Hepatic Medicine : Evidence and Research最新文献

Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease that may progress to fibrosis or cirrhosis. Treatment options are currently limited. Ursodeoxycholic acid (UDCA) remains first-line therapy and has been proven to normalize serum biochemistries, halt histologic disease progression, and lead to patient survival comparable to the general population. Obeticholic acid (OCA) was recently approved as adjunct therapy in PBC patients with inadequate response or intolerance to UDCA. However, OCA has been associated with worsening pruritus in clinical studies which may limit its use in this patient population. Several studies are currently underway to address the lack of treatment options for PBC. Of these, fibrates, which have been used in Japan for over a decade, have produced promising results. Furthermore, as currently approved therapies for PBC do not address the potentially debilitating clinical symptoms of PBC such as pruritus and fatigue, supplemental therapy is often required for symptom control.

Thrombocytopenia is a frequent complication in patients with cirrhosis. As many as 84% of patients with cirrhosis have thrombocytopenia, and it is an independent variable indicative of advanced disease and poor prognosis. Although there is great concern that it may aggravate bleeding during surgical procedures, there is limited evidence to inform decisions regarding the treatment of cirrhotic patients with thrombocytopenia undergoing invasive procedures. Finally, there is evidence that platelets play a significant role in liver regeneration. In this report, the clinical implications of thrombocytopenia in cirrhotic patients are reviewed. The utility of platelet counts in the prognosis of cirrhosis and relationship to complications of advanced liver disease, including portal hypertension, esophageal varices, and hepatocellular carcinoma. The impact of low platelet counts on bleeding complications during invasive procedures is outlined. Finally, the role of platelets and potential adverse impact in liver regeneration is reviewed.

Purpose: Transient elastography (TE) using FibroScan (FS) has been established to non-invasively assess liver fibrosis and steatosis. The aim of this study was to compare the recently introduced FibroTouch (FT) device with the established FS with respect to liver stiffness and CAP.

Patients and methods: Thirty-nine patients with and without liver disease were included. All patients were measured three times with FS (FibroScan 530 compact, Echosens, France) and FT (FibroTouch-FT100, Wuxi Hisky Med, China). For FS, M and XL probe were used according to the manufacturer's specifications. For steatosis, CAP and the comparable FT equivalent UAP (ultrasound attenuation parameter) was determined. Finally, FT and FS were explored in liver tissue-mimicking phantoms.

Results: LS between FS and FT correlated well with r=0.91. Root-mean-square (RMS) of the coefficient of variation for LS was better in FS (11.1% vs 27.4%). Bland-Altman analysis showed a 3.1 kPa mean overestimation of LS by FT. In addition, UAP strongly and linearly depended on the BMI following UAP=3.02 × BMI+186. In phantoms, a similar relation was found with UAP (phantom)= 3.78 × BMI + 146 suggesting that UAP is directly calculated from entered BMI instead of assessing shear-wave attenuation. Consequently, RMS-CV was lower for FT (6.0% vs 9.7%). However, if using different BMI, CV-RMS for FT increased to 12.7%. LS of a patient with manifest liver cirrhosis and ascites was 38.8 kPa using the FS-XL probe but almost normal with FT (7.2 kPa).

Conclusion: Although LS by FT shows good correlation with LS-FS, it has larger variation, continuously overestimates LS and completely fails in ascites. Moreover, FT-UAP seems to be a misleading parameter for steatosis assessment because it is at least in part calculated from mandatory entered patient data. In conclusion, novel LS cut-off values need to be defined for LS-FT and usage of UAP is not recommended.

Aim: Cholangiocarcinoma is endemic in southeast Asia, generally developing from liver fluke infestation. However, diagnostic imaging of early-stage disease is challenging. The aim of this work is to investigate relaxometry (specifically, T2 mapping) as a method of exploiting the higher signal-to-noise ratio (SNR) of internal coils for improved reception of magnetic resonance signals, despite their non-uniform sensitivity.

Methods: Ex vivo T2 mapping was carried out at 3T on fixed resection specimens from Thai cholangiocarcinoma patients using an mGRASE sequence and an endoscope coil based on a thin-film magneto-inductive waveguide and designed ultimately for internal use.

Results: Disease-induced changes including granulomatous inflammation, intraepithelial neoplasia and intraductal tumours were correlated with histopathology, and relaxation data were compared with mono- and bi-exponential models of T2 relaxation. An approximately 10-fold local advantage in SNR compared to a 16-element torso coil was demonstrated using the endoscope coil, and improved tissue differentiation was obtained without contrast agents.

Conclusion: The performance advantage above follows directly from the inverse relation between the component of the standard deviation of T2 due to thermal noise and the SNR, and offers an effective method of exploiting the SNR advantage of internal coils. No correction is required, avoiding the need for tracking, relaxing constraints on coil and slice orientation and providing rapid visualization.

Background: Primary human hepatocytes (PHHs) are the ideal candidates for studying critical liver functions such as drug metabolism and toxicity. However, as they are isolated from discarded livers that are unsuitable for transplantation, they possess limited expansion ability in vitro and their enzymatic functions deteriorate rapidly because they are often of poor quality. Therefore, there is a compelling reason to find reliable alternative sources of hepatocytes.

Methods: In this study, we report on efficient and robust differentiation of embryonic stem cells (ESC) from the common marmoset Callithrix jacchus into functional hepatocyte-like cells (HLC) using a simple, and reproducible three-step procedure. ESC-derived HLCs were examined by morphological analysis and tested for their expression of hepatocyte-specific markers using a combination of immunohistochemistry, RT-PCR, and biochemical assays. Primary human hepatocytes were used as controls.

Results: ESC-derived HLCs expressed each of the hepatocyte-specific markers tested, including albumin; α-fetoprotein; asialoglycoprotein receptor 1; α-1 antitrypsin; hepatocyte nuclear factors 1α and 4; cytokeratin 18; hepatocyte growth factor receptor; transferrin; tyrosine aminotransferase; alkaline phosphatase; c-reactive protein; cytochrome P450 enzymes CYP1A2, CYP2E1 and CYP3A4; and coagulation factors FVII and FIX. They were functionally competent as demonstrated by biochemical assays in addition to producing urea.

Conclusion: Our data strongly suggest that marmoset HLCs possess characteristics similar to those of PHHs. They could, therefore, be invaluable for studies on drug metabolism and cell transplantation therapy for a variety of liver disorders. Because of the similarities in the anatomical and physiological features of the common marmoset to that of humans, Callithrix jacchus is an appropriate animal model to study human disease conditions and cellular functions.

Advances in imaging, pathology and therapy have resulted in major improvements in the management of cholangiocarcinomas; the mortality has come down and with it there has been an improved 5-year survival. Surgical resection remains the treatment of choice and reports from high volume centres have shown an increase in resectability rates, R0 resection, a decrease in mortality and an improvement in 5-year survival; however, the operative morbidity remains high, pointing towards the complexity of the management of these difficult lesions. Complete excision is also often limited by the locally advanced nature of the disease at the time of diagnosis and a proportion of patients who were earlier deemed resectable on imaging are found to have unresectable disease at the time of operation. Neoadjuvant therapy has had only a limited impact on survival. Liver transplantation is also an option in a few patients following strict criteria for selection. Since the large majority of patients are only diagnosed at the late stages of the disease palliation (endoscopic or surgical) is an important part of treatment. Portal vein embolisation and pre-operative biliary drainage have had a major impact on outcomes. Major liver resection with caudate lobe removal remains the standard operation and procedures like routine vascular resection and liver transplant should only be carried out in experienced centres. Improvements in both neo as well as adjuvant therapy may lead to a standardized protocol in the future, as well as an improvement in survival.