A 2-year multicenter, double-blind, randomized, placebo-controlled study of bezafibrate for the treatment of primary biliary cholangitis in patients with inadequate biochemical response to ursodeoxycholic acid therapy (Bezurso)

IntroductionThere is a need to classify patients at genetic risk for drug seeking behavior prior to or upon entry to chemical dependency programs.MethodsThe prevalence of seven risk alleles (DRD2 = A1; SLC6A3 (DAT) = 10R; DRD4 = 3R or 7R; 5HTTLPR = L or LA; MAO = 3R; COMT = G) and corresponding severity risk score (Low (LS) = 1–36%, moderate (MS) = 37–50%, and high (HS) = 51–100%) were calculated. Group 1 consisted of 16 Caucasian male psycho-stimulant addicts, and Group 2 consisted of 10 Chinese male heroin addicts (9 were genotyped). qEEG and fMRI visualized the impact of Neuroadaptagen Amino-Acid Therapy complex on mesolimbic system activation.Results[Findings by Group]74% of the combined groups had a moderate to high genetic addiction risk score (GARS). One acute dose of KB220-IV variant in heroin addicts having brain abnormalities was found to normalize qEEG. Additionally, a randomized double-blind placebo controlled study involving oral KB220-Z variant established qEEG normalization of reward circuitry in abstinent psycho-stimulant abusers (P < 0.03).ConclusionsWe cautiously suggest that long-term activation of dopaminergic receptors will lead to D2 receptor proliferation and enhanced “dopamine sensitivity,” thus reducing aberrant craving behavior especially in carriers of the DRD2 A1 allele. Although supported by 20 clinical trials, KB220-Z awaits PET scanning to determine its chronic effects on D2 receptor numbers.

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Worse Response to Ursodeoxycholic Acid in Primary Biliary Cholangitis Patients with Autoimmune Hepatitis Features

Digestive Diseases ◽

10.1159/000513331 ◽

2020 ◽

Author(s):

Maoyao Wen ◽

Ruoting Men ◽

Xiaoli Fan ◽

Yi Shen ◽

Ping Ni ◽

...

Keyword(s):

Autoimmune Hepatitis ◽

Ursodeoxycholic Acid ◽

Total Bilirubin ◽

Response Rate ◽

Immunosuppressive Agents ◽

Biochemical Response ◽

Primary Biliary Cholangitis ◽

Lower Response Rate ◽

One Year ◽

Glutamyl Transpeptidase

Background: There is limited evidence on the treatment response of primary biliary cholangitis (PBC) with autoimmune hepatitis (AIH) features but not meet the criteria of PBC-AIH syndromes. This study was to elucidate the clinical characteristics of PBC patients with features of AIH. Methods: We included patients with diagnostic criteria of PBC. All patients were treated with ursodeoxycholic acid (UDCA) and without immunosuppressive agents for more than one year. The biochemical response was evaluated at one year after treatment of UCDA. Results: Among 432 patients with PBC, 166 (38.4%) patients did not achieve biochemical response within one year of UDCA treatment. Non-responders had lower albumin (ALB) level and higher immunoglobulin G (IgG), alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) and total bilirubin (TB) levels (P < 0.05). The response rates were significantly lower in patients with elevated level of IgG or ALT or AST. Moreover, the higher the IgG or AST level was, the lower the response rate was in patients with PBC regardless of cirrhosis. For patients with cirrhosis, there was no differences among patients with different level of ALT. Patients in the PBC with AIH features group had a significant lower response rate than patients in the PBC-only group. Among the 139 patients who underwent liver biopsy, 54 were non-responsive to UDCA and 48 (88.9%) shown mild interface hepatitis. Conclusion: In conclusion, PBC patients with AIH features had a worse response to UDCA therapy.

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