Background/Aims Bezafibrate (BZF), a dual peroxisome proliferator-activated receptor/pregnane X receptor agonist, has demonstrated efficacy in combination with ursodeoxycholic acid (UDCA) for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Although one of the therapeutic effects of BZF is suppression of bile acid synthesis, its specific impact on bile acid synthesis pathways has not been thoroughly explored. This study investigated bile acid profiles, synthesis intermediates, and their associations with liver biochemistries in patients with PBC and PSC, and evaluated the impact of BZF treatment on these associations.
Methods We enrolled 30 patients with PBC, 10 with PSC, and 30 control subjects. We measured total bile acids, bile acid components, plasma levels of 7α-hydroxycholesterol (7α-OH-C), 7α-hydroxy-4-cholesten-3-one (C4), and 27-hydroxycholesterol (27-OH-C) to assess the classic and alternative bile acid synthesis pathways and analyzed the association with liver biochemistries with and without BZF treatment.
Results Total bile acid levels were elevated in PBC and PSC compared to controls, correlating significantly with liver biochemistries. BZF treatment significantly suppressed the classic pathway, as evidenced by reduced 7α-OH-C and C4 levels. However, 27-OH-C levels, possibly reflecting the alternative pathway activity, were not reduced in those with elevated liver biochemistries despite BZF treatment, suggesting incomplete suppression of alternative pathway in patients with suboptimal BZF response.
Conclusions These findings indicate that while BZF effectively suppresses the classic pathway, alternative pathway activity may compromise its therapeutic efficacy in treatment-resistant cases, highlighting the need for novel therapies inhibiting the alternative pathway in patients with inadequate response to BZF.
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Background/Aims A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC.
Methods In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events.
Results The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p=0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well tolerated.
Conclusions HK-660S is well tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis (cris.nih.go.kr, Number KCT0006590).
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Background/Aims Sclerosing hepatocellular carcinoma (HCC) is an unusual subtype of HCC that is
characterized by an embedded dense fibrous stroma in the tubular neoplastic structures. We aimed to
assess the surgical approaches and outcomes of sclerosing HCC. Methods: We retrospectively analyzed
the clinicopathologic features of 6 patients with sclerosing HCC who underwent surgical treatment at Asan
Medical Center between July 1989 and December 2005. Results: Six HCC patients with sclerosing HCC were
diagnosed out of the total 1390 HCC patients (0.43%) during the study period. The mean age was 58 years and
4 patients were male. Weight loss and abdominal pain were the most common symptoms. The serum calcium
and phosphorus levels were normal in all the patients. All of them were hepatitis B surface antigen-positive,
but none was positive for hepatitis C. All the lesions were solitary. The tumor size ranged from 45 to 150 mm
in diameter (median size: 81 mm). We performed right trisegmentectomy (n=1), central bisegmentectomy (n=1),
right anterior segmentectomy (n=1), ex-vivo resection and autotransplantation (n=1) and right posterior
segmentectomy (n=2). The median overall survival and disease free-survival periods were 24 months and 9.5
months, respectively. Conclusions: The incidence of sclerosing HCC was very low. Sclerosing HCC was often
not correctly diagnosed before an operation, but performing resection prolonged the patients’ survival and their
prognosis was not worse than that for ordinary HCC. Our experience implicates that aggressive surgical
treatment for sclerosing HCC is beneficial for patient survival. (Korean J Hepatol 2006;12:412-419)
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