Korean J Gastroenterol.  2021 Apr;77(4):179-189. 10.4166/kjg.2020.158.

Efficacy and Safety of Biphenyl Dimethyl Dicarboxylate and Ursodeoxycholic Acid Combination in Chronic Hepatitis Related to Metabolic Syndrome Components

• Heo NY
• Park SH
• Choi JH
• Kim E
• Kim TO
• Park J
• Lee J
• Park YE
• Oh EH
• Hwang JS
• Jeong SJ

• KMID: 2515139
• DOI: http://doi.org/10.4166/kjg.2020.158

Abstract

Background/Aims
Steatohepatitis related to metabolic syndrome is a chronic liver disease prevalent in patients not only with non-alcoholic steatohepatitis but also with alcoholic liver disease and chronic viral hepatitis. On the other hand, there is limited data on the effects of hepatotonic agents in these patients. Therefore, this study evaluated the efficacy of a combined hepatotonic agent in this population.
Methods
Thirty-three adults with chronic hepatitis and one or more components of metabolic syndrome were assigned randomly to receive biphenyl dimethyl dicarboxylate/ursodeoxycholic acid or a placebo for 24 weeks. The primary outcome was the normalization of ALT (≤40 U/L). The secondary outcomes were the change in controlled attenuation parameter, transient elastography, and Chronic Liver Disease Questionnaire score.
Results
The 33 patients were assigned randomly to two groups. Eight (50%) of 16 patients who received the intervention drug showed the normalization of ALT, whereas only one (6%) of 17 patients in the placebo group did so. In contrast, the change in controlled attenuation, transient elastography, and Chronic Liver Disease Questionnaire were similar in the two groups. ALT was changed significantly during the four assessment periods, and this change was affected by the group. The interaction between the group and time was also significant. AST was changed significantly during the same period. This change was not affected by the group.
Conclusions
Biphenyl dimethyl dicarboxylate/ursodeoxycholic acid combination reduced ALT in chronic liver disease related to metabolic syndrome. On the other hand, there is no evidence that this leads to improved hepatic steatosis and fibrosis within 6 months.

Keyword

Steatohepatitis; Hepatotonics; Alanine transaminase

Figure

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  Fig. 1 Flow chart of study enrollment.

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  Fig. 2 Comparison of ALT normalization at 24 weeks in intention-to-treat and per-protocol analysis. ALT, alanine aminotransferase; ITT, intention-to-treat; PP, per-protocol.

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  Fig. 3 Changes in liver enzymes and metabolic parameters: (A) weight, (B) BMI, (C) ALT, (D) AST, (E) GGT, (F) glucose, and (G) systemic blood pressure according to treatment group. BMI, body mass index; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma glutamyltranspeptidase.

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  Fig. 4 Comparison of the changes in serum ALT and serum AST levels during the treatment period between groups in an intention-to-treat analysis. (A) ALT, two-way repeated-measures ANCOVA adjusted for the change of BMI during the treatment period. (B) AST, 2-way repeated measures ANCOVA adjusted for the change in BMI during the treatment period. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index.

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