Usefulness of combination therapy with Daclatasvir plus Asunaprevir in chronic hepatitis C patients with chronic kidney disease.

AIM: Combination therapy with Daclatasvir (DCV) plus Asunaprevir (ASV) has been proven effective in patients with chronic hepatitis C virus (HCV) infection. However, little is known as to the effect of this therapy in patients with reduced renal function. Focusing on CKD patients whose renal function has declined, the present trial addresses the efficacy and safety of this combination therapy in CKD patients with reduced estimated glomerular filtration rate (eGFR). MATERIALS AND METHODS: The study design is a single-center, retrospective longitudinal observational study enrolling 106 patients with (n = 29) or without (n = 77) CKD. After the treatment with combined DCV with ASV for chronic HCV genotype 1b, patients were followed for a total of 48 weeks and the comparison was made in clinical parameters between the two groups. RESULTS: (1) The majority of patients in both groups achieved sustained virological response at 24 weeks (90.8 % in the non-CKD group, and 93.1 % in the CKD). (2)The reduction rate in HCV-RNA levels 2 weeks after commencing the treatment was faster in the CKD group than that in the non-CKD group (81.8 vs. 79.2 %, p < 0.01). (3) Three patients in the CKD group and 6 patients in the non-CKD group withdrew from the treatment because of the adverse events. CONCLUSION: Combination therapy with DCV plus ASV for chronic HCV genotype 1b infection is useful and tolerable, not only in patients with normal eGFR, but also in those with CKD with declined eGFR. Viral eradication at an early phase of the treatment appears to be faster in CKD patients.

Effectiveness of a fixed combination formula of ombitasvir/paritaprevir/ritonavir for hepatitis C virus infection in patients on maintenance haemodialysis.

A fixed-dose formula that combines Ombitasvir (OBV), Paritaprevir (PTV) and Ritonavir (RTV) has been launched into the field of anti-HCV therapy in Japan for patients infected with HCV genotypes 1 and 2 in 2015. However, little is yet known as to the efficacy and safety of this novel therapy in patients on maintenance haemodialysis (HD). The present report describes a preliminary experience in 10 patients (five males and five females) who underwent maintenance HD. All of them had HCV genotype 1b, without having the resistance-associated variants at Y93 or L31 in the nonstructural proteins 5A (NS5A) region. After the treatment, eight patients successfully achieved virus eradication and sustained a virological response at 12 weeks (SVR12). In addition, mac-2 binding protein glycosylation isomer (M2BPGi), a biomarker for liver fibrosis, was reduced after the therapy. Two patients withdrew from the therapy due to the development of erythema multiforme and a strong drowsiness, respectively. These results suggest that triple therapy combining OBV, PTV and RTV is effective in achieving SVR12 in most of the HCV-infected patients on HD. In addition, this combination therapy contributed to retard the progression of liver fibrosis. However, we suggest that further trial will be required to establish its clinical efficacy and safety.

Randomized study comparing vitamin D3 and 1α-Hydroxyvitamin D3 in combination with pegylated interferon/ribavirin therapy for chronic hepatitis C.

BACKGROUND AND AIM: An intention-to-treat prospective randomized study was carried out to compare the potentiation of antiviral efficacies between cholecalciferol, non-activated vitamin D3 supplement, and alfacalcidol, activated 1α-Hydroxyvitamin D3 [1α (OH)-vitamin D3]. METHODS: Chronic hepatitis patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV-RNA levels greater than 5 Log IU/mL received oral administration of cholecalciferol (2000 IU/day) or alfacalcidol (0.5 µg/day) for 4 weeks, and then they were given pegylated interferon (Peg-IFN)-α2a plus ribavirin therapy in combination with either vitamin D3 for 48 or 72 weeks according to the response-guided manner. RESULTS: A total of 36 patients were evaluated. Serum 25-hydroxyvitamin D3 [25(OH)-D3] levels were increased only in patients in the cholecalciferol group during the lead-in vitamin D administration, and the levels at 4 weeks were higher in these patients than in those in the alfacalcidol group (P < 0.001), while serum 1α,25-dihydroxyvitamin D3 [1α,25(OH)2 -D3] levels were not different between both groups. Rapid virological response was obtained in six (33%) patients in the cholecalciferol group; the ratio was higher than that in the alfacalcidol group (one patient; 6%, P < 0.05). Serum HCV-RNA level decline at 4 weeks of combined Peg-IFN-α2a plus ribavirin therapy compared with the baseline levels were greater in the cholecalciferol group (4.6 Log IU/mL) than in the alfacalcidol group (3.5 Log IU/mL) (P < 0.05), when four patients showing null response to the therapy was excluded. However, both complete early virological response and sustained viral response rates were not different between both groups. CONCLUSION: Cholecalciferol produced superior potentiation of the antiviral activity than alfacalcidol only during the initial periods of combined Peg-IFN-α2a plus ribavirin therapy through upregulation of serum 25(OH)-D3 levels.

[A case of autoimmune pancreatitis associated with ulcerative colitis].

A 31-year-old man was admitted to our hospital because of upper abdominal pain. He had been diagnosed with ulcerative colitis (UC) at age 28, but the disease has been in remission since then. On admission, he had slight fever, abdominal pain, and bloody stools six times a day, and the serum levels of pancreatic enzyme and IgG4 were elevated. Diffuse enlargement of the pancreas was detected by abdominal computed tomography; furthermore, narrowing of the main pancreatic duct was revealed using endoscopic retrograde cholangiopancreatography. Based on these findings, he was given a diagnosis of autoimmune pancreatitis (AIP) associated with UC. Both diseases improved without using steroids. After discharge, he has not had any recurrence of AIP or UC despite not being on steroid treatment, although the serum IgG4 level has shown a slight tendency to elevate.

A multicenter study to clarify the optimal HCV-RNA negative period during combined therapy with pegylated interferon plus ribavirin in patients with chronic hepatitis caused by HCV genotype 2.

OBJECTIVE: A multicenter open trial was performed to clarify the optimal duration of combined pegylated interferon (Peg-IFN) plus ribavirin therapy in patients with chronic hepatitis caused by HCV genotype 2. METHODS: A total of 100 patients seen between 2005 and 2007 received the combination therapy for 4 to 52 weeks. The cutoff value of the HCV-RNA-negative (titers under 1.7 Log IU/mL) period during the therapy to predict sustained virological response (SVR) was determined by ROC curve and multivariate logistic regression analyses. The result was validated in 48 patients between 2008 and 2009. RESULTS: SVR was achieved in 78 patients. Serum HCV-RNA titers decreased to less than 1.7 Log IU/mL at 4 weeks of the therapy in 60 patients. The SVR rate in these patients was 85%, which was significantly higher than that of remaining 40 patients with a SVR rate of 68%. An HCV-RNA-negative period of ≥17 weeks was selected as the cutoff value, which showed a significant odds ratio of 4.77 for SVR. Among the 35 patients who showed a decrease of the serum HCV-RNA of less than 1.7 Log IU/mL between 8 and 16 weeks of therapy, the SVR rate was significantly higher in 16 patients with a serum HCV-RNA-negative period of ≥17 weeks (94%) than in 19 patients in whom the period was less than 17 weeks (63%). Similar results were obtained in the subsequent validation study. CONCLUSION: Prolonged combined Peg-IFN plus ribavirin therapy, with an HCV-RNA-negative period of ≥17 weeks, yielded good therapeutic outcomes in patients with chronic HCV genotype 2 hepatitis.