Tomomi Iwai

Autotaxin as a novel serum marker of liver fibrosis

BACKGROUND The clinical significance of autotaxin (ATX), a key enzyme for the production of the bioactive lysophospholipid lysophosphatidic acid remains unknown. Serum ATX enzymatic activity reportedly increases in parallel with liver fibrosis and exhibits a gender difference. METHODS Serum ATX antigen level, measured easier than the activity, was evaluated as a marker of liver fibrosis in 2 cohorts of chronic liver disease caused by hepatitis C virus. RESULTS In the first cohort, serum ATX level correlated significantly with liver fibrosis stage and was the best parameter for prediction of cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.756 in male and 0.760 in female, when compared with serum hyaluronic acid and aminotransferase-to-platelet ratio index, an established marker of liver fibrosis. In another cohort, serum ATX level correlated significantly with liver stiffness, a novel reliable marker of liver fibrosis, being the second-best parameter in male (AUROC, 0.799) and in female (AUROC, 0.876) for prediction of significant fibrosis, and the best parameter in male (AUROC, 0.863) and the third-best parameter in female (AUROC, 0.872) for prediction of cirrhosis, both of which were judged by liver stiffness. CONCLUSIONS Serum ATX level may be a novel marker of liver fibrosis.

Thrombocytopenia is more severe in patients with advanced chronic hepatitis C than B with the same grade of liver stiffness and splenomegaly.

Background and aimThe mechanism responsible for thrombocytopenia in chronic liver diseases (CLD) is not yet fully understood. The prevalence of thrombocytopenia has been reported to be higher in patients with hepatitis C virus-related hepatocellular carcinoma (CLD-C) than in those with hepatitis B virus-related hepatocellular carcinoma (CDC-B). We have examined the potential difference in thrombocytopenia between patients with CLD-B and those with CLD-C in terms of liver fibrosis adjustment and splenomegaly.MethodsThe study cohort consisted of 102 patients with CLD-B and 143 patients with CLD-C were enrolled. Liver stiffness, which is reported to be well correlated with the degree of liver fibrosis, was measured by transient elastography.ResultsThe analysis of covariance with liver stiffness as a covariate revealed that the platelet count was lower in CLD-C patients than in CLD-B patients. Following stratification for liver stiffness, thrombocytopenia was found to be more severe in CLD-C patients than CLD-B patients with advanced liver stiffness, whereas the degree of splenomegaly was not significantly different. The plasma thrombopoietin level was not different between CLD-B and CLD-C patients with advanced liver stiffness, and the immature platelet number was lower in CLD-C patients despite thrombocytopenia being more severe in these patients.ConclusionsCLD-C patients with advanced liver stiffness presented with more severe levels of thrombocytopenia than CLD-B patients even with the same grade of splenomegaly. Impaired platelet production rather than enhanced platelet destruction may underlie the mechanism responsible for thrombocytopenia in patients with CLD.

Potential associations between perihepatic lymph node enlargement and liver fibrosis, hepatocellular injury or hepatocarcinogenesis in chronic hepatitis B virus infection

Although perihepatic lymph node enlargement (PLNE) is frequently observed in chronic liver disease, little is known about PLNE in chronic hepatitis B virus (HBV) infection. We aimed to evaluate this issue.

Perihepatic lymph node enlargement is a negative predictor for sustained responses to pegylated interferon‐α and ribavirin therapy for Japanese patients infected with hepatitis C virus genotype 1

 Although perihepatic lymph node enlargement (PLNE) is reportedly associated with the negative outcome of interferon therapy for chronic hepatitis C, there were limitations in that the results were obtained in patients with various genotypes, viral loads and treatment regimens. We aimed to precisely clarify the significance of PLNE in interferon therapy for chronic hepatitis C.

Perihepatic lymph node enlargement observed at a general health examination: A cross‐sectional study

Although perihepatic lymph node enlargement (PLNE) is known as a common finding in chronic liver disease, it can be found occasionally at a general health examination. We aimed to clarify the clinical significance of PLNE in general.

Eradication of hepatitis C virus is associated with the attenuation of steatosis as evaluated using a controlled attenuation parameter

Chronic hepatitis C virus (HCV) infection was shown to cause hepatic steatosis or suppression of serum lipid levels. However, little is known about the changes in hepatic steatosis following HCV eradication. We aimed to evaluate this issue using the controlled attenuation parameter (CAP), which was recently shown to provide a standardized non-invasive measure of hepatic steatosis. We enrolled 70 patients with chronic HCV infections and steatosis (CAP of over 248 dB/m) who had achieved a sustained viral response at 12 weeks after discontinuation of antiviral treatment using direct-acting antivirals (DAA). We then evaluated the state of hepatic steatosis before and after HCV eradication. We also investigated the changes in serum parameters such as cholesterol and glucose levels. The median value of CAP level decreased significantly after HCV eradication from 273 dB/m to 265 dB/m (P = 0.034). Also, LDL and HDL cholesterol levels increased significantly after HCV eradication (P = 0.002 and P = 0.027, respectively). In conclusion, a decrease in hepatic steatosis after HCV eradication with DAA was revealed in chronic hepatitis C patients with significant steatosis. Cancellation of the viral effect is a possible underlying cause of hepatic steatosis improvement and increase in HDL and LDL cholesterol levels.

Disappearance of Perihepatic Lymph Node Enlargement after hepatitis C viral eradication with direct acting antivirals

Perihepatic lymph node enlargement (PLNE) which has been shown to be negatively associated with hepatocellular carcinoma (HCC) occurrence is frequently observed in chronic liver disease; however, changes in the state of perihepatic lymph nodes after eradication of hepatitis C virus (HCV) have not been investigated yet. We aimed to evaluate this issue. We enrolled 472 patients with chronic HCV infection who achieved viral eradication with direct‐acting antivirals (DAA). We investigated whether the status of perihepatic lymph nodes changed before and after HCV eradication (primary endpoint). We also evaluated the association between PLNE and clinical findings such as liver fibrosis or hepatocellular injury before HCV eradication (secondary endpoint). Perihepatic lymph node enlargement was detected in 164 of 472 (34.7%) patients before DAA treatment. Surprisingly, disappearance of PLNE was observed in 23.8% (39 patients) of all PLNE‐positive patients after eradication of HCV. Disappearance of PLNE was not associated with baseline clinical parameters or changing rates of clinical findings before and after DAA treatment. At baseline, presence of PLNE was significantly associated with a lower serum HCV‐RNA level (P = .03), a higher serum AST level (P = .004) and a higher ALT level (P < .001) after adjustment for sex and age. In conclusion, PLNEs became undetectable after DAA treatment in 23.8% of PLNE‐positive patients. Further study with a longer follow‐up period is needed to clarify the clinical importance of this phenomenon especially in relationship with the risk of HCC development.

Identification of liver fibrosis using the hepatic vein waveform in patients with Fontan circulation: Liver fibrosis in Fontan patients

Liver fibrosis caused by congestive hepatopathy has emerged as an important complication after Fontan procedure. We evaluated the utility of the hepatic vein (HV) waveform using Doppler ultrasound for identification of liver fibrosis in Fontan patients.

The power Doppler twinkling artefact associated with periarticular calcification induced by intra-articular corticosteroid injection in patients with rheumatoid arthritis

Intra-articular corticosteroid injections are widely used to treat rheumatoid arthritis (RA).1 Although they are useful in combination with other antirheumatic agents, some side effects have been reported including subcutaneous atrophy, septic arthritis, avascular necrosis, and rarely, periarticular calcification.2–4 We report here two RA cases that presented with periarticular calcification. Case 1. A 51-year-old woman suffering from RA for 6 years was treated with methotrexate 16 mg weekly, abatacept 500 mg monthly and triamcinolone acetonide injection on the radial side of the right third proximal interphalangeal (PIP) joint approximately once a month (22 times for the third PIP joint in total). While disease activity scores for 28 joints maintained low disease activity, a hand radiograph showed progressive periarticular calcifications on the injected radial side (figure 1A–C). Joint ultrasonography revealed hyperechoic regions in the joint cavity with posterior power Doppler (PD) signals (figure 2A). Spectral Doppler sonography was performed to evaluate the nature of the PD signals, and an artefactual spectral signal without any definable flow pattern was observed (figure 2B). This finding was obviously different from the true RA synovitis finding detected on her right first metacarpophalangeal joint (figure 2C). …