Kayoko Sugawara

Acute liver failure in Japan: definition, classification, and prediction of the outcome

Acute liver failure is a clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to severe impairment of liver function caused by massive or submassive liver necrosis. Viral hepatitis is the most important and frequent cause of acute liver failure in Japan. The diagnostic criteria for fulminant hepatitis, including that caused by viral infections, autoimmune hepatitis, and drug allergy induced-liver damage, were first established in 1981. Considering the discrepancies between the definition of fulminant hepatitis in Japan and the definitions of acute liver failure in the United States and Europe, the Intractable Hepato-Biliary Disease Study Group established the diagnostic criteria for “acute liver failure” for Japan in 2011, and performed a nationwide survey of patients seen in 2010 to clarify the demographic and clinical features and outcomes of these patients. According to the survey, the survival rates of patients receiving medical treatment alone were low, especially in those with hepatic encephalopathy, despite artificial liver support, consisting of plasma exchange and hemodiafiltration, being provided to almost all patients in Japan. Thus, liver transplantation is inevitable to rescue most patients with hepatic encephalopathy. The indications for liver transplantation had, until recently, been determined according to the guideline published by the Acute Liver Failure Study Group in 1996. Recently, however, the Intractable Hepato-Biliary Disease Study Group established a scoring system to predict the outcomes of acute liver failure patients. Algorithms for outcome prediction have also been developed based on data-mining analyses. These novel guidelines need further evaluation to determine their usefulness.

Development of rare resistance-associated variants that are extremely tolerant against NS5A inhibitors during daclatasvir/asunaprevir therapy by a two-hit mechanism

The virologic characteristics of resistance‐associated variants (RAVs) developing in patients receiving dual oral therapy with daclatasvir/asunaprevir, including those with previous triple therapy with simeprevir, were evaluated.

Therapeutic strategy for patients with bleeding rectal varices complicating liver cirrhosis

Although rupture of rectal varices is rarely encountered, it may provoke massive and fatal hemorrhage in patients with liver cirrhosis. We examined the clinical features of patients showing bleeding from rectal varices to establish a suitable therapeutic strategy for the lesions.

Long‐Term Outcome of 154 Patients Receiving Balloon‐Occluded Retrograde Transvenous Obliteration for Gastric Fundal Varices

This study aims to clarify the long‐term outcome of therapeutic strategies including balloon‐occluded retrograde transvenous obliteration (B‐RTO) for patients with gastric fundal varices.

Balloon-occluded retrograde transvenous obliteration using a microballoon catheter for intractable gastric fundal varices.

Balloon‐occluded retrograde transvenous obliteration (B‐RTO) is recognized as the standard therapy for patients with gastric fundal varices in Japan; however, the procedure is difficult when drainage veins other than the gastrorenal shunt developed. The efficacy and safety of B‐RTO using a microballoon catheter for such patients were evaluated.

A case of liver cirrhosis due to hepatits C virus infection complicating giant anorectal varices treated with balloon-occluded retrograde transvenous obliteration.

A 73-year-old man with liver cirrhosis due to hepatitis C virus infection was admitted to our hospital because of massive bleeding from external varices. Colonoscopic examination revealed that giant anorectal varices had developed between the anus and rectal ampulla, and had ruptured at the perianal site. On three-dimensional computed tomography imaging, the feeding and drainage vessels of the varices were identified as the inferior mesenteric vein and right inferior hemorrhoidal vein, respectively. Endoscopic therapies were not employed for the bleeding varices, because the blood flow volume of the feeding vessel was extremely large. Balloon-occluded retrograde transvenous obliteration (B-RTO) was therefore carried out through the drainage vessels. The variceal blood flow disappeared after B-RTO therapy, and the varices decreased in size with thrombus formation verified by colonoscopy. Bleeding from the external varices also ceased. B-RTO therapy may be an effective approach for giant anorectal varices presenting as a complication in liver cirrhosis patients in whom the main drainage vessels can be determined.

Transcatheter arterial chemoembolization for hepatocellular carcinoma: Comparison of the therapeutic efficacies between miriplatin and epirubicin.

The therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using miriplatin was evaluated in comparison with that using epirubicin in patients with hepatocellular carcinoma (HCC).

“Reversi‐type virologic failure” involved in the development of non‐structural protein 5A resistance‐associated variants (RAVs) in patients with genotype 1b hepatitis C carrying no signature RAVs at baseline

The therapeutic efficacy of daclatasvir/asunaprevir was inferior in patients with non‐structural protein 5A (NS5A)‐R30Q mutant hepatitis C virus strains at baseline, compared with those with wild‐type strains, even though the half maximal effective concentration of NS5A inhibitors was lower in mutant strains than in wild‐type strains. In these patients, R30Q and Y93H mutant strains, which are highly resistant to NS5A inhibitors, emerged at virologic failure. The mechanisms involved in such virologic failure were examined.

“Reversi-Type Virologic Failure” Involved in the Development of NS5A-RAVs in Patients with Genotype 1b HCV Carrying No Signature RAVs at Baseline

The therapeutic efficacy of daclatasvir/asunaprevir was inferior in patients with non‐structural protein 5A (NS5A)‐R30Q mutant hepatitis C virus strains at baseline, compared with those with wild‐type strains, even though the half maximal effective concentration of NS5A inhibitors was lower in mutant strains than in wild‐type strains. In these patients, R30Q and Y93H mutant strains, which are highly resistant to NS5A inhibitors, emerged at virologic failure. The mechanisms involved in such virologic failure were examined.

Multicenter prospective study to optimize the efficacy of triple therapy with telaprevir in patients with genotype 1b hepatitis C virus infection according to an algorithm based on the drug Adherence, IL‐28B Gene Allele and Viral Response Trial (AG & RGT)

To optimize the therapeutic efficacy of NS3/4A protease inhibitors, a multicenter prospective study was performed according to an algorithm based on the Adherence, IL‐28B Gene Allele and Viral Response Trial (AG & RGT).