Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis.

Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 μg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate.

Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9–99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident.

Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated.

Trial Registration Clinical-Trials.gov Identifier: NCT03020082

Hepatitis C virus (HCV) infects at least 150 million people chronically worldwide. It is a major risk factor for cirrhosis, hepatocellular carcinoma, and death. Direct-acting antiviral therapy is very efficacious in treating HCV infection but it is inaccessible and unavailable in some developing countries. Therefore, searching for more effective and easily accessible regimens remains an urgent need. The aim of this article is to review the anti-HCV effects of herbal medicines from experimental to clinical evidence, and discuss current issues, hurdles and future perspectives for their application from bench to bedside. Numerous in vitro studies have indicated that many herbs work effectively in exerting anti-HCV activities. Yet, only a few animal experiments have been conducted that demonstrate the anti-HCV effects of these medicines; in addition, these results do not show an ability to eliminate the virus completely from the infected animals. Thus far, clinical trials have produced inconclusive anti-HCV results in terms of efficacy and safety, presumably due to the lack of the quality of methodologies used in the trials. In conclusion, despite apparent anti-HCV activities in vitro, clinical efficacy and safety of herbal medicines for the treatment of HCV infection have not been revealed convincingly. More animal studies using ideal models and more well-designed clinical trials with a larger sample sizes and longer treatment periods, taking the body habitus into consideration, are required to further assess the efficacy and safety of herbal medicines for HCV infection.

Biliary mucinous cystadenomas are cystic neoplasms commonly mistaken for simple cysts. They are rare and generally benign tumors, often incidentally found on imaging and during unrelated surgical interventions. They tend to be slow growing though may reach symptomatic dimensions. Misdiagnosis of biliary mucinous cystadenomas may have serious consequences secondary to their potential for malignant transformation into biliary mucinous cystadenocarcinomas. Here, we review the epidemiology, etiology, pathology, diagnostic modalities, histology, and available treatment methods for mucinous cystadenomas reported in current literature.

The clinical management of portal vein thrombosis (PVT) remains ambiguous due to its heterogeneous presentations and its associations with liver disease, malignancy, and hypercoagulable states. The natural history and clinical outcome of PVT are highly variable, dependent upon size, extent and degree of the thrombotic occlusion, as well as the physiological impact of patient comorbidities. While existing clinical guidelines consistently recommend low molecular weight heparin or vitamin K antagonist anticoagulation in cirrhotic patients with symptomatic acute PVT, management of asymptomatic and chronic PVT may need to be determined on a case-by-case basis, factoring in the state of underlying liver disease. In general, patients with PVT and underlying malignancy should be anticoagulated to alleviate symptoms and prevent recurrences that could disrupt the cancer management. However, existing clinical data does not support routine anticoagulation of cirrhotic patients with asymptomatic PVT in the absence of underlying cancer. While low molecular weight heparin and vitamin K antagonist remain the most commonly used agents in PVT, an emerging body of clinical evidence now suggests that direct-acting oral anticoagulants may be used safely and effectively in PVT. As such, direct-acting oral anticoagulants may offer a more convenient anticoagulation alternative for PVT management in future practice.

Background and Aims: Fatty infiltration of liver may induce insulin resistance (IR), and a proportion of patients with nonalcoholic fatty liver disease (NAFLD) is diagnosed with nonalcoholic steatohepatitis. Transient elastography is gaining popularity as a means of non-invasively determining both liver stiffness (fibrosis level) and degree of fatty infiltration, expressed as controlled attenuation parameter (CAP) value.

Methods: The aims of this study were to investigate the association between IR and level of fatty liver, and to identify the group at a greater risk of nonalcoholic steatohepatitis using transient elastography and other noninvasive fibrosis markers. A total of 169 patients without chronic hepatitis B and C were analyzed.

Results: The CAP value was significantly associated with IR (HOMA-IR ≥2.5; AUROC = 0.81), and the optimal cut-off to discriminate IR was 264 dB/m. The liver stiffness measurement and aspartate aminotransferase-to-platelet ratio index values were significantly higher for CAP ≥264 than in CAP <264. The 9 patients among the overall 169 patients (5.3%) and among the 102 NAFLD patients (8.8%) who showed ≥264 dB and ≥7.0 kPa in transient elastography could represent good candidates for liver biopsy.

Conclusions: Evaluation of NAFLD based on CAP values was useful in diagnosing IR. About 9% of NAFLD patients in a Japanese outpatient clinic with a few metabolic complications might be considered good candidates for liver biopsy to confirm nonalcoholic steatohepatitis.

Forty percent of the world’s population is at risk of Plasmodium vivax infection. Relapse is a feature of malaria caused by P. vivax and P. ovale due to the presence of the parasite’s hypnozoite stage that allows it to stay dormant in the human liver. The associated morbidity and economic burden is high, as P. vivax causes severe anemia, miscarriage among pregnant women, malnutrition, and developmental delay in young children due to its chronic relapsing nature. Till recently, for more than 60 years the only licensed antimalarial with proven hypnozoitocidal activity was primaquine. The World Health Organization recommends a regimen of 3-day chloroquine plus 14 days of primaquine for radical cure. Poor adherence to the primaquine course limits its public health benefit on a large scale. Tafenoquine is an 8-aminoquinoline with slower elimination rate, hence a single dose of it is sufficient for hypnozoitocidal activity. Additionally, the schizontocidal activity of tafenoquine makes it a superior drug to the currently available antimalarials, which are mostly single stage specific. Recently, tafenoquine was approved in the USA and Australia for the radical cure of P. vivax malaria in patients aged ≥16 years who are receiving appropriate antimalarial therapy for acute P. vivax malaria, and for the prophylaxis of malaria in patients aged ≥18 years. We have reviewed the available literature of tafenoquine here, and this article explores the possibility of tafenoquine as a key tool for control and elimination of malaria.

Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) appears to be suitable for malignant gastric outlet obstruction (GOO), serving as a hybrid treatment that includes the advantages of a long unobstructed period and less invasiveness. Two patients each, described in this report, had an unresectable cancer and underwent endoscopic metal stent placement in the stenotic enteric segment of a malignant GOO, which resulted in frequent stent replacement. EUS-GE was then performed with a fully covered, self-expandable, lumen-apposing metal stent, which combined a cautery tip-equipped access catheter. The patients’ symptoms of nausea and vomiting were rapidly alleviated and did not recur during the follow-up period of 6 months. EUS-GE appears to be feasible after obstruction of a metal stent in a tumor segment. It may be a preferred alternative in patients with malignant GOO.

Response to biologic therapies in severe asthma is variable, with patients being either nonresponders, responders or super-responders. There is currently no explanation for this variation in response. If asthma-specific inflammatory pathways are part of a wider network of pathogenic mechanisms (including systemic inflammation), then the state of this wider network could either help or hinder the effect of the biologic. People with severe asthma are often polysymptomatic with a variable frequency of nonrespiratory symptoms. Application of existing network theory would predict that high systemic inflammation, measurable by the frequency of nonrespiratory symptoms, should decrease the effectiveness of biologics, a prediction consistent with the limited existing data. A detailed examination of the relationship between biologic response and the frequency or profile of nonrespiratory symptoms would provide a testable prediction of this hypothesis. The clinical presentation of super-responders is consistent with biologics sometimes having a positive effect on the pathology (level of dysregulation) in a network system. If that were the case, then network theory predicts the possibility of a short-term increase in nonrespiratory symptoms prior to the improvement reported by super-responders. If biologics lead to less network dysregulation in some patients, then this raises the possibility of new applications for this therapy and of an improved response to biologics if lifestyle improvement is started prior to biologic therapy.

Background and Aims: The association between portal-systemic shunt and hepatocellular carcinoma (HCC) development in patients who have cirrhosis is still controversial. This systematic review with meta-analysis was performed to systematically clarify the potential role of portal-systemic shunt in the development of HCC.

Methods: The PubMed, Embase, and Cochrane Library databases were searched for potentially eligible literature. Meta-analysis with random-effects model was performed to combine the incidence rates of HCC after portal-systemic shunt. Finally, seven studies were included. In the present review, we mainly focused on 859 patients (365 in the transjugular intrahepatic portal-systemic shunt (TIPS) group and 494 in the non-TIPS group) from five studies to analyze incidence rates after TIPS.

Results: At the end of follow-up, there were 66 (18%, 66/365) patients who developed HCC after TIPS intervention and 63 (13%, 63/494) patients who developed HCC after non-TIPS treatments. Pooled estimates with random-effects model did not demonstrate a significant increase of incidence of HCC after TIPS (risk ratio: 1.37 [confidence interval (CI): 0.96 to 1.97]; p = 0.08) compared with non-TIPS treatments. Subgroup analyses for those patients with transplanted liver also did not detect a significant difference between the TIPS group and non-TIPS group (risk ratio: 1.10 [CI: 0.59 to 2.07]; p = 0.75).

Conclusions: Current evidence suggests that portal-systemic shunt is not associated with a higher risk of HCC development in cirrhotic patients.

Background and Aims: Acetaminophen (APAP) is the leading cause of drug overdose and hepatotoxicity worldwide, including in Thailand. Patterns of overdose and hospital management are known to have significant impacts on the outcomes of APAP overdose, and these factors vary from country to country. Therefore, this study aimed to analyze clinical characteristics of Thai patients with APAP overdose in terms of overdose patterns, clinical presentation, treatment and outcomes.

Methods: In this retrospective analytical study, medical records of adult patients hospitalized with a diagnosis of APAP overdose at Rajavithi Hospital, Bangkok, between January 2013 and December 2017 were reviewed.

Results: A total of 184 patients diagnosed with APAP overdose were included. The median age was 22 (15–76) years and the majority were female (79.9%). Most overdoses were intended self-poisoning ingestion (90.8%) with a median dose of 10.5 g (4.5–50). A total of 121 patients were treated with N-acetylcysteine with a median visit-to-N-acetylcysteine time of 2 (0.5–15) h. Overall, 15.6% developed mild hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >3 times the upper limit of normal), 6.4% developed severe hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >10 times the upper limit of normal and international normalized ratio >2.0) and 3 patients developed acute liver failure (1 patient resolved spontaneously and 2 patients, neither of whom had a liver transplant, died). Significant predictors for hepatotoxicity included older age, chronic alcohol drinking, repeated taking of medication for more than 8 h (staggered ingestion), long duration between ingestion and hospital visit, alcohol coingestion, abdominal pain symptoms, and acute kidney injury.

Conclusions: Most cases of APAP overdose in Thailand appear to be young women with intentional ingestion. With prompt management, most patients (76.4%) did not develop significant hepatotoxicity; nevertheless, despite N-acetylcysteine therapy, hepatotoxicity including acute liver failure was observed in a small proportion of patients, particularly those with unintentional overdose and chronic alcohol drinking.

Hepatitis B virus (HBV) immunization is safe and has been accepted worldwide as a routine practice. The target of such vaccination is to induce the immune response in the host, resulting in the prevention of replication of HBV. There are several immunological and clinical factors which determine the clinical efficacy and safety of the HBV vaccine. In this article we have highlighted the response of the host immune system to HBV vaccination (immunogenicity), efficacy, and safety of the vaccine, issues with booster dosing, paths of development (preclinical and clinical) of the HBV vaccine, novel and upcoming strategies for improvement of HBV vaccination, and the concept of therapeutic HBV vaccination. The different aspects and regulatory recommendations pertaining to HBV vaccine development are also discussed. The new strategies for improvement of HBV vaccination include pre-S1 and pre-S2 portions of the HBV surface antigen, increasing the antigen dose, accelerated vaccination schedules, alternative vaccination route, use of adjuvants like immunostimulatory DNA sequences, etc. Therapeutic vaccination is being explored for initiation of a multifunctional and multispecific T cell response against the major HBV antigens and also effective activation of humoral immunity for viral control.

Background and Aims: Hepatitis C virus (HCV)-infected organs are underutilized. We aimed to assess the safety and efficacy of direct-acting antiviral agents (DAAs) therapy in HCV viremic patients who are transplanted with a liver from a HCV viremic donor.

Methods: We conducted a retrospective study, including patients seen from July 2015 to April 2017. HCV viremic patients transplanted with a liver from a HCV viremic donor and subsequently treated with DAAs were included. Outcomes assessed included undetectable viral load at 12 weeks after completing DAA therapy (sustained virologic response, SVR12), adverse events, and interactions with immunosuppression.

Results: Twenty-four HCV viremic recipients received livers from HCV viremic donors. Median age was 63 years, and the majority (79.2%) were genotype 1a. Donors and recipients were viremic at the time of transplant. Median modified model for end-stage liver disease score was 19, and median time on the waitlist was 81 days. Median time from transplant to initiation of DAA therapy was 123 days. Several DAA regimens were used and 15 (62.5%) patients did not receive ribavirin. Treatment duration ranged from 12 to 24 weeks. Twenty-three (95.8%) patients achieved SVR12. Five (20.8%) patients developed adverse events; however, none required DAA discontinuation.

Conclusions: DAA therapy was efficacious and well tolerated in HCV viremic recipients who underwent liver transplantation from a HCV viremic donor.

The role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) has evolved over the past few decades with the advancement of technology and improved imaging. Radiotherapy can offer high local control rates in unresectable HCC, including cases with major vascular involvement, and can provide a modality to help bridge patients to potentially curative resection or transplantation. In metastatic cases, radiotherapy can provide good palliation. This review focuses on the common radiotherapy treatment modalities used for HCC, provides outcome comparisons of these radiotherapy techniques to outcomes with other treatment modalities for HCC, and highlights the discrepancy of the role of radiotherapy in HCC amongst the current available treatment guidelines.

We report here a case of a 54-year-old man who developed subarachnoid hemorrhage following cardiopulmonary resuscitation. Both computed tomography scans performed respectively within 24 h and on day 3 indicated a normal physical condition. The computed tomography scan conducted 7 days after the cardiopulmonary resuscitation revealed diffuse cerebral edema and subarachnoid hemorrhage. The existence of blood in cerebrospinal fluid was confirmed by lumbar puncture. We propose that ischemia/reperfusion response plays an important role in the development of post-resuscitation subarachnoid hemorrhage.

Background and Aims: The metabolic acid-base disorders have a high incidence of acute kidney injury (AKI) in critically ill cirrhotic patients (CICPs). The aims of our study were to ascertain the composition of metabolic acidosis of CICPs with AKI and explore its relationship with hospital mortality.

Methods: Three-hundred and eighty consecutive CICPs with AKI were eligible for the cohort study. Demographic, clinical and laboratory parameters were recorded and arterial acid-base state was analyzed by the Stewart and Gilfix methodology.

Results: Net metabolic acidosis, lactic acidosis, acidosis owing to unmeasured anions, acidemia, and dilutional acidosis were less frequent in the non-survival group compared to the survival group of CICPs. The presence of acidemia, acidosis owing to unmeasured anions, and lactic acidosis were independently associated with increased risk of intensive care unit 30-day mortality, with hazard ratios of 2.11 (95% confidence interval (CI): 1.43–3.12), 3.38 (95% CI: 2.36–4.84), and 2.16 (95% CI: 1.47–3.35), respectively. After full adjustment for confounders, the relationship between acidosis owing to unmeasured anions with hospital mortality was still significant, with hazard ratio of 2.29 (95% CI: 1.22–4.30). Furthermore, arterial lactate concentration in combination with chronic liver failure-sequential organ failure assessment and BEUMA had the strongest ability to differentiate 30-day mortality (area under the receiver operating characteristic curve: 0.79, 95% CI: 0.74–0.83).

Conclusions: CICPs with AKI exhibit a complex metabolic acidosis during intensive care unit admission. Lactic acidosis and BEUMA, novel markers of acid-base disorders, show promise in predicting mortality rate of CICPs with AKI.

This study aimed to examine the difference in expression of matrix metalloproteinases (MMPs) in ameloblastoma and other benign tumors or normal tissue of the jaw, and ameloblastic carcinoma, and to investigate the correlation of expression of MMPs with patient prognosis.

Studies were identified in the major electronic databases (Medline, EMBASE and Cochrane Library) using the keywords “matrix metalloproteinases” and “ameloblastoma” OR “ameloblastic carcinoma”, and a quantitative meta-analysis was conducted.

Fourteen studies were included in this systematic review. Twelve studies representing a total number of 471 cases qualified for the meta-analysis. The analysis revealed a higher MMP-2 expression in ameloblastoma than in the other benign odontogenic tumors, showing a significant inter-group difference (odds ratio [OR]: 5.33; 95% confidence interval (CI): [1.36, 25.62]; p = 0.02). A lower MMP-2 expression was found for the ameloblastoma than in the ameloblastic carcinoma, with a non-significant inter-group difference (OR: 0.12; 95% CI: [0.01, 1.02]; p = 0.05). Finally, a lower MMP-9 expression was found for the follicular subgroup compared to that in other subgroups of ameloblastoma, showing a significant inter-group difference (OR: 0.15; 95% CI: [0.05, 0.48]; p = 0.001).

We found that MMP-2 expression in ameloblastoma is higher than that in other benign tumors or normal tissue of jaw, and that MMP-9 expression in the follicular subgroup of ameloblastoma is lower than that in other pathology subgroups of ameloblastoma. What is more important, the MMPs expression in ameloblastoma was found to be significantly correlated with many clinicopathologic features of ameloblastoma. However, some limitations weakened the power of this meta-analysis.