Liver assessment using Gd-EOB-DTPA-enhanced magnetic resonance imaging in primary biliary cholangitis patients.

PURPOSE: To evaluate the feasibility of utilizing gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for the assessment of Child-Pugh class and for differentiating between patients with primary biliary cholangitis (PBC) and posthepatitic cirrhosis. MATERIALS AND METHODS: 45 PBC patients and 45 posthepatitic cirrhosis patients were enrolled and Gd-EOB-DTPA-enhanced MRI was applied. The average relative signal enhancement (RE) of the liver and average contrast to noise ratio (CNR) of common bile duct at 4, 20, and 50 min between different Child-Pugh classes of PBC patients were compared. The RE and CNR in all timepoints in patients with the same Child-Pugh class were compared between PBC patients and posthepatitic cirrhosis patients. RESULTS: The RE of liver and CNR of common bile duct at 4, 20, and 50 min was significantly different between all Child-Pugh classes of PBC patients. There were also no significant differences in the RE of liver and CNR of common bile duct in all timepoints between patients with PBC and posthepatitic cirrhosis in the same Child-Pugh class. CONCLUSION: Gd-EOB-DTPA-enhanced MRI is feasible for liver function assessment in PBC patients. However, the ability of this modality in differentiating liver cirrhosis of different etiologies requires further investigation.

Red blood cell distribution width to platelet ratio levels in assessment of histologic severity in patients with primary biliary cholangitis.

We aimed to investigate the relationship between the histologic severity and red blood cell distribution width to platelet ratio (RPR) in patients with primary biliary cholangitis (PBC). One hundred and seven consecutive patients with liver biopsy-proven and as yet treatment-naïve PBC were enrolled as the primary and validation cohort. The histologic stages were divided into early stage (Scheuer's stage 1 & 2) and late stage (Scheuer's stage 3 & 4). The overall patient demographics, clinical manifestations, hematological tests and biochemical profile were retrospectively collected from our database. Both groups were compared in terms of RPR, aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4) and AST/ALT ratio (AAR). Of the 77 patients in the primary cohort, a total of 24 (31.2%) had early stage PBC, whereas 53 (68.8%) represented late stage. Patients with late stage PBC showed significantly higher red blood cell distribution width (15.5 vs. 14.1%, p = .016), RPR (0.15 vs. 0.09, p < .001), direct bilirubin (32.4 vs. 12.9 µmol/L, p = .041), FIB-4 (3.41 vs. 6.34, p = .001) and significantly lower platelet (132.8 vs. 185.8 × 109/L, p = .002). The area under the curve, cut-off value, sensitivity, specificity, positive predictive value, negative predictive value for determining late stage were 0.74, 0.14, 49.1%, 95.8%, 96.3% and 46.0%, respectively. Additionally, high RPR may also serve as a prognostic indicator for 18-month mortality. In conclusion, RPR can be used as a non-invasive and effective predictor of histologic severity in patients with PBC.

Magnetic resonance imaging and spectroscopy for differential assessment of liver abnormalities induced by Opisthorchis felineus in an animal model.

BACKGROUND: European liver fluke Opisthorchis felineus, causing opisthorchiasis disease, is widespread in Russia, Ukraine, Kazakhstan and sporadically detected in the EU countries. O. felineus infection leads to hepatobiliary pathological changes, cholangitis, fibrosis and, in severe cases, malignant transformation of bile ducts. Due to absence of specific symptoms, the infection is frequently neglected for a long period. The association of opisthorchiasis with almost incurable bile duct cancer and rising international migration of people that increases the risk of the parasitic etiology of liver fibrosis in non-endemic regions determine high demand for development of approaches to opisthorchiasis detection. METHODOLOGY/PRINCIPAL FINDINGS: In vivo magnetic resonance imaging and spectroscopy (MRI and MRS) were applied for differential assessment of hepatic abnormalities induced by O. felineus in an experimental animal model. Correlations of the MR-findings with the histological data as well as the data of the biochemical analysis of liver tissue were found. MRI provides valuable information about the severity of liver impairments induced by opisthorchiasis. An MR image of O. felineus infected liver has a characteristic pattern that differs from that of closely related liver fluke infections. 1H and 31P MRS in combination with biochemical analysis data showed that O. felineus infection disturbed hepatic metabolism of the host, which was accompanied by cholesterol accumulation in the liver. CONCLUSIONS: A non-invasive approach based on the magnetic resonance technique is very advantageous and may be successfully used not only for diagnosing and evaluating liver damage induced by O. felineus, but also for investigating metabolic changes arising in the infected organ. Since damages induced by the liver fluke take place in different liver lobes, MRI has the potential to overcome liver biopsy sampling variability that limits predictive validity of biopsy analysis for staging liver fluke-induced fibrosis.

Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that mainly affects middle-aged women. Obeticholic acid (OCA), which was recently approved by the Food and Drug Administration for PBC treatment, has demonstrated positive effects on biochemical markers of liver function. Our objective was to evaluate the long-term clinical impact and cost-effectiveness of OCA as a second-line treatment for PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. We developed a mathematical model to simulate the lifetime course of PBC patients treated with OCA+UDCA versus UDCA alone. Efficacy data were derived from the phase 3 PBC OCA International Study of Efficacy trial, and the natural history of PBC was informed by published clinical studies. Model outcomes were validated using the PBC Global Study. We found that in comparison with UDCA, OCA+UDCA could decrease the 15-year cumulative incidences of decompensated cirrhosis from 12.2% to 4.5%, hepatocellular carcinoma from 9.1% to 4.0%, liver transplants from 4.5% to 1.2%, and liver-related deaths from 16.2% to 5.7% and increase 15-year transplant-free survival from 61.1% to 72.9%. The lifetime cost of PBC treatment would increase from $63,000 to $902,000 (1,330% increment). The discounted quality-adjusted life years with UDCA and OCA+UDCA were 10.74 and 11.78, respectively, and the corresponding costs were $142,300 and $633,900, resulting in an incremental cost-effectiveness ratio of $473,400/quality-adjusted life year gained. The results were most sensitive to the cost of OCA. CONCLUSION: OCA is a promising new therapy to substantially improve the long-term outcomes of PBC patients, but at its current annual price of $69,350, it is not cost-effective using a willingness-to-pay threshold of $100,000/quality-adjusted life year; pricing below $18,450/year is needed to make OCA cost-effective. (Hepatology 2017;65:920-928).

Clinical evaluation of the Tokyo Guidelines 2013 for severity assessment of acute cholangitis.

BACKGROUND: We evaluated the severity assessment criteria for acute cholangitis (AC) of the Tokyo Guidelines 2013 (TG13) and developed a scoring system for predicting the need for urgent/early biliary drainage. METHODS: We retrospectively reviewed 66 AC cases prospectively managed based on the TG07 and divided into an urgent/early biliary drainage group (n = 30) and elective biliary drainage group (n = 36). RESULTS: There were 26 mild, 27 moderate, and 13 severe cases based on the TG13. The TG13 assessment in 12 of the 17 cases requiring early biliary drainage based on the TG07 was moderate, but underestimated the other five cases as mild AC. When five predictors (blood urea nitrogen >20 mg/dL, SIRS presence, platelet count <120 000/µL, serum albumin level <3.0 g/dL, age ≥75 years old) were used to devise a scoring system, the receiver-operator characteristic curve of the scores showed good test performance for predicting the need for urgent/early biliary drainage. The area under the curve (AUC) was 0.95 and higher than the TG13 AUC (0.80). CONCLUSIONS: The TG13 is practical, but some AC cases requiring urgent/early biliary drainage were underestimated as mild AC. The scoring system allows identification of high-risk AC patients and will improve the TG13.

Documenting correct assessment of biliary anatomy during laparoscopic cholecystectomy.

BACKGROUND: Correct assessment of biliary anatomy can be documented by photographs showing the "critical view of safety" (CVS) but also by intraoperative cholangiography (IOC). METHODS: Photographs of the CVS and IOC images for 63 patients were presented to three expert observers in a random and blinded fashion. The observers answered questions pertaining to whether the biliary anatomy had been conclusively documented. RESULTS: The CVS photographs were judged to be "conclusive" in 27%, "probable" in 35%, and "inconclusive" in 38% of the cases. The IOC images performed better and were judged to be "conclusive" in 57%, "probable" in 25%, and "inconclusive" in 18% of the cases (P < 0.001 compared with the photographs). The observers indicated that they would feel comfortable transecting the cystic duct based on the CVS photographs in 52% of the cases and based on the IOC images in 73% of the cases (P = 0.004). The interobserver agreement was moderate for both methods (kappa values, 0.4-0.5). For patients with a history of cholecystitis, both the CVS photographs and the IOC images were less frequently judged to be sufficient for transection of the cystic duct (P = 0.006 and 0.017, respectively). CONCLUSION: In this series, IOC was superior to photographs of the CVS for documentation of the biliary anatomy during laparoscopic cholecystectomy. However, both methods were judged to be conclusive only for a limited proportion of patients, especially in the case of cholecystitis. This study highlights that documenting assessment of the biliary anatomy is not as straightforward as it seems and that protocols are necessary, especially if the images may be used for medicolegal purposes. Documentation of the biliary anatomy should be addressed during training courses for laparoscopic surgery.

Transgastric transhepatic endosonography-guided biliary drainage: histological assessment of its sinus tract in an autopsy case.

Endosonography-guided biliary drainage (ESBD) is gaining attention as a promising drainage technique for obstructive jaundice. However, histological changes resulting from ESBD have not been well understood. We had an opportunity to histologically investigate the influence of ESBD, established between the left hepatic duct and the stomach, on the relevant organs in an autopsy case with bile duct cancer extending from the pancreatic head to the hepatic hilum with duodenal invasion. Localized fibrous connective tissues were present around and along the sinus tract, including the connection between the surfaces of the left lobe of the liver and the gastric serosa, without hemorrhage, inflammatory changes, or cancer invasion. The inside of the ESBD stent was slightly stenotic at the intramural portion of the stomach due to proliferation of granulation tissue. No bile stasis or abscess was observed in the left lobe. These results are quite suggestive of the high safety and efficacy of ESBD with adequate performance.