Transient elastography-derived liver stiffness measurements were found to be useful for predicting liver infiltration in a case of mature T-cell neoplasm involving liver dysfunction

Transient elastography (TE) is a novel, non-invasive imaging technique for measuring liver stiffness (LS). It is considered to be useful for predicting the severity of fibrosis and the risk of cirrhosis or hepatocellular carcinoma. However, the association between the presence of diffuse regions of increased cell density in the liver and elevated LS values has not been assessed. We experienced a case in which a mature T-cell neoplasm had invaded the liver, but the infiltrating lesion was not detected by contrast-enhanced computed tomography (CT) or fluorodeoxyglucose positron emission tomography/CT scans. Instead, the tumor’s presence was indicated by the change in the patient’s TE-derived LS values after chemotherapy. At diagnosis liver dysfunction was detected in a biochemical examination, and mean LS value was as high as 25.4 kPa [interquartile range (IQR): 0.3, success rate (SR):100%]. After chemotherapy, the patient’s mean LS value fell to 4.3 kPa (IQR: 0.8, SR:100%). A follow-up pathological investigation demonstrated that proliferating abnormal T-cells were no longer present in the patient’s liver. This is the first report to describe the use of LS data to support a diagnosis of liver infiltration by tumor cells exhibiting a portal and sinusoidal distribution pattern rather than a focal pattern. Elevated TE-derived LS values should lead to hepatic tumor infiltration being considered during initial examinations or a suspicion of recurrence during follow-up examination of lymphoma patients who achieve complete remission, even when radiological investigations do not detect abnormalities in the liver.     

A case of Mikulicz's disease complicated by autoimmune pancreatitis, in which impaired glucose tolerance was improved by glucocorticoid treatment]

A 73-year-old woman had experienced dry mouth and swellings of both upper eyelids from 1998. In October 2003, she also developed bilateral submandibular swellings, and was diagnosed with diabetes mellitus and prescribed antidiabetic medication. She consulted our hospital in the summer of 2004 due to the exacerbation of eyelid swelling, and was admitted in October 2004. Keratoconjunctivitis sicca was not present. CT and MRI of the head showed bilateral enlargement of the lacrimal and submandibular glands. Serological investigations revealed hypergammaglobulinemia, but as antinuclear antibody and anti-SS-A antibody were absent, further investigation was performed. Serum concentrations of IgG4 were elevated and biopsy of the minor salivary gland revealed a severe infiltration of IgG4-positive plasmacytes. The patient was therefore diagnosed with Mikulicz's disease. Abdominal CT demonstrated diffuse pancreatic swelling, and endoscopic retrograde cholangio-pancreatography revealed stricture of the common bile duct and main pancreatic duct, suggesting the complication of autoimmune pancreatitis. Treatment was commenced with 40 mg/day of prednisolone. This resulted in rapid resolution of the lacrimal and submandibular gland swellings and recovery of salivary gland function. Diffuse swelling of the pancreas and stricture of the common bile duct and main pancreatic duct also improved, and endogenous insulin secretion increased. Both Mikulicz's disease and autoimmune pancreatitis presented with elevated serum IgG4 and infiltration of IgG4-expressing plasma cells into the glandular tissues. We recently proposed the new diagnostic entity of "IgG4-related plasmacytic exocrinopathy"; however, if diabetes mellitus in autoimmune pancreatitis was caused by direct dysfunction of pancreatic cells, we must reconsider this pathogenesis and consider a wider concept including exocrine as well as endocrine glands. This case, in which both types of glands were affected, is therefore of considerable interest.     

Autoantibody to the liver arginase present in sera of patients with autoimmune hepatitis and chronic hepatitis.

We have reported previously that immunization of rat liver arginase in rabbits induced autoantibody that is reactive with their own liver arginase and has cytotoxic activity to their hepatocytes. This promoted us to investigate whether or not such an autoantibody is present in sera of patients with certain hepatic disorders, since the liver arginase is dominant in the liver and highly homologous in structure among ureotelic animals. By Western blot analysis, sera from patients with chronic hepatitis and autoimmune hepatitis were shown to have an autoantibody reacting with purified human liver arginase. Since the autoantibody was also reactive with liver arginase of rat origin to almost the same extent as that of human origin, ELISA with rat liver arginase as a coating antigen was developed and used for the quantification of the autoantibody. Prominent increase of the anti-liver arginase autoantibody was found in autoimmune hepatitis, moderate increase in chronic liver diseases, and no increase in acute hepatitis or normal controls by the ELISA. These results suggest that the increased anti-liver arginase autoantibody might involve in some parts in the pathophysiology of the hepatitic disorders. Assay of the autoantibody can also be utilized as a marker for the differentiation of certain hepatitis.     

Performance of the international classifications criteria for autoimmune hepatitis diagnosis in Mexican patients

The revised score of the International Autoimmune Hepatitis Group (R-IAIHG) and the simplified criteria (SC) are used for diagnosis of autoimmune hepatitis (AIH). Our aim is to evaluate the performance of these classifications to differentiate AIH from other autoimmune liver diseases. The frequency of diagnosis of definite AIH was similar both by the R-IAIHG and the SC systems (41% versus 40%), whereas diagnosis of probable AIH was made more commonly by the R-IAIHG than the SC (59% versus 29%), and 23 patients that have been graded as definite (n?=?7) or probable (n?=?16) AIH by the R-IAIHG had non-diagnostic scores by the SC system. The scoring systems rendered concordant diagnosis of definite (n?=?15) and probable (n?=?13) AIH in 28/73 patients (38%). Discordant diagnoses of AIH were rendered in 45/73 patients (62%). The R-IAIHG exhibited a sensitivity of 95%, specificity of 90%, and positive predictive value (PPV) and negative predictive value (NPV) of 93% for both. On the other hand, the SC had a lower sensitivity (65%) but a higher specificity (100%), PPV of 100%, and NPV of 68%. In conclusion, both international scoring systems diagnosed the same number of cases as definite AIH. The R-IAIHG showed a higher sensitivity in diagnosing AIH, whereas the SC showed a higher specificity. SC are easier to apply at the bedside and exclude more patients that could have a different etiology.     

Clinical use of liver biopsy for the diagnosis and management of inactive and asymptomatic hepatitis B virus carriers in Bangladesh

Patients with inactive chronic hepatitis B virus (HBV) infection are assumed to be free from liver disease. Accordingly, antiviral drug treatment is not recommended for these patients. However, the extent of liver damage in these patients has not been evaluated fully. The aim of this study was to evaluate the extent of liver damage in patients with inactive HBV. Liver biopsy was conducted in 141 inactive HBV carriers [HBeAg‐negative, low levels of HBV DNA (≤10,000 copies/ml) and normal levels of serum alanine aminotransferase (ALT)]. The extent of hepatic inflammation and fibrosis was evaluated in these patients by examining liver biopsy specimens. Although the patients were inactive HBV carriers, mild to moderate levels of necroinflammation (HAI necroinflammation score HAI‐N1 ≥ 7) were detected in 36 of 141 (26%) patients. Seventeen patients had a severe degree of hepatic fibrosis (HAI fibrosis score HAI‐F ≥ 3). A total of 10 patients had both considerable necroinflammation (HAI‐N1≥7) and severe fibrosis (HAI‐F ≥3). All 10 patients with significant hepatic inflammation and fibrosis were male and older than 25 years. However, all were HBeAg‐negative and expressed low levels of HBV DNA and normal ALT levels. The study demonstrates that features of liver damage were present in a considerable number of the patients. Assessment of liver biopsy specimens in a larger cohort of inactive HBV carriers is necessary to establish management guidelines for such patients. J. Med. Virol. 82:1350–1354, 2010. © 2010 Wiley‐Liss, Inc.     

A thoracic-epidural granulocytic sarcoma case that was diagnosed preceding the onset of and that recurred co-incidental to acute promyelocytic leukemia, which developed after surgical treatment

Granulocytic sarcoma or chloroma is a tumor seen in myelocytic leukemia. Spinal epidural onset is rare and is generally seen before or together with the onset of myelocytic leukemia. An epidural mass located at the 2nd-5th thoracic levels in an 18-year-old male patient was pathologically diagnosed as granulocytic sarcoma. Radiotherapy was performed after surgical intervention. Ten months later, he was re-admitted with abdominal pain. At this time, an epidural mass at the 6th-9th thoracic levels was detected on magnetic resonance imaging, and acute promyelocytic leukemia was diagnosed. After systemic chemotherapy, partial remission was achieved. We aimed to present this rare case with its remarkable follow-up findings.     

Morphometry of liver parenchyma in needle biopsy specimens from patients with alcoholic liver disease: preliminary variables for the diagnosis and prognosis of cirrhosis

The diagnosis of liver cirrhosis depends on assessing fibrosis and architectural alterations of the liver. In a needle biopsy specimen the connective tissue is often inadequately sampled, which leads to an uncertain diagnosis. Parenchymal features alone are currently insufficient. We, therefore, carried out a comprehensive morphometric study to detect parenchymal structures that may be useful in the diagnosis and prognosis of cirrhosis. Five human liver biopsy specimens were selected from each of four alcoholic disease groups: fatty liver, alcoholic hepatitis, cirrhosis with greater-than-5-yr survival, and cirrhosis with less-than-2-yr survival. Volume fractions (Vv) and surface densities (Sv) were determined stereologically for parenchymal and hepatocellular compartments in electron micrographs. The differences between noncirrhosis and cirrhosis were (a) a doubling of the Vv of parenchymal interstitial space, (b) a nearly 25% increase in the Sv of hepatocyte plasma membrane, (c) a nearly 50% increase in the Sv of hepatocyte RER, and (d) a decrease in the Sv of the outer mitochondrial membrane. The significant difference between the greater than 5-yr and the less than 2-yr survivors of cirrhosis was the marked decrease in hepatocyte nuclear Vv in the latter group. Statistical analysis of our data showed that optimal sampling is achieved with as few as three micrographs from one block of tissue per biopsy specimen.     

FIB-4指数对慢性乙型肝炎患者肝纤维化的诊断价值

目的 探讨FIB-4指数对慢性乙型肝炎肝纤维化的诊断价值.方法 212例慢性乙型肝炎患者行肝活检并同时留取血清标本,检测ALT、AST、PLT等指标,并根据其结果结合患者的年龄计算出FIB-4的数值.根据肝纤维化分期设定3个判定点,分别为显著纤维化（S2～S4期）,严重纤维化（S3～S4期）和肝硬化（S4期）.以肝活检病理结果为金标准绘制出FIB-4的受试者工作特征曲线（ROC）,计算曲线下面积（AUC）,评价其对慢性乙型肝炎肝纤维化的诊断价值.结果 212例肝活检患者中S0期3例（1.4%）,S1期49例（23.1%）,S2期66例（31.1%）,S3期50例（23.6%）,S4期44例（20.8%）,即显著纤维化者（S2～S4期）160例（75.5%）,严重纤维化者（S3～S4期）94例（44.3%）,肝硬化者（S4期）44例（20.8%）.FIB-4指数对3个判定点的AUC值分别为0.733（95%（CI：0.660～0.806,P〈0.01）、0.746（95%CI：0.679～0.813,P〈0.01）、0.756（95%CI：0.687～0.825,P〈0.01）.结论 FIB-4指数是一种简单的、准确的、经济的非创性诊断方法,可以较准确地估计慢性乙型肝炎患者有无显著纤维化,使多数患者避免肝穿刺活检.     

FIB-4指数对慢性乙型肝炎患者肝纤维化的诊断价值

目的 探讨FIB-4指数对慢性乙型肝炎肝纤维化的诊断价值.方法 212例慢性乙型肝炎患者行肝活检并同时留取血清标本,检测ALT、AST、PLT等指标,并根据其结果结合患者的年龄计算出FIB-4的数值.根据肝纤维化分期设定3个判定点,分别为显著纤维化(S2～S4期),严重纤维化(S3～S4期)和肝硬化(S4期).以肝活检病理结果为金标准绘制出FIB-4的受试者工作特征曲线(ROC),计算曲线下面积(AUC),评价其对慢性乙型肝炎肝纤维化的诊断价值.结果 212例肝活检患者中S0期3例(1.4%),S1期49例(23.1%),S2期66例(31.1%),S3期50例(23.6%),S4期44例(20.8%),即显著纤维化者(S2～S4期)160例(75.5%),严重纤维化者(S3～S4期)94例(44.3%),肝硬化者(S4期)44例(20.8%).FIB-4指数对3个判定点的AUC值分别为0.733(95%(CI:0.660～0.806,P<0.01)、0.746(95%CI:0.679～0.813,P<0.01)、0.756(95%CI:0.687～0.825,P<0.01).结论 FIB-4指数是一种简单的、准确的、经济的非创性诊断方法,可以较准确地估计慢性乙型肝炎患者有无显著纤维化,使多数患者避免肝穿刺活检.     

FIB-4指数对慢性乙型肝炎患者肝纤维化的诊断价值

目的 探讨FIB-4指数对慢性乙型肝炎肝纤维化的诊断价值.方法 212例慢性乙型肝炎患者行肝活检并同时留取血清标本,检测ALT、AST、PLT等指标,并根据其结果结合患者的年龄计算出FIB-4的数值.根据肝纤维化分期设定3个判定点,分别为显著纤维化(S2～S4期),严重纤维化(S3～S4期)和肝硬化(S4期).以肝活检病理结果为金标准绘制出FIB-4的受试者工作特征曲线(ROC),计算曲线下面积(AUC),评价其对慢性乙型肝炎肝纤维化的诊断价值.结果 212例肝活检患者中S0期3例(1.4%),S1期49例(23.1%),S2期66例(31.1%),S3期50例(23.6%),S4期44例(20.8%),即显著纤维化者(S2～S4期)160例(75.5%),严重纤维化者(S3～S4期)94例(44.3%),肝硬化者(S4期)44例(20.8%).FIB-4指数对3个判定点的AUC值分别为0.733(95%(CI:0.660～0.806,P<0.01)、0.746(95%CI:0.679～0.813,P<0.01)、0.756(95%CI:0.687～0.825,P<0.01).结论 FIB-4指数是一种简单的、准确的、经济的非创性诊断方法,可以较准确地估计慢性乙型肝炎患者有无显著纤维化,使多数患者避免肝穿刺活检.