Liver fibrosis progression predicts survival in patients with primary biliary cirrhosis

Namisaki, Tadashi; Moriya, Kyoji; Noguchi, Ryuichi; Kitade, Mitsuteru; Kawaratani, Hideto; Yamao, Junichi; Mitoro, Akira; Yoshida, Motoyuki; Sawai, Masayoshi; Uejima, Masakazu; Mashitani, Tsuyoshi; Takeda, Kosuke; Okada, Yasushi; Kaji, Kosuke; Takaya, Hiroaki; Aihara, Yosuke; Douhara, Akitoshi; Nishimura, Norihisa; Sawada, Yasuhiko; Sato, Shinya; Seki, Kazuhiko; Yoshiji, Hitoshi

doi:10.1111/hepr.12746

Cited by 16 publications

(24 citation statements)

References 31 publications

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“…Treatment with ursodeoxycholic acid (UDCA) reportedly improves the prognosis of patients with PBC and produces an optimal biochemical response to UDCA . We have recently reported that a decrease in γ‐glutamyl transpeptidase (GGT) levels from baseline by >69% at 1 year after the initiation of UDCA treatment is predictive of the risk of developing end‐stage liver disease in patients with PBC (Nara definition) . Patients who have been treated with UDCA at an early histological stage of PBC have a similar life expectancy to the general population, and only a few will ever develop cirrhosis .…”

Section: Introductionmentioning

confidence: 99%

“…proposed a new histological staging system to evaluate PBC progression that takes into account histological heterogeneity . Long‐term prognosis is predicted by portal‐bridging fibrosis based on either the Scheuer or Nakanuma staging systems . Several studies have reported that UDCA treatment delays fibrosis progression of paired liver biopsies in patients with PBC in the early histological stages .…”

Section: Introductionmentioning

confidence: 99%

“…3,4 We have recently reported that a decrease in γ-glutamyl transpeptidase (GGT) levels from baseline by >69% at 1 year after the initiation of UDCA treatment is predictive of the risk of developing end-stage liver disease in patients with PBC (Nara definition). 5 Patients who have been treated with UDCA at an early histological stage of PBC have a similar life expectancy to the general population, and only a few will ever develop cirrhosis. 6 Emerging evidence suggests that more patients are being diagnosed and treated at early stages of the disease, 7 which emphasizes the importance of determining potential surrogate end-points to identify those patients who might benefit from additional therapy.…”

Section: Introductionmentioning

confidence: 99%

“…10 Long-term prognosis is predicted by portal-bridging fibrosis based on either the Scheuer or Nakanuma staging systems. 5 Several studies have reported that UDCA treatment delays fibrosis progression of paired liver biopsies in patients with PBC in the early histological stages. 11,12 However, the beneficial effects of UDCA on the clinical outcomes of patients with advanced stages of PBC remain controversial.…”

Section: Introductionmentioning

confidence: 99%

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Identification of clinical risk factors for histological progression of primary biliary cholangitis

Fujinaga

Namisaki

Moriya

et al. 2019

Hepatology Research

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Aim To identify laboratory predictors of histological progression (HP) of primary biliary cholangitis (PBC). Methods Sequential biopsies were carried out on 35 (11.4%) of 308 patients with PBC treated with ursodeoxycholic acid (UDCA). Patients were divided into high γ‐glutamyl transpeptidase (GGT) (n = 18) and low GGT (n = 17) groups, based on the median value of GGT at baseline. Patients were then categorized as showing HP (progressive group, PG) or lacking HP (non‐progressive group, NPG) according to the Scheuer and Nakanuma classifications, with the latter grading liver fibrosis (fibrosis score) and bile duct loss (BDL score). Results According to the Scheuer definition, 12 patients had HP and 23 did not. According to the Nakanuma definition, 8 and 27 patients were in the PG and NPG groups, respectively. The fibrosis and BDL scores progressed in 13 and 8 patients, respectively, whereas 22 and 25 patients did not show HP, respectively. Fisher's exact probability test analysis revealed that the rate of HP using the Nakanuma fibrosis score was significantly higher in the high GGT group compared to the low GGT group (P < 0.05). However, no significant correlation was found between the HP of PBC and the biochemical response to UDCA therapy. Both univariate and multivariate logistic regression analyses indicated that the serum GGT level at baseline is an independent risk factor for an increased Nakanuma fibrosis score. Conclusions The level of serum GGT at baseline is significantly associated with liver fibrosis progression in PBC, and therefore could help to predict the HP of PBC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of clinical risk factors for histological progression of primary biliary cholangitis

Fujinaga

Namisaki

Moriya

et al. 2019

Hepatology Research

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“…The G protein-coupled Mas receptor has been recognized as the main receptor for angiotensin (1)(2)(3)(4)(5)(6)(7). Binding of angiotensin (1)(2)(3)(4)(5)(6)(7) to Mas activates a counter-regulatory pathway with antifibrotic, anti-inflammatory, and vasodilatory effects. 65 Cultured activated human HSCs have been shown to express RAS components and synthesize angiotensin II, 67 which has been proposed to be a trigger for the profibrogenic mediator CTGF.…”

Section: Mediators Of Myofibroblast Precursor Cell Activationmentioning

confidence: 99%

Hepatic Fibrosis in Dogs

Eulenberg

Lidbury

2017

Veterinary Internal Medicne

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Hepatic fibrosis is commonly diagnosed in dogs, often as a sequela to chronic hepatitis (CH). The development of fibrosis is a crucial event in the progression of hepatic disease that is of prognostic value. The pathophysiology of hepatic fibrosis in human patients and rodent models has been studied extensively. Although less is known about this process in dogs, evidence suggests that fibrogenic mechanisms are similar between species and that activation of hepatic stellate cells is a key step. Diagnosis and staging of hepatic fibrosis in dogs requires histopathological examination of a liver biopsy specimen. However, performing a liver biopsy is invasive and assessment of fibrotic stage is complicated by the absence of a universally accepted staging scheme in veterinary medicine. Serum biomarkers that can discriminate among different fibrosis stages are used in human patients, but such markers must be more completely evaluated in dogs before clinical use. When successful treatment of its underlying cause is feasible, reversal of hepatic fibrosis has been shown to be possible in rodent models and human patients. Reversal of fibrosis has not been well documented in dogs, but successful treatment of CH is possible. In human medicine, better understanding of the pathomechanisms of hepatic fibrosis is leading to the development of novel treatment strategies. In time, these may be applied to dogs. This article comparatively reviews the pathogenesis of hepatic fibrosis, its diagnosis, and its treatment in dogs.

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Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis

Bowlus

Pockros

Kremer

et al. 2020

Clinical Gastroenterology and Hepatology

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BACKGROUND & AIMS:There is debate over whether patients with inflammatory bowel diseases (IBD) treated with biologics that are not tumor necrosis factor antagonists (such as vedolizumab or ustekinumab) should receive concomitant treatment with immunomodulators. We conducted a meta-analysis to compare the efficacy and safety of concomitant immunomodulator therapy vs vedolizumab or ustekinumab monotherapy. METHODS:In a systematic search of publications, through July 31, 2019, we identified 33 studies (6 randomized controlled trials and 27 cohort studies) of patients with IBD treated with vedolizumab or ustekinumab. The primary outcome was clinical benefit, including clinical remission, clinical response, or physician global assessment in patients who did vs did not receive combination therapy with an immunomodulator. Secondary outcomes were endoscopic improvement and safety. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs. RESULTS:Overall, combination therapy was not associated with better clinical outcomes in patients receiving vedolizumab (16 studies: OR, 0.84; 95% CI, 0.68-1.05; I2[13.9%; Q test P [ .17) or ustekinumab (15 studies: OR, 1.1; 95% CI, 0.87-1.38; I2 [ 11%; Q test P [ .28). Results were consistent in subgroup analyses, with no difference in clinical remission or response in induction vs maintenance studies or in patients with Crohn's disease vs ulcerative colitis in studies of vedolizumab. Combination therapy was not associated with better endoscopic outcomes in patients receiving vedolizumab (3 studies: OR, 1.13; 95% CI, 0.48-2.68; I2 [ 0; Q test P[.96) or ustekinumab (2 studies: OR, 0.58; 95% CI, 0.21-1.16; I2 [ 47%; Q test P [ .17). Combination therapy was not associated with an increase in adverse events during vedolizumab therapy (4 studies: OR, 1.17; 95% CI, 0.75-1.84; I2 [ 0; Q test P [ .110). CONCLUSIONS:In a meta-analysis of data from studies of patients with IBD, we found that combining vedolizumab or ustekinumab with an immunomodulator is no more effective than monotherapy in induction or maintenance of remission.

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Liver fibrosis progression predicts survival in patients with primary biliary cirrhosis

Cited by 16 publications

References 31 publications

Identification of clinical risk factors for histological progression of primary biliary cholangitis

Identification of clinical risk factors for histological progression of primary biliary cholangitis

Hepatic Fibrosis in Dogs

Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis

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