Real-world efficacy of daclatasvir and asunaprevir with respect to resistance-associated substitutions

AIM To investigate daclatasvir(DCV) and asunaprevir(ASV) efficacy in hepatitis C(HCV) patients, with respect to resistance-associated substitutions(RASs).METHODS A total of 392 HCV-infected patients from multiple centers were included in this study. We evaluated their clinical courses and sustained virologic responses(SVR) according to pretreatment factors(gender, age, history of interferon-based regimens, platelet counts, level of viremia, pretreatment NA5A:L31, and Y93 substitutions). We also analyzed the pretreatment and post-treatment major RASs of NS3:D168, NS5A:L31 and Y93 substitutions using a direct-sequencing method in 17 patients who were unable to achieve SVR at 12 wk after treatment completion(SVR12).RESULTS The overall SVR12 rate was 88.3%. Thirty-one patients discontinued treatment before 24 wk because of adverse events, 23 of whom achieved SVR12. There were no significant differences in SVR12 rates with respect to gender, age, history of interferon-based regimens, and platelet counts. The SVR12 rate in patients with viral loads of ≥ 6.0 log IU/m L was significantly lower than those with viral loads of < 6.0 log IU/m L(P < 0.001). The SVR12 rate in patients with Y93 substitution-positive was significantly lower than those with Y93 substitution-negative(P < 0.001). The L31 substitution-positive group showed a lower SVR12 rate than the L31 substitution-negative group, but the difference was not statistically significant. Seventeen patients who did not achieve SVR12 and had available pretreatment and post-treatment sera had additional RASs in NS3:D168, NS5:L31, and Y93 substitution at treatment failure.CONCLUSION Combination of DCV and ASV is associated with a high SVR rate. Baseline RASs should be thoroughly assessed to avoid additional RASs after treatment failure.

Comparison of peg-interferon, ribavirin plus telaprevir vs simeprevir by propensity score matching

AIM: To compare efficacy of telaprevir(TVR) and simeprevir(SMV) combined with pegylated interferon(PEG-IFN) and ribavirin(RBV) while treating chronic hepatitis C(CHC). METHODS: In all, 306 CHC patients were included in this study. There were 159 patients in the TVR combination therapy group and 147 patients in the SMV combination therapy group. To evaluate pretreatment factors contributing to sustained virological response at 12 wk(SVR12), univariate and multivariate analyses were performed in TVR and SMV groups. To adjust for patient background between TVR and SMV groups, propensity score matching was performed. Virological response during treatment and SVR12 were evaluated.RESULTS: Overall rates of SVR12 [undetectable serum hepatitis C virus(HCV) RNA levels] were 79.2% and 69.4% in TVR and SMV groups, respectively. Patients in the SMV group were older, had higher serum HCV RNA levels, lower hemoglobin, higher prevalence of unfavorable interleukin-28B(IL28B) genotype(rs8099917), and poorer response to previous PEG-IFN and RBV treatment. Propensity score matching was performed to adjust for backgrounds(n = 104) and demonstrated SVR12 rates of 74.0% and 73.1% in the TVR and SMV groups, respectively. In the TVR group, discontinuation rates were higher because of adverse events; however, breakthrough and nonresponse was more frequent in the in SMV group. Multivariate analysis revealed IL28 B genotype(rs8099917) as the only independent predictive factor of SVR12 in both groups.CONCLUSION: SVR12 rates were almost identical following propensity score matching.

Colovesical fistula caused by glucocorticoid therapy for IgG4-related intrapelvic mass

IgG4-related disease(IgG4-RD) is an immune-mediated fibroinflammatory disorder that can occur in almost all systemic organs and generally responds to corticosteroid treatment. We report a rare case of an IgG4-related intrapelvic mass lesion that responded to steroid therapy but caused a fistula between the sigmoid colon and bladder. A 71-year-old man was followed after treatment for hepatocellular carcinoma. Follow-up computed tomography(CT) incidentally depicted left hydronephrosis with an ill-demarcated intrapelvic mass lesion. This lesion was histologically diagnosed as IgG4-RD by open biopsy, and peroral steroid therapy was initiated. One month after starting steroids, a colovesical fistula was detected by follow-up CT. A colostomy and urethral catheterization were emergently performed. The patient recovered and the mass lesion was drastically minimized by the initiation of glucocorticoids; however, he still needs urethral catheterization. IgG4-RD develops in various systemic organs and generally responds well to steroids. Clinicians must be watchful for the complications of responses to corticosteroids, such as fistulization, when the mass lesion of IgG4-RD is adjacent to multiple luminal organs.

A Review of Non-operative Treatments for Hepatocellular Carcinoma with Advanced Portal Vein Tumor Thrombus

Portal vein tumor thrombus (PVTT) frequently occurs with the progression of hepatocellular carcinoma (HCC) and is an important factor in determining the prognosis of HCC.In many cases of HCC with advanced PVTT,treatment is difficult because the tumor has considerable extension into the liver,and portal hypertension is a frequent complication.The standard therapy for unresectable HCC with advanced PVTT is sorafenib therapy in patients with good hepatic function.However,the outcomes of sorafenib therapy are not completely satisfactory,making the development of another therapy an urgent task.Therefore,this review aims to summarize non-operative treatments for HCC with advanced PVTT and discuss future perspectives based on those therapies,including therapies still being developed.

Epidemiology of hepatocellular carcinoma in nonalcoholic fatty liver disease

Along with the changes in our food culture and lifestyle,conditions such as obesity,diabetes mellitus,and metabolicsyndrome have been on the rise,and the incidence of nonalcoholic fatty liver disease(NAFLD),which is closelyrelated to these diseases,has also increased rapidly.Despite being a risk factor for the development of hepatocellularcarcinoma(HCC),NAFLD has no established screening method,and HCC originating from NAFLD often tends to be discovered in its advanced and symptomatic stages,which has become an important clinical problem.Even though the carcinogenicity rate among the entire population of NAFLD patients is not high compared to that of patients with viral hepatitis,since HCC also often develops from non-cirrhotic livers,it is difficult to narrow down the cases that need to be under surveillance.Going forward,it will be important to clarify the clinical characteristics and genetic background of NAFLD-related HCC and establish not only a useful surveillance method but also preventive methods.