ) !� B '����� �� ���8������ �%�� !& =��) "%�* �) ��� &���/@ "%��O =��) !N� �����% ;���� �%���8��:��* . ����

N��� �� ��E?�A% �P� �) � �8� ������� I�� ��% !����� '�,) '�� : ;�%���E C'����� ���� !;�������� !")���9 !�8)�� !;�< ��� =��) !2���)�

;�)���� ���R� '�G���% !;���8�� "������ .��� � � (�: ;�� �� �B�1 =��>?� ��O �� ��6�� �) ��� =��>?� �� � �)��) ;�� �� '����� ;�� S��* .

0 1 1- 1 2: ؛ س ا ل ن ه م 3 8 3 1، گ و ا ر ش

كبد چرب غيرالكلي، استئاتو هپاتيت، پاتولوژي كبدي: هاي كليديواژه

����� �������� � � :�����

* ����� ����� : �� �� � ������� � �� ����� ������ � ��� �� ���� �!

"���# $%� �&���' (��� ���)�����

*+�! :,-./-01���� :0/--0.2

E-mail: [email protected]

1. macrovesicular fatty changes

2. Mallory bodies

3. random

4. desialylated

5. HBsAg

110

1383تابستان / 2شماره / سال نهم/ گوارش

����� ��� ��� ������(Non-Alcoholic Steatohepatitis)

1383تابستان / 2شماره / سال نهم/ گوارش

111

����������

�� ���� ��� ���� � � ��� ������� �� ����� �� � �����!� �"#�

�� #��$ ���� �%&'�� ()� �� #�*� +����,NASH ��-%� )� ( + ����

�&�. #� /$#0/2 �"#� )� ( 3 �%&'�� #� �� � 4��)-� 5���6 % 4�'��

(8� )� ( . ���� (:�� �;'� ��<�=��� >��* ��� �� ?-�� ��#�@�� A<�

�@� #��$ ��� �%&'�� ()� ����, �������� B �#�@�� C3�� D'! ���#��E

�# �-@F �� ��@G� ��$�3 ��H�� C� ���C .

I'�: NAFLD ��� ��'@J (��@; #�0K �� 2L ��@G� �"#� �� 4�C �': )���� ( . ���� � #� ����� ��#�@�� �3# �� �F �� � M���H�!� ��

/�H�E (�?J �3�� +/���� N�O�� ���� ��� ��� C� /��H��E �� ��#�@�� ���� �����P�� ��� 3 ���F ��Q�#�@�� ���8 �# C� R& +����S �� ���F

+��F �%&'�� 3 �!��,'�'8TU/V % ��<=���� (���W�'��X-8� �� ?-�� ���'� )�� ( . #� Y��� �Bizzaro H�� NAFLD 5��� (�<�J ���-���:

/�H�E ��'� 4�'� �'Z ��,�������� #� ���� ��� (8� )� ( .

��� ���� � A<� #� �#�@�� I'�: �8TK �� 6K �[��8 ���, 3 ����& �� �F\ (8� 4�: )� ( . � �� #']� ??�$ ��� �: ����C #� �#��@��

����� C� M�� ��-������ I'�: 3 ��'�#'� ����^� �� �# �E �F �:�� �� _���#� �$�* ��F �# �# I'`'� ��� ���� ���� � ��3 ����� .

�� ����

�� �<=���� (���W�'��X-8� #'!3 ��@� 4 �$�* + ����W���W�� )�� ( 3 (�����

I'� 2 �� 4��� �': )�� ( . C� ���� � a� #�22 �%&'�� ���!�#� ?�-���� ���

�<=���� (���W�'��X-8� + 3 �$�* / �� �#�@�� #� ��$2K �'�;3 #��@����

(:�� )� ( . � #� ������� ����W���W��2K �� bK �� 4��� ��#�@�� �"#� �': )�� (

RcJ�� 3 ����W���W�� �� ?-�� ��#�@�� C� �@�� �3�d #� ��!���,'�'8 �8#��

�-:�� >�* ��� ��� )� ( . e3�; #� ��#��� f��'Jg 4�: �"?Z ��� .

(���W� hS�$ ���� �#C #� ����� �.'�'����&� NASH #����%�

���* +(8� /Q� ������� � #� �FBacon 3 4���#��[�� (�����`3

�'� 3�i-� ����� +�: �-i, 5�� #� �j�E �� �#�@�� �.'�'����&� .

��������� ���� ��� ��� ���

���� #� C'�� �<=���� (���W�'��X-8� H�.'��& �#�� #��$ N�Q�� C� �� .

���k� l�8� �� ���k� �� N'8'� �� » ���` 3� «9 (�!������& 3 f����

�! 3� �O�-� �-!���& C3���! 3 (���W�'��X-8� �� 4��8 C'��X-8� E �����

�� �HO� �:�� )�� ( . h�@�O�� A;'� ���'%�� �� (�3��� e3� ���` #�

e'<8 #� ���* �� ���� ��� �': . '�����%�� l�-8� a� N3� ���`

e�=���# ���'� C� �:�� �#���'-�� #� �m�%�� ��CE ��� �� (8� . R�&

C� ���'-�8 ���'� 3 ����W�� �'�8���%���& �� ��'�� ��d C� M���

�C�%F�& /%���=� �-�E 3 �J�!� ��� ������ e'�<�8 ������%�� +

e'<8 4#�-8 ��� ��� ��10 e��! �� ��': �����'-�8 n:�� �� 3 ����

�� �O�� ���Q-�� M�& 3 >�Q-�� (�����W�'��X-8� I3�: ��� ������, .

�� �k� �� +�*�, �8# C3��� #� �<d�� 3� C� M�� ��#�@�� �Z�� #�

�:�� �op� �#�@�� (!���& 3 >�Q-�� )�� ( . ��� (��3����� e�d �� ��

�#�� ���<F M�� ���'%�� .

�-�E �'�@� +��-W� +��� ��E ��'-)� ����%�� ���-���� 3 �� ����

4�3# ����C #� �� ��-%� �=�-�. �� ���'� ����8 #� 3��i� A;'�

���, q<-G� ��#�@�� ������ ) /-�#'[��g ( .

��� ���� ��� ���!��"

��� C'��X-8� � ��� �d C� M�� h@O� ����& ����� #� ����%�<,

(8� . f<J #� h@O� ��� e3�;t (8� 4�: �"?Z .

����� : ����� �����NASH

��� ����6) ������ ��� ����� 7����� ()��(

��� ��� ��

��� ������� ����)!� �" #$ %&�� �%��' #$!"()��(

!��'� *+�� ��,-�8

� �.' � %"/�� 0���11 ��2�3��'��� !/��� ���'��

���'"�:

�1�/4�45" 6����7�3��'�����8� 6��'"��4�4+9 6�4;�4�4< !�4�

�" 6=>�?��+����@6�����%����'��+ �A/ � ���?8� B���� !��

%/C ��C�

���"���A �D�5)��(

����� :��� �� �� �!" #�$� �%��&' () �*�+!%,

�� �� ��� ��� �������

���� ��� �� � � �

��������� ��� ����������� �

TPN

�������

���� � !"� ����������#�$ %&��� %& ��'� (11

�)*�������#�$+�,

*������ -�./�0���

� � ��$�� ��1)���+�2�&

���� ���������� ��� � ����� �� ���

���+�� ��1)�B5

34$� ��� ����

%5�652,�� ��1)�A) 5� �5��5�5#5�, ��5� �528�59 ��5��

���� :�;��#$��(

9. "Two Hits"

10. satellite cells

11. VLDL (Very Low Density Lipoprotein)

6. truncal obesity 7. Body Mass Index (BMI) 8. Total Parenteral Nutrition (TPN)

������ ����� � ������� �

112

1383تابستان / 2شماره / سال نهم/ گوارش

������� � �� ��

� ���������� ���� ��������� ������ �� ������� �� �!�"!

�"� ����#$������� ���� %&'! . �(��! )��*������ ����� +��� �(,

- �� /�(��$ 0�'�$ ������� �� �!�"! �� � ),�1 �� )2��3 ��4

)! 0��� )56�� '�7 8'1 �� �� 9��! :������ ���3 . �� ��� '� 09;

<�=� :�!�> �(���� ?�1 � )56��'�7 ����#$������� �� 9��! :������

% �5@ )2��4 ��� 0�3 0�$�A! ������� �� �!�"! %�� ����� )�� ( .

����� �������� )56��'�7 ����#$������� �� 9��! :������ �� �����

������ )���� . �����#$������� � ��� ��2,� ��� 'B��A� C5D! ���

� ��� �*������ �� )�E'�$ 0'@ <!�3 )56��'�7 'F� �� G� �� ���

)! ��H�� <!�; �3 � .

����%�I� J�;�� �*��'1 K�������! �� '��L� �� ������� �� �!�"!

���%I� /)D�=! �*�I�� �� %���#�� �M�� '� ���'�����5�@ )�� (

���� �� �3��'� ���%I� ���> 8'1 �$12 )! ��3 . ���� )�!����

)! ����! '� N�H� �� �(���� �(( G� �� O�5� �� ��'��5@ .

���� ����P��� ��#�� K�%�> ����2I �"�� �� ��(Q�$ ���> 8'1 �$

O�6���� ����� ���%I� J;�� )! :P�� � ���> �$ ���3 )�� ( . '�R�� ���

)! S�"�� :���"�I T��U �� ������� 'F� �� )D�=! �!�"! ���

��(&���! �� :���9�'V�I 0��� 8'1 ��& ��H�� �� 'H(! �*(� �$�

�� 8�*��� �� � �3 �$��M )�� ( .

� �������TNF-α K��������W�! �� ���> 8'1 �$���� ���#� /

����� �"� ������� �� �!�"! )��W��! .

������� ���� �

O�W���� �*��'1 :�������&�'� ����5�X�� J;�� :P��&� ���> �$

��5@ :�1 )�����&� )��> ���! )��5� '��MY � ����!����� /:���E /

��!��� ����&���C )! ���3 )��� �� ( . '�� )�(�! )��"��! �$��3

:����&� )��> �"� O�5� C��> �$�& �� �$ �� )�3��� ��& �$

���� ��Z �������&� ['��� .

12. FFA (Free Fatty Acids)

(�-.�* �/�:0%1.� �!2 3�4 �&' �5�.�*6!7��8

���� ��� ����� ���� �(Non-Alcoholic Steatohepatitis)

1383تابستان / 2شماره / سال نهم/ گوارش

113

���

O�6���� �"�� �� �$> :P�� � ���> �$ ) ���� :��'Z ��Fe3+ ���

Fe2+ ( )� ( ��H�� E������%���I������ �� ��� �6�! �� �'��I

�"� )56��'�7 ����#$������� �3�� ��3�� . ���� )�!'�� ̂ ��D�

_�� ����'I :�������� C57� �� �$> ��Z 'R� �� �� ��`! %�!>

)! 0��� )56��'�7 ����#$������� �� 9��! ��3 . )�W���E T�'��L� ��

:EHFE ) ����!' ��$ :E ( 0�3 a��%@ :������ �� )M'� ���� )�� ( .

�������� T�2��D! )M'� �W�> ��Z �� ��� ��� �$> bD� ��� )4����� )�� (

c'� ��'V���'� +��3� :�%�! �� )� ( G��E������� �� )(���� T�3 ��

NASH /�((& ���� ��� ���3 ������� �� �!�"! ��$> ����%�I�

��& �3�� ��3�� ��Z )4����� )�� ( .

�����13

���#� 0�3 b3'� �*�I�� �� )�'1 d'�e! ��I���� K�R(� ��

)! G� :�� �� E'�� �( . �2��D! G� �� )�� ( �����#� )!'� bD�

�� 9��! :������ ��NASH )4����� )� 0��� ��� ��BMI :��������

��� ��3��� . )! 'R� �� ��(1 ��� �!�"! ���%I� �� ���#� � ���

8'1 �$���� ����� ���%I� /������� ��*�X��� ���A� �����

)��*���14 �� / )��%������NASH �"� ��� � )�� ( .

������ ���� � � ��

)� �3� ��� 8'W�! 0�� �$ f�'4 �� � <6�� ����� / ���$������

:E��> )�� ( / ��� ����> )�� ( ��%H� / O��2�I'���7 �'VU �*6��

g'��#�� :�' �� �$ )! �������&� C��> ���A� �� �������

%�E����NASH �3�� 'F�! .

��� � ����� �� �� �

�� �Z�� �� /+�h�! )��� )@��� ��� ���(�$ ������ )(���� '��

��� 0�A� SXA! )���� / )� )�*�@> ����� ��& ��� K5�!

��� )56�� 8'1 �� �� '�*� )56��'�7 ����#$������� ) �"� i jk

/C��'� �� ����lm % ��op % iq % ��ji ( % )�� ( . �� )�@��� �� ��!�

9��! :������ O��2! �$�$�3 0��3 ��>'� K��� ���� )� ( . /��1'�@

����� �(��! )D��'3 �(, �� ���! :��� )�� ( / ���Z r�����'��E�

)W(&���15 / ����! �����$ 16 J�;��� ����� s��� )����� �� �'��I

)! �'�� ��� �� ����� �I'A�� O����� ���%I� ��3 . +��H! ��

' Y )! ��3 �& p �� -l :������ �U�� �� �� �'�� )! 9��! ���3

'B�� �'�� '$ <`! %���� '��5����#$ c�(����& �� 9��� t'2! ��

����� ��', )�� ( . ��I�� C��> �$ �(3 � ) ��� )�,��1 :�%�! �� ����

��� ���2� �� '�A�� ���$� :� �$�& ����� )*@> . ���� ���

ui ���� �(, /),�1 /O��AST �� ALT G� �� '�@�%� )�� ( / :�%�!

8�*��� sZ�� �������� )� ( :��(; �� �$���2! )����B�A��� <"��!

0��3 ̂ 'D! �� �'��I v�(( ���� .Ratziu ��Z�� G�� ��(��

G�E������6�(�5 17 /�� '�L�! ��*1 �� 0��V��� �� �� BMI b�D�� /

'� ��'V���'��(�!> ����> ��'��5@(ALT) c'� ) K������� �� c���!

BAAT�Triglyceride /ALT /Age /Body Mass Index ( ̂ '�D�!

0�' ��� �� /:> �� � ik )��� v��� s���� /O�� �� '��'� '�A�� ��

-p '� bD� /N�'! '�!'� c'@�5� b�D�� ���� )!'� ��'��5@

ALT :�A� ��� v�($� '�A�� O����� ����� ��� ������ �I'A��

��� ?�1 :������ �� �'��I .

�����

�!9; :�� )56��'�7 8'1 �� �� 9��! :������ C57� )�(�������

�(��$ w /)B��M x2h '�R� )U�e�M�'�7 K�9; /) ��� ����! ��

/��& )@�%� ��� ���, K*�! x�VM )������ ��� �� )B�I�

)! 0��� K63 ���� ��3 . '�$��R�� �*(� ����! C57� �� ��'�2��3

��� �� �'65�; T�9�M� /����� . �� :��M �$��'V���'��(�!>

qk )! ���%I� :������ �U�� ���� ����AST/ALT C57� '����&

�� ��� G� )�� ( ) 9��! :������ �� ����"! �� �� � )56�� 8'1 �� ��

� ����2! ���� ��� �*�> �� '�A��- ��� ( )�� ( . /���� �'��I �I'A�� ��

����AST/ALT )! ���%I� %�� ���� ��,� �� ����! ��� � ����

�� )3�� �� �'�� ��1� :������ �� S�XA� �������#�$���������

)! )56��'�7 �$� . ����V�I ���6�> )!'� bD� / <���!�����5�@ ��!�@

r��'� �����#� / ����'I ) :������ �� )��� �� ( / ��'V���'� +��3� ) ��l

��jj :������ �U�� ( )! ���%I� �(��� . ����%�I� <�`�! )���9�M�

)5�� ���!'�'� :�!� ���%I� /����(PT) ��6�! ��!���> �$�

�� ��� �5�'! ��3 0��� G��'�� .

:�A� )I�'@���� )��'� �� )�3��� ��������E� �'#�$ G� v�($�

^�A��� ��� )�'1 )�� ( . )! K$ �'�� ��M d'U ����� ��5�; �� 'R� /

��(� ��H�� )I�'@���� �� )*��A! ��� . )�@P�� ���������

C��'� �� �������� S�XA� �� )I�'@����pq qo �� ��U��

C��'� �� �'��I S�XA�mm pq ��� �U�� )�� ( . )� )� ��6�� 13. leptin 14. proinflammatory

15. ballooning degeneration 16. Mallory hyaline 17. clinico-biological score

������ ����� � ������� �

114

1383تابستان / 2شماره / سال نهم/ گوارش

MRI )! ($� S�XA� �� �������� �(���� � ) <W3y ( ����2� �'� )� /

�(���� C��(! �'��I �� 8�*��� :�%�! )�� ( . C57� �� ����! / �����������

�� )�2�h��! �������� ��� �6�! ����! �� )� ��� 'A�(! T��U

��3 0��� . ���� ��� )� '�� :�%�! �� )I�'@���� �� )� ��� ��6��

0��� 0���3� �� �$ )! ��3 MRI '�A�� G� ��� 0�(( )�� ( .

��'�*� �� )����� a� S�XA� ���2� / ��� )*@> :�%��!

��� :�!�� '�Fz� . C��U )M'� '��� �����! �� �� �� )����� :�'R�

)! ��U�� �((& :

� ��Z � �eXA! K�9; �� �!%! ����

� O�=4 )@�%�

� )(�����

� �*A��!�> �� O9�M� �'! �$> �� |�

� ����� �(, / ��� �'I G� �� |'V! ),�1 ��ui O��

�� ��� a� l O�� G� �� 0�! ����� �� 0��� �U'I )! �� ��3

)! 0��� a��!> ����� �� T�! ��� �� ��3i )�� m/i c'@�5� �� :�

�$�W� ��M . T�! ��� )4 �� '@� �*��!�> �� �'65�; )�2����4

d'U )����� �� :���� ��� �6�! /��3 �' 'R� .

� ���!"� #�$� �$ %& �'�����( �) ���) *�$�

�> T�'��L� � C �� )V5�X! )��(3 )�5�6���'���7 �����#$�������

0�3 a��%@ ��� � �� :> )! �5�Z '������� 8��*��� /�������� �� :���

O�5� )W(&��� r���'�E� /'�5&���I��! )5� �'�����I /����& �$

��� ���� /�'�� /����! ����$ c��Z� /��~��(�� :E��W��5@ �$

������#$ )��5� ���$ �� /8��� ��$���I ��!%�! 8��*����� /�$

�'& 0��3� �$> N�H� )����& �'W� /c�����'@�#�� ) �*563- o ( .

���� :�� �� ���� � ��� ��� ���� ���� ��

18. trichrome

���� : �������� ��� ������ �� �������� ������ . �� �� : �� ���� !"�� �� #" ������� #" �� �$�!% �%�� &'�"�( )(�* ��+

�� ,�-/ �� ���0����� 1��� 2� ����/ � � . &�3(��/ 4��� ( ��5�� )� ��67 8/� #% ���$�3 )� ��09 )� ) ����� )���<% ( )(��=> ��?�"� ( ��

�� ���� � ��'(2�A�� ��+ . ��� �� : 2(��� �% ���� �������� ��� ������ . 8/� )!��B C(�D )� 18 4(�/ �%�� )(�* ,�+ ��/�� 4�* �� )�

(�?�3 3�% �� ��EF�2 �� ,�-/ �� � � .

����: ����� �� � ���!� )��" #�$ ( ��� �%�� ���� � &�'*+�,� -�.�/�

�� 0���1� ���� � 2 ��3����45�� ���� 6 �� 7� 2�����.

���� ��� ����� ���� �(Non-Alcoholic Steatohepatitis)

1383تابستان / 2شماره / سال نهم/ گوارش

115

��6� � ��� ��� �3�� �Z�� :> �� ���� � � ��$���I T����

� ��� ���� :������ �� ����2! )! 0���X� T�'����L� �� �(��! )� ����

)! :�A� �� 9��! :� �� �� )� /�($� '���7 8'1 �� �*������

)56�� 8�*��� �$��I �� ���� T��� ^�A��� 0���� '���A���� )����

)! ��3 .

� C��> )��'� �*Z ���Z a� �� ��'�M� �������� ��� )��(3

��� 0�3 ��*(A�� ) ( ) ��Z �* � � . ( ��Z�� ���2� �$���2!19

�5�X! 8�*��� /�������� T�3 <!�3 ) 8�� ��I )���� ( T�'��L�

O�5� )W(&��� )! ��& �$ �(3�� . �5�'!20 �'��I �B�� [��� '�

) ��~��(�� ��� �'��I �� / ��� d�'4�21 d�'�4� �'�����I ��

8�� �$��I22 �'�� ���*� �� 0�(�� <� �'��I ( )! ���2� ��3 .

�������� �� 0��� 0�'�$ ^�A��� � a��M �������� )����V(� K���M

�(��$ . :�3 )W(&���23 / ^�A��� )5�I'��� / ����! ����$ ��Z ��

�� 0�'!� � ����M��(�3 G�����9 )56��'�7 ����#$������� :��(;

)! ����� �'��I ��� �� �I'A�� �'� '�A�� r��3 /���3 .

)��'� �� �I�� )��(3 �� /:������ ll �� )����Z�� ����! �U��

)! 0�$�A! S�XA� �� �� �'��I ��3 . �� �'�� �� ���3 �'��I

-i �'�� /�U�� <!�&24 ��ju ����! �U�� ��� 0�3 a��%@ )� ( .

�����:���� �� ����� ������� ���� ��� ��� ��!��"��

#G�� H�I����� ������ )��% )����0=/�(�J/ )�A%

K�=L(Mild) #G�� MN �������� )���� ��� ����� ( �� ��� ����� ���� % �������� ��! "�#���� �����$ ��� &�'� *"+,��� �-�

.�/�$ ��01��2� ��3 *��! 4��� .�+� �#5 ��6� ��� ��)PMN (±����6# .� �� ��7-8 �� 4�#��, ��9

:�6; <�=�� �� &�>� <�=�� � �� *"��#��? @;��

O����(Moderate) #G�� MP .3�� ��������� A�� ��! "�#���� *�������� �� �� .�/�$ �� ��0 .-3�� @-��B ���-C� ��-3 *PMN ��

.�/�$ "�2� � � � ��8 4�'� ��� &�'� *"��#��? @;�� ��780 D-���� �-� :-�6; &�>� <�=�� *�!��

"��#��? @;�� <�� ��78

���+(Severe) #G�� MQ "� ��! "�#���� *E�#��? � � ��������.� .3�� @��B "'F$ .�/�$ �� 4G� 0 @-��B "��#��? @;�� <�=�� *

@H� .3��PMN *4�#��, PMN�������� 4�'� ��� 4�! "�#���� ���± <�-=�� I&�>-� :-�6; <�-=��

<�� ��78 &�>� D���� �� :�6;

����# :��$�% ��� ���� ��� ��� ��!��"�� ����

2(�?�3

#�*��N ���J ��#�� � � � ��8 / .�/�$ "�2� � �04��+� �� "$�$�� *

#�*��P ���J ��#�� � � � ��8 / .�/�$ "�2� � �0 <�� ��78 L�9� 4��+� �� "$�$�� � ��8 �� 4�'�

#�*��Q ���J ��#�� � � � ��8 / .�/�$ "�2� � �04��+� �� "$�$�� 4�#$� @, � ��8 �� 4�'� <�� ��78 � ��8

#�*��R � ��

������� ���

�� �!%! �*������ C57� ) O�Z� ( )�,�'���I� S��XA� ��

)! ��', )56��'�7 8'1 �� ����� ��'�@ . �� )� T�6� � �H�> ��

^'3 A��!�> O�� * � ?�'���I� C�Z��! �� ���� ��Z :������

���� �� )�������� �� <�, S�XA� /��3 )56��'�7 ����#$�������

�� �*(� :������il )�� ( �� mj/l % )� ( )! ���z� )����� �� ����! ���3

) :�%�! ��� )56�� 8'1 �� ��pl ��� �U�� ( .

�������#�$�������� )2D, �� �� S�XA� 0�� ���B� �� )�����

��� )56��'�7 .

19. grade

20. stage

21. perivenular

22. preportal

23. ballooning

24. well-established

������ ����� � ������� �

116

1383تابستان / 2شماره / سال نهم/ گوارش

� ��� � ���� �������� ��� ���� ����

'h�� O�� �� �������#�$����������� �'� 'F�! )2D, :�!��

)56��'�7 ����� ��Z ��� �� 'H(! ����! ���$ �~ x�5��X! �*3�

��$ � 0�3 )��!�� C��U s�$ fI��� ���! ��($ G� ��'�, :�'�R��

��I'B� ��� ) O�Zl .( �*��!�� ��� � �����; ��', '�� ��=! � �� ����� :

�� ! ��"# $���% &� '

��� ����

)! :� �$� �� ����� )2��4 ��� �$��'V���'��(�!> :�3

���*� %�� ���M�� ��3 'H(! �� )�� ( . K*! s�6� > ���� �� ��� :

)H���� :� �$� ) � �� �� 99`!��� ��V$ �� c'@ ( �3�� .

)B(�'@ ���325 )! ����� ���Z �� )��Z )�D�=! �*�I�� �� �*��'1

�� �� ����#$������� �������� ���A� J;�� ��3 . T���U '�$ ��

:������ ?�1 � ���3 f��A� )H���� :� �$� �� ����, ���� .

�$��� �*(� � ) :��!�� �� �&NASH 0��� :��A� f�I��! ����

� T��������26 ��!�'����� 27 0��� ��� )���� ( .

����& : ��� � ��� ��� ��� ���� '�( )�*% �+�%�� ��!(��

,2( ��'�� ( �S��� T �D

��I��$��� 4��AD

��A���I/���� 4��AD ( T �D

���������� 4��AD ( T �D

1���I/� #% ���I* T��!3� )��% �/����(���

&���

����#��� ����

)�?D )�6�%�� T �D )��% �/����(���

M���828

4�##���=� ���HMG CoA���� �� 29) �=#������(

)�?D 1 B T �D

,���ID� ��/B����� U3�F� &���V ( �

&���$���30�� *�&���+�� @���� �@���� ���� @�, ,31

&�$���� @���$�? E�

N��#2�32

&���'�2��

1������ �

1�����(E

1���D� 33� ������=I3 (

&�J���34

&���

&��� @�����6+8 @���#�35

��(� 2� �+�/ ��ID�(�/� T �D

O����� "�$?@�������P ����

1�D���� #V��S� �����

&������ ����"��=�� ��� /O�$Q ��8

"�$?���� �R ���TNF�+�$����$? 4�$�� ���

TNF) <�'�+��26#�� *"+���#,&�2�8(

&������ S� N ���"��=���R ��� /� ��8 �R

1=�ID��� 2� �+�/ W�� �?D )��% ���?�3(!%

)�% ,�/���$2�%)�5� �� ( 4������/(�� X�

��D ����6�

O�+�������� ��� ��� ���� *@�� LT� �� <�#�3�

�$��� @�� LT� .U��� .� "$���'�� "'J�� ��V�,

&'�� ������ .�2W ����A B

�?D �/���

����, :������� �� � � ������ ������� ��������

"2X� <5 ��Y ��� �� "!�$ ���Y ���'��

1�� ������

)B *C D(

"S�� ����� Y�'�

��+2� ���'�� �6? ���'Y�Z� "�$? &�+���

.� � � �6[ � �� ��������;&'��

31. propylthiouracil (PTU)

32. selenium

33. cholines

34. betaine

35. linoleyl phosphatidylcholine

25. starvation

26. orlistat

27. sibutramine

28. fibrates

29. HMG CoA reductase inhibitors

30. carnitine

����� ��� ��� ������(Non-Alcoholic Steatohepatitis)

1383تابستان / 2شماره / سال نهم/ گوارش

117

� ���������� ����� ������ ���

:�A� � ) ���! ��($ �(1 '$ '�F�� v�($� �(, K�R(�36 ����2I '�

0��!����� ��� �� �3�� )56��'�7 ����#$������� ����� �I'A��

:�!�� /��� ������ � �� ������ ������� � ��� ����! �� )6� �(,

�� 9��! �(, :������NASH �'�@ ��', 'R� �! . ��!�"! )$�'�$

�� ������� ��NASH :�����(��������� �� 0��V��� �� 'H(! ��$37 ��

��=! T�2��D! ��� 0�3 . )5; ����� 0�((& ����!� ����� K7� )�� (

�5; �� t���; ��& ���3 ���M �6�'!> ����� �� �$��� ��� .

��=! ����� s2��D! �(1 �� ��!��V�! K��%��> ��$��& �� ��$

��� 0��� :�A� fI�! ��& )� ( .

������ ����� ���������

'�'#�$ O'�( ��� 9��! :������ �� ��� �6�! %�� )!��'��5@

�3�� ��V! )56��'�7 8'1 �� ����� . KZ <��'��I38 �� �2� u ��V$

r��'� <�!���5@�!�@ �$��'V���'��(�!> bD� /:�!�� ��������#��39 ��

�$� ��� . )(2! T�V� /:�!�� :���� �� �6(�� C��Z s�6� ���� ���

'� ̂ �D� ����� 0��� ���� :�!�� �� � )������� )!'� ��'��5@

�3��� ��Z ����� 0���� ���� � )������� )�� ( . KZ ��6��! <��'��I

'� �� :������ �� K$ ��� ��� :��������� �� K�$ ��� ��'��5@

'� ��'��5@ )2��4 �3�� ��V! . /����"! �� T�'��I�5 )��*! '�Fz�

��� ��3��� )�� ( .

�����40

'�A�� T�2��D! ����� �'� �� ���#� �"� NASH �� ��� ����

���#� �� 0��V��� ��> ��3 SXA! ��%�'� ���� ��V! :������ ��� ��

���#� ����2I ��*! �� .

�� ���� ���! �� ��"#�$� �% �� ��& ��'� ��

��� ( ���� ����� �

-�%���E

��!���E �� ������� � ['��� �"� �� �Z�� �� NASH ����! ��� ��I'@ ��', ��""=! �Z�� . �2��D! � ��$�� /:�� ��� ��

)(2! ����!��� d'e! O���� �� )!'� �$��'V���'��(�!> ���E �� �& ��� :�A� ND, �� /:> ���! K�%�> )�2��4'�7 ̂ �D� :��$ �� �$

)! ��� �A@ . �� �� ��2h ���*� 'B�� �2��D! ��I�� ��� )����(�3

��!��� �� 0��V���E ��� 0�3 0��� :�A� )�� ( . ��!��� ����"! ��E �� K�%�> /:�'�� �� ������ �� ��& �$�� �� �� % )��Z�� :������

�I�� ���*� �� �� )��(3�� % �3 0��� ����! )�� ( . �� /K� s�(��%$ )� :��� ['��� :��� 'DM 0�3 J;�� :�!�� �� ��eeX�! C57�

NASH ��!��� �� E �((& 0��V��� . �*(�!��� :�!%�$ 0��V��� E C r��'� � '� )� 0��� �$�& �� �'��I :�%�! ��� ��$���(�!>

��� 0���� 'F�! ��& 8�*��� )�� ( .

./����041

< ��'� ) ����� ��� :�M )�'1 v���> ( �� )��> ��U�M )�������� � )(2! �$� J;�� �Z�� <��, K�%�> bD� ��� �� �$ 0�3 ��� / )��

��2h � '� :> '�Fz� �I�� )��(3 SXA! :������ ���� )� ( .

-��"���1

K�'! ��M 0��@ v��e;42 ��3�� <��� �� )��> ��U�M )����� � �� �� �*������ '� T�2��D! ��� 0��� :�A� 'F�! . �2��D! ��($ '� �

'� ������5�� '�Fz� �NASH ��� 0�A� c�H�� )� d'�e! :> �� ���������� �� �!�"! �*��'1 :������� �'� �$� �� 'H(!

�(, :������ ���'�� ��� 0�3 )�� ( .

� ( ������� �� ���� ����43

����� ���� ��`! '�Fz� )� � G��� (UDCA) )!'� bD� '�

K�%�> ��� 0���� ���z� �� 'B�� ��2�! T�2��D! �� �� �$ )�� ( .

����"! :> T�'��I�5 �� �& ��� :�A�UDCA b�D� ���*� �� 'H(!

����V�I ���6�>ALT )! �������� %�� )!'� ��'@ / � '�� )�

����� )���(1 '�Fz� �'��I �� 8�*��� :�%�! )�� ( .

�� �������� ��� ��� �� :� ?�1 �� �5; �� ���3 �& �3�� 'F�!

K& ��� ��� 0��� ) ( .

� ( ��� �� �

2��D! �� )&�� )�� K�%�> �$� �� �$ �eI �� r�44 s��5X�

�$> 0�'�$ :> ���� ��Z )� ( . ��$> :�%�! :�' K / d'�U �� '�R��

�*Z ��Z :E HFE ����� ���*� �� / ��� ��V! )�� ( .

��() ��&��*�

/0�3 '&Y E����%�I���� �� �Z�� �� �� <��6! ���� �� �������

� )������� O���� ��TPN ��1� NASH 0�3 ��� )! ����V�! ������

41. probucol

42. silybum marianum

43. ursodeoxycholic acid (UDCA)

44. phlebotomy

36. control of hyperglycemia

37. thiazolidinedions (TZDs)

38. gemfibrozil

39. GGTP

40. Leptin

������ ��� ���� ���������� �

118

1383تابستان / 2شماره / سال نهم/ گوارش

�3�� )�� ( . ��~��� ) ���� )2��4 �������! ( [�� ������! <�����>45 ��

���%I� )! �H��� �� �$� '� 8��� N��! ���� �� �$��'��5@

)! ������� � ['��� ��3 . ����~��� d'e! � ��� 0�3 0��� :�A�

O�! �� )����� �$ )����� )! �������� �� N��! ��3 )�� ( .

�+�,�- ��&����

���� ��������� � ��� ��

�� O���� �� �& )������� '� �� �� �� ��� �3� �$ ����� ��������

����� 0�'& )��> �� 0��V��� G����� �$ ) )5� ���6�!B O�����'�! (

��� 0��� 'F�! ��� �� )� ( .

����� ��� �!"� � �

)�2� �"� �� �Z�� �� �� ���� �$ �� '�B��� )M'� ���A� ��

)��*��� ��� <��'! x�2�� �'��I '�F�! �$��� �� 0��V��� /��&

��&���� '� ��2�! T�2��D! +�h�! �$ ��� .

� ��� ���� ���

��Z �� ���! �� ���� ���%I� NASH ��*���I'�A��� ���V�z�!

c��H��� ��� ��($ ��I'B� T��U ����� ��� :�!�� �� '�B�A1

T�2��D! 0�'��@ '� ��� ���� . )�!�%��� :������ s�$ �� )���� :�!��

���� . )�����7 K��E� G�� �� � ��3 ��U�� :������ s�$ �� ����

)��> +���� �� � O��2�! :���� � )�'1 ����! '���"! �$ ) ��&

�B!� 8'1 �$���� ��� o )! �3�� ( ��� �(( 0��V��� �������

)��� ����2I a�� �(( +'3 �� . K� ����� t���; �� �Z�� ��

)��� ������!������� ���$��� )������� :����� '��D��ME ��������

����� )� � ��� � )! �$��� ��� / :�!�� O� �M :��(; �� �(����

���� T��U �� ��� �� �� .

. ���/ �'

)! )56��'�7 ����#$������� ��� �'�� �� 'H(! ���*� �� �����

���� ���� ����� :> :�!�� � ��3 �� <!� :���I� �� �� . ��

�2� ����� /)56��'�7 ����#$������� �� 9��! :������ �� )� �U��

)! ��; %�� �� ����� �� �(& )�� ( . O'���(� :� ��$� ���'��(�

� �������� ����� �� ����� �� �2� <�, /)!��#��'#�$ )���5@'#�$

�Z�� ���! �3�� .

������ �� ��*���) 0���� ���1�!

�� ��� �(1 ���e� %���1��� :�&��& �� ����#$������� +��3

)! �3 w K$ )� �� )56��'�7 ����#$������� :�( � �� )�6�� :���(�;

)! ��M�(3 :� �� �� �� K*! �*������ ��3 / '�!� ���� ��

)! ����%�I� ���� ���! �3��*� ���*� �� )3�� �� �� �����

�3�� :� �� �� ),�1 +��3 )�� ( .NASH �*�@P� :� �� �� '���

���� �� :

� O�� �� K :� �� �� ����� '�A�� +��3

� :�'�� �� '�A�� ) ��� +��3

� '�'#�$ �� )!��'��5@ )�'1 T�9�M� c'I ��'�2��3 :��(; )�� (

S�XA� �� NASH )���� ��!���! /:� �� �� / ��*��������

G������! ) G���� �'��I :��5� ( ���; �(1 )F�� �*������

������� �� �!�"! )�(������'#�$ 0�'�$ ���3 �� ���� .

��2'� ��&������ ���! � ��*���) 3�4 �'� 5��6�� ��%7�

8 ��

)e�XA� �$���2! �� )6� �6�> �� '���7 8'�1 ��� �*������

)56�� '�!� ���� )�� /���� �� �!%! �*������ <5; '��� �� /

�*�@P� � ��� ����! �M�(3 c%5��! )(���� �I�� )����(�3

NAFLD �*������ '��� 46 �� ����� )�� ( . ������� �� � )������� ��

'B�� �� K$ �� ���� ��� �6�! /�(��$ 9��!» c� s��'h«

�3��� �������� )��*(� �� �'�����I �'6� /8�*��� �I'A�� C��

0��'A�� ��3 )� ( .

�� ���ik ����#$ �� 9��! :������ �U�� C /�!%! �� �I�� )���(3

����� �������� ��M )�� ( .BMI ['� �����E �� '�� '�F��! <!��;

�� �������� ��� :������ �(��$ )� ( .

46. Overlapping 45. S-adenosylmethionine

����� ��� ��� ������(Non-Alcoholic Steatohepatitis)

1383تابستان / 2شماره / سال نهم/ گوارش

119

1. Ludwig J, Viggiano TR, McGill DB et al. Nonalcoholic

steatohepatitis: Mayo Clinic experiences with a hitherto

unnamed disease. Mayo Clin Proc 1980; 55: 434–8.

2. Matteoni C, Younossi ZM, McCullough A.

nonalcoholic fatty liver disease: a spectrum of clinical

patholigical severity. Gastroenterology 1999; 116:

1413-9.

3. Falk-ytter Y, McCullough AJ, Younossi J et al. Clinical

features and natural history of nonalcoholic steatosis

syndromes. Sem Liver Disease 2001; 21: 17-26.

4. Clouston AD, Powell EE. Interaction of non-alcoholic

fatty liver disease with other liver diseases. Best Pract

Res Clin Gastroenterol 2002; 16: 767-81.

5. Storey E, Anderson GJ, Mark U et al. Desialylated

transferrin as a serological marker of chronic excessive

alcohol ingestion. Lancet 1987; 1: 1292-4.

6. Propst A, Propst T, Judmaie G et al. Prognosis in

nonalcoholic steatohepatitis (letter). Gastroenterology

1995; 108: 1607.

7. Nonomura A, Mizukami Y, Unoura M et al.

Clinicopathologic study of alcohol-like liver disease in

non-alcoholics; Non-alcoholic steatohepatitis and

fibrosis. Gastroenterol Jpn 1992; 27: 521-8.

8. Walness IR, Lentz JS. Fatty liver hepoatitis

(steatohepatitis) and obesity: an autopsy study with

analysis of risk factors. Hepatology 1990; 12: 1106-10.

9. Clark JM, Brancati FL, Deihl AM. Nonalcoholic fatty

liver disease: the most common cause of abnormal liver

enzymes in the U.S. poulation [abstract].

Gastroenterolgy 2001; 120(Suppl 1): A65.

10. Diehl AM. An update on nonalcoholic steatohepatitis.

AGA postgraduate 2000; 20: 63-76.

11. ������� � ����� ��� �� ������ ������� ����� ������ �������� .

���� ����!�"� �� #$$% &'(��� ���"� �� )% *+,-/� ������" �����

0��� �� ����1 �$��/ ���� ��-������ &� )% ��2�$��3 4���1 5�,6

78�9:;7 . ��<��= � ��>?6 �������� &@��� 9:79 ABC ::8�E9.

12. Bizzaro N, Tremolada F, Casarin C et al. Serum alanine

aminotransferase levels among volunteer blood donors:

effect of sex, alcohol intake and obesity. Ital J

gastroenterol 1992; 14: 237-41.

13. Baldridge AD, Perez-Atayde AR, Graeme-Cook F et al.

Idiopathic steatohepatitis in childhood: a multicenter

retrospective study. J Pediatr 1995; 127: 700-4.

14. Diehl AM, Goodman Z, Ishak KG. Alcohol-like disease

in nonalcoholics. Gastroenterology 1988; 95: 1056-62.

15. Pinto HC, Baptista A, Camilo ME et al. Nonalcoholic

steatohepatitis. Clinicopathological comparison with

alcoholic hepatitis in ambulatory and hospitalized

patients. Dig Dis Sci 1996; 41: 172-9.

16. Powel EE, Cooksley JGE, Hanson R et al. The natural

history of nonalcoholic steatohepatitis: a follow-up

study of 42 patients follow for up to 21 years.

Hepatology 1990; 11: 74-80.

17. Assy N, Kaita K, Mymin D et al. Fatty infiltration of

liver in hyperlipidemic patients. Dig Dis Sci 2000; 45:

1929-34.

18. Ruderman N, Chisholm D, Pi-Sunyer X et al. The

metabolically obese, normal-weight individual

revisited. Diabetes 1998; 47: 699-713.

19. Cello JP, Grendell JH. The liver in systemic conditions.

In: Zakim D, Boyer TD, editors. Hepatology.

Philadelphia: WB Saunders; 1990. p. 1428.

20. Struben VMD, Hespenheide EE, Caldwell SH.

Nonalcoholic steatohepatitis and cryptogenic cirrhosis

within kindreds. Am J Med 2000; 108: 9-13.

21. Day CP, James OFW. Steatohepatitis: a tale of “two

hits”? Gastroenterology 1998; 114: 842-5.

22. Agrawal S, Bonkovsky HL. Management of

nonalcoholic steatohepatitis. J Clin Ganstroenterol

2002; 35: 253-61.

23. Kral JG, Lundholm K, Bjorntorp P et al. Hepatic lipid

metabolism in severe human obesity. Metabolism 1977;

26: 1025-31.

24. Angulo P. Nanalcoholic fatty liver disease. N Engl J

Med 2002; 346: 1221-31.

25. Sanyal AJ, Campbell-Sargent C, Mirshahi F et al.

Nonalcoholic steatohepatitis: association of insulin

resistance and mitochondrial abnormalities.

Gastroenterology 2001; 120: 1183-92.

26. Woods JR Jr, Plessinger MA, Fantel A. An introduction

to reactive oxygen species and their possible roles in

substance abuse. Obstet Gynecol Clin North Am 1998;

25: 219-36.

27. Bonkovsky HL, Jawaid Q, Tortorelli K et al. Non-

alcoholic steatohepatitis and iron: increased prevalence

of mutations of the HFE gene in non-alcoholic

steatohepatitis. J Hepatol 1999; 31: 421–9.

28. Bonkovsky HL, Jawaid Q, Tortorelli K et al. Non-

alcoholic steatohepatitis and iron: increased prevalence

of mutations of the HFE gene in non-alcoholic

steatohepatitis. J Hepatol 1999; 31: 421–9.

29. Angulo P, Keach JC, Batts KP et al. Independent

predictors of liver fibrosis in patients with nonalcoholic

steatohepatitis. Hepatology 1999; 30: 1356–62.

30. Mendler MH, Turlin B, Moirand R et al. Insulin

resistance- associated hepatic iron overload.

Gastroenterology 1999; 117:1155-63.

31. Uygun A, Kadayifici A, Yesilova G et al. Serum leptin

levels in patients with nonalcoholic steatohepatitis. Am

J Gastroenterol 2000; 95: 3584–89.

32. Kaplan LM. Leptin, obesity, and liver disease.

Gastroenterology 1998; 115: 997– 1001.

33. Wigg AJ, Roberts-Thomson IC, Dymock RB et al. The

role of small intestinal bacterial overgrowth, intestinal

����

������ ��� ���� ���������� �

120

1383تابستان / 2شماره / سال نهم/ گوارش

permeability, endotoxaemia, and tumour necrosis factor

alpha in the pathogenesis of nonalcoholic

steatohepatitis. Gut 2001; 48: 206-11.

34. Galambos JT. Natural history of alcoholic hepatitis III.

Histological changes. Gastroenterology 1972; 63:

1026.

35. Sheth SG, Chopra S. Nonalcoholic steatohepatitis.

UpToDate 10.3, 2002

36. Caldwell SH, Oelsner DH, Iezzoni JC et al.

Cryptogenic cirrhosis: clinical characterization and risk

factors for underlying disease. Hepatology 1999; 29:

664.

37. Bugianesi E, Leone N, Vanni E et al. Expanding the

natural history of nonalcoholic steatohepatitis: from

cryptogenic cirrhosis to hepatocellular carcinoma.

Gastroenterology 2002; 123: 134.

38. Ratziu V, Giral P, Charlotte F et al. Liver fibrosis in

overweight patients. Gastroenterology 2000; 118:

1117-23.

39. Garcia-Monzon C, Martin-Perez E, lacono OL et al.

Characterization of pathogenetic and prognostic factors

of nonalcoholic steatohepatitis associated with obesity.

J Hepatol 2000; 33: 716-24.

40. Daryani NE, Mirmomen Sh, Bahrami H et al. Clinical

and histopathological features of nanalcoholic

steatohepatitis in Iranian patients. Gut 2002; 51 (Suppl

III) A252.

41. Sorbi D, Boynton J, Lindor KD. The ratio of aspartate

aminotransferase to alanine aminotransferase: Potential

value in differentiating nonalcoholic steatohepatitis

from alcoholic liver disease. Am J Gastroenterol 1999;

94: 1018-22.

42. Franzese A, Vajro P, Argenziano A et al. Liver

involvement in obese children: ultrasonography and

liver enzyme levels at diagnosis and during follow-up

in an Italian population. Dig Dis Sci 1997; 42: 1428-32.

43. Joseph AE, Saverymuttu SH, al-Sam S et al.

Comparison of liver histology with ultrasonography in

assessing diffuse parenchymal liver disease. Clin

Radiol 1991;43:26-31.

44. Rofsky NM, Fleshaker H. CT and MRI of diffuse liver

disease. Semin Ultrasound CT MR 1995; 16: 16-33.

45. Debaere C, Rigauts H, Laukens P. Transient focal fatty

liver infiltration mimicking liver metastasis. J Belge

Radiol 1998; 81: 174-5.

46. Brunt EM, Janney CG, Di Bisceglie AM et al.

Nonalcoholic steatohepatitis: a proposal for grading

and staging the histological lesions. Am J Gastroenterol

1999; 94: 2467-74.

47. Teli MR, James OFW, Burt AD et al. The natural

history of nonalcoholic fatty liver: a follow-up study.

Hepatology 1995; 22: 1714-9.

48. Van Ness MM, Diehl AM. Is liver biopsy useful in the

evaluation of patients with chronically elevated liver

enzymes? Ann Intern Med 1989; 111: 473-8.

49. Daryani NE, Mirmomen SH, Bahrami H et al. Clinical

and histological features of nonalcoholic

steatophepatitis in Iranian patients. Under press. Acta

Medica Iranica 2002.

50. Ueno T, Sugawara H, Sujako K et al. Therapeutic

effects of restricted diet and exercise in obese patients

with fatty liver. J Hepatol 1997; 27: 103–7.

51. Assy N, Israel F, Svalb S et al. Orlistat (Xenical)

reverses fatty liver disease and improves hepatic

fibrosis in obese patients with NASH [abstract].

Hepatology 2001; 34: 251A.

52. Sabuncu T, Nazligul Y, Karaoglanoglu M et al. The

effects of sibutramine and orlistat on the

ultrasonographic findings, insulin resistance and liver

enzyme levels in obese patients with non-alcoholic

steatohepatitis. Rom J Gastroenterol 2003; 12: 189-92.

53. Caldwell SH, Hespenheide EE, Redick JA et al. A pilot

study of a thiazolidinedione, troglitazone, in

nonalcoholic steatohepatitis. Am J Gastroenterol 2001;

96: 519–25.

54. Coyle WJ, Delaney N, Yoshihashi A et al. Metformin

treatment in patients with nonalcoholic steatohepatitis

[abstract]. Gastroenterology 1999; 116: A1198.

55. Basaranoglu M, Acbay O, Sonsuz A. A controlled trial

of gemfibrozil in the treatment of patients with

nonalcoholic steatohepatitis. J Hepatol 1999; 31: 384.

56. Laurin J, Lindor KD, Crippin JS et al. Ursodeoxycholic

acid or clofibrate in the treatment of non-alcohol-

induced steatohepatitis: a pilot study. Hepatology 1996;

23: 1464–7.

57. Hasegawa T, Yoneda M, Nakamura K et al. Plasma

transforming growth factor-beta1 level and efficacy of

alpha-tocopherol in patients with non-alcoholic

steatohepatitis: a pilot study. Aliment Pharmacol Ther

2001; 15: 1667-72.

58. Daryani NE, Mirmomen Sh, Farahvash MJ et al.

Vitamin E in the treatment of patients with

nonalcoholic steatohepatitis: a placebo- controlled

double- blind study. Gut 2002; 51 (Suppl III) A15.

59. Harrison SA, Torgerson S, Hayashi P et al. Vitamin E

and vitamin C treatment improves fibrosis in patients

with nonalcoholic steatohepatitis. Am J Gastroenterol.

2003; 98: 2485-90.

60. Malekzadeh R, Merat S, Sotoudeh M et al. Probucol in

the treatment of non-alcoholic steatohepatitis: a

placebo-controlled double-blind study [abstract].

Gastroenterology 2002, 122(Suppl 1):A-24.

61. Velussi M, Cernigoi AM, De Monte A et al. Long term

(12 months) treatment with an anti-oxidant drug

(silymarin) is effective on hyperinsulinemia, exogenous

insulin need, and malondialdehyde levels in cirrhotic

diabetic patients. J Hepatol 1997; 26: 871–9.

62. Guma G, Viola L, Thome M et al. Ursodeoxycholic

acid in the treatment on nonalcoholic steatohepatitis:

results of a prospective clinical controlled trial

[abstract]. Hepatology 1997; 26: A387.

����� ��� ��� ������(Non-Alcoholic Steatohepatitis)

1383تابستان / 2شماره / سال نهم/ گوارش

121

63. Tokar JL, Berg CL. Therapeutic options in

nonalcoholic fatty liver disease. Curr Treat Option

Gastroenterol 2002; 5: 425-36.

64. Vajro P, Franzese A: Lack of efficacy of

ursodeoxycholic acid for the treatment of liver

abnormalities in obese children. J Pediatr 2000; 136:

739–43.

65. Desai TK, Chiorean M. Phlebotomy reduces

transaminase levels in patients with chronic non-

alcoholic steatohepatitis [Abstract]. Gastroenterology

1998; 114: A1233.

66. Facchini FS, Hua NW, Stoohs RA. Effect of iron

depletion in carbohydrateintolerant patients with

clinical evidence of non-alcoholic fatty liver disease.

Gastroenterology 2002; 122: 931–9.

67. Palombo JD, Schnure F, Bistrian BR et al.

Improvement of liver function tests by administration

of L-carnitine to a carnitine-deficient patient receiving

home parenteral nutrition: a case report. J Parenteral

Enteral Nutr 1987; 11: 88–92.

68. Abdelmalek MF, Angulo P, Jorgensen RA et al.

Betaine, a promising new agent for patients with

nonalcoholic steatohepatitis: results of a pilot study. Am

J Gastroenterol 2001; 96: 2711.

69. Pappo I, Becovier H, Berry EM et al. Polymyxin B

reduces cecal flora, TNF production and hepatic

steatosis during total parenteral nutrition in rat. J Clin

Res 1991; 51: 106–12.

70. Molloy RM, Komorowski R, Varma RR. Recurrent

nonalcoholic steatohepatitis and cirrhosis after liver

transplantation. Liver Transpl Surg 1997; 3:177.

71. Saibara T, Onishi S, Ogawa Y et al. Bezafibrate for

tamoxifen-induced nonalcoholic steatohepatitis. Lancet

1999; 353: 1802.

72. Roberts EA. Steatohepatitis in children. Best Prac Res

Clin Gastroenterol 2002; 16: 749-65.

73. Brunt EM. Nonalcoholic steatohepatitis: definition and

pathology. Sem Liv Dis 2001; 21: 3-16.

74. Day CP, James OFW. Hepatic steatosis: innocent

bystander or guilty party? Hepatology 1998; 27: 1463-

6.

75. Hourigan LF, MacDonald GA, Purdie D et al. Fibrosis

in chronic hepatitis C correlates significantly with body

mass index and steatosis. Hepatology 1999; 29: 1215-9.

76. Adinolfi LE, Gambardella M, Andreana A et al.

Steatosis accelerates the progression of liver damage of

chronic hepatitis C patients and correlates with specific

HCV genotype and visceral obesity. Hepatology 2001;

33: 1358-64.

Non-Alcoholic Steatohepatitis (NASH)

ABSTRACT

The term “Non- Alcoholic Steatohepatitis (NASH)” is applied when

sonographic and pathologic view of liver shows alcoholic hepatitis

changes without history of alcohol consumption. Radiologic findings can

easily make the diagnosis and liver biopsy confirms the initial suspicion.

It is showed that up to 43.5% of patients with asymptomatic abnormal

liver transferases levels have some degrees of NASH, which suggest

the importance of being familiar with the issue and how to approach and

treat it. NASH is commonly accompanied with diabetes mellitus

(especially type II), obesity and hyperlipidemia. These findings support

the theory in which insulin resistance is the mainstay of NASH

pathophysiology. The natural history of NASH is unclear but surely it is

far better than alcoholic related liver disease. It is estimated that up to

8% of patients would meet cirrhosis, considering risk factors such as

obesity and features found in biopsy specimen. Steatosis,

polymorphonuclear lobular inflammation, ballooning degeneration,

hyaline- Mallory bodies and cirrhosis are among different pathologies

seen in biopsy. It is important to rule out other chronic liver diseases

including drug induced liver disease, chronic viral hepatitis, and

metabolic and autoimmune liver diseases to establish the diagnosis of

NASH. There is no definite treatment for NASH. Therapeutic measures

are categorized as reducing risk factors and using hepatocellular

protective agents. The former includes weight reduction, treating

hyperinsulinemia and diabetes, control of hypertriglyceridemia and

leptin. Protective agents are anti-oxidants like vitamin E and/ or C,

probucol, silymarin, ursodeoxycholic acid, reducing iron load, N-acetyl

cystein, food supplements and cytokines. Increasing rate of NASH is

reported among children and adolescences, which could be due to

growing amount of obesity in these age groups. Govaresh 2004; 9: 110-21

Keywords: Non-alcoholic fatty liver, Steatohepatitis, Liver pathology

Ebrahimi Daryani N

Gastroenterology Dept., Imam

Khomeini Hospital,

Tehran University of Medical

Sciences

Bahrami H

Imam Khomeini Hospital,

Tehran University of Medical

Sciences

Haghpanah B

Imam Khomeini Hospital,

Tehran University of Medical

Sciences

Hashtroudi AA

Imam Khomeini Hospital,

Tehran University of Medical

Sciences

Corresponding Author: Nasser Ebrahimi Daryani MD, No.

130. next to Shahid Naseri Ave.,

Valiasr Ave. Tehran, Iran.

Tel: +98 21 8799446

Fax: +98 21 8799840

E-mail:

[email protected]

Non-Alcoholic Steatohepatitis (NASH)

147

Govaresh\ Vol. 9\ No. 2\Summer 2004