Naoki Kawagishi

Comparing the risk of hepatitis B virus reactivation between direct-acting antiviral therapies and interferon-based therapies for hepatitis C

Hepatitis B virus (HBV) reactivation has been reported during antihepatitis C treatment in patients with hepatitis C virus (HCV) and HBV co‐infection. We aimed to evaluate the frequency and risk factors of HBV reactivation during anti‐HCV therapy and compared those between interferon (IFN)‐free direct‐acting antiviral (DAA) therapies and IFN‐based therapies. Three hundred and twenty‐two patients with HCV infection receiving anti‐HCV therapy were retrospectively screened. The baseline HBV infection statuses of all eligible patients and the HBV‐DNA level of all patients with current or previous HBV infection were examined at the end of treatment. In patients with baseline anti‐HBs positivity, changes in anti‐HBs titre were evaluated. Of 287 patients who met the inclusion criteria, 157 had current (n=4) or previous (n=153) HBV infection; 85 were treated with IFN‐free DAA therapies and 72 were treated with IFN‐based therapies. Six patients experienced HBV reactivation (n=2) or HBV reappearance (n=4) after IFN‐free DAA therapies, while no patient developed HBV reactivation after IFN‐based therapies. The risk factors of HBV reactivation or reappearance were DAA therapies and a reduction in anti‐HBs titre to <12 mIU mL−1 by the end of treatment. The decline changes of anti‐HBs titre were significantly higher in patients treated with DAA therapies. Although HBV reactivation hepatitis was not observed, three of four patients with HBV reactivation or reappearance after achieving HCV eradication had viremia 8 weeks after completion of therapy. A significant proportion of patients develop HBV reactivation or reappearance without hepatitis after IFN‐free DAA therapies. Low levels of anti‐HBs and their decrease to <12 mIU mL−1 after treatment are significant risk factors for HBV reactivation or reappearance.

Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction: SOF/RBV for patients with renal dysfunction

The safety and efficacy of sofosbuvir (SOF) and ribavirin (RBV) have not been well clarified in patients with renal dysfunction because clinical trials have not included such patients. We evaluated the safety and efficacy of SOF and RBV for genotype 2 hepatitis C virus (HCV)‐infected patients with renal dysfunction.

Add-on effects of fluvastatin in simeprevir/pegylated-interferon/ribavirin combination therapy for patients with genotype 1 hepatitis C virus infection: A randomized controlled study: FLV add-on SMV/Peg-IFN/RBV therapy

The Japan Society of Hepatology guidelines indicate that hepatitis C virus (HCV) protease inhibitor combination therapy with simeprevir (SMV), pegylated‐interferon (Peg‐IFN), and ribavirin (RBV) is a therapeutic option for patients who fail to respond to a direct direct‐acting antiviral‐containing regimen. However, treatment outcomes have room for improvement. Fluvastatin (FLV) add‐on treatment in Peg‐IFN and RBV combination therapy for HCV‐infected patients significantly improved the sustained virologic response (SVR), but the add‐on effect of FLV on SMV combination therapy is not well understood.

L‐Carnitine Suppresses Loss of Skeletal Muscle Mass in Patients With Liver Cirrhosis

Liver cirrhosis (LC) is a major cause of secondary sarcopenia. Sarcopenia makes the prognosis worse; thus, novel therapeutic options for sarcopenia in patients with LC are urgently required as they are currently limited. In this retrospective study, 158 patients with LC were screened, and 35 of those patients who were treated with L‐carnitine for more than 6 months and for whom skeletal muscle mass changes could be evaluated by computer tomography were enrolled. Of the 158 patients, 79 patients who did not receive L‐carnitine supplementation served as controls. Cases and controls were propensity score matched for age, sex, presence of hepatocellular carcinoma, and branched chain amino acid administration, and changes in skeletal muscle mass and clinical data were compared. The 35 patients who received L‐carnitine supplementation and 35 propensity score‐matched patients who did not receive carnitine supplementation comprised the final enrollment. Compared with control patients, patients who received L‐carnitine had significantly worse liver function, which is associated with rapid progress of skeletal muscle depletion. However, loss of skeletal muscle mass was significantly suppressed in patients receiving L‐carnitine, and a significant effect was observed in patient subgroups stratified by age, sex, presence of hepatocellular carcinoma, and branched chain amino acid administration. The change ratios of most laboratory data, including vitamin D and insulin‐like growth factor 1 levels, were similar in the two groups, but ammonia levels were significantly less in those receiving L‐carnitine. However, even in patients receiving L‐carnitine but not showing an ammonia decrease, loss of skeletal muscle was significantly suppressed. Conclusion: L‐carnitine suppresses loss of skeletal muscle mass and may therefore be a novel therapeutic option for sarcopenia in patients with LC. (Hepatology Communications 2018; 00:000‐000)

Apocrine mixed tumour on the abdomen: an atypical location

Mixed tumour of the skin is a rare, benign skin adnexal tumour presenting as a firm, intradermal or subcutaneous, asymptomatic, slow-growing nodule. It is characterized by the coexistence of epithelial and mesenchymal features, and is usually classified as apocrine or eccrine variants [1]. The apocrine variant, also termed apocrine mixed tumour (AMT), is more common; this variant exhibits differentiation in the epithelial, myoepithelial, and stromal components, and often shows decapitation secretion. The predilection sites of AMT are the head and neck regions (especially the nose, upper lip, and cheeks, where folliculosebaceous-apocrine units are well developed); development in other areas is rare. Here, we report a case of AMT on the right side of the abdomen, which is an extremely unusual site of occurrence. A 61-year-old woman presented with a painless, slowgrowing mass on the right abdomen, which had developed over a five-year period (figure 1A). Physical examination showed a firm, solitary, mobile, painless nodule of 20 mm in diameter. The overlying skin was normal. The lesion was surgically excised. Histopathological examination showed a well-circumscribed tumour invading the subcutis, which had the characteristic structure of a solid area surrounded by large multiple cysts (figure 1C). The solid area was composed of several parts that exhibited multilineage differentiation into cartilage, tubular structures, and myxoid stroma (figure 1D). The cysts contained notably tubular structures with decapitation secretion (figure 1E). Immunohistochemically, duct epithelial cells stained positive for CAM5.2, epithelial membrane antigen, and gross cystic disease fluid protein 15 (figure 1F). Spindle cells were positive for alpha-smooth muscle actin, S-100 protein, CAM5.2, vimentin, and p16. Oestrogen receptor, progesterone receptor, and Ki-67 (figure 1G) were negative, both in the ductal epithelial cells and the spindle cells. The tumour was not associated with mammary gland tissue and showed no malignancy features. A diagnosis of AMT was made. No relapse was observed at a one-year follow-up visit. AMT accounts for less than 0.098% of all primary cutaneous tumours [2]. Based on a survey of the literature, 219 AMT lesions were identified in which the location was specified; the majority (92%) were on the head and neck region, and a small minority (2.3%) on the trunk [3]. Therefore, our case on the right abdomen is extremely unusual. AMT is a benign tumour, but malignant variants have been reported. Watarai et al. identified 43 cases of malignant mixed tumours of the skin. Only 28% of these malignant cases were on the head and neck, and they occurred more frequently on the lower limbs (35%), upper limbs (23%), and trunk (14%) [4]. Therefore, complete excision of AMT, especially when located on areas other than the head or neck, is the best therapeutic option. Close follow-up is recommended. AMT is considered analogous to pleomorphic adenoma of the salivary glands, and similar neoplasms also exist in the breast [5]. Characteristic findings of the present case are the location of the lesion and the prominent apocrine differentiation, which suggests an association with mammary gland A B