An Analysis of Risk Factors for Developing Hepatocellular Carcinoma in a Group of Hepatitis C Patients with Stage 3 Fibrosis following Interferon Therapy

The risk of Hepatocellular carcinoma (HCC) is high in HCV-infected patients who have biochemically and histologically active chronic hepatitis. To observe the long prognosis of Chronic Hepatitis C (CHC) patients with stage 3 fibrosis (F3), 55 CHC patients after initial Interferon (IFN) therapy were followed up for up to 12 years (average 9.8 ± 2.3 years). According to the annual average alanine aminotransferase (ALT) levels, patients were grouped into, low (ALT ≦ 30 IU/l); moderate (ALT >30 <80 IU/l) and high (ALT ≧ 80 IU/l) ALT groups. Eleven patients were re-treated with IFN. During the follow-up period of 12 years, HCC developed in 26 patients with an average annual incidence of 3.9%. Biochemical responders to initial IFN therapy (n = 8) and those re-treated with IFN (n = 10), except 1, did not develop HCC. Cox regression analysis to evaluate risk factors for HCC occurrence, found development of Liver Cirrhosis within 3 years of initial IFN therapy(P = 0.05) and the 3 year annual average ALT post initial IFN therapy (P = 0.033) to be significant. The 12 year annual average ALT was also found to be significantly related to HCC occurrence (P = 0.016), on univariate analysis. Patients belonging to the continuously low ALT group (ALT ≦ 30 IU/l for ≧3 years), did not develop HCC or receive IFN re-treatment. In CHC patients with F3, after initial IFN therapy, keeping ALT continuously low, below 30 IU/l for 3 years or more seems important. Continuing treatment with anti-inflammatory drugs along with subsequent IFN re-treatment may prevent or delay HCC even in elderly patients

Efficacy and safety of temporary biliary stent for prevention of post-ERCP cholangitis after endoscopic common bile duct stone removal: a retrospective study

　Although post-endoscopic retrograde cholangiopancreatography (ERCP) cholangitis (PEC) is not as severe as post-ERCP pancreatitis, this complication should not be disregarded. The aim of the present study was to evaluate the efficacy of a temporary biliary stent for prevention of PEC. Between April 2011 and May 2017, 190 patients underwent complete stone removal in a first session of ERCP at our hospital. Using propensity score matching, 72 pairs were enrolled in this study. After common bile duct (CBD) stone removal, the endoscopists decided to insert a temporary biliary stent if necessary. The incident rate of PEC was significantly lower in the stent group than the no-stent group (1% vs. 11%, p = 0.03). The length of hospital stay was also significantly shorter in the stent group than the no-stent group (5 days vs. 7 days, p < 0.01). In the stent group, one case had stent migration into the bile duct and two cases had a mooring stent at the papilla after 1 month. Multivariate analysis identified the pancreatic guide wire technique as a risk factor for PEC. We demonstrated that a temporary biliary stent reduced the incidence of PEC significantly and the outcome of its placement contributed to shortening the hospital stay. Furthermore, the placement of a temporary biliary stent caused fewer adverse effects than expected. Mooring stents were noted in three cases, which were confirmed by plain abdominal X-ray, but the patients had no symptoms. In two cases, the stent remained in the orifice of the papilla, and in one case it migrated into the CBD. All three stents were retrieved by elective endoscopic procedures. In conclusion, a temporary biliary stent can reduce the incidence of PEC and shorten the length of hospital stay without severe adverse outcomes

非アルコール性脂肪性肝炎の経過中に筋強直性ジストロフィーと診断された1例

症例は42歳女性で,弟に筋強直性ジストロフィーがある.脂肪肝と診断され,外来通院していたが,肝生検を施行され非アルコール性脂肪性肝炎(non-alcoholic steatohepatitis: NASH)と診断された.一方,今回入院の数年前より歩行が遅く,神経内科外来に紹介され精査目的で入院した.斧状顔貌を認めたが,grip myotoniaやpercussion myotoniaは明らかではなかった.四肢の筋力は正常だが, 歩行はやや緩徐であった.血液検査では総コレステロール,γGTP及びHOMA-IRの高値を認めた.針筋電図では,刺入時に急降下爆撃音が聴取された.遺伝子検査にてDMプロテインキナーゼ遺伝子のCTG反復配列が約1,300回と増幅を認めた.筋強直性ジストロフィーの家族歴,針筋電図検査,遺伝子検査から筋強直性ジストロフィー1型と確定診断した.筋強直性ジストロフィーは骨格筋の障害の他に,様々な臓器の障害をきたすことが知られているが,NASHを合併した報告例はごく少数である.近年NASHあるいは非アルコール性脂肪性肝疾患(non-alcoholic fatty liver disease: NAFLD)患者は急増しており,それらの中に筋強直性ジストロフィーが合併している場合があることも念頭に置くべきと考える.We report the case of a 42-year-old woman diagnosed with myotonic dystrophy during the clinical course of non-alcoholic steatohepatitis (NASH). She had been diagnosed fatty liver at age 33. When she was 40 years old, histopathological findings of a liver biopsy specimen indicated NASH. After that, she complained of gait disturbance. Brain CT and MRI revealed skull thickening, calcification of falx cerebri and atrophy of the lateral pterygoid muscles. She had a hatchet face. Her muscle strength was normal; she did not have grip myotonia nor percussion myotonia. On laboratory data, total cholesterol was 254 mg/dl, γGTP was 118 U/l, CK was 148 U/l, fasting plasma glucose was 103 mg/dl, fasting plasma insulin was 15.6 μU/ml, homeostasis model assessment-insulin resistance (HOMA-IR) was 3.967. A dive-bomber sound was heard on needle EMG. DM protein kinase gene analysis showed increase of CTG repeat. Occurrence of myotonic dystrophy during the clinical course of NASH is rare. NASH/non-alcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. Insulin resistance in patients with myotonic dystrophy is highly prevalent and is due to a splicing abnormality of the insulin receptor in muscle tissue. In our patient, HOMA-IR was elevated and suggested an increase of insulin resistance. Thus, the risk of developing myotonic dystrophy should be considered in patients with NASH/NAFLD

Prevalence and Outcomes of Acute Hepatitis B in Okayama, Japan, 2006-2010

Hepatitis B virus (HBV) is one of the major viruses causing acute hepatitis. Recently, the incidence of acute hepatitis with genotype A has been increasing in Japan. The aim of this study was to investigate acute hepatitis B (AHB) in Okayama prefecture, with special attention to HBV genotype A. AHB patients who visited one of 12 general hospitals in Okayama prefecture between 2006 and 2010 were retrospectively analyzed. Over the course of the study period, 128 patients were diagnosed with AHB. Sexual transmission was supposed in the majority of patients (78 patients, 61%), including 59 (76%) having sex with heterosexual partners. The genotypes of HBV were assessed in 90 patients (70%), of whom 27 patients were infected with genotype A, 5 with genotype B, and 58 with genotype C. The prevalence of genotype A was significantly higher among male patients (28.7%), aged 20-29 (35.6%, p＜0.01), among men who had sex with men (100%, p＜0.005), and among patients having sex with unspecified partners (44.8%, p＜0.005). Genotype A was not a significant factor associated with delayed HBsAg disappearance. Caution should be exercised with regard to sexually transmissible diseases in order to slow the pandemic spread of AHB due to genotype A

Four cases of gastric cancer in patients with autoimmune gastritis

　Here, we report on four cases of gastric cancer in patients with autoimmune gastritis (AIG). AIG is characterized by the corpus-predominant atrophic gastritis with preserved antrum caused by autoimmune mechanisms. Although AIG is a high risk factor for gastric cancer and neuroendocrine tumors (NET), there are few reports describing the characteristics of gastric cancer in patients with AIG. In this case report, all four cases were diagnosed as having AIG by endoscopic findings and the presence of extra-gastric autoimmune diseases before the treatment for gastric cancer

Genetic Polymorphisms of the Human PNPLA3 Gene Are Strongly Associated with Severity of Non-Alcoholic Fatty Liver Disease in Japanese

Nonalcoholic fatty liver disease (NAFLD) includes a broad range of liver pathologies from simple steatosis to cirrhosis and fibrosis, in which a subtype accompanying hepatocyte degeneration and fibrosis is classified as nonalcoholic steatohepatitis (NASH). NASH accounts for approximately 10-30% of NAFLD and causes a higher frequency of liver-related death, and its progression of NASH has been considered to be complex involving multiple genetic factors interacting with the environment and lifestyle.To identify genetic factors related to NAFLD in the Japanese, we performed a genome-wide association study recruiting 529 histologically diagnosed NAFLD patients and 932 population controls. A significant association was observed for a cluster of SNPs in PNPLA3 on chromosome 22q13 with the strongest p-value of 1.4 × 10(-10) (OR = 1.66, 95%CI: 1.43-1.94) for rs738409. Rs738409 also showed the strongest association (p = 3.6 × 10(-6)) with the histological classifications proposed by Matteoni and colleagues based on the degree of inflammation, ballooning degeneration, fibrosis and Mallory-Denk body. In addition, there were marked differences in rs738409 genotype distributions between type4 subgroup corresponding to NASH and the other three subgroups (p = 4.8 × 10(-6), OR = 1.96, 95%CI: 1.47-2.62). Moreover, a subgroup analysis of NAFLD patients against controls showed a significant association of rs738409 with type4 (p = 1.7 × 10(-16), OR = 2.18, 95%CI: 1.81-2.63) whereas no association was obtained for type1 to type3 (p = 0.41). Rs738409 also showed strong associations with three clinical traits related to the prognosis of NAFLD, namely, levels of hyaluronic acid (p = 4.6 × 10(-4)), HbA1c (p = 0.0011) and iron deposition in the liver (p = 5.6 × 10(-4)).With these results we clearly demonstrated that Matteoni type4 NAFLD is both a genetically and clinically different subset from the other spectrums of the disease and that the PNPLA3 gene is strongly associated with the progression of NASH in Japanese population

Combination of shear-wave elastography and liver fibrosis markers predicts severe fibrosis in patients with non-alcoholic steatohepatitis

　非アルコール性脂肪性肝疾患（Non-alcoholic fatty liver disease：NAFLD）の中から予後の悪い線維化が進展した非アルコール性脂肪肝炎（Non-alcoholic steatohepatitis：NASH）を非侵襲的診断法にて拾い上げることが重要である．今回，バイオマーカーやshear wave elastography（以下 SWE）を組み合わせた非侵襲的診断における肝線維化進展症例の診断能の向上について検討を行った．肝生検および SWE を施行し，肝線維化マーカーを測定した NAFLD 患者140名を対象とし，SWE 値と肝線維化マーカーの測定を行い線維化進展例（stage3以上）の診断の拾い上げについて検討した．各種線維化マーカーは stage3-4の線維化進展例で有意に上昇を認め，SWE においてはstage2の段階から上昇し，他の線維化マーカーより早い段階から NASH の線維化の診断ができた．SWE，Ⅳ型コラーゲン7S，WFA+M2BP，P-Ⅲ-P，ヒアルロン酸，FIB4 index における stage3以上の AUC はそれぞれ0.86，0.83，0.79，0.75，0.75，0.77であった．さらに SWE と線維化マーカーを組み合わせたところ，AUC はそれぞれ0.92，0.88，0.86，0.88，0.88で診断能の上昇を認めた．特に SWE とⅣ型コラーゲン7S の診断能が最も優れていた．NASH における SWE は簡便に線維化進展の診断が可能であり，バイオマーカーを組み合わせることで肝線維化診断能が上昇した．以上より線維化の軽度な NASH 症例や非アルコール性脂肪肝（Non-alcoholic fatty liver：NAFL）を識別し，肝生検を減少させる可能性があり，NAFLD の予後の改善に繋がると思われた．　In the recent years, the incidence of nonalcoholic fatty liver disease (NAFLD) is increasing rapidly worldwide. It is important to detect nonalcoholic steatohepatitis (NASH) with a poor prognosis in patients with NAFLD using noninvasive diagnostic methods. Conventional ultrasound (US) is the most common, low-cost technique for NASH diagnosis and improving patient prognosis. We studied the usefulness of US elastography (shear-wave elastography [SWE]) in diagnosing liver fibrosis (LF) with NAFLD and examined the possibility of improving the diagnosis of patients with advanced LF by combining SWE and LF-marker testing. The subjects were 140 patients with NAFLD who underwent liver biopsies, SWE, and LF-marker tests, such as type IV collagen 7S, Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA[+]-M2BP), P-Ⅲ-P, hyaluronic acid, and fibrosis-4 (FIB4) index, at the General Medical Center, Kawasaki Medical School. We evaluated the efficacy of combined SWE and LF-marker tests to diagnose advanced LF (stage ≥3). SWE was performed using 3.75-MHz probes (Canon Aplio 500, JAPAN). There were minimal differences in LF-marker levels for NASH stages 0–2, whereas significantly increased LF-marker levels were observed in patients with advanced LF (stages 3 and 4). SWE showed significantly elevated LF-marker levels at stage 2 compared with stages 0–1, and NASH was detected earlier than other LF markers. The areas under the receiver-operating characteristic curves (AUCs) for SWE, type IV collagen 7S, WFA(+)-M2BP, P-Ⅲ-P, hyaluronic acid, and FIB4 index for stage ≥3 were 0.86, 0.83, 0.79, 0.75, 0.75, and 0.77, respectively. With combined SWE and LF markers, the AUCs increased to 0.92, 0.88, 0.86, 0.88, and 0.88, respectively, showing increased diagnostic ability compared to that of single markers. The diagnostic ability of combined SWE and type IV collagen 7S was superior to that of other combinations. In addition, we detected that most cases were in stage ≥3 on combining SWE and LF markers. SWE for NASH can simply diagnose LF progression; the diagnostic capacity of SWE for LF improves in combination with LF-marker tests. It may be possible to detect the need for liver biopsy and treatment or follow-up, as well as reduce the number of liver biopsies by identifying NAFLD with low LF levels

当院で経験したA 型胃炎の４例

A 型胃炎は稀な疾患で，悪性貧血や胃癌，胃NET の発生母地として知られている．抗胃壁細胞抗体陽性，高ガストリン血症，さらに胃体部を中心とした萎縮性胃炎が診断基準とされている．今回，過去１年に４例のA 型胃炎を診断した．全例で自覚症状は見られなかったが，内視鏡検査での逆萎縮所見からA 型胃炎を疑い，胃生検の病理所見と血液検査で確診した．A 型胃炎が他の自己免疫性疾患に合併することが多いとされているが，本症例にも高齢発症のBasedow 病が１例あり，A 型胃炎は日本でも決してまれな疾患ではないと考えられた．診断には内視鏡所見からA 型胃炎を疑うことが重要で，胃生検や血清ガストリンと抗胃壁細胞抗体の測定を行うことにより確診できる．Type A gastritis is a rare disease and is known as a cause of various conditions including pernicious anaemia, gastric cancer and gastric NETs (Neuroendocrine tumour). The diagnostic criteria of type A gastritis include positive parietal cell antibody, hypergastrinaemia and the presence of atrophic gastritis mainly corpus predominantly atrophic gastritis. We diagnosed four cases of type A gastritis in the past year in our hospital. Although they were all asymptomatic, type A gastritis was suspected by the endoscopic findings (the reverse atrophy) and all confirmed by pathological examination of biopsy specimens and blood test subsequently. It is well known that the patients with autoimmune disease are frequently associated with type A gastritis and there is a case of late onset of Basedow’s disease in our case report. Our study suggests that type A gastritis is not as rare as initially thought in Japan. In order to diagnose type A gastritis, it is important to have a high index of suspicion with endoscopic findings, and to confirm it with gastric biopsy, serum gastrin level and parietal cell antibody