Hepatitis C (HCV) is a viral infection that affects an estimated 71 million people worldwide, with over 1 million new infections yearly. While medical treatments exist, HCV continues to be a significant public health concern. Primary prevention and transmission risk factor identification remain key in helping decrease disease prevalence. While intravenous drug use, healthcare exposure (i.e. blood transfusions and surgical care), and body modification (i.e. tattooing and piercings) are well accepted risk factors for HCV transmission, others remain controversial. Because dental practice is often associated with procedures and bleeding, the possibility of HCV transmission seemed reasonable to investigate. Here, we review the evidence for dental care as a potential risk factor for HCV transmission. We identified a total of 1,180 manuscripts related to HCV and dental care, of which 26 manuscripts were included in the study after exclusionary criteria were applied. As per our review of the available literature, in the developing world, the improper use of sterile technique and lack of provider education likely increases the risk of HCV transmission during dental care. In developed nations, on the other hand, general dental care does not appear to be a significant risk factor for HCV transmission in non-intravenous drug user patients; although, the improper use and reuse of anesthetics during procedures poses a rare potential risk for viral transmission.

Liver cirrhosis progresses through multiple clinical stages which culminate in either death or liver transplantation. Availability of organs, timely listing and prompt receipt of donor-livers pose difficulties in improving transplant-listed and transplant outcomes. In this regard, regenerative therapies, particularly with granulocyte colony-stimulating factor (GCSF), has become a lucrative option for improving transplant-free survival. However, the literature is confusing with regards to patient selection and real outcomes. In this exhaustive review, we describe the basics of liver fibrosis and cirrhosis through novel insights from a therapeutic point of view, discuss preclinical studies on GCSF in advanced liver disease to improve on clinical utility, shed light on the pertinent literature of GCSF in advanced cirrhosis, and provide astute inputs on growth factor therapy in decompensated cirrhosis.

The chemical composition of Melanthera scandens (MS) methanol (MeOH) extract is yet to be fully comprehended. Chemical composition of a plant extract is closely related to the biological activity of the plant material, in phytomedicine. In this study, chemical analyses of MS extracts were carried out with the aim of identifying the organic chemical constituents.

Powdered MS leaf was soxhlet extracted with dichloromethane and MeOH. The solvent extracts were analyzed using electrospray ionization-mass spectrometer and GC-MS (fatty acid methyl ester and trimethylsilyl derivatives). Fresh MS leaves were cold extracted with MeOH for biological studies and isolation of compounds. The MeOH extract was screened for phytochemical constituents and partitioned with n-hexane, ethyl acetate (EtOAc) and n-butanol to give the respective fractions. The n-hexane fraction was examined for volatile constituents using gas chromatography-mass spectrometry. Antibacterial study of n-hexane, EtOAc, butanol fractions and crude MeOH extract was undertaken; extract and fractions were screened against E. coli, P. aeruginosa, B. subtilis, B. cerus and S. aureus. The minimum inhibitory concentration and minimum bactericidal concentration of the EtOAc fraction (the most active) were determined using the macrobroth dilution method, and the fraction was subjected to column fractionation. Eluents were monitored by thin-layer chromatography. The combined fractions that exhibited antibacterial activity were further purified to obtain isolates which were characterized by spectroscopic techniques – nuclear magnetic resonance, Fourier transform infrared, gas chromatography-mass spectrometry (fatty acid methyl ester and trimethylsilyl) and electrospray ionization-mass spectrometer.

Phytochemical screening of MS extracts showed the presence of alkaloids, tannins, cardiac glycoside, saponins and steroid, while flavonoid was not detected. The n-hexane fraction, EtOAc fraction, and crude MeOH extract inhibited the growth of Bacillus species, while the butanol fraction did not display any activity against the tested microbes. The EtOAc fraction showed the greatest activity. Gas chromatography-mass spectrometry analysis of the n-hexane fraction identified 14 compounds, among which phytol was of highest percentage composition. Ten different compounds were identified in the dichloromethane extract, consisting mainly of oleanane and ursolane derivatives. Electrospray ionization-mass spectrometer analysis tentatively identified 5 triterpenoid glycosides.

The MEOH extract and its fractions, except the n-butanol fraction, inhibited the activity of Bacillus species considerably, from among the tested microbes, to varying degrees. A total of 54 different bioactive chemical compounds were identified in the leaf extract of MS. These compounds contribute to its biological activities, including antibacterial, thereby justifying its use in ethno-medicine to manage diseases caused by pathogenic microorganisms.

Background and Aims: Ravidasvir (RDV) is a new generation pangenotypic hepatitis C virus (HCV) NS5A inhibitor, with high barrier to baseline resistance-associated species. This is the first phase 2/3 study conducted in Mainland China confirming the efficacy and safety of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks in treatment-naïve noncirrhotic patients with genotype 1 infection in a large population.

Methods: In this multicenter, randomized, double-blinded, placebo-controlled phase 2/3 trial (NCT03362814), we enrolled 424 treatment-naïve, noncirrhotic adult HCV genotype 1 patients. All patients were randomized at 3:1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day (body weight <75/≥75 kg) (n = 318) or placebo (n = 106) for 12 weeks. The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment, and the safety was evaluated and compared between treatment and placebo groups.

Results: The overall rate of sustained virological response at 12 weeks after treatment is 99% (306/309, 95%, CI: 97%–100%) under per protocol set analysis. All patients harboring baseline NS5A resistance-associated species in the treatment group (76/76, per protocol set) achieved sustained virological response at 12 weeks after treatment. No treatment-related serious adverse events were reported. Laboratory abnormalities showed mild or moderate severity (grade 1 and grade 2) in liver function tests.

Conclusions: In treatment-naïve, noncirrhotic HCV Chinese patients infected with HCV genotype 1, all-oral regimen of RDV + ritonavir-boosted danoprevir + ribavirin for 12 weeks was highly efficacious, safe, and well tolerated.

Amoxicillin-clavulanate (AC) is a common cause of drug-induced liver injury, either cholestatic or mixed with hepatitis pattern. Rarely, AC causes granulomatous hepatitis. We report a new case of AC-induced granulomatous hepatitis documented by liver biopsy, with complete resolution of any histological sequelae on a follow-up liver biopsy after AC was withdrawn.

Thyroid disorder and diabetes are associated endocrine disorders. Patients with either one of the disorders are at great risk of developing the other. The co-existence of type-2 diabetes mellitus (T2DM) and hypothyroidism with clinical evidence of effect on one another has not been reported until today.

This prospective study involved 702 patients. Each participant’s blood sugar levels and thyroid profiles were statistically analyzed using unpaired t-test.

The incidence of hypothyroidism and hyperthyroidism in diabetic patients was 20.2% and 1.71% respectively, while the incidence of type-1 diabetes mellitus and T2DM in thyroid dysfunction patients was 0.56% and 19.03% respectively. The mean fasting blood sugars and postprandial blood sugar levels, triiodothyronine, thyroxine and Thyroid stimulating hormone levels of hypothyroid patients with T2DM (157.2 ± 4.779, 231.7 ± 6.291, 1.123 ± 0.065, 8.643 ± 1.519 and 12.22 ± 1.974) were not significantly different (p > 0.05) from those in T2DM patients with hypothyroidism (153.6 ± 7.181, 236.6 ± 9.504, 1.091 ± 0.013, 7.971 ± 1.024 and 12.09 ± 1.48). These findings were above the normal range (fasting blood sugar of 70–110 mg/dL; postprandial blood sugar of >140 mg/dL) thyroid stimulating hormone of 0.39–6.16 mIU/L in both type of patients, with the exception of triiodothyronine and thyroxine.

We report clinical evidence of association between hypothyroidism and diabetes mellitus with the highest incidence of hypothyroidism in T2DM with four major findings, suggesting regular thyroid and glycemic level evaluations for diabetic and hypothyroid patients respectively. Thus adjustment of dosage of levothyroxine is necessary, with prompt monitoring and reduction of the dose of insulin or oral hypoglycemic drugs to avoid hypoglycemia and its complications.

Diabetic nephropathy is the most common microvascular complication of diabetes mellitus. With the increasing prevalence of diabetes mellitus, diabetic neuropathy has become the primary cause of chronic nephropathy cases. Diabetes mellitus and chronic nephropathy exert certain effects on the digestive system. diabetic neuropathy patients also have digestive system symptoms and gastrointestinal diseases, with most presenting such problems as decreased gastrointestinal tract tension, insufficient gastric motility, decreased contractility, and delayed gastric emptying; these problems are often accompanied by symptoms of digestive system dysfunction, such as constipation, dry stool, tenesmus. This article will summarize and discuss the effects and mechanism of diabetic neuropathy involving the digestive system.

In recent years, evidence supporting the theory of obesity paradox has increased, showing that obese/overweight people with prevalent chronic diseases experience lower mortality compared with patients of normal weight. So far, evidence is most comprehensive in cardiovascular and chronic renal diseases; however, published studies are prone to many biases, enabling us to reach a definite conclusion. Available data in chronic liver disease is scarce and ambiguous. Obesity is traditionally associated with nonalcoholic fatty liver disease and steatosis in viral hepatitis and as such one would not expect the obesity paradox to be a real possibility in liver disease. Yet, there seem to be new data indicating the opposite – the obesity paradox exists in severe and end-stage liver cirrhosis, which could be attributed to a better lean mass in patients with higher body mass index, meaning that sarcopenia, as one of the most important prognostic factors of survival, is less likely to be present. Nonetheless, the problem of various methodological problems addressing the association between body weight and mortality, which is present both in liver disease and other chronic diseases, are preventing us from attaining an unanimous conclusion. Still, we should be aware that the obesity paradox might be true, especially in severe and end-stage illness. This suggests focusing our efforts toward preserving or building up fat-free mass and decreasing inflammatory activity responsible for catabolism and sarcopenia, and implying that the underlaying cause should be treated.

Background and Aims: Although autologous bone marrow stem cell (BMSC) transplantation is an effective treatment for liver cirrhosis, there are few reports describing the optimal delivery route and number of injected BMSCs.

Methods: A literature search was conducted using PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, and EBSCO. A meta-analysis was performed to assess the effect of BMSCs on liver and coagulation function indices. Subgroup analysis was performed based on number of injected BMSCs, delivery route, and length of follow-up.

Results: A total of 15 studies were selected from among 1903 potential studies for analysis. Autologous BMSC transplantation significantly improved aspartate aminotransferase, total bilirubin, albumin, prothrombin time, prothrombin activity, prothrombin concentration, Child-Pugh score, and model for end-stage liver disease. In the subgroup analysis of cell numbers, all four of the indices were significantly improved when the number of BMSCs was >4 × 108. The subgroup analysis referring to the delivery route showed that arterial infusion increased the therapeutic effect over venous infusion. Finally, in the subgroup analysis of follow-up length, the results showed that BMSC therapy significantly improved liver function at 2 weeks after transplantation. In addition, this therapy improved coagulation 4 weeks after the transplant, with a maintenance of efficacy for up to 24 weeks.

Conclusions: Autologous BMSC therapy is beneficial for liver improvement and coagulation in patients with liver cirrhosis. The therapeutic effect was generated at 2–4 weeks after transplantation. The effect lasted for 24 weeks but no more than 48 weeks. The greatest benefit to patients was observed with a 4 × 108 autologous BMSC transplant via the hepatic artery.

Background and Aims: The perinatal transmission of hepatitis B virus (HBV) remains an important global health problem. Here, a systematic review and meta-analysis were conducted to evaluate the evidence regarding the efficacy and maternal/fetal safety of treating pregnant women with lamivudine, telbivudine (LdT), and tenofovir (TDF).

Methods: A PubMed and Scopus search resulted in 1,076 records, which were reduced to 36, containing 7,717 pregnant women with chronic HBV infection and 7467 infants meeting the inclusion criteria. The latest search was in August 2019.

Results: Treatment with LdT, but not lamivudine and TDF, could significantly reduce the hepatitis B virus surface antigen-positive rate (odds ratio (OR) = 0.37) in infants; it also led to higher rates of hepatitis B e antigen loss (OR = 12.14), hepatitis B e antigen seroconversion (OR = 8.93), and alanine aminotransferase normalization in mothers (OR = 1.49). Each of these treatments was able to significantly reduce HBV DNA positivity at birth (total OR = 0.19) and mother-to-child-transmission of HBV (total OR = 0.15), and to cause higher rates of HBV DNA suppression in mothers (total OR = 25.53). However, nucleos(t)ide analogues might also be involved in creatine kinase elevation (total OR = 7.48). In contrast, no significant association was found between nucleos(t)ide analogue therapy and preterm/premature births, congenital malformation, low birth weight, and abortion or fetal/infant death. The results suggested LdT’s high capability of preventing mother-to-child-transmission. However, TDF failed to show significant associations to a reduced risk of mother-to-child-transmission, probably due to the low number of patients included.

Conclusions: Although using either lamivudine, LdT, or TDF could lead to more favorable maternal/fetal outcomes, LdT seemed to show more potential in resolving certain infant- and maternal-related outcomes. More studies on the safety profile of such treatments are required.

The use of complementary and alternative medicines (CAMs) for treatment of acute and chronic diseases is on the rise world over, especially in Asian countries, and mostly in China and India. Drug-induced liver injury (DILI) due to CAM is increasingly reported in the literature from multiple centers all around the world and with large-number patient series published from the West, mostly based on nation-wide DILI networks and multicenter collaboration. Comprehensive DILI networks are lacking among major Asian countries with high incidence of CAM practices. Chinese medical societies dealing with drug toxicity, CAM practice and hepatobiliary disease have adopted an integrated approach to establishing identification, diagnosis and treatment of CAM-related DILI, representing a systematic approach that could be iterated by other countries for improving patient outcomes. In this exhaustive review, we provide published data on CAM-related DILI in Asia, with detail on incidences along with analysis of patient population and their clinical outcomes. Concise and clear discussion on commonly implicated CAM agents in major Asian countries and associated chemical and toxicology analyses as well as descriptions of liver biopsy findings are discussed with future directions.

The aim of this article was to review the roles of Helicobacter pylori-induced antralization in gastric carcinogenesis and its implications in clinical practice. A search of PubMed/PubMed Central, Web of Science, and China National Knowledge Infrastructure was performed in December 2018 to retrieve all literature related to antralization (or antralisation), pyloric (or pseudopyloric) glands, pyloric (or pseudopyloric) metaplasia, or pyloric (or pseudopyloric) gland metaplasia, and spasmolytic polypeptide-expressing metaplasia (or SPEM). Among the synonyms, antralization and SPEM, which are derived in the same mechanisms at the molecular, cellular and tissue levels, are more commonly used in recent studies. Antralization (or SPEM) is associated with H. pylori infection, atrophic gastritis and intestinal metaplasia, while H. pylori eradication may reverse antralization. It is proposed that H. pylori infection leads to inflammation in the gastric mucosa and apoptosis of the epithelial cells of the proximal stomach, including gastric incisura, body and fundus. The stem cells proliferate and transform into mucous cells and form antral-type mucosa (i.e. antralization). Subsequently, H. pylori-induced antralization, if not controlled, may develop into atrophic gastritis, intestinal metaplasia, dysplasia, and early intestinal-type gastric cancer. Although many biomarkers, including the spasmolytic polypeptide and mucin 6, are specifically expressed in the gastric mucosa with antralization, none of them are evaluated for the clinical diagnosis of antralization. H. pylori-induced antralization (or SPEM) is believed to be an initiating and reversible stage of gastric carcinogenesis. Identification of antralization would help make an early intervention to cease or even reverse the process toward the development of gastric cancer. Currently, the “gold standard” for diagnosing antralization is pathology, which is invasive and time consuming. A non-invasive and convenient method that accurately and specifically diagnoses antralization is urgently required.

Background and Aims: Data are limited on the use of pegylated-interferon alpha-2a (peg-IFNα) in Chinese patients with chronic hepatitis B virus (HBV) infection (CHB). We evaluated the effectiveness and safety of peg-IFNα in Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice.

Methods: In this prospective, multicenter, observational, non-interventional cohort study, patients were assessed for up to 1 year after peg-IFNα treatment cessation. Treating physicians established the dosing and treatment duration according to Chinese clinical practice. Effectiveness of peg-IFNα treatment was measured by the percentage of: patients with HBV DNA <2000 IU/mL and loss of hepatitis B surface antigen (commonly known as HBsAg); HBV DNA level at end of treatment (EOT), and 6 months and 1 year posttreatment; and time course change in quantitative HBV DNA and HBsAg.

Results: At EOT, 6 months posttreatment, and 1 year posttreatment, the percentage of patients with HBV DNA <2000 IU/mL was 90.0%, 81.8%, and 82.2%, and that of patients with HBsAg loss was 6.5%, 9.4%, and 9.5%, respectively. The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment. The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment. The incidence of adverse events was 52.0%.

Conclusions: Peg-IFNα has the potential to provide functional cure (HBsAg loss) for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China.

Clinical Trial Registration: ClinicalTrials.gov (NCT01730508).

Chronic hepatitis B virus infection continues to be a major health burden worldwide. It can cause various degrees of liver damage and is strongly associated with the development of liver cirrhosis and hepatocellular carcinoma. Covalently closed circular DNA in the nucleus of infected cells cannot be disabled by present therapies which may lead to HBV persistence and relapse. In this review, we summarized the current knowledge on hepatitis B virus covalently closed circular DNA and its potential role as a therapeutic target.

Scintigraphy imaging is based on the uptake of radiopharmaceuticals by a tissue or organ. Hepatosplenic scintigraphy involves the uptake of labelled colloid by the mononuclear phagocyte system. The radiocolloid distribution in the body, where 80–90% is taken up by the liver, 5–10% by the spleen and 5% by the bone marrow, has the disadvantage of obscuring the rim of the spleen in patients with liver hypertrophy. However, the spleen takes up proportionally more particles if they are larger. While only 10–15% of 99mTc-sulfur colloid particles of 0.4 µ diameter are taken up by the spleen, about 90% of denatured red blood cells (RBCs), approximately 7 µm in diameter, are trapped in the splenic tissue. Because of this, labelled denatured RBCs are used for selective spleen imaging. RBCs present many disadvantages that preclude their use in clinical practice, as the steps involved in efficient labelling and denaturation of RBCs are labor-intensive, time-consuming, and not widely available. Therefore, an alternative method to denatured RBCs is highly desirable. Microbubbles, ultrasound-enhanced agents, are promising candidates for use as an alternative to damaged RBCs. Labelling of microbubbles is potentially simpler, safer, and less expensive. Furthermore, denatured RBCs and ultrasound contrast agents share certain characteristics, such as their size, shape, membrane composition and pharmacokinetics. Based on these similarities, the latter should be tested as an alternative carrier in scintillation scanning. Aside from the potential application of labelled microbubbles as a carrier alternative to denatured RBCs, they could also be used instead of natural RBCs for applications including the investigation of gastrointestinal bleeding, cardiovascular imaging studies, and to localize hemangiomas. Finally, they could be used in renal transplant recipients as a marker of rejection and as an adjunct to the diagnosis in certain diseases in which the immune response includes phagocytic cells.

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.