Magnetic resonance imaging evidence of hippocampal structural changes in patients with primary biliary cholangitis.

INTRODUCTION: Behavioral symptoms are commonly reported by patients with primary biliary cholangitis (PBC). In other patient populations, symptoms are commonly associated with hippocampal volume reduction linked to neuroinflammation (inferred from regional iron deposition), as demonstrated by magnetic resonance imaging (MRI). We hypothesized that PBC patients would exhibit reduced volume and increased iron deposition of the hippocampus. METHODS: Seventeen female non-cirrhotic PBC patients and 17 age/gender-matched controls underwent 3-Tesla T1-weighted MRI and quantitative susceptibility mapping (QSM; an indicator of iron deposition). The hippocampus and its subfields were segmented from T1 images using Freesurfer, and susceptibility of the whole hippocampus was calculated from QSM images. Volume and susceptibility were compared between groups, and associations with PBC-40 score and disease indicators (years since diagnosis, Fibroscan value, alkaline phosphatase level, clinical response to ursodeoxycholic acid (UDCA)) were investigated. RESULTS: PBC patients exhibited significantly reduced hippocampal volume (p = 0.023) and increased susceptibility (p = 0.048). Subfield volumes were reduced for the subiculum, molecular layer, granule cell layer of the dentate gyrus and CA4 (p < 0.05). Fibroscan value was significantly correlated with PBC-40 (Spearman's rho = 0.499; p = 0.041) and disease duration (Spearman's rho = 0.568; p = 0.017). DISCUSSION: Our findings suggest hippocampal changes occur early in the disease course of PBC, similar in magnitude to those observed in major depressive disorder and neurodegenerative diseases. TRANSLATIONAL IMPACT: Clinical management of PBC could include early interventional strategies that promote hippocampal neurogenesis that may beneficially impact behavioral symptoms and improve quality of life.

Multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2.

AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues. METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with Sirius Red staining. RESULTS: Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls (P < 0.0001). These pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 ± 0.2 (severe) in DBTC-treated animals vs score 0 (normal) in sham-treated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with Sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma, infiltration of inflammatory cells, degeneration, vacuolization, and necrosis of acinar cells and distention of pancreatic ducts. Extent of pancreatic damage and pancreatitis were scored 3.6 ± 0.4 (severe) for DBTC-treated in contrast to score 0 (normal) in sham-treated animals. The gall bladder became expanded with ductal distention, and occasional bile stones were detected along with microscopic hepatic lesions. DBTC-treated animals developed splenic hypertrophy with increased weight and length (P < 0.01) along with thymic atrophy (P < 0.001). Finally, colitic lesions and colitis were prominent in DBTC-treated animals and scored 3.4 ± 0.3 (moderately severe) vs 0 (normal) for the sham-treated animals. CONCLUSION: This is the first report of chronic inflammatory multiorgan hepatobiliary pancreatitis, along with fibrosis and calculi formation induced reliably utilizing oral DBTC administration in TNFR1/R2 deficient mice.

[Areflux choledochoduodenostomy in surgery of acute cholangitis].

The work presents an analysis of results of using an original areflux choledochoduodenoanastomosis in 32 patients with acute cholangitis developed against the background of bile hypertension. The method of correction of mechanical jaundice is supposed to be formed in the area of biliodigestive fistula of the bicuspid invagination valve from the mucosal-submucosal layers (RF Patent No 2302831 of 20.07.2007). The introduction into clinical practice of the developed method of choledochoduodenostomy allowed not only arresting cholangiogenous infection in cases of obturatuional lesions of bile ducts, avoiding lethality and severe complications in the early postoperative period, but also prevention of the development of reflux-cholangitis.