Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions: Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Cystic Primary Hepatic Neuroendocrine Tumor.

Neuroendocrine tumors (NETs) can arise throughout the body. Most NETs in the liver are metastatic tumors; primary hepatic NET (PHNET) is extremely rare. A diagnosis of PHNET is very difficult. No single modality can diagnose PHNET by itself, and it often resembles other hypervascular masses of the liver. This paper reports the case of a 51-year old female with a large hepatic mass. Unlike most of PHNETs reported previously, it was composed of a solid mass with mainly multiple cystic lesions, which led to an erroneous diagnosis of hepatic mucinous cystadenoma or cystadenocarcinoma. PHNET with cystic lesions is extremely rare, and the features are not well studied. This case may help physicians suspect PHNET in a differential diagnosis of an atypical hepatic mass.

The clinical impact of gut microbiota in chronic kidney disease.

Gut microorganisms play critical roles in both maintaining host homeostasis and the development of diverse diseases. Gut dysbiosis, an alteration of the composition and function of gut microorganisms, is commonly seen in patients with chronic kidney disease (CKD). CKD itself contributes to a disruption of the symbiotic relationship between the gut microbiota and the host, while the resulting gut dysbiosis may play a part in stage progression of CKD. This bidirectional relationship supports the concept that the gut microbiota is considered a novel focus for the pathogenesis and management of CKD. This article examines the interaction between the gut microbiota and the kidney, the mutual effects of dysbiosis and CKD, and possible treatment options to restore gut eubiosis, and reduce CKD progression and its related complications.

Perception and attitudes of medical students on clinical clerkship in the era of the Coronavirus Disease 2019 pandemic.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) has been placing severe strain on global healthcare systems and medical education programs, leading to growing demands for medical students to assume the role of preliminary healthcare providers. OBJECTIVES: To assess the perception and attitudes of medical students about clinical clerkship training during the COVID-19 pandemic. DESIGN: A cross-sectional survey with web-based 3-fields/14-items questionnaire was conducted, from April 7 to 14, 2020, to evaluate their self-assessed perception and attitudes on clerkship training of hospital practice under the COVID-19 outbreak and spread among 161 (78 on pre-clerkship course, 83 on clinical clerkship course) medical students at Dankook University College of Medicine, Cheonan, Republic of Korea. RESULTS: Of the 151 medical students who completed the survey, 81 students (53.7%) considered themselves familiar with COVID-19. Although the students were concerned about the spread of the virus during clinical clerkship training, 118 (78.1%) students preferred the clerkship training in a hospital practice. The students in the clinical clerkship program preferred this over those in the pre-clerkship program (85.7% vs. 70.2%, P = 0.03), primarily because a clinical clerkship could not be replaced by an online class during the COVID-19 pandemic. In addition, their responses indicated, in order of significance, fear of not completing the clerkship course on time, willingness to participate as a preliminary healthcare provider in pandemic, the potential waste of tuition, and belief that a hospital is rather safe. The change in the academic calendar had not a positive impact on the lifestyles of many students. CONCLUSIONS: In circumstances such as the COVID-19 pandemic, educational strategies to clinical clerkship training for medical students should be developed to provide them with the opportunity to be actively involved in hospital practice under strict safety guidance focused on preventing virus infection and transmission.

Clinical Patterns and Outcome of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) may develop into liver cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to compare the clinical patterns and survival outcomes of NAFLD-related HCC patients and those of alcoholic liver disease (ALD)-related or hepatitis B virus (HBV)-related HCC patients. Methods: A total of 622 HCC patients with associated NAFLD (n = 56), ALD (n = 173), or HBV infection (n = 393) were enrolled. The clinical characteristics and survival were analyzed according to the underlying liver diseases. Results: NAFLD-related HCC patients were more commonly older women and had more metabolic risk factors but were less likely to have cirrhosis and ascites, compared to ALD-related or HBV-related HCC patients. NAFLD-related HCC more often had an infiltrative pattern (P=0.047), a larger tumor (P=0.001), more macrovascular invasion (P=0.022), and exceeded the Milan criteria (P=0.001), but was less frequently diagnosed during tumor surveillance (P=0.025). Survival analysis did not show any difference among NAFLD-related, ALD-related, and HBV-related HCC patients. Furthermore, propensity score matching analysis did not reveal a significant difference in the median survival between the different groups (NAFLD vs. ALD, 14.0 months [95% confidence interval (CI), 2.0-26.0] vs. 13.0 months [95% CI, 0-26.3]; P=0.667, NAFLD vs. HBV, 14.0 months [95% CI, 2.0-26.0] vs. 12.0 months [95% CI, 4.3-17.8]; P=0.573). Conclusions: NAFLD-related HCCs were more often detected at an advanced stage with infiltrative patterns, although they showed no significant difference in survival compared to ALD-related or HBV-related HCCs. A future prospective research should be focused on identifying NAFLD patients who require strict surveillance in order to early detect and timely treat HCC.

Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study.

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m2 (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m2 along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m2. CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m2 and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.

Hepatitis C virus infection in chronic kidney disease: paradigm shift in management.

Hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is associated with increased liver-related morbidity and mortality rates, accelerated progression to end-stage renal disease, and risk of cardiovascular events. CKD patients with HCV infection require antiviral therapy. Pegylated interferon (peg-IFN) plus ribavirin was the standard of care for HCV-infected CKD patients before the introduction of first-generation direct-acting antiviral (DAA) oral anti-HCV agents. Peg-IFN-based treatment has a low virologic response rate and poor compliance, resulting in a high dropout rate. Recently, several clinical trials of all-DAA combination regimens have reported excellent antiviral efficacy and few adverse drug reactions in HCV-infected patients with CKD. These positive results have revolutionized the treatment of chronic HCV infection in this population. In this review, we address the impact of chronic HCV infection in CKD patients, and discuss their management using next-generation DAAs.

Efficacy and safety of sofosbuvir plus ribavirin for Korean patients with hepatitis C virus genotype 2 infection: A retrospective multi-institutional study.

BACKGROUND/AIMS: Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. METHODS: We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. RESULTS: A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27-96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. CONCLUSION: A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection.

Development of tenofovir disoproxil fumarate resistance after complete viral suppression in a patient with treatment-naïve chronic hepatitis B: A case report and review of the literature.

Tenofovir disoproxil fumarate (TDF) is a potent nucleotide analogue that is recommended as first-line therapy for patients with chronic hepatitis B. The results of a longitudinal study of TDF treatment demonstrated no development of resistance. We observed one treatment-naïve chronic hepatitis B (CHB) patient who developed TDF resistance after complete viral suppression during long-term TDF treatment. A 37-year-old HBeAg-positive man received TDF 300 mg/d for 43 mo. The hepatitis B virus (HBV) DNA titer was 8 log10 copies/mL at baseline and became undetectable at 16 mo after treatment. However, the HBV DNA titer rebounded to 7.5 log10 copies/mL at 43 mo after treatment. We performed full sequencing to find mutation sites associated with virologic breakthrough. The results showed 9 mutation sites, most of which had not been well-known as mutation sites. We changed the therapy from tenofovir to entecavir with a regimen of 0.5 mg once daily. After 4 mo, the HBV DNA titer decreased to 267 copies/mL, and the liver enzyme levels were normalized.

The Performance of Serum Biomarkers for Predicting Fibrosis in Patients with Chronic Viral Hepatitis.

BACKGROUND/AIMS: The invasiveness of a liver biopsy and its inconsistent results have prompted efforts to develop noninvasive tools to evaluate the severity of chronic hepatitis. This study was intended to assess the performance of serum biomarkers for predicting liver fibrosis in patients with chronic viral hepatitis. METHODS: A total of 302 patients with chronic hepatitis B or C, who had undergone liver biopsy, were retrospectively enrolled. We investigated the diagnostic accuracy of several clinical factors for predicting advanced fibrosis (F≥3). RESULTS: The study population included 227 patients with chronic hepatitis B, 73 patients with chronic hepatitis C, and 2 patients with co-infection (hepatitis B and C). Histological cirrhosis was identified in 16.2% of the study population. The grade of porto-periportal activity was more correlated with the stage of chronic hepatitis compared with that of lobular activity (r=0.640 vs. r=0.171). Fibrosis stage was correlated with platelet count (r=-0.520), aspartate aminotransferase to platelet ratio index (APRI) (r=0.390), prothrombin time (r=0.376), and albumin (r=-0.357). For the diagnosis of advanced fibrosis, platelet count and APRI were the most predictive variables (AUROC=0.752, and 0.713, respectively). CONCLUSIONS: In a hepatitis B endemic region, platelet count and APRI could be considered as reliable non-invasive markers for predicting fibrosis of chronic viral hepatitis. However, it is necessary to validate the diagnostic accuracy of these markers in another population.

Safety and efficacy of tenofovir in chronic hepatitis B-related decompensated cirrhosis.

AIM: To evaluate the safety and efficacy of tenofovir disoproxil fumarate (TDF) as a first-line therapy in decompensated liver disease. METHODS: We enrolled 174 chronic hepatitis B-related liver cirrhosis patients treated with 300 mg/d TDF at six Korean centers. Of the 174 cirrhosis patients, 57 were assigned to the decompensated cirrhosis group and 117 were assigned to the compensated cirrhosis group. We followed the patients for 12 mo and evaluated clinical outcomes, including biochemical, virological, and serological responses. We also evaluated changes in hepatic and renal function and compared the decompensated and compensated cirrhosis groups. RESULTS: The 1-year complete virological response (CVR) and Hepatitis B e antigen (HBeAg) seroconversion were seen in 70.2% and 14.2% in the decompensated cirrhosis group, respectively. The rates of HBeAg seroconversion/loss and ALT normalization at month 12 were similar in both groups. TDF treatment was also effective for decreasing the level of hepatitis B virus (HBV) DNA in both groups, but CVR was higher in the compensated group (88.9% vs 70.2%, P = 0.005). Tenofovir treatment for 12 mo resulted in improved Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores in decompensated group (P < 0.001). Of the 57 decompensated patients, 39 (68.4%) achieved CTP class A and 27 (49.1%) showed improvement in the CTP score of 2 points after 12 mo of TDF. The observed rate of confirmed 0.5 mg/dL increases in serum levels of creatinine in the decompensated and compensated cirrhosis group were 7.0% and 2.5%, respectively (P < 1.000). CONCLUSION: TDF therapy in decompensated cirrhosis patients was effective for decreasing HBV DNA levels and improving hepatic function with relatively lower CVR than in compensated cirrhosis. Thus, physicians should carefully monitor not only renal function but also treatment responses when using TDF in decompensated cirrhosis patients.

Impact of antiviral therapy on hepatocellular carcinoma and mortality in patients with chronic hepatitis C: systematic review and meta-analysis.

BACKGROUND: The long-term clinical outcomes of antiviral therapy for patients with chronic hepatitis C are uncertain in terms of hepatitis C virus (HCV)-related morbidity and mortality according to the response to antiviral therapy. This study aimed to assess the impact of antiviral treatment on the development of HCC and mortality in patients with chronic HCV infection. METHODS: A systematic review was conducted for studies that evaluated the antiviral efficacy for patients with chronic hepatitis C or assessed the development of HCC or mortality between SVR (sustained virologic response) and non-SVR patients. The methodological quality of the enrolled publications was evaluated using Risk of Bias table or Newcastle-Ottawa scale. Random-effect model meta-analyses and meta-regression were performed. Publication bias was assessed. RESULTS: In total, 59 studies (4 RCTs, 15 prospective and 40 retrospective cohort studies) were included. Antiviral treatment was associated with reduced development of HCC (vs. no treatment; OR 0.392, 95% CI 0.275-0.557), and this effect was intensified when SVR was achieved (vs. no SVR, OR: 0.203, 95% CI 0.164-0.251). Antiviral treatment was associated with lower all-cause mortality (vs. no treatment; OR 0.380, 95% CI 0.295-0.489) and liver-specific mortality (OR 0.363, 95% CI 0.260-0.508). This rate was also intensified when SVR was achieved [all-cause mortality (vs. no SVR, OR 0.255, 95% CI 0.199-0.326), liver-specific mortality (OR 0.126, 95% CI 0.094-0.169)]. Sensitivity analyses revealed robust results, and a small study effect was minimal. CONCLUSIONS: In patients with chronic hepatitis C, antiviral therapy can reduce the development of HCC and mortality, especially when SVR is achieved.

Efficacy and safety of daclatasvir plus asunaprevir for Korean patients with HCV genotype Ib infection: a retrospective multi-institutional study.

BACKGROUND/AIMS: The combination of daclatasvir (DCV) and asunaprevir (ASV) has demonstrated a high sustained virologic response at 12 weeks (SVR12) and a low rate of adverse events in previous clinical studies. The purpose of this study was to clarify the results of treatment and side effects in Korean patients with chronic hepatitis C virus (HCV) genotype Ib infection. METHODS: We retrospectively analyzed clinical data from chronic HCV genotype Ib patients treated with DCV+ASV from August 2015 to September 2016 at five hospitals in the Daejeon-Chungcheong area. RESULTS: A total of 152 patients were examined for resistance associated variants (RAVs). Among them, 15 (9.9%) were positive for Y93 and one (0.7%) was positive for L31. Of 126 patients treated with DCV+ASV, 83 patients completed treatment and 76 patients were included in safety and efficacy analysis. Five (6.6%) were positive for Y93 and 12 (15.8%) exhibited cirrhotic change. DCV+ASV was the first-line treatment for 58 (76.3%) patients. Eleven (14.5%) patients relapsed after previous treatment that included interferon and seven (9.2%) of these patients were found to be intolerant of interferon. Adverse events occurred in 10 (13.2%) patients and two patients stopped the medication because of severe itching and skin rash. SVR12 was 89.5% (68/76) in all patients and 91.5% (65/71) in RAV-negative patients. CONCLUSIONS: DCV+ASV showed good efficacy in patients with HCV Ib infection in Korea. Close monitoring is needed for severe adverse events and treatment failure, which were uncommon.

Vigorous Periprocedural Hydration With Lactated Ringer's Solution Reduces the Risk of Pancreatitis After Retrograde Cholangiopancreatography in Hospitalized Patients.

BACKGROUND & AIMS: Vigorous intravenous fluid resuscitation (IVFR) was reported to reduce post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in a pilot study. We performed a randomized, double-blind controlled trial to establish whether periprocedural vigorous IVFR reduces the risk of post-ERCP pancreatitis. METHODS: A total of 510 patients with native papilla at 3 tertiary referral centers in Korea were randomly assigned (1:1) to groups given vigorous IVFR (lactated Ringer's solution in an initial bolus of 10 mL/kg before the procedure, 3 mL/kg/h during the procedure, for 8 hours after the procedure, and a post-procedure bolus of 10 mL/kg) or a standard IVFR (lactated Ringer's solution at 1.5 mL/kg/h during and for 8 hours after the procedure). The primary end point of the study was the development of post-ERCP pancreatitis, and the secondary end point was severity of pancreatitis, hyperamylasemia, and fluid overload. RESULTS: The main indications for ERCP were choledocholithiasis (58%) and malignant biliary stricture (27%). Post-ERCP pancreatitis developed in 11 patients in the vigorous IVFR group (4.3%) and 25 patients in the standard IVFR group (9.8%) (relative risk, 0.41; 95% CI, 0.20-0.86; P = .016). Moderate or severe acute pancreatitis occurred in a significantly smaller proportion of patients in the vigorous IVFR group (0.4%) than in the standard IVFR group (2.0%; P = .040). One patient in the vigorous IVFR group developed peripheral edema. CONCLUSIONS: In a double-blind, randomized controlled trial, we found vigorous periprocedural intravenous hydration with lactated Ringer's solution to reduce the incidence and severity of post-ERCP pancreatitis in average-risk and high-risk cases. IVFR is not associated with increased adverse events. ClinicalTrials.gov number: NCT02308891.

Collision tumor of hepatocellular carcinoma and neuroendocrine carcinoma involving the liver: Case report and review of the literature.

Primary hepatic neuroendocrine carcinoma (NEC) with concurrent occurrence of hepatocellular carcinoma (HCC) of the liver is very rare. Only 8 cases have been reported in the literature. Concurrent occurrence of HCC and NEC in the liver is classified as combined type or collision type by histological distributional patterns; only 2 cases have been reported. Herein, we report a case of collision type concurrent occurrence of HCC and NEC, in which primary hepatic NEC was in only a small portion of the nodule, which is different from the 2 previously reported cases. A 72-year-old male with chronic hepatitis C was admitted to our hospital for a hepatic mass detected by liver computed tomography (CT) at another clinic. Because the nodule was in hepatic segment 3 and had proper radiologic findings for diagnosis of HCC, including enhancement in the arterial phase and wash-out in the portal and delay phases, the patient was treated with laparoscopic left lateral sectionectomy. The pathology demonstrated that the nodule was 2.5 cm and was moderately differentiated HCC. However, a 3 mm-sized focal neuroendocrine carcinoma was also detected on the capsule of the nodule. The tumor was concluded to be a collision type with HCC and primary hepatic NEC. After the surgery, for follow-up, the patient underwent a liver CT every 3 mo. Five multiple nodules were found in the right hepatic lobe on the follow-up liver CT 6 mo post-operatively. As the features of the nodules in the liver CT and MRI were different from that of HCC, a liver biopsy was performed. Intrahepatic recurrent NEC was proven after the liver biopsy, which showed the same pathologic features with the specimen obtained 6 mo ago. Palliative chemotherapy with a combination of etoposide and cisplatin has been administered for 4 months, showing partial response.

[Acute Kidney Injury in Cirrhotic Patients with Portal Hypertension].

Acute kidney injury (AKI) is one of the most common manifestations encountered in clinical practice. It is associated with high morbidity and mortality in cirrhotic pre- and post-transplantation patients. Hepatorenal syndrome (HRS), a special form of AKI in cirrhotic patients, was recognized as a consequence of renal vasoconstriction from systemic/renal hemodynamic alterations developed in advanced cirrhosis with portal hypertension. Recently, multiple factors-such as infection/inflammation, underlying glomerulonephritis, bile cast, or increased abdominal pressure-have been considered to contribute to renal dysfunction in cirrhotic patients, which were presumed to induce HRS. Moreover, in addition to changing the definition of AKI in the nephrologic guidelines, the new AKI definition for early diagnosis and intervention based on characteristics of liver cirrhosis has been proposed in an international meeting. This article provides a comprehensive and recent review of AKI definition, laying out the topics in accordance with the pathophysiologic mechanisms and therapeutic interventions of AKI in cirrhotic patients with portal hypertension.

Clinical Impact of Viral Load on the Development of Hepatocellular Carcinoma and Liver-Related Mortality in Patients with Hepatitis C Virus Infection.

Aim. This study aimed to assess clinical impact of hepatitis C viral load on the development of hepatocellular carcinoma (HCC) and liver-related mortality in HCV-infected patients. Methods. A total of 111 subjects with chronic HCV infection who were available for serum quantitation of HCV RNA were recruited in this retrospective cohort. Cox-proportional hazards models were used to calculate hazard ratio (HR) of developing HCC and liver-related mortality according to serum HCV RNA titers. Results. HCC was developed in 14 patients during follow-up period. The cumulative risk of HCC development was higher in subjects with high HCV RNA titer (log HCV RNA IU/mL > 6) than subjects with low titer (log HCV RNA IU/mL ≦ 6) (HR = 4.63, P = 0.032), giving an incidence rate of 474.1 and 111.5 per 10,000 person-years, respectively. Old age (HR = 9.71, P = 0.014), accompanying cirrhosis (HR = 19.34, P = 0.004), and low platelet count (HR = 13.97, P = 0.009) were other independent risk factors for the development of HCC. Liver-related death occurred in 7 patients. Accompanying cirrhosis (HR = 6.13, P = 0.012) and low albumin level (HR = 9.17, P = 0.002), but not HCV RNA titer, were significant risk factors related to liver-related mortality. Conclusion. Serum HCV RNA titer may be considered an independent risk factor for the development of HCC but not liver-related mortality.

Emerging therapeutics and relevant targets for chronic Hepatitis B.

Chronic hepatitis B virus (HBV) infection is a global health problem for the pursuit of complete virus eradication and immunity acquisition to prevent liver disease progression. Currently, interferon-alpha, with the underlying mechanism of host immunomodulation, and nucleos(t)ide analogs, with the underlying mechanism of inhibition of viral replication, are used for the treatment of patients with chronic hepatitis B. Despite remarkable improvement in the virological, serological, biochemical, and histological response to current therapeutics, we are still far from meeting the therapeutic goals, e.g., clearance of HBV DNA/covalently closed circular DNA (cccDNA) in the serum/liver tissue and seroconversion of hepatitis B surface antigen (HBsAg) to anti-HBs in the present antiviral era. Recently, HBV replication cycle-related, viral RNA interference-based, and host immune-mediated therapeutic targets and relevant anti-HBV agents have been newly introduced and investigated in the preclinical and clinical fields. This review discusses emerging therapeutics and relevant targets in the management of chronic hepatitis B.