Chae HB, et al. Korean J Hepatol. 2009 Dec;15(Suppl 6):S13-S24. http://dx.doi.org/10.3350/kjhep.2009.15.S6.S13

Choi SY, et al. J Korean Med Sci. 2013 Sep;28(9):1293-1301. https://doi.org/10.3346/jkms.2013.28.9.1293

Currently, two direct‐acting antivirals (DAAs) show well‐established efficacy against hepatitis C virus (HCV), namely, first‐wave protease inhibitors telaprevir and boceprevir. Most clinical trials have examined DAAs in combination with standard of care (SOC) regimens. Future therapeutic drugs were divided into three categories. They are second‐wave protease inhibitors, second‐generation protease inhibitors, and polymerase inhibitors. Second‐wave protease inhibitors are more improved form and can be administered once a day. Oral drug combinations can be favored because interferon (IFN) not only has to be given as intradermal injection, but also can cause several serious side effects. Combination of drugs with different mechanisms shows a good sustained virological response (SVR). But several mutations are associated with viral resistance to DAAs. Therefore, genotypic resistance data may provide insights into strategies aimed at maximizing SVR rates and minimizing resistance. Combined drug regimens are necessary to prevent the emergence of drug‐resistant HCV. Many promising DAA candidates have been identified. Of these, a triple regimen containing sofosbuvir shows promise, and treatment with daclatasvir plus asunaprevir yields a high SVR rate (95%). Oral drug combinations will be standard of care in the near future.

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9–15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

To identify the factors associated with virologic breakthrough and to select a subgroup of patients who respond well to lamivudine without developing virologic breakthrough (VBT). Of 79 patients who had received lamivudine therapy for 9-57 mo, 34 were HBeAg-positive and 45 were HBeAg-negative, 24 developed virologic breakthrough and 55 did not. Clinical and virologic factors were compared between the two groups. The median duration of therapy was 25 (9-57) mo. Virologic breakthrough was defined as a > 1 log HBV DNA increase following initial suppression. When several factors, including gender, duration of infection, baseline HBV DNA, and baseline ALT in HBeAg-positive chronic hepatitis patients were analyzed by logistic regression, the most important predictor of virologic breakthrough was the baseline HBV DNA (r2 = 0.12, P < 0.05). When HBeAg-positive chronic hepatitis patients were divided into two groups by a point of 6.6 log HBV DNA, the incidence of virologic breakthough between two groups was significantly different. Lamivudine may remain an effective first line therapy for those HBeAg-positive patients with a baseline HBV DNA < 6.6 log10 copies/mL.