The association of the serum levels of myostatin, follistatin, and interleukin-6 with sarcopenia, and their impacts on survival in patients with hepatocellular carcinoma

Background/Aims@#The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival. @*Methods@#Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017. @*Results@#The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients. @*Conclusions@#The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.

A Case of Autoimmune Hepatitis after Occupational Exposure to N,N-Dimethylformamide

N,N-dimethylformamide (DMF), a widely used solvent in the chemical industry, is known to induce toxic hepatitis. However, there have been no reported cases of DMF-associated autoimmune hepatitis. A 31-year-old healthy man working at a glove factory since July 2015 had intermittently put his bare hands into a diluted DMF solution for his first 15 days at work. After 2 months, he felt nausea, fatigue, and hand cramping, and a jaundice followed. His laboratory findings showed positive autoantibodies and elevated immunoglobulin G (IgG), and his liver biopsy pathology was typical of autoimmune hepatitis (AIH). Prednisolone and azathioprine therapy began, and he recovered rapidly without adverse events. Though his liver chemistry was normalized, the IgG level remained persistently upper normal range. His 2nd liver biopsy performed in April 2019 showed mild portal activity, and he was well under a low dose immunosuppressive therapy up to April 2020. This case warns of the hazard of occupational exposure to DMF, and clinicians should be aware of DMF-related AIH for timely initiation of immunosuppressive therapy.

Comparison of the Diagnostic Usefulness of Conventional Magnification and Near-focus Methods with Narrow-band Imaging for Gastric Epithelial Tumors

BACKGROUND/AIMS: Dual-focus two-stage optical lens technology has been introduced recently. In near-focus mode (NFM), endoscopists can easily examine the mucosal tissue and capillary networks. This study compared the magnified images obtained using NFM and the conventional magnification method (CMM) under narrow-band imaging in patients with gastric epithelial tumors. MATERIALS AND METHODS: An experienced endoscopist performed endoscopy using NFM and CMM in patients with gastric epithelial tumors. We studied 40 images from 40 endoscopy sessions in 20 selected patients. Ten endoscopists rated the image quality independently on a 5-point Likert scale (from poor=1 to excellent=5) in terms of microsurface structure, microvascular structure, and the demarcation line. RESULTS: The gastric epithelial tumors comprised 10 cases of early gastric cancer, 2 of high-grade dysplasia, and 8 of low-grade dysplasia. The median number of magnified images for each method was 11. The mean observation time (+/-SD) for magnification was 99.9+/-64.1 s in NFM and 91.5+/-64.6 s in CMM (P=0.54). The image quality score for the microsurface structure was higher with NFM than CMM (4.09+/-0.39 vs. 3.73+/-0.40, P=0.015), while that for microvascular structure was lower with NFM than in CMM (3.53+/-0.45 vs. 4.29+/-0.45, P=0.001). CONCLUSIONS: Magnification using NFM provides higher-quality images of the microsurface structure, although its optical zoom is limited compared with CMM. Since NFM can obtain magnified images easily by pushing a button on the scope, it is useful for evaluating gastric epithelial tumors.

Use of 18F-FDG PET to predict tumor progression and survival in patients with intermediate hepatocellular carcinoma treated by transarterial chemoembolization

BACKGROUND/AIMS: 18F-Fluorodeoxyglucose positron-emission tomography (18F-FDG PET) has been used to assess the biological behavior of hepatocellular carcinoma (HCC). In this study, we investigated the usefulness of 18F-FDG PET for predicting tumor progression and survival in patients with intermediate Barcelona Clinic Liver Cancer (BCLC) intermediate-stage HCC treated by transarterial chemoembolization (TACE). METHODS: From February 2006 to March 2013, 210 patients treated with TACE, including 77 patients with BCLC intermediate-stage HCC, underwent examination by 18F-FDG PET. 18F-FDG uptake was calculated based on the tumor maximum (Tmax) standardized uptake value (SUV), the liver mean (Lmean) SUV, and the ratio of the Tmax SUV to the Lmean SUV (Tmax/Lmean). RESULTS: The mean follow-up period for the 77 patients (52 males, 25 females; average age, 63.3 years) was 22.2 months. The median time to progression of HCC in patients with a low Tmax/Lmean ( or = 1.83) was 17 and 6 months, respectively (p < 0.001). The median overall survival time of patients with a low and high Tmax/Lmean was 44 and 14 months, respectively (p = 0.003). Multivariate analysis revealed that the Tmax/Lmean was an independent predictor of overall survival (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.210 to 3.156; p = 0.006) and tumor progression (HR, 2.05; 95% CI, 1.264 to 3.308; p = 0.004). CONCLUSIONS: 18F-FDG uptake calculated by the Tmax/Lmean using PET predicted tumor progression and survival in patients with BCLC intermediate-stage HCC treated by TACE.

Hepatic and Splenic Infarction and Bowel Ischemia Following Endoscopic Ultrasound-Guided Celiac Plexus Neurolysis

Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) is a well-established intervention to palliate malignant pain. We report a patient who developed hepatic and splenic infarction and bowel ischemia following EUS-CPN. A 69-year-old man with known lung cancer and pancreatic metastasis was transferred for debilitating, significant epigastric pain for several months. The patient underwent EUS-CPN to palliate the pain. After the procedure, the patient complained continuously of abdominal pain, nausea, and vomiting; hematemesis and hematochezia were newly developed. Abdominal computed tomography revealed infarction of the liver and spleen and ischemia of the stomach and proximal small bowel. On esophagogastroduodenoscopy, hemorrhagic gastroduodenitis, and multiple gastric ulcers were noted without active bleeding. The patient expired on postoperative day 27 despite the best supportive care.

The clinical features of drug-induced liver injury observed through liver biopsy: focus on relevancy to autoimmune hepatitis

BACKGROUND/AIMS: Accurate diagnosis of drug-induced liver injury (DILI) is difficult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH. METHODS: The clinical, serologic, and histologic findings of 29 patients were compared and analyzed. The patients were aged 46.2+/-12.8 years (mean+/-SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively. RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase levels were 662.2+/-574.8 U/L, 905.4+/-794.9 U/L, 12.9+/-10.8 mg/dL, 195.8+/-123.3 U/L, and 255.3+/-280.8 U/L, respectively. According to serologic and histologic findings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited significantly higher AST levels (537.1+/-519.1 vs. 1043.3+/-600.5 U/L), globulin levels (2.7+/-0.4 vs. 3.3+/-0.5 g/dL), and prothrombin time (12.9+/-2.4 vs. 15.2+/-3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplified AIH score was 3.7+/-0.9 in the DILI group and 6.5+/-0.9 in the AIH group (P<0.001). CONCLUSIONS: Accurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered.

Chilaiditi's Sign in the Colon of Adult Patients: A Case Series and Literature Review Including 55 Cases

Chilaiditi's sign refers to a condition in which the right colon or, rarely, the small intestine is interposed between the liver and the right hemidiaphragm. Recognizing this sign is important, because it may present with a variety of abdominal symptoms and may be confused with a surgical abdomen leading to unnecessary surgical intervention. Management is usually conservative unless complications such as volvulus or obstruction occur. Previous reports focused on the complications and surgical management of Chilaiditi's sign. We present a report of three cases of Chilaiditi's sign that were managed non-surgically, together with an updated review of the English literature.

Prognostic indicators in primary biliary cirrhosis: significance of revised IAHG (International Autoimmune Hepatitis Group) score

BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a slowly progressing autoimmune disease of the liver that is characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Serum total bilirubin is one of the various prognostic factors that have been proposed. A recent study found that PBC with accompanying autoimmune hepatitis (AIH) carries a negative prognosis. This study examined the clinical characteristics of PBC and analyzed the factors that affect its prognosis. METHODS: Patients diagnosed with PBC between January 1998 and December 2010 based on clinical and histopathological findings were compiled and analyzed retrospectively. RESULTS: Among 27 patients, 24 (1 male and 23 females, ages 50.0+/-9.3 years) were followed up. The follow-up period was 8.6+/-0.9 years. Of the 24 patients, 9 patients progressed to liver cirrhosis (LC). Comparison between patients who did and did not progress to LC revealed statistically significant differences in the patients' serum total bilirubin (2.7+/-1.8 vs. 0.8+/-0.4, P=0.012), the Mayo risk score (5.1+/-0.7 vs. 3.9+/-0.6, P=0.001), the revised IAHG (International Autoimmune Hepatitis Group) score (9.2+/-2.3 vs. 5.4+/-3.0, P=0.004) and frequency of AIH overlap (5/9 [55.6%] vs. 0/15 [0%], P=0.001) at the time of diagnosis. CONCLUSIONS: We propose that serum total bilirubin, the Mayo risk score, and the revised IAHG score at the time of diagnosis are helpful for predicting PBC prognosis. In particular, since all of the patients with accompanying AIH progressed to LC, the presence of overlap syndrome at the time of diagnosis is helpful for predicting PBC prognosis and providing an adequate treatment.