Aileen Wee

Pericholangitis in chronic ulcerative colitis: primary sclerosing cholangitis of the small bile ducts?

Review of liver biopsy specimens, autopsy specimens, and clinical records of 107 patients with chronic ulcerative colitis and hepatobiliary diseases showed pericholangitis (defined as small-duct primary sclerosing cholangitis) in 37 (35%), primary sclerosing cholangitis (defined as large-duct primary sclerosing cholangitis) in 18 (17%), chronic active hepatitis in 14 (13%), cryptogenic cirrhosis in 12 (11%), and miscellaneous lesions including malignancies in 26 (24%). Documented cirrhosis was present or developed in 37 patients (35%). The spectrum of histologic features of small-duct primary sclerosing cholangitis was indistinguishable from that of confirmed large-duct primary sclerosing cholangitis. In 6 of the 18 patients who eventually developed the large-duct disease, biopsy evidence 1 to 12 years earlier had shown small-duct primary sclerosing cholangitis. Thus, small-duct and large-duct primary sclerosing cholangitis seem to be components of a disease spectrum.

Hepatobiliary carcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis

Hepatobiliary carcinomas were found in eight patients with chronic ulcerative colitis (CUC) and primary sclerosing cholangitis (large-duct PSC; five cases) or pericholangitis (small-duct PSC; three cases). The tumors were extrahepatic in five cases and intrahepatic in two; in one case the neoplasm affected both liver and gallbladder. The tumors in seven patients were glandular and, sometimes, cystic and papillary; in the remaining patient a combined hepatocellular carcinoma and cholangiocarcinoma was found. The latter tumor seemed to arise from regenerative nodules in secondary biliary cirrhosis complicating PSC. The presence of carcinoma in situ in areas of fibrous cholangitis, the multicentric origin of the tumor, the presence of tumor-free large-duct PSC or small-duct PSC (pericholangitis) at a distance from the carcinomatous areas, and the documentation, in some cases, of long-standing inflammatory hepatobiliary disease prior to the discovery of the tumors would seem to confirm the clinical impression that carcinomas may develop in pre-existing PSC. The appearance of hepatobiliary carcinomas in patients with classic PSC and in patients with pericholangitis supports previous evidence indicating that cholangiographically diagnosed large-duct PSC and histologically diagnosed small-duct PSC (pericholangitis) are manifestations of a shared condition that could be named PSC syndrome. The findings of the present study indicate that the PSC syndrome predisposes patients for the development of bile duct carcinoma. Most patients with CUC and bile duct carcinoma seem to have PSC prior to the development of the hepatobiliary tumor.

Non‐invasive models for predicting histology in patients with chronic hepatitis B

Abstract: Background and aim: In contrast to chronic hepatitis C (CHC), few studies had been performed in assessing non‐invasive models for predicting significant fibrosis or cirrhosis in chronic hepatitis B (CHB) patients. We aimed to evaluate non‐invasive markers for diagnosing significant fibrosis/cirrhosis in patients with CHB, and to evaluate accuracy of models from CHC in CHB patients.

A randomized controlled pilot study of Pentoxifylline in patients with non-alcoholic steatohepatitis (NASH)

PurposeTumor necrosis factor-α (TNF-α) is implicated in non-alcoholic steatohepatitis (NASH). Pentoxifylline inhibits TNF-α. We wanted to evaluate the efficacy of Pentoxifylline on NASH patients.MethodsPatients with biopsy proven NASH and persistently elevated alanine aminotransferase (ALT) greater than 1.5 times the upper limit of normal were randomized to 3xa0months of treatment with a step 1 American Heart Association diet and daily exercise with Pentoxifylline or placebo. Liver function tests, serum lipids and TNF-α, Interleukin 6 (IL-6), and plasma hyaluronic acid were measured at baseline, at weeks 6 and 12. Categorical data were analyzed by Fisher’s exact test while independent sample t-test and Mann–Whitney test were used for continuous data.ResultsEleven patients were randomized into the Pentoxifylline and nine to the placebo group. After 3xa0months of treatment body mass index (BMI), ALT and aspartate aminotransferase (AST) decreased significantly in both groups. There was no difference between the two groups in reduction of BMI (Pxa0=xa00.897). There was significantly greater reduction in AST in the Pentoxifylline group (Pxa0=xa00.038). There was a trend toward lower ALT level (Pxa0=xa00.065) in the Pentoxifylline group. TNF-α and IL-6 decreased significantly in both groups after treatment, but there was no significant difference between the two groups.ConclusionThree months of Pentoxifylline treatment in combination with diet and exercise results in significantly greater reduction in AST levels in patients with NASH as compared with controls.

Prevalence and clinical associations of posttransplant fatty liver disease

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) could recur after liver transplant in patients with preexisting NAFLD, and has recently been reported to occur after transplant in patients transplanted without preexisting NAFLD. The literature on posttransplant NAFLD is limited. We aimed to study the prevalence of posttransplant NAFLD in patients transplanted for non‐NAFLD‐related liver diseases.

Diagnostic utility of immunohistochemistry in hepatocellular carcinoma, its variants and their mimics.

Hepatocellular carcinoma (HCC) is known for its histomorphologic heterogeneity. Immunohistochemistry (IHC) can help in the comparative morphologic evaluation of HCC, its variants and their mimics. Some of these diagnostic challenges can be attributed to (i) the variety of neoplasms that can arise from the hepatic stem cell lineage; (ii) the spectrum of well-differentiated hepatocellular nodular lesions; (iii) the liver being a target for metastases with some of these histologic entities mimicking variants of HCC or actually arising in the liver; and (iv) the limitations of serum α-fetoprotein (AFP). The role of IHC is in the distinction of benign hepatocellular nodules from reactive hepatocytes; WD-HCC from benign hepatocellular nodules; poorly differentiated HCC from cholangiocarcinoma and metastases; and determination of histogenesis of malignant tumor; and of primary site of origin of malignant tumor. A panel of antibodies has more discriminant value. AFP expression usually indicates malignancy in a hepatocellular nodule and hepatocytic histogenesis of a malignancy. Polyclonal carcinoembryonic antigen (pCEA) and CD10 stain bile canaliculi in better-differentiated HCC. HepPar1 is generally accepted as a hepatocytic marker. However, not all HCC stain uniformly and not all HepPar1-positive tumors are of hepatocytic origin or arise in the liver. Mature hepatocytes and hepatocellular nodules stain with CAM 5.2, CK 8, and 18 but not with CK 7, 19, 20, or AE1/AE3. Biliary epithelium expresses CK 7 and 19. CD 34 highlights sinusoidal capillarization. AFP, pCEA/CD10, and CD34 are useful for ascertainment of malignancy in hepatocellular nodules; HepPar1 and cytokeratins to be included if histogenesis is the issue. IHC results should be interpreted in the larger context of the case.

Fibro-C-Index: comprehensive, morphology-based quantification of liver fibrosis using second harmonic generation and two-photon microscopy

We develop a standardized, fully automated, quantification system for liver fibrosis assessment using second harmonic generation microscopy and a morphology-based quantification algorithm. Liver fibrosis is associated with an abnormal increase in collagen as a result of chronic liver diseases. Histopathological scoring is the most commonly used method for liver fibrosis assessment, where a liver biopsy is stained and scored by experienced pathologists. Due to the intrinsic limited sensitivity and operator-dependent variations, there exist high inter- and intraobserver discrepancies. We validate our quantification system, Fibro-C-Index, with a comprehensive animal study and demonstrate its potential application in clinical diagnosis to reduce inter- and intraobserver discrepancies.

Fine needle aspiration biopsy of the liver : Algorithmic approach and current issues in the diagnosis of hepatocellular carcinoma

The role of fine needle aspiration biopsy (FNAB) in the evaluation of focal liver lesions has evolved. Guided FNAB is still useful to procure a tissue diagnosis if clinical, biochemical and radiologic findings are inconclusive. Major diagnostic issues include: (i) Distinction of benign hepatocellular nodular lesions from reactive hepatocytes, (ii) Distinction of well-differentiated hepatocellular carcinoma (WD-HCC) from benign hepatocellular nodular lesions, (iii) Distinction of poorly differentiated HCC from cholangiocarcinoma and metastatic carcinomas, (iv) Determination of histogenesis of malignant tumor, and (v) Determination of primary site of origin of malignant tumor. This review gives a general overview of hepatic FNAB; outlines an algorithmic approach to cytodiagnosis with emphasis on HCC, its variants and their mimics; and addresses current diagnostic issues. Close radiologic surveillance of high-risk cirrhotic patients has resulted in the increasing detection of smaller lesions with many subjected to biopsy for tissue characterization. The need for tissue confirmation in clinically obvious HCC is questioned due to risk of malignant seeding. When a biopsy is indicated, core needle biopsy is favored over FNAB. The inherent difficulty of distinguishing small/early HCC from benign hepatocellular nodular lesions has resulted in indeterminate reports. Changing concepts in the understanding of the biological behavior and morphologic evolution of HCC and its precursors; and the current lack of agreement on the morphologic criteria for distinguishing high-grade dysplastic lesions (with small cell change) from WD-HCC, have profound impact on nomenclature, cytohistologic interpretation and management. Optimization of hepatic FNAB to enhance the yield and accuracy of diagnoses requires close clinicopathologic correlation; combined cytohistologic approach; judicious use of ancillary tests; and skilled healthcare teams.

Focal Nodular Hyperplasia and Hepatocellular Adenoma around the World Viewed through the Scope of the Immunopathological Classification

Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign hepatocellular tumors. The risk of bleeding and malignant transformation of HCA are strong arguments to differentiate HCA from FNH. Despite great progress that has been made in the differential radiological diagnosis of the 2 types of nodules, liver biopsy is sometimes necessary to separate the 2 entities. Identification of HCA subtypes using immunohistochemical techniques, namely, HNF1A-inactivated HCA (35–40%), inflammatory HCA (IHCA), and beta-catenin-mutated inflammatory HCA (b-IHCA) (50–55%), beta-catenin-activated HCA (5–10%), and unclassified HCA (10%) has greatly improved the diagnostic accuracy of benign hepatocellular nodules. If HCA malignant transformation occurs in all HCA subgroups, the risk is by far the highest in the β-catenin-mutated subgroups (b-HCA, b-IHCA). In the coming decade the management of HCA will be more dependent on the identification of HCA subtypes, particularly for smaller nodules (<5u2009cm) in terms of imaging, follow-up, and resection.

Fine needle aspiration biopsy of hepatocellular carcinoma and hepatocellular nodular lesions: role, controversies and approach to diagnosis

A. Weeu2028Fine needle aspiration biopsy of hepatocellular carcinoma and hepatocellular nodular lesions: role, controversies and appr oach to diagnosis