A 66-year-old, interferon-ineligible, treatment-naive man who was diagnosed with chronic hepatitis C due to hepatitis C virus genotype 1b began combination therapy with daclatasvir and asunaprevir. On day 14 of treatm...A 66-year-old, interferon-ineligible, treatment-naive man who was diagnosed with chronic hepatitis C due to hepatitis C virus genotype 1b began combination therapy with daclatasvir and asunaprevir. On day 14 of treatment, hepatic reserve and renal function deterioration was observed, while his transaminase levels were normal. Both daclatasvir and asunaprevir were discontinued on day 18 of treatment, because the patient complained of dark urine and a rash on his trunk and four limbs. After discontinuing antiviral therapy, the abnormal laboratory finding and clinical manifestations gradually improved, without recurrence. Our case fulfilled the diagnostic criteria of probable drug reaction with eosinophilia and systemic symptom(DRESS) syndrome. Despite the 18-d treatment, sustained virological response 12 was achieved. Based on the clinical course, we concluded that there was a clear cause-and-effect relationship between the treatment and adverse events. To our knowledge, this patient represents the first case of probable DRESS syndrome that includes concomitant deterioration of hepatic reserve and renal function due to combination therapy with daclatasvir and asunaprevir, regardless of normalization of transaminase levels. Our case suggests that we should pay attention not only to the transaminase levels but also to allergic symptoms associated with organ involvement during combination therapy with daclatasvir and asunaprevir.展开更多
BACKGROUND Sodium glucose cotransporter 2(SGLT2)inhibitors are newly developed oral antidiabetic drugs.SGLT2 is primarily expressed in the kidneys and reabsorbs approximately 90%of the glucose filtered by the renal gl...BACKGROUND Sodium glucose cotransporter 2(SGLT2)inhibitors are newly developed oral antidiabetic drugs.SGLT2 is primarily expressed in the kidneys and reabsorbs approximately 90%of the glucose filtered by the renal glomeruli.SGLT2 inhibitors lower glucose levels independently of insulin action by facilitating urinary glucose excretion.The SGLT2 inhibitor ipragliflozin has reportedly improved liver steatosis in animal models and clinical studies.However,the mechanisms by which SGLT2 inhibitors improve liver steatosis are not fully understood.AIM To investigate the ameliorative effects of ipragliflozin on liver steatosis and the mechanisms of these effects in obese mice.METHODS We analyzed 8-wk-old male obese(ob/ob)mice that were randomly divided into a group receiving a normal chow diet and a group receiving a normal chow diet supplemented with ipragliflozin(3 mg/kg or 10 mg/kg)for 4 wk.We also analyzed their lean sex-matched littermates receiving a normal chow diet as another control group. Body weight and liver weight were evaluated, and liverhistology, immunoblotting, and reverse transcription-polymerase chain reactionanalyses were performed.RESULTSHepatic lipid accumulation was significantly ameliorated in ob/ob mice treatedwith 10 mg/kg ipragliflozin compared to untreated ob/ob mice irrespective ofbody weight changes. Ipragliflozin had no appreciable effects on hepatic oxidativestress-related gene expression levels or macrophage infiltration, but significantlyreduced hepatic interleukin-1β (IL-1β) mRNA expression levels. Ipragliflozinincreased both the mRNA and protein expression levels of sirtuin 1 (SIRT1) in theliver. The hepatic mRNA levels of peroxisome proliferator-activated receptor γcoactivator 1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα),and fibroblast growth factor-21 (FGF21) were also significantly higher inipragliflozin-treated ob/ob mice than in untreated ob/ob mice.CONCLUSIONOur study suggests that the liver steatosis-ameliorating effects of ipragliflozin inob/ob mice may be mediated partly by hepatic SIRT1 signaling, possibly throughthe PGC-1α/PPARα-FGF21 pathway.展开更多
文摘A 66-year-old, interferon-ineligible, treatment-naive man who was diagnosed with chronic hepatitis C due to hepatitis C virus genotype 1b began combination therapy with daclatasvir and asunaprevir. On day 14 of treatment, hepatic reserve and renal function deterioration was observed, while his transaminase levels were normal. Both daclatasvir and asunaprevir were discontinued on day 18 of treatment, because the patient complained of dark urine and a rash on his trunk and four limbs. After discontinuing antiviral therapy, the abnormal laboratory finding and clinical manifestations gradually improved, without recurrence. Our case fulfilled the diagnostic criteria of probable drug reaction with eosinophilia and systemic symptom(DRESS) syndrome. Despite the 18-d treatment, sustained virological response 12 was achieved. Based on the clinical course, we concluded that there was a clear cause-and-effect relationship between the treatment and adverse events. To our knowledge, this patient represents the first case of probable DRESS syndrome that includes concomitant deterioration of hepatic reserve and renal function due to combination therapy with daclatasvir and asunaprevir, regardless of normalization of transaminase levels. Our case suggests that we should pay attention not only to the transaminase levels but also to allergic symptoms associated with organ involvement during combination therapy with daclatasvir and asunaprevir.
文摘BACKGROUND Sodium glucose cotransporter 2(SGLT2)inhibitors are newly developed oral antidiabetic drugs.SGLT2 is primarily expressed in the kidneys and reabsorbs approximately 90%of the glucose filtered by the renal glomeruli.SGLT2 inhibitors lower glucose levels independently of insulin action by facilitating urinary glucose excretion.The SGLT2 inhibitor ipragliflozin has reportedly improved liver steatosis in animal models and clinical studies.However,the mechanisms by which SGLT2 inhibitors improve liver steatosis are not fully understood.AIM To investigate the ameliorative effects of ipragliflozin on liver steatosis and the mechanisms of these effects in obese mice.METHODS We analyzed 8-wk-old male obese(ob/ob)mice that were randomly divided into a group receiving a normal chow diet and a group receiving a normal chow diet supplemented with ipragliflozin(3 mg/kg or 10 mg/kg)for 4 wk.We also analyzed their lean sex-matched littermates receiving a normal chow diet as another control group. Body weight and liver weight were evaluated, and liverhistology, immunoblotting, and reverse transcription-polymerase chain reactionanalyses were performed.RESULTSHepatic lipid accumulation was significantly ameliorated in ob/ob mice treatedwith 10 mg/kg ipragliflozin compared to untreated ob/ob mice irrespective ofbody weight changes. Ipragliflozin had no appreciable effects on hepatic oxidativestress-related gene expression levels or macrophage infiltration, but significantlyreduced hepatic interleukin-1β (IL-1β) mRNA expression levels. Ipragliflozinincreased both the mRNA and protein expression levels of sirtuin 1 (SIRT1) in theliver. The hepatic mRNA levels of peroxisome proliferator-activated receptor γcoactivator 1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα),and fibroblast growth factor-21 (FGF21) were also significantly higher inipragliflozin-treated ob/ob mice than in untreated ob/ob mice.CONCLUSIONOur study suggests that the liver steatosis-ameliorating effects of ipragliflozin inob/ob mice may be mediated partly by hepatic SIRT1 signaling, possibly throughthe PGC-1α/PPARα-FGF21 pathway.
