The Diagnosis, Pathophysiology, and Treatment of Chronic Hepatitis E Virus Infection-A Condition Affecting Immunocompromised Patients.

Hepatitis E is a zoonosis caused by hepatitis E virus (HEV), which was first discovered 40 years ago. Twenty million HEV infections worldwide are estimated each year. Most hepatitis E cases are self-limiting acute hepatitis, but the virus has been recognized to cause chronic hepatitis. Following the first case report of chronic hepatitis E (CHE) in a transplant recipient, CHE has recently been identified as associated with chronic liver damage induced by HEV genotypes 3, 4, and 7-usually in immunocompromised patients such as transplant recipients. In addition, patients infected with HIV and those receiving chemotherapy for malignancy, along with patients with rheumatic disease and COVID-19, have recently been reported as having CHE. CHE can be easily misdiagnosed by usual diagnostic methods of antibody response, such as anti-HEV IgM or IgA, because of the low antibody response in the immunosuppressive condition. HEV RNA should be evaluated in these patients, and appropriate treatments-such as ribavirin-should be given to prevent progression to liver cirrhosis or liver failure. While still rare, cases of CHE in immunocompetent patients have been reported, and care must be taken not to overlook these instances. Herein, we conduct an overview of hepatitis E, including recent research developments and management of CHE, in order to improve our understanding of such cases. The early diagnosis and treatment of CHE should be performed to decrease instances of hepatitis-virus-related deaths around the world.

Anti-VEGF Treatment Strategies for 3 Subtypes of Neovascular Age-Related Macular Degeneration in a Clinical Setting: A Multicenter Cohort Study in Japan.

PURPOSE: Neovascular age-related macular degeneration (nAMD) is classified into typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This study investigated clinical features of the 3 subtypes and visual outcome associated with treatment regimens in a large cohort of patients with nAMD in a clinical setting. DESIGN: Retrospective multicenter cohort study. PARTICIPANTS: Five hundred patients with treatment-naive nAMD (268 tAMD, 200 PCV, and 32 RAP) initiated with anti-VEGF agents and followed for 1 year. METHODS: Medical records were reviewed to extract demographic data, best-corrected visual acuity at baseline and 1 year after treatment initiation, spectral-domain OCT findings, baseline fellow eye condition, systemic factors, treatment strategies, and number of intravitreal injections in the first year. MAIN OUTCOME MEASURES: Primary outcome measures were anti-VEGF treatment strategy (ranibizumab or aflibercept, anti-VEGF regimen, concomitant photodynamic therapy, drug switch), best-corrected visual acuity at 1 year, and factors associated with visual acuity. RESULTS: Patients with RAP were significantly older, were more commonly women, and had more macular lesions in fellow eye than patients with tAMD and PCV. Smoking history and diabetes prevalence were not different among the 3 subtypes. Frequencies of subretinal fluid were higher and intraretinal fluid were lower in tAMD and PCV than in RAP, whereas serous pigment epithelial detachment and subretinal hemorrhage were higher in PCV than in tAMD and RAP. Choice of anti-VEGF agents and treatment regimens did not differ among 3 subtypes. The aflibercept-to-ranibizumab ratio was approximately 7:3. The mean number of injections in 1 year was 5.3 ± 2.4 in nAMD overall, which was significantly less in pro re nata (PRN) than in treat and extend (TAE) regardless of the anti-VEGF agent. Best-corrected visual acuity improved in all 3 subtypes, although it was not significant in patients with RAP. CONCLUSIONS: This clinical study demonstrates that treatment regimens were similar in 3 subtypes and aflibercept was used in 70% of all patients. Approximately 5 injections were given in the first year regardless of the anti-VEGF agent, which was significantly less in PRN regimen than in TAE. Visual acuity improvement was observed after 1-year anti-VEGF therapy in all 3 subtypes, but was not significant in RAP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Endoscopic and video capsule endoscopic observation of Yersinia enterocolitis.

A woman in her late 20s suffered from epigastralgia following lower abdominal pain with diarrhea. Kampo medicine relieved the complaints, but the pain recurred a month later. She had immigrated from Vietnam to Japan 6 months before the onset of the abdominal pain. Blood test findings were almost within normal limits, except for mild C-reactive protein elevation and positive Helicobacter pylori antibody findings. Colonoscopy revealed an edematous cobblestone-like appearance at the end of the ileum with irregular ulceration mimicking Crohn's disease. Video capsule endoscopy was performed to detect lesions in the small intestine and demonstrated irregular ileal ulcer, reminiscent of Crohn's disease. A biopsy performed during colonoscopy demonstrated granulomatous inflammation with a moderate accumulation of plasma cells and mononuclear cells. The bacterial culture of the biopsy specimen proved the growth of Yersinia enterocolitica. Levofloxacin 500 mg for 7 days rapidly relieved abdominal pain. Yersinia enterocolitis is rare in developed countries, but as a differential diagnosis for Crohn's disease, it is important to treat. This is the first case report of the video capsule endoscopy findings of Yersinia enterocolitis. Video capsule endoscopy can help to confirm the spread of the lesions of Yersinia enterocolitis.

Two cases of hepatocellular carcinoma successfully treated by carbon ion radiotherapy after atezolizumab plus bevacizumab treatment.

We herein report two cases of huge hepatocellular carcinoma (HCC) that were successfully treated by carbon ion radiotherapy after atezolizumab plus bevacizumab treatment. Case 1, an 84-year-old man, was diagnosed with HCC (maximum diameter: 11 cm) with portal invasion and presented HCC rupture. After obtaining hemostasis with transcatheter embolization, three cycles of atezolizumab-bevacizumab therapy were administered, and marked shrinkage of the HCC was confirmed. However, he developed jaundice, liver damage and cerebral subcortical hemorrhage. Thus, atezolizumab-bevacizumab therapy was discontinued. Total bilirubin, transaminase levels, and physical activity improved well with prednisolone, an antihypertensive agent, and rehabilitation. Thus, treatment with carbon ion radiotherapy (CIRT) was added, and the treatment effect at 4 months after CIRT was judged as a complete response (CR) according to the modified response evaluation criteria in solid tumors (mRECIST). Case 2, a 68-year-old man, was diagnosed with HCC (maximum diameter: 14 cm). Hepatic resection was difficult because the residual liver volume after treatment would be insufficient. Five cycles of atezolizumab-bevacizumab therapy were performed, and marked shrinkage of the HCC to a maximum diameter of 9 cm was confirmed. The treatment was converted to CIRT, and atezolizumab-bevacizumab therapy resumed one month after CIRT. The treatment effect at 3 months after CIRT was judged as CR according to mRECIST. Although conversion therapy after atezolizumab-bevacizumab therapy, including surgery and radiofrequency ablation, have been reported, CIRT may be a promising new tool for conversion therapy for HCC.

Risk Factors for Legal Blindness in 237 Japanese Patients with Exogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential risk factors for visual prognosis in Japanese patients with exogenous endophthalmitis. METHODS: In this retrospective observational multicenter cohort study, risk factors for legal blindness at 12 weeks after treatment initiation were evaluated based on patient characteristics, initial BCVA, causative events, pathogens, ocular symptoms, duration from symptom onset to initial treatment, and selected treatments. RESULTS: Overall, 23.1% of eyes developed legal blindness. The six risk factors for legal blindness were presence of eye pain, pathogen identification, poor BCVA at the initial visit, longer duration from symptom onset to initial treatment, type of causative event, and type of causative pathogen. Regarding the type of causative pathogen, coagulase-negative staphylococci was associated with a better visual impairment outcome. CONCLUSION: Exogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatment, as well as other advances in medical knowledge and technology.

Recurrence of hepatocellular carcinoma after radiofrequency ablation in a poor-risk patient with chronic renal failure and other complications successfully treated with stereotactic body radiotherapy.

The patient was an 85-year-old man with hepatitis C-related liver cirrhosis and chronic renal failure caused by diabetes mellitus under maintenance hemodialysis (HD) who developed hepatocellular carcinoma (HCC) after achieving a sustained viral response with direct acting antiviral therapy 1 year and 3 months previously. HCC located near the right hepatic vein was treated by radiofrequency ablation (RFA) but recurrent disease accompanied by hepatic vein invasion was detected 3 months after RFA. The recurrent HCC was curatively treated with stereotactic body radiotherapy (SBRT). The patient had additional complications, including grade III AV block controlled by a pacemaker, colonic adenoma resected by endoscopic mucosal resection, and a small cerebral aneurysm, which was untreated. At 2 years after SBRT, there had been no recurrence of HCC. In this old HCC patient with various complications including HD with polypharmacy, multidisciplinary treatment, including SBRT, enabled the patient to achieve complete remission and maintain a good quality of life.

Chronic hepatitis E in an elderly immunocompetent patient who achieved a sustained virologic response with ribavirin treatment.

A woman in her late 70 s was diagnosed with liver injury at a health examination. Despite treatment with ursodeoxycholic acid at a nearby hospital, her transaminase levels elevated in two peaks. She was transferred to our hospital 77 days after the health examination. She weighed 42 kg and had a low body mass index of 19.8 kg/m2. Viral markers, including immunoglobulin A (IgA) against hepatitis E virus (anti-HEV IgA), were negative. Drug-induced liver injury was negligible. We suspected autoimmune hepatitis because of the patient's female gender and positive antinuclear antibody. However, prednisolone and azathioprine failed to completely improve her hepatitis. On day 643, anti-HEV IgA was re-evaluated and found to be positive. She was diagnosed with autochthonous chronic hepatitis E because the virus strains in the preserved serum on day 77 and the serum on day 643 had identical nucleotide sequences (genotype 3a). Following prednisolone and azathioprine discontinuation, ribavirin (RBV) was administered for 3 months. HEV RNA disappeared and remained negative for more than 6 months after the cessation of RBV. The HEV RNA titer of 6.2 log10 copies/mL on day 77 was unusually high 2.5 months after the onset, suggesting that hepatitis E had already been chronic before immunosuppressive treatment for possible autoimmune hepatitis. After getting married at 23 years old, she had been a housewife and had no comorbidities that might deteriorate her immunity. Chronicity should be kept in mind when encountering HEV infection in elderly and underweight patients.

Risk Factors for Legal Blindness in 77 Japanese Patients with Endogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential predictive factors for visual prognosis in Japanese patients with endogenous endophthalmitis. DESIGN: Retrospective observational multicenter cohort study. METHODS: We examined the characteristics of 77 Japanese patients with endogenous endophthalmitis and performed statistical analyses of these real-world data. The primary endpoint was the identification of factors associated with visual prognosis. We examined differences between patients in the better vision and legal blindness groups at 12 weeks after treatment initiation. RESULTS: The five risk factors for visual impairment at 12 weeks after treatment initiation were presence of pressure injuries, severe clinical symptoms (presence of eye pain and ciliary injection), pathogen identification, and poor best-corrected visual acuity at baseline. Staphylococcus aureus and fungus were associated with a better visual impairment outcome. CONCLUSIONS: Endogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatments, as well as other advances in medical knowledge and technology.

Case of pneumatosis cystoides intestinalis with intra-abdominal free air developed during treatment with voglibose.

Contrast-enhanced computed tomography (CT) scan (portal phase) at the onset. Emphysema is detected in the ileal wall (b, c: Arrows) and free air is detected in the abdominal cavity (a: Arrowhead). CT scan imaging settings: (a-c) window level (WL) 60 and window width (WW) 300. (d-f) WL 0 and WW 433. By changing the imaging settings, intestinal emphysema and free air can be more easily identified.

Comparison of minimally invasive glaucoma surgery with trabecular micro-bypass stent and microhook ab interno trabeculotomy performed in conjunction with cataract surgery.

AIM: To evaluate the effectuality and safety of cataract surgery combined with either ab interno trabeculotomy by the microhook (µLOT) or a single iStent® trabecular bypass implantation (iStent) in eyes with cataract and mild-to-moderate glaucoma. METHODS: This study enrolled subjects with mild-to-moderate open angle glaucoma with visually significant cataract who used two or more ophthalmic antiglaucoma agents between 60 and 90y of age. Patients underwent cataract surgery cooperated with either implantation of an iStent (iStent-phaco) or excisional goniotomy with the µLOT (µLOT-phaco). Patients underwent µLOT-phaco in the eye with lower the mean deviation, according to the Humphrey field analyzer, while iStent-phaco was carried out on the other eye. Intraocular pressure (IOP) pre- and post-surgery, alterations in anterior chamber flare (ACF), and corneal endothelial cell density (ECD) were estimated. RESULTS: Twenty subjects were enrolled (mean age: 73.6±7.3y). The mean medicated preoperative IOP was 16.7 mm Hg in the µLOT and 16.2 mm Hg in the iStent eyes. The mean final IOP at 12mo was 13.6 mm Hg in the µLOT eyes and 13.6 mm Hg in the iStent eyes, representing a 17.8% and 17.2% reduction, respectively. The preoperative ACF in the µLOT eyes was 9.5 pc/ms and it returned to normal in 30d postoperatively, with a value of 11.4 pc/ms. In the iStent eyes, ACF was 9.6 pc/ms preoperatively and it returned to normal by 7d postoperatively (11.2 pc/ms at day 7), demonstrating that postoperative inflammation was less in the iStent eyes. The corneal ECD in both groups was not significantly decreased. CONCLUSION: In this study, iStent and µLOT are both effective through 12mo of follow-up. Safety is more favorable in the iStent eyes, based on early anterior chamber inflammation.

Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.

AIMS/INTRODUCTION: In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. MATERIALS AND METHODS: This is a real-world clinical study including 1,552 patients with treatment-naïve center-involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years. RESULTS: From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 µm in C1, -108.8 µm in C2, -100.6 µm in C3, and -89.5 µm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001). CONCLUSIONS: Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.

Changes of esophageal varices in hepatitis C patients after achievement of a sustained viral response by direct-acting antivirals.

Objectives: The changes in portal hypertension after achieving a sustained viral response (SVR) by direct-acting antivirals (DAAs) have not been fully elucidated. Consequently, noninvasive and inexpensive predictors need to be investigated. We therefore explored factors associated with the progression of EVs after the achievement of an SVR with DAAs in patients with chronic hepatitis C. Methods: Eighty-nine patients, who had achieved an SVR with DAAs and could have their esophagogastroduodenoscopy (EGD) findings compared between before DAAs administration and after achieving an SVR achievement were enrolled in this study. We compared the patients with and without EVs progression. Furthermore, the cumulative progression rates of EVs were also analyzed. Results: The fibrosis-4 index (FIB-4) before DAAs administration was the only significant factor for the progression of EVs after an SVR (odds ratios: 1.2, 95% confidence intervals: 1.05-1.38, p = 0.01). In a receiver operating characteristics analysis, the cut-off of FIB-4 for the progression of EVs was 8.41 (sensitivity: 0.63, specificity: 0.86, positive predictive value: 0.31, negative predictive value: 0.96), namely EVs of those with more than 8.41 of FIB-4 progressed and those with less than 8.41 of FIB-4 did not. Conclusions: As patients with FIB-4 ≥ 8.41 may have progressions of EVs, periodic surveillance by EGD should be continued in such cases, even after an SVR is achieved.

Axonal Protection by Netarsudil, a ROCK Inhibitor, Is Linked to an AMPK-Autophagy Pathway in TNF-Induced Optic Nerve Degeneration.

Purpose: Netarsudil, a Rho kinase inhibitor with norepinephrine transport inhibitory effect, lowers intraocular pressure, however, its effect on axon damage remains to be elucidated. The aim of the current study was to investigate the effect of netarsudil on TNF-induced axon loss and to examine whether it affects phosphorylated-AMP-activated kinase (p-AMPK) and autophagy in the optic nerve. Methods: Intravitreal administration of TNF or TNF with netarsudil was carried out on rats and quantification of axon number was determined. Electron microscopy determined autophagosome numbers. Localization of p-AMPK expression was examined by immunohistochemistry. The changes in p62, LC3-II, and p-AMPK levels were estimated in the optic nerve by immunoblot analysis. The effect of an AMPK activator A769662 or an AMPK inhibitor dorsomorphin on axon number was evaluated. Results: Morphometric analysis revealed apparent protection by netarsudil against TNF-induced axon degeneration. Netarsudil increased autophagosome numbers inside axons. Netarsudil treatment significantly upregulated optic nerve LC3-II levels in both the TNF-treated eyes and the control eyes. Increased p62 protein level induced by TNF was significantly ameliorated by netarsudil. The netarsudil administration alone lessened p62 levels. Netarsudil significantly upregulated the optic nerve p-AMPK levels. A769662 exhibited obvious axonal protection against TNF-induced damage. A769662 treatment upregulated LC3-II levels and the increment of p62 level induced by TNF was significantly ameliorated by A769662. Immunohistochemical analysis revealed that p-AMPK is present in axons. Netarsudil-mediated axonal protection was significantly suppressed by dorsomorphin administration. Conclusions: Netarsudil upregulated p-AMPK and autophagy. Netarsudil-mediated axonal protection may be associated with upregulated p-AMPK.

Efficacy of Zinc Acetate Treatment for Patients with Decompensated Liver Cirrhosis Complicated by Hypozincemia.

The aim of this study was to evaluate the efficacy of zinc acetate treatment for patients with decompensated liver cirrhosis complicated by hypozincemia. We retrospectively analyzed 49 patients with decompensated liver cirrhosis complicated by hypozincemia who received zinc acetate treatment from August 2017 to March 2020. The relationships between serum zinc levels and several parameters including the prognosis, sarcopenia, and immunity were evaluated. Serum zinc levels measured at 3 months post-treatment and the incidence of adverse events were also determined. The median age was 69.0 years (IQR:59.5-78.8) and the male to female ratio was 29:20. Twenty-seven patients had a Child-Pugh classification of B and 22 had a Child-Pugh classification of C; the median Child-Pugh score was 9.0 (IQR, 8.0-11.0). The median serum zinc levels measured at 3 months post-treatment (74.7 (IQR, 50.0-101.0) µg/dL) were significantly elevated in comparison to the pre-treatment levels (43.0 (IQR, 34.0-51.0) µg/dL, P < 0.0001). The overall survival of patients with pre-treatment serum zinc levels of ≥60 µg/dL was significantly better than that of those with pre-treatment serum zinc levels of <60 µg/dL (P = 0.013). The survival of patients with zinc levels of ≥70 µg/dL at 3 months post-treatment was significantly better than those with levels of <70 µg/dL (P = 0.013). The serum albumin level, Child-Pugh score, albumin-bilirubin (ALBI) score and model for end-stage liver disease (MELD) score were identified as factors predicting a good response at 3 months post-treatment. There were no significant relations between the pretreatment serum zinc levels and skeletal muscle mass, lymphocyte count, and neutrophil lymphocyte ratio. There were no obvious problematic adverse events in patients who received zinc acetate treatment. The patients with higher basal zinc levels and good responders to zinc acetate treatment had a better prognosis. Zinc acetate was useful and safe for patients with decompensated liver cirrhosis complicated by hypozincemia.

Massive Polycystic Liver with a Poor Performance Status Successfully Treated by ABO-incompatible Adult Living-donor Liver Transplantation While Overcoming Complications.

We encountered a 47-year-old woman with polycystic liver disease (PLD) and severe malnutrition successfully treated by living-donor liver transplantation (LDLT). Her PLD became symptomatic with abdominal distension and appetite loss. Transcatheter arterial embolization and percutaneous cyst drainage failed to improve her symptoms. ABO-incompatible LDLT from her husband was performed after rituximab administration and mycophenolate mofetil introduction. Although she showed severe postoperative complications, she ultimately regained the ability to walk and was discharged. Because advanced PLD cases are difficult to treat conservatively or with surgery, like fenestration and hepatectomy, liver transplantation should be considered before it becomes too late.

Efficacy of Fovea-Sparing Internal Limiting Membrane Peeling for Epiretinal Membrane Foveoschisis.

INTRODUCTION: The aim of the study was to investigate the outcomes of vitrectomy with fovea-sparing internal limiting membrane (ILM) peeling (FSIP) for epiretinal membrane (ERM) foveoschisis based on new optical coherence tomography definitions. METHODS: Twenty-three eyes of 22 patients (69.7 ± 9.9 years old) who underwent vitrectomy with FSIP without gas tamponade for ERM foveoschisis were analyzed. All patients underwent follow-up examinations for at least 12 months. In the FSIP technique, the ILM is peeled off in a donut shape, preserving the foveal ILM. The logarithm of the minimal angle of resolution best-corrected visual acuity (BCVA), central macular thickness (CMT), and surgical complications were examined. RESULTS: The BCVA at 12 months improved significantly from baseline (p < 0.001). Baseline ellipsoid zone defects were found in 2 eyes (9%), and all defective eyes had recovered at 12 months. CMT decreased significantly from baseline (p < 0.001). Acute macular edema, full-thickness macular hole, and recurrence of ERM were not observed during follow-up. DISCUSSION/CONCLUSION: FSIP achieved good visual outcome and retinal morphological change. Moreover, FSIP might avoid acute macular edema in ERM foveoschisis surgery.

Effect of 48-week pemafibrate on non-alcoholic fatty liver disease with hypertriglyceridemia, as evaluated by the FibroScan-aspartate aminotransferase score.

BACKGROUND AND AIM: This retrospective study investigated the effect of 48-week pemafibrate therapy in non-alcoholic fatty liver disease (NAFLD) with hypertriglyceridemia, as evaluated by the FibroScan-aspartate aminotransferase (FAST) score. METHODS: A total of 31 NAFLD patients who were treated with pemafibrate in Gunma Saiseikai Maebashi Hospital and Kusunoki Hospital from September 2018 to April 2020 were included in the current study. We used the FAST score, which is a novel index of steatohepatitis that can be calculated based on the AST value, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM), to evaluate the effect of pemafibrate treatment. RESULTS: The median age was 64.0 (interquartile range [IQR] 55.0-75.0) years and 14 patients (45.2%) were male. Median body mass index was 26.8 (IQR 23.8-28.8). Hypertension and diabetes mellitus were detected in 14 (45.2%) and five (16.1%) patients, respectively. Fasting triglyceride and high-density lipoprotein cholesterol were significantly improved (P < 0.001 and 0.013, respectively) and the AST, alanine aminotransferase (ALT), alkaline phosphatase, and γ-glutamyl transpeptidase values were significantly decreased during pemafibrate treatment (P = 0.041, <0.001, <0.001, and <0.001, respectively). While the LSM value and CAP value did not differ to a statistically significant extent (P = 0.19 and 0.140, respectively), the FAST score was significantly improved during pemafibrate treatment (P = 0.029). The delta FAST score was found to be correlated with the variations of ALT (r = 0.504, P = 0.005), which represents the effect of pemafibrate. CONCLUSIONS: Pemafibrate improved the FAST score due to the hepatic anti-inflammatory effect, indicating that pemafibrate may prevent disease progression in NAFLD patients with hypertriglyceridemia.

Follow-up after Direct-acting Antiviral Treatment for Chronic Hepatitis C Virus Infection: Most Patients Are Followed Appropriately.

Objective Chronic hepatitis C virus (HCV) infection carries a residual risk of hepatocarcinogenesis even after viral elimination, so appropriate follow-up is necessary. The present study investigated the current hospital visits and hepatocarcinogenesis status of patients who received daclatasvir plus asunaprevir treatment (DCV+ASV) to determine whether or not appropriate follow-up was being performed. Methods We retrospectively analyzed hepatocarcinogenesis, the overall survival, and the length of hospital visits in 442 patients who applied for the medical expense subsidy system for viral hepatitis and received DCV+ASV treatment in Gunma Prefecture between October 2014 and December 2015. This also included 61 patients who had a history of hepatocellular carcinoma (HCC). Results Among 442 patients, 388 achieved a sustained viral response (SVR) by DCV+ASV therapy (87.8%), and 95.9% achieved an SVR if additional treatment was included. HCC was found in 75 cases (17.0%). A history of HCC, the FIB-4 index and the treatment effect SVR were determined to be factors affecting the incidence of HCC. Regarding the follow-up rate, 89.9% of patients continued to regularly visit the hospital after 5 years of treatment. However, patients ≤60 years old had significantly lower persistence rates than older patients. The persistence rate of hospital visits to the same institution was 67.7% over a 5-year period, which was significantly better in small and medium-sized institutions than in large, specialized institutions (71.7% vs. 63.9%, p=0.039). Conclusion Patients with direct-acting antiviral treatment generally received adequate follow-up, but younger patients had a slightly higher rate of follow-up interruption and were considered to need support.

Shorter Axial Length Is a Risk Factor for Proliferative Vitreoretinopathy Grade C in Eyes Unmodified by Surgical Invasion.

PURPOSE: To investigate the risk factors for the development of proliferative vitreoretinopathy grade C (PVR-C), independent of prior surgical invasion. METHODS: Patients who underwent surgery for rhegmatogenous retinal detachment were prospectively registered with the Japan-Retinal Detachment Registry, organized by the Japanese Retina and Vitreous Society, between February 2016 and March 2017. Data obtained from general ophthalmic examinations performed before and at 1, 3, and 6 months after surgery were analyzed. RESULTS: We included 2013 eyes of 2013 patients (men, 1326 (65.9%); mean age, 55.2 ± 15.2 years) from amongst 3446 registered patients. Preoperative PVR-C was observed in 3.6% of patients. Propensity score matching revealed that a shorter axial length (AL) was a risk factor for preoperative PVR-C (OR (Odds Ratio), 0.81; 95% CI (Confidence Interval), 0.69 to 0.96; p = 0.015), which was a risk factor for surgical failure (OR, 4.22; 95% CI, 1.12 to 15.93; p = 0.034); the association was particularly significant for eyes with an AL < 25.0 mm (p = 0.016), while it was insignificant for eyes with an AL ≥ 25.0 mm. CONCLUSIONS: A shorter AL was related to the development of PVR-C before surgical invasion. Our results will help elucidate the fundamental pathogenesis of PVR and caution clinicians to meticulously examine eyes with a shorter AL to detect retinal detachment before PVR development.

Impact of M2BPGi on the Hepatocarcinogenesis after the Combination Therapy with Daclatasvir and Asunaprevir for Hepatitis C.

The clinical significance of mac-2 binding protein glycosylation isomer (M2BPGi) levels based on virological responses due to antiviral therapy has not been fully evaluated. We compared the change before and 24 weeks after the therapy with daclatasvir and asunaprevir (DCV+ASV) of M2BPGi levels with those of other fibrosis markers in 73 chronic hepatitis C cases. Moreover, we examined the association between M2BPGi levels and hepatocarcinogenesis in sustained virological response (SVR) and non-SVR cases. M2BPGi levels were significantly improved at post-treatment week 24 (PTW24) in SVR but not non-SVR cases, whereas the changes of other fibrosis markers showed the same tendency in both SVR and non-SVR cases. M2BPGi levels were well correlated with other fibrosis markers at baseline but not PTW24. The incidence of hepatocellular carcinoma (HCC) was significantly associated with M2BPGi levels at PTW24. The achievement of SVR significantly affected the improvement of M2BPGi levels that best reflected the effect of direct-acting antivirals among the fibrosis markers. Furthermore, M2BPGi levels at PTW24 were also associated with the incidence of HCC in only SVR cases. However, the rapid decrease of M2BPGi levels might reflect the amelioration of liver inflammation rather than the improvement of liver fibrosis, which should be further elucidated.