Non-pulmonary involvement in COVID-19: A systemic disease rather than a pure respiratory infection.

During the early phase of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), diagnosis was difficult due to the diversity in symptoms and imaging findings and the variability of disease presentation. Pulmonary manifestations are reportedly the main clinical presentations of COVID-19 patients. Scientists are working hard on a myriad of clinical, epidemiological, and biological aspects to better understand SARS-CoV-2 infection, aiming to mitigate the ongoing disaster. Many reports have documented the involvement of various body systems and organs apart from the respiratory tract including the gastrointestinal, liver, immune system, renal, and neurological systems. Such involvement will result in diverse presentations related to effects on these systems. Other presentations such as coagulation defects and cutaneous manifestation may also occur. Patients with specific comorbidities including obesity, diabetes, and hypertension have increased morbidity and mortality risks with COVID-19.

Hemostatic system and COVID-19 crosstalk: A review of the available evidence.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant coronavirus disease 2019 (COVID-19) pandemic, respiratory manifestations have been the mainstay of clinical diagnosis, laboratory evaluations, and radiological investigations. As time passed, other pathological aspects of SARS-CoV-2 have been revealed. Various hemostatic abnormalities have been reported since the rise of the pandemic, which was sometimes superficial, transient, or fatal. Mild thrombocytopenia, thrombocytosis, venous, arterial thromboembolism, and disseminated intravascular coagulation are among the many hemostatic events associated with COVID-19. Venous thromboembolism necessitating therapeutic doses of anticoagulants is more frequently seen in severe cases of COVID-19, especially in patients admitted to intensive care units. Hemorrhagic complications rarely arise in COVID-19 patients either due to a hemostatic imbalance resulting from severe disease or as a complication of over anticoagulation. Although the pathogenesis of coagulation disturbance in SARS-CoV-2 infection is not yet understood, professional societies recommend prophylactic antithrombotic therapy in severe cases, especially in the presence of abnormal coagulation indices. The review article discusses the various available evidence on coagulation disorders, management strategies, outcomes, and prognosis associated with COVID-19 coagulopathy, which raises awareness about the importance of anticoagulation therapy for COVID-19 patients to guard against possible thromboembolic events.

Role of EUS in detection of liver metastasis not seen by computed tomography or magnetic resonance imaging during staging of pancreatic, gastrointestinal, and thoracic malignancies.

BACKGROUND AND OBJECTIVES: Liver metastases might not be detected by computed tomography (CT) and magnetic resonance imaging (MRI) due to their small size, but they can be detected by EUS. Furthermore, EUS-FNA has a significant impact on improving the diagnostic accuracy of EUS. The purpose of this study was to assess the feasibility of EUS in detection of occult small hepatic focal lesions at the time of primary tumor staging, not seen by CT or MRI. METHODS: This prospective study included 730 patients who underwent EUS for staging or sampling of gastrointestinal, pancreatic, or thoracic malignancy. The liver was examined thoroughly for detection of occult lesions. CT or MRI was done within 1 week of EUS examination. RESULTS: EUS examination of the liver detected focal lesions in 150 patients (20.5%) and metastases in 118 patients (16.2%); meanwhile, CT and MRI detected focal lesions in 99 patients (13.6%) and metastases in 82 patients (11.2%). EUS missed focal lesions in 7 patients, 6 of which were liver metastases (1.0% and 0.8%, respectively), while CT and MRI missed focal lesions in 58 patients, 42 of which were metastases (7.9% and 5.8%, respectively), which were detected by EUS. CONCLUSION: Thorough dedicated EUS examination of the liver is a feasible useful tool for detection of small hepatic lesions missed by CT and MRI. It is not considered an extra financial burden to the patient or health-care system because those patients are indicated for EUS examination for evaluation of their original lesion in the first place. Furthermore, EUS-FNA can add another advantage in diagnosing the etiology of such lesions.

Elevated Serum Cyclophilin D Level is Associated with Nonalcoholic Fatty Liver Disease and Higher Fibrosis Scores in Patients with Diabetes Mellitus.

BACKGROUND: Cyclophilin D (CypD) is a mitochondrial matrix protein involved in liver steatosis and fibrosis in vitro. However, the role of CypD in the development of fatty liver and liver fibrosis in humans has not been determined. PURPOSE: To measure the serum level of CypD in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD) and to assess its relation to the presence of hepatic steatosis and fibrosis in this group of patients. PATIENTS AND METHODS: In this cross-sectional study, 30 patients with diabetes and NAFLD were compared to 30 patients with diabetes without NAFLD and 30 age- and sex-matched healthy subjects. Abdominal ultrasound was used to diagnose NAFLD. Serum CypD was measured using ELISA. Fibrosis-4 (FIB-4) index, AST to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) were used as markers of liver fibrosis in patients with NAFLD. Patients with NAFLD were divided into two subgroups based on FIB-4 index: patients with liver fibrosis (FIB-4 >1.45) and patients without liver fibrosis (FIB-4 <1.45). CypD and other clinical and biochemical parameters were validated as predictors of NAFLD and liver fibrosis in diabetic patients in multivariate logistic regression analysis. RESULTS: Diabetic patients with NAFLD had higher serum CypD levels than those without NAFLD (11.65±2.96 vs 6.58±1.90 ng/mL, respectively, P <0.001). Correlation analysis revealed a significant positive correlation between CypD and FIB-4 index (P=0.001), APRI (P=0.013) and NFS (P<0.001). GGT and CypD were the only predictors of NAFLD. For the prediction of significant fibrosis, AUROC of CypD was 0.835 with a cutoff >14.05 ng/mL provides specificity of 81.8% and sensitivity of 75%. CONCLUSION: Serum CypD is related to hepatic steatosis and fibrosis in diabetic patients. Serum CypD may thus provide a novel marker and therapeutic target of NAFLD and liver fibrosis.

COVID-induced pancreatitis: case report.

BACKGROUND: Although the frequent respiratory affection in COVID-19, it is well established that it could be presented with a wide variation of gastrointestinal symptoms; however, it is the effect on the pancreas remains unclear. CASE PRESENTATION: We report a case of female patient, who was diagnosed with COVID-19 infection. A week later, the patient developed an attack of acute pancreatitis. Other causes of acute pancreatitis were excluded. Therefore, this was attributed to SARS-COV2 infection. CONCLUSION: The case raises awareness about the possibility of acute pancreatitis in COVID-19. Also emphasize the importance of measuring serum amylase and lipase in patients with COVID-19.

Barriers for resuming endoscopy service in the context of COVID-19 pandemic: A multicenter survey from Egypt.

BACKGROUND: The current coronavirus disease 2019 (COVID-19) pandemic has affected routine endoscopy service across the gastroenterology community. This led to the suspension of service provision for elective cases. AIM: To assess the potential barriers for resuming the endoscopy service in Egypt. METHODS: A national online survey, four domains, was disseminated over a period of 4 wk in August 2020. The primary outcome of the survey was to determine the impact of the COVID-19 pandemic on the endoscopy service and barriers to the full resumption of a disabled center(s). RESULTS: A hundred and thirteen Egyptian endoscopy centers participated in the survey. The waiting list was increased by ≥ 50% in 44.9% of areas with clusters of COVID-19 cases (n = 49) and in 35.5% of areas with sporadic cases (n = 62). Thirty nine (34.8%) centers suffered from staff shortage, which was considered a barrier against service resumption by 86.4% of centers in per-protocol analysis. In multivariate analysis, the burden of cases in the unit locality, staff shortage/recovery and the availability of separate designated rooms for COVID-19 cases could markedly affect the resumption of endoscopy practice (P = 0.029, < 0.001 and 0.02, respectively) and Odd's ratio (0.15, 1.8 and 0.16, respectively). CONCLUSION: The COVID-19 pandemic has led to restrictions in endoscopic volumes. The staff shortage/recovery and the availability of COVID-19 designed rooms are the most important barriers against recovery. Increasing working hours and dividing endoscopy staff into teams may help to overcome the current situation.

Endoscopic intervention in a case proven latterly to be a COVID-19.

BACKGROUND: COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the newly developed worldwide outbreak of coronavirus disease with a high rate of mortality especially among elderly and multiple co-morbid personnel. Asymptomatic COVID-19-infected patients are a well-known source of transmission of infection. The risk of exposure to respiratory secretions and/or feces is hardly avoidable during the endoscopic procedure; also, the aerosol and droplets take up to an hour disperse, so they remain a risk to staff and other patients after they leave the room; therefore, strict infectious precautions should be taken by all health care workers to limit the virus spread. MAIN BODY: We present an endoscopic trial of duodenal stent insertion in non-operable gastric carcinoma that is proven 2 days later to be a COVID-19-positive case. Fortunately, no one of the health care workers that came in contact with the case becomes infected owing to the proper infection control measures. CONCLUSION: We recommended that the endoscopy examination and procedures should be strictly limited to urgent cases to minimize the risk of virus infection among health care workers.

Liver transplantation in the era of COVID-19.

Liver transplantation is considered the ultimate solution for patients with end-stage chronic liver disease or acute liver failure. Patients with liver transplant need special care starting from preoperative preparation, surgical intervention ending with postoperative care. Transplanted patients have to receive immunosuppressive therapy to prevent rejection. Such a state of immune suppression could predispose to different types of infections in liver transplant recipients. Currently, the world is suffering a pandemic caused by a new strain of the coronavirus family called COVID-19. Certain infection control precautions are needed to protect immunocompromised and vulnerable patients, including liver transplant candidates and recipients from acquiring COVID-19 infection. Restricting non-transplant elective surgical procedures, managing transplant patients in separate outpatient clinics, and in-patient wards can prevent transmission of infection both to patients and healthcare workers. Telemedicine can help in the triage of patients to screen for symptoms of COVID-19 before their regular appointment. Management of immunosuppressive therapy and drug-drug interactions in liver transplant recipients infected with COVID-19 should be cautiously practiced to prevent rejection and effectively treat the underlying infection. In this report, we are trying to summarize available evidence about different aspects of the management of liver transplant candidates and recipients in the era of COVID-19.

Retreatment of chronic hepatitis C patients who failed previous therapy with directly acting antivirals: A multicenter study.

AIM OF THE STUDY: The current study aimed to evaluate the efficacy of different DAAs regimens in the treatment of chronic hepatitis C (CHC) Egyptian patients who failed to achieve SVR after their treatment with SOF-based regimens. METHODS: This was a retrospective observational multicenter study that included CHC patients that failed to achieve cure on SOF-based regimens who were re-treated using different DAAs regimen and were allocated according to national guidelines for the treatment of hepatitis C. Primary outcome was to assess the SVR12 rate among prior non-responders after retreatment with a second course of DAAs. RESULTS: Our study included 172 patients who failed to achieve SVR after treatment with SOF-based treatment regimen [age: 51.2 ± 11.3, 58.7% men]. Included patients were retreated using SOF/DCV/RBV, SOF/ r/PAR /OMB /RBV, SOF/DCV/SIM, SOF/LDV ± RBV or SIM/SOF. SVR12 was successfully attained in 95.35% (164/172) of the included non-responders. CONCLUSION: The current multicenter study proved the efficacy of various DAAs regimens issued by the National Committee for Control of Viral Hepatitis for retreatment of relapsed CHC Egyptian patients.

Correction to: Prevalence of prolonged QT interval in patients with HCV-related chronic liver disease.

Following publication of the original article [1], the authors reported that the family name of Mohamed El Kassas was incorrectly published as Mohamed ElKassas.

Prevalence of prolonged QT interval in patients with HCV-related chronic liver disease.

BACKGROUND: Hepatitis C virus (HCV) is a common disease in Egypt with a high socioeconomic burden and extra-hepatic manifestations as QT prolongation, but previous studies included mainly patients with advanced liver disease, so in this study, we aimed to delineate the prevalence of QT prolongation in early-stage HCV patients. RESULTS: The study included 874 HCV patients with early cirrhosis; in Child's class A, 57 (6.5%) patients had prolonged QT interval corrected (QTc). There was significant higher proportion of cirrhotic patients in the prolonged QTc group (31.6%) vs. in the normal QTc group (11.5%). QTc was 424.39 ± 36.6 vs. 411.51 ± 32.89 ms in cirrhotic and non-cirrhotic patients, respectively (P, 0.001). There was significant higher proportion of Fibrosis 4 (FIB-4) ≥ 1.45 score in the prolonged QTc (77.2%) vs. in the normal QTc group (56.8%) (P, 0.003). QTc interval was 417.76 ± 34.12 ms in patients with FIB-4 score ≥ 1.45 vs. 406.78 ± 31.95 ms in those with FIB-4 < 1.45 (P, < 0.001). FIB-4 score value of 2.108 predicted prolonged QTc with a sensitivity of 63.2% and a specificity of 64.5% (P, < 0.001). Twenty-four patients of long QTc group sent ECGs after HCV eradication, and 19 patients (79%) showed QTc normalization. CONCLUSIONS: HCV is associated with QTc prolongation even in patients with early chronic liver disease stages without significant fibrosis. Also, it is related to the degree of fibrosis and cirrhosis. At a cutoff value of 2.108, FIB-4 score can predict prolonged QTc. HCV eradication is associated with a high incidence of QTc normalization.

A significant upsurge of body mass index in patients with chronic hepatitis C successfully treated with direct-acting antiviral regimens.

BACKGROUND/AIMS: There is less data regarding the changes in body mass index (BMI) after treating hepatitis C virus (HCV) patients with new direct-acting antiviral agents (DAAs). This study aimed to assess the changes in BMI in chronic HCV patients treated with DAAs in Egypt and to explore other factors influencing this change. MATERIALS AND METHODS: The data of chronic HCV patients who received antiviral therapy with new DAAs in one of Egypt's specialized viral hepatitis treatment centers were retrospectively analyzed. In addition to the routine clinical and laboratory workup, changes in body weight during and after treatment were monitored and BMI was calculated. Viral load was measured at 12 weeks post-treatment to assess a sustained virological response. Patients with documented thyroid abnormalities, bariatric surgery, or ensuing special diets were excluded. BMI of >30 was taken as the cutoff for pa¬tients with obesity. RESULTS: The study included 162 patients with a mean age of 48.56±11.49 years, of whom 61.1% were males, 16% were treatment-experienced, 12% were diabetic, and 29% were obese. Treatment duration was 12 weeks in 84% of patients and 24 weeks in 16% of patients. There was a significant increase in BMI post-treatment as compared to pretreatment measures (28.68±5.35 vs 28.18±4.55) (p=0.03). BMI changes were constant regardless of cirrhosis or previous treatment experience. CONCLUSION: Treatment of chronic HCV with DAAs was associated with increased body mass index. Further studies are needed to explore if this effect is secondary to treatment with DAAs or is an improvement in the liver function and lifestyle of treated patients.

Egyptian liver library: An indexed database for liver disease evidence in Egypt.

Liver diseases are among the most challenging health care problems worldwide. In Egypt, we established different care programs to combat liver diseases including schistosomiasis and viral hepatitides. A lot of research work addressing liver diseases in Egypt have been published with special focus on these two major fields. Other liver disease seems to be neglected although present and contributing to the liver disease burden in Egypt. In this report we reviewed the available evidence published from Egypt and elucidate areas of weakness and future research needs. Our search for Egyptian liver disease evidence retrieved 4683 articles, 67% of them were relevant to the topic. Out of the relevant articles; 1646/3265 (50.4%) were discussing clinical science, 1131 (34.7%) were discussing basic science and 488 (14.9%) were discussing both basic and clinical sciences. Cairo university (16.8%, n = 513) and Mansoura university (9.3%, n = 285) had the largest number of publications related to liver disease in Egypt respectively. The most commonly reported diseases were hepatitis C in 719/3361 articles (21.4%), parasitic liver infestations in 663 articles (19.7%), hepatocellular carcinoma in 544 articles (16.2%), liver fibrosis or cirrhosis in 537 articles (16%), and drug induced liver injury in 516 articles (15.4%). Most of the reviewed articles (36%) were discussing treatment of chronic liver diseases (n = 1201) followed by diagnostics (28%, n = 940), pathogenesis and pathophysiology (21%, n = 706). This review will direct attention to areas with less research like hepatitis B related liver disease, HIV/HCV co-infections, and non-alcoholic fatty liver disease (NAFLD) to encourage future research in these topics. In conclusion; our results ring a bell inviting the development of a roadmap for liver research in Egypt targeting to put future policies to cover areas of weakness in liver research with an ultimate goal of tackling liver disease and its overwhelming socioeconomic burden in our developing country.

Real-world results of direct-acting antivirals use for the treatment of chronic hepatitis C in old patients.

BACKGROUND AND AIM: Old people with chronic hepatitis C (HCV) were considered a difficult-to-treat category with more frequent adverse events until recently. Interferon-free direct-acting antivirals (DAAs) improved treatment adherence and quality of life of old patients. In this study, we aimed at reporting the real-world efficacy and safety of DAAs, in addition to predictors of sustained virological response (SVR) in old chronic HCV population. METHODS: This is a prospective observational intention-to-treat analysis that included old chronic hepatitis C genotype-4 patients (> 65 years) treated in a single specialized viral hepatitis treatment center in Egypt. Treatment regimens were allocated according to national guidelines for treatment of hepatitis C. Primary outcome was undetectable HCV-RNA at 12-week post-treatment by PCR. Secondary outcomes were identification of predictors of SVR and assessment of safety related issues. RESULTS: Our study included 864 patients (64% females) with mean age of 67.7 ± 2.8 years. Overall SVR rate was 98.9% while SVR rates for sofosbuvir/daclatasvir/ribavirin, paritaprevir/ombitasvir/ritonavir/ribavirin, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir/ribavirin, sofosbuvir/simeprevir/daclatasvir/ribavirin, sofosbuvir/simeprevir, interferon/sofosbuvir/ribavirin and sofosbuvir/ribavirin were 100%, 100%, 100%, 100%, 100%, 99.3%, 98% and 94.2%, respectively. DAAs were well tolerated. None of the patients discontinued the treatment due to adverse effects. Higher albumin, higher platelet count, lower bilirubin and lower stage of fibrosis were among predictors of favourable response. CONCLUSION: Different DAAs regimens were safe and effective in old Egyptian patients with chronic HCV.

Towards hepatitis C virus elimination: Egyptian experience, achievements and limitations.

Worldwide, more than one million people die each year from hepatitis C virus (HCV) related diseases, and over 300 million people are chronically infected with hepatitis B or C. Egypt used to be on the top of the countries with heavy HCV burden. Some countries are making advances in elimination of HCV, yet multiple factors preventing progress; remain for the majority. These factors include lack of global funding sources for treatment, late diagnosis, poor data, and inadequate screening. Treatment of HCV in Egypt has become one of the top national priorities since 2007. Egypt started a national treatment program intending to provide cure for Egyptian HCV-infected patients. Mass HCV treatment program had started using Pegylated interferon and ribavirin between 2007 and 2014. Yet, with the development of highly-effective direct acting antivirals (DAAs) for HCV, elimination of viral hepatitis has become a real possibility. The Egyptian National Committee for the Control of Viral Hepatitis did its best to provide Egyptian HCV patients with DAAs. Egypt adopted a strategy that represents a model of care that could help other countries with high HCV prevalence rate in their battle against HCV. This review covers the effects of HCV management in Egyptian real life settings and the outcome of different treatment protocols. Also, it deals with the current and future strategies for HCV prevention and screening as well as the challenges facing HCV elimination and the prospect of future eradication of HCV.

An account of the real-life hepatitis C management in a single specialized viral hepatitis treatment centre in Egypt: results of treating 7042 patients with 7 different direct acting antiviral regimens.

BACKGROUND: A large Egyptian treatment program for HCV was launched in2014 after the introduction of direct-acting antiviral agents (DAAs). This program depended mainly on establishing specialized independent centres for HCV treatment. These centres represent the major strengths in the Egyptian model of care, as they provide integrated care for HCV patients and have enabled Egypt to treat more than one million patients in 3 years. The New Cairo Viral Hepatitis Treatment Center (NCVHTC) is an example of these specialized centres. METHODS: The Egyptian experience in the management of HCV was evaluated by analysing the data of real-life HCV management in the NCVHTC from 2014 to 2017. Results of different treatment regimens in addition to their strengths, limitations and areas for improvement are discussed in this report. RESULTS: A total of 7042 HCV patients have been evaluated for treatment in the NCVHTC. Among them, 5517 patients received treatment by seven different DAA regimens with excellent results. CONCLUSIONS: All regimens were highly effective at treating HCV in a real-life setting, apart from SOF/RBV, which was the least effective. A nationwide screening program and enhancing the follow-up of treated patients are the main missing pillars in the Egyptian model.

Risk of hepatitis B virus reactivation with direct-acting antivirals against hepatitis C virus: A cohort study from Egypt and meta-analysis of published data.

BACKGROUND & AIMS: Hepatitis B virus (HBV) reactivation in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAAs) became an issue. However, its frequency has been poorly estimated, because of the varying definitions used and evaluation of heterogeneous study populations, including those concurrently treated for HBV. METHODS: We prospectively followed HBV surface antigen (HBsAg)-positive Egyptians undergoing interferon-free DAAs, to estimate the risk of HBV reactivation and HBV-related hepatitis. We also conducted a meta-analysis to estimate the reactivation risk using published data obtained from a systematic review of PubMed/Embase, in addition to our Egyptian data. We applied a standard definition of HBV reactivation proposed by the international liver associations (APASL and AASLD). RESULTS: Of 4471 CHC patients, 35 HBsAg-positive patients started interferon-free DAAs without HBV nucleos(t)ide analogues in our Egyptian cohort. Ten experienced HBV reactivation (28.6%), of whom 1 developed hepatitis (10.0%). Our systematic review identified 18 papers. The pooled reactivation risk in HBsAg-positive patients was 18.2% (95% CI: 7.9%-30.7%) without HBV therapy and 0.0% (95% CI: 0.0%-0.0%) with HBV nucleos(t)ide analogue. The pooled risk of hepatitis in those with HBV reactivation was 12.6% (95% CI: 0.0%-34.7%). The pooled reactivation risk in HBsAg-negative, antibody to HBV core antigen-positive (anti-HBc-positive) patients was negligible (0.1%, 95% CI: 0.0%-0.3%), irrespective of the presence of antibody to HBsAg (anti-HBs). CONCLUSIONS: We confirmed high HBV reactivation risk in HBsAg-positive patients undergoing DAAs, with only a minority developing clinically important hepatitis. The risk is negligible for HBsAg-negative anti-HBc-positive patients.

Real time endoscopic ultrasound elastography and strain ratio in the diagnosis of solid pancreatic lesions.

AIM: To evaluate the accuracy of the elastography score combined to the strain ratio in the diagnosis of solid pancreatic lesions (SPL). METHODS: A total of 172 patients with SPL identified by endoscopic ultrasound were enrolled in the study to evaluate the efficacy of elastography and strain ratio in differentiating malignant from benign lesions. The semi quantitative score of elastography was represented by the strain ratio method. Two areas were selected, area (A) representing the region of interest and area (B) representing the normal area. Area (B) was then divided by area (A). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated by comparing diagnoses made by elastography, strain ratio and final diagnoses. RESULTS: SPL were shown to be benign in 49 patients and malignant in 123 patients. Elastography alone had a sensitivity of 99%, a specificity of 63%, and an accuracy of 88%, a PPV of 87% and an NPV of 96%. The best cut-off level of strain ratio to obtain the maximal area under the curve was 7.8 with a sensitivity of 92%, specificity of 77%, PPV of 91%, NPV of 80% and an accuracy of 88%. Another estimated cut off strain ratio level of 3.8 had a higher sensitivity of 99% and NPV of 96%, but with less specificity, PPV and accuracy 53%, 84% and 86%, respectively. Adding both elastography to strain ratio resulted in a sensitivity of 98%, specificity of 77%, PPV of 91%, NPV of 95% and accuracy of 92% for the diagnosis of SPL. CONCLUSION: Combining elastography to strain ratio increases the accuracy of the differentiation of benign from malignant SPL.

Toll-like receptors-2 and -9 (TLR2 and TLR9) gene polymorphism in patients with type 2 diabetes and diabetic foot.

Toll-like receptors (TLRs) are innate immune receptors that mediate the inflammatory response in diabetes mellitus (DM). The aim of this study is to evaluate the association of TLR2 and TLR9 gene polymorphism in patients with type 2 DM (T2DM) and diabetic foot (DF).The study included 90 subjects divided into group I (30 patients with T2DM and DF), group II (30 patients with T2DM and no evidence of DF), and group III (normal control subjects). TLR2 (1350 T/C, rs3804100) and TLR9 (1237 T/C, rs5743836) genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for all subjects.There was a statistically significant difference in the distribution of TLR9-1237 T/C genotypes between groups I and II (P < .029) as well as between groups I and III (P < .001). Calculated risk estimation revealed that TLR9-1237 polymorphism conferred almost 20 times increased risk of DF disorders in T2DM (OR = 20, 95% CI = 5.38-74.30). There was no statistical difference in the distribution of TLR2-1350T/C genotypes between the 3 groups.TLR9-1237 T/C gene polymorphism may be considered as a molecular risk for DF among patients with T2DM.

Discovery and preclinical development of dasabuvir for the treatment of hepatitis C infection.

INTRODUCTION: Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality. Positively, the introduction of new directly-acting antivirals (DAAs) have led to dramatic improvements in response rates to antiviral therapy. Furthermore, newer generations of DAAs have demonstrated better safety profiles as well as efficacy than older generations. Current treatment recommendations are based on different combinations of DAAs. Current combination therapies rely on agents that target the different steps of viral replication by using different molecules from various DAAs families. Areas covered: In this review, the authors summarize data from of one of the recently developed NS5B polymerase inhibitors, dasabuvir, formerly known as ABT-333. Herein, the authors discuss the drug discovery data for dasabuvir including data from preclinical, toxicological resistance studies. The authors also review dasabuvir's clinical efficacy across various clinical challenges, in addition to its limitations in clinical practice. Expert opinion: Dasabuvir represents an important medical advance when used as a combination therapy for HCV. Unfortunately, it does present limitations like low genotypic coverage and further research is still required to address some of the lingering issues.