Shingo Arakaki

Inhibition of intracellular hepatitis C virus replication by nelfinavir and synergistic effect with interferon-α

Summary.  Liver diseases associated with hepatitis C virus (HCV) infection have become the major cause of mortality in patients with human immunodeficiency virus (HIV) infection since the introduction of highly active anti‐retroviral therapy. HCV‐related liver disease is more severe in HIV‐infected patients than in non‐HIV‐infected patients, but the standard therapies used to treat chronic hepatitis C in HCV/HIV coinfected patients are the same as those for patients infected with HCV alone. HIV protease inhibitors might have potential to down‐regulate HCV load of HCV/HIV coinfected patients. In this study, we evaluated the effects of nelfinavir on intracellular HCV replication using the HCV replicon system. We constructed an HCV replicon expressing a neomycin‐selectable chimeric firefly luciferase reporter protein. Cytotoxicity and apoptosis induced by nelfinavir were assessed and synergism between nelfinavir and interferon (IFN) was calculated using CalcuSyn analysis. Nelfinavir dose‐dependently repressed HCV replication at low concentrations (IC50, 9.88 μmol/L). Nelfinavir failed to induce cytotoxicity or apoptosis at concentrations that inhibited HCV replication. Clinical concentrations of nelfinavir (5 μmol/L) combined with IFN showed synergistic inhibition of HCV replication in our replicon model. Our results suggest that the direct effects of nelfinavir on the HCV subgenome and its synergism with IFN could improve clinical responses to IFN therapy in HCV/HIV coinfected patients.

Cytomegalovirus-associated gastric ulcer: a diagnostic challenge in a patient of fulminant hepatitis with steroid pulse therapy.

A 69-year-old woman presented with malaise. She had had organising pneumonia with the treatment of prednisolone. A diagnosis of fulminant hepatitis was made and steroid pulse therapy was initiated. Ten days later, a colonic resection with a colostomy was performed because of the perforated diverticulitis of the sigmoid colon. She presented with epigastric pain and melena after surgery. Despite the administration of the proton pump inhibitor, an endoscopy revealed multiple deep, punched-out ulcers of the stomach. Biopsy specimen showed cytomegalovirus (CMV) infection. The melena and CMV antigenemia was improved with ganciclovir; however the patient died from worsening of hepatic failure. We emphasise that CMV-associated gastric ulcers should be considered in the differential diagnosis of gastric ulcers in patients treated with immunosuppressive drugs.

Tuberculous Lymphadenopathy Mimicking Pancreatic Neoplasm

Abdominal tuberculosis (TB) is the sixth most common location of extrapulmonary TB involvement. Because its symptoms and signs are often nonspecific, laboratory and imaging findings mimic other diseases including carcinoma. Therefore, the diagnosis of abdominal TB is challenging. We herein report a case of 74-year-old woman who presented with abdominal pain, anorexia, and weight loss. She had been given a diagnosis of pancreatic head carcinoma. Laboratory data was unremarkable except for elevated erythrocyte sedimentation rate, CA125, and sIL-2R. CT scan revealed multiple enlarged peripancreatic lymph nodes and concentric thickening of the ileocecal wall. Colonoscopy demonstrated deformed ileocecal valve and erosions. Histological examination showed epithelioid granulomas. Laparoscopy revealed numerous white tubercles diffusely covering the parietal peritoneum. Histopathological images of peripancreatic lymph node revealed large multiple caseating granulomas surrounded by Langhans_giant cells and epithelioid cells. Polymerase chain reaction and culture of the specimens were positive for Mycobacterium tuberculosis. Tuberculous lymphadenopathy, colitis, and peritonitis were finally diagnosed. She responded well to the antitubercular treatment.

“Playboy Bunny” Sign of Congestive Heart Failure

In emergency, ultrasound has been widely used as a noninvasive and effective examination to evaluate congestive heart failure. We highlight “Playboy Bunny” sign as a reliable marker and an important clue to the diagnosis of passive hepatic congestion, caused by congestive heart failure.

Acute haemorrhagic rectal ulcer in fulminant hepatitis

A 38-year-old man who had been an inactive hepatitis B virus carrier presented with jaundice (duration 5 days). He was diagnosed as having fulminant hepatitis B and was admitted to the intensive care unit for continuous haemodiafiltration with plasma exchange. By 4 days later, he was in shock with sudden onset, painless, massive exsanguinating haematochezia requiring 1200 ml of red blood cell transfusion. A CT scan …

Erratum for factors associated with visceral fat accumulation in the general population in Okinawa, Japan (World J Gastrointest Pharmacol Ther 2016; 7: 261-267)

[This corrects the article on p. 261 in vol. 7, PMID: 27158542.].

Phylogenetic and phylodynamic analyses of hepatitis C virus subtype 1a in Okinawa, Japan

Okinawa Island, located in Southern Japan, has a higher prevalence rate of hepatitis C virus subtype 1a (HCV‐1a) infection than that in mainland Japan. Okinawa has a history of US military occupation after World War II. To elucidate the transmission history of HCV‐1a in Okinawa, 26 whole‐genome sequences were obtained from 29 patients during 2011‐2016. Phylogenetic trees were reconstructed to identify the origin and characteristics of HCV‐1a in Okinawa with epidemiological information. A phylogenetic tree based on whole‐genome sequencing revealed that all of the samples were located below the US branches. Additionally, we identified one cluster comprised of 17 strains (Okinawa, n = 16; United States, n = 1). The majority of the patients in this cluster were people who inject drugs (PWID), indicating the presence of a people who inject drugs (PWID) cluster. Subsequently, Bayesian analyses were employed to reveal viral population dynamics. Intriguingly, a phylodynamic analysis uncovered a substantial increase in effective population size of HCV‐1a from 1965 to 1980 and a slight increase in mid‐2000, which were associated with an increase in illicit drug use in Okinawa. The estimated divergence time of the PWID cluster was 1967.6 (1964.2‐1971.1). These findings suggest that HCV‐1a was introduced into Okinawa from the United States in the late 1960s, coincident with the Vietnam War. Subsequently, HCV‐1a might have spread among the Japanese population with the spread of injecting drug use. Our study provides an understanding of HCV transmission dynamics in Okinawa, as well as the key role of PWID in HCV transmission.