Immune-Escape Mutations Are Prevalent among Patients with a Coexistence of HBsAg and Anti-HBs in a Tertiary Liver Center in the United States.

The concurrent seropositivity of HBsAg and anti-HBs has been described among patients with chronic hepatitis B (CHB), but its prevalence is variable. HBV S-gene mutations can affect the antigenicity of HBsAg. Patients with mutations in the 'α' determinant region of the S gene can develop severe HBV reactivation under immunosuppression. In this study at a tertiary liver center in the United States, we evaluated the frequency and virological characteristics of the HBsAg mutations among CHB patients with the presence of both HBsAg and anti-HBs. In this cohort, 45 (2.1%) of 2178 patients were identified to have a coexistence of HBsAg and anti-HBs, and 24 had available sera for the genome analysis of the Pre-S1, Pre-S2, and S regions. The frequency of mutations in the S gene was significantly higher among those older than 50 years (mean 8.5 vs. 5.4 mutations per subject, p = 0.03). Twelve patients (50%) had mutations in the 'α' determinant region of the S gene. Mutations at amino acid position 126 were most common in eight subjects. Three had a mutation at position 133. Only one patient had a mutation at position 145-the classic vaccine-escape mutation. Despite the universal HBV vaccination program, the vaccine-escape mutant is rare in our cohort of predominantly Asian patients.

An Interesting Case of Possible Left Atrium Thrombus Versus Fungal Mass in a Patient With Ischemic Cardiomyopathy.

Left atrial masses can present diagnostic challenges due to the wide range of etiologies they can encompass. We present a unique case of a 48-year-old patient with ischemic cardiomyopathy and end-stage renal disease (ESRD) on hemodialysis, who developed a left atrial mass after undergoing intervention with drug-eluting stents. The differential diagnosis included left atrial thrombus versus fungal mass. The patient presented with chest pain and subsequently developed sepsis during the hospital stay, with further workup revealing evidence of fungemia. Transthoracic echocardiography (TTE) demonstrated the presence of a new mass in the left atria. The challenge was to differentiate between a left atrial thrombus and a fungal mass. The patient was managed with a combination of antifungal therapy and anticoagulation and was discharged home. This case highlights the diagnostic complexities and management considerations associated with left atrial masses in patients with underlying ischemic cardiomyopathy, ESRD, and septic complication versus cardiogenic shock. Accurate differentiation between left atrial thrombus and fungal mass is crucial to guide appropriate treatment strategies. A multidisciplinary approach involving cardiology, infectious diseases, and nephrology is essential in managing such complex cases.

Case of cryoglobulinaemia associated with chronic hepatitis B.

We present a case of a woman in her 50s with chronic hepatitis B (CHB) who had a longstanding history of arthralgia and swollen joints associated with severe fatigue. Investigations were consistent with a diagnosis of hepatitis B virus (HBV)-related cryoglobulinaemia. Two months after treatment with tenofovir alafenamide, an antiviral therapy for HBV, there was a significant improvement of her symptoms and undetectable serum cryoglobulins. Cryoglobulinaemia is a relatively rare extrahepatic manifestation of HBV infection and only presents in about 2%-4% of the patients with CHB. Its clinical manifestations include purpura, renal dysfunction, arthralgias and neuropathy. Since the presentation of cryoglobulinaemia in CHB can be non-specific, one needs to have a high index of suspicion to avoid delay in diagnosis and treatment.

Risk of hepatocellular carcinoma after hepatitis C virus cure.

Hepatitis C virus (HCV) is a significant cause of hepatocellular carcinoma (HCC). The direct-acting antivirals marked a new era of HCV therapy and are associated with greater than 95% cure rate. Successful treatment of chronic hepatitis C greatly reduces the risk of HCC. A proportion of patients, especially those with pre-existing cirrhosis, remain at risk for HCC despite sustained virologic response (SVR). Diabetes mellitus, hepatic steatosis, alcohol consumption and lack of fibrosis regression are associated with risks of HCC after HCV cure. Noninvasive modalities such as aspartate aminotransferase to platelet ratio index and fibrosis-4 index and transient elastography have been used to monitor hepatic fibrosis. More recently, various fibrosis scores have been combined with clinical parameters and other novel biomarkers to predict risks of HCC for patients who achieved SVR. These models still need to be validated and standardized prior to applying to routine clinical care.

Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma.

Alpha-fetoprotein (AFP) is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma (HCC) in combination with ultrasound and other imaging modalities. Its utility is limited because of both low sensitivity and specificity, and discrepancies among the different methods of measurements. Moreover, its accuracy varies according to patient characteristics and the AFP cut-off values used. Combination of AFP with novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73) and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC. Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis. Hereditary and other non-hepatic disorders can also cause AFP elevation.

Novel Therapies of Hepatitis B and D.

Hepatitis B virus (HBV) infection is a global public health issue and is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Hepatitis D virus (HDV) requires the hepatitis B surface antigen (HBsAg) to replicate. The eradication of HBV, therefore, can also cure HDV. The current therapies for chronic hepatitis B and D are suboptimal and cannot definitely cure the viruses. In order to achieve functional or complete cure of these infections, novel therapeutic agents that target the various sites of the viral replicative cycle are necessary. Furthermore, novel immunomodulatory agents are also essential to achieve viral clearance. Many of these new promising compounds such as entry inhibitors, covalently closed circular DNA (cccDNA) inhibitors, small interfering RNAs (siRNAs), capsid assembly modulators and nucleic acid polymers are in various stages of clinical developments. In this review article, we provided a comprehensive overview of the structure and lifecycle of HBV, the limitations of the current therapies and a summary of the novel therapeutic agents for both HDV and HBV infection.

Large Emphysematous Bullae Mimicking As A Pneumothorax Leading To Unnecessary Chest Tube Insertion And Iatrogenic Pneumothorax.

Pneumothorax (Pnx) is the presence of air or gas in the pleural space which hinders the lungs to function appropriately. Pneumothorax that presents in the absence of any underlying aetiology is called primary spontaneous pneumothorax (PSP) and on the other hand, it may present as a complication of underlying lung disease which is known as secondary spontaneous pneumothorax (SSP). Iatrogenic Pneumothorax (IP) is a type of SSP and is caused by medical interventional procedures which include transthoracic needle biopsy (24%), sub clavicular catheterization (22%), thoracocentesis (20%), transbronchial biopsy (10%), pleural biopsy (8%) and positive pressure ventilation (7%). We had a 51-year-old patient with a history of COPD/emphysema who presented with respiratory distress. Large bullae were mistaken as pneumothorax, unnecessary Chest Tube Insertion (thoracostomy) was performed resulting in IP. An extensive review of the literature shows there are only a few reported cases of unnecessary thoracotomy and IP in settings of giant bulla mimicking pneumothorax. Iatrogenic Pneumothorax resulting from giant bullae mimicking pneumothorax leading to unnecessary chest tube insertion. Physicians should be aware of such aetiology of pneumothorax as it has been rarely reported in the literature.

Reinfection of COVID-19 in Pakistan: A First Case Report.

Since its spread across the world, coronavirus disease 2019 (COVID-19) has posed a severe public health threat, and many unanswered questions about COVID-19 remain. Antibodies have been detected a few days after the onset of infection, and in some patients, these antibodies wane quickly. To date, it is unknown whether all infected patients induce an adequate protective immune response or how long this effect remains. Here, a first case report of COVID-19 reinfection in Pakistan is reported within two months of complete recovery from the first severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection - confirmed with two sequential negative nasopharyngeal swabs.

Takotsubo Cardiomyopathy Triggered by the Death of Pets (Cats): Two Case Reports.

Takotsubo cardiomyopathy otherwise called stress cardiomyopathy, which results in debilitating of a segment of heart muscles, is a sort of non-ischemic cardiomyopathy, set off by stress. We describe two case reports of takotsubo cardiomyopathy triggered by the significant stressful event being the death of pet cats. The rare nature of the type of stressor and the manifestation is something to be considered by healthcare providers.

Locked-in Syndrome in a Young Patient Due to SARS-CoV-2: A Case Report.

Coronavirus disease 2019 (COVID-19), apart from commonly involving the respiratory system, has its impact on the central nervous system, with a wide spectrum of clinical presentations ranging from headaches to ischemic strokes. The ongoing research regarding this novel disease has found that there is a very high prevalence of thrombotic episodes especially in critically ill patients when compared to severe presentation of other viral illnesses. This COVID-19-associated coagulopathy has a very complex etiology with the ability to form thrombus in arteries, veins, and microvasculatures of different organs. We present a unique case of a young woman with underlying COVID-19 who unfortunately developed locked-in syndrome due to bilateral pontine infarction during the course of her illness.

Acute Upper Limb Ischemia Due To Arterial Thrombosis in a Mild COVID-19 Patient: A Case Report.

Coronavirus disease 2019 (COVID-19) which has now been declared a global pandemic, initially began as a pneumonia caused by novel coronavirus called severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in Wuhan, China. COVID-19, in addition to respiratory symptoms, is also being recognized to have different manifestations including myocardial infarction, seizures, meningitis, diarrhea, and coagulopathy. Here we report a case of a 75-year-old female patient with mild COVID-19 who later developed acute limb ischemia due to arterial thrombosis to highlight that, contrary to the association of coagulopathy with severe COVID-19, thrombosis can also occur in patients with mild COVID-19.

A Review of the Risk Factors Associated With Poor Outcomes in Patients With Coronavirus Disease 2019.

The global pandemic of coronavirus disease 2019 (COVID-19) and its rapid spread throughout the globe is of much concern. With little known about the peculiar virus and the changing mortality and morbidity, we attempt to review the risk factors associated with significant outcome.  We conducted a review of the information available in medical journals published on COVID-19 risk factors associated with poor outcomes using PubMed®, Google Scholar, and material published online. The risk factors associated with poor outcome were kept in particular consideration. A total of 96 articles were thoroughly reviewed and analyzed so as to highlight the risk factors and the subsequent disease presentation that were present in patients with COVID-19. With little data available in this regard, emphasis and consideration of risk factors might help health care workers preclude the worst outcome. From the aforementioned search we can conclude that the most prevalent risk factors were reported to be hypertension followed by diabetes. In terms of mortality, age greater than 65 was the most significant risk factor. Among non-survivors, coagulation profile including d-dimers, prothrombin time, and inflammatory markers like erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum ferritin levels were very deranged. Much emphasis and consideration in relation to risk factors must be deliberated by health care workers so as to prevent severe outcomes and mitigate appropriate treatment modalities.

Meningitis as an Initial Presentation of COVID-19: A Case Report.

The common presenting symptoms of fever, fatigue, and mild respiratory symptoms like dry cough, are associated with COVID-19, however, patients can also develop neurological manifestations like headache, anosmia, hyposmia, dysgeusia, meningitis, encephalitis, and acute cerebrovascular accidents during the disease. Although very rare, these neurological manifestations are sometimes the sole initial presenting complaint of COVID-19. This case report discusses patients where the initial presenting symptoms seemed to be exclusive to meningitis but the later diagnosis was COVID-19. It is important to increase awareness of these rare presentations in physicians and healthcare workers and facilitate early diagnosis and management to prevent the horizontal spread of the disease.

Treatment Options for COVID-19: A Review.

Background: The recent COVID-19 pandemic sweeping the globe has caused great concern worldwide. Due to the limited evidence available on the dynamics of the virus and effective treatment options available, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a huge impact in terms of morbidity and mortality. The economic impact is still to be assessed. Aims: The purpose of this article is to review the evidence for the multiple treatment options available, to consider the future of this global pandemic, and to identify some potential options that could revolutionize the treatment of COVID-19. Moreover, this article underscores the sheer importance of repurposing some of the available antiviral and antimicrobial agents that have long been in use so as to have an effective and expeditious response to this widespread pandemic and the need to conduct a multicenter global randomized controlled trial to find an effective single antiviral agent or a cocktail of available antimicrobial agents. Method: We thoroughly searched and reviewed various case reports, retrospective analyses, and in vitro studies published in PubMed, EMBASE, and Google Scholar regarding the treatment options used for SARS-CoV, MERS-CoV, and SARS-CoV-2 since its outbreak in an attempt to highlight treatments with the most promising results. Conclusion: We are currently facing one of the worst pandemics in history. Although SARS-CoV-2 is associated with a lower mortality rate than are SARS-CoV and MERS-CoV, its higher infectivity is making it a far more serious threat. Unfortunately, no vaccine against SARS-CoV-2 or effective drug regimen for COVID-19 currently exists. Drug repurposing of available antiviral agents may provide a respite; moreover, a cocktail of antiviral agents may be helpful in treating this disease. Here, we have highlighted a few available antimicrobial agents that could be very effective in treating COVID-19; indeed, a number of trials are underway to detect and confirm the efficacy of these agents.

Neurological Manifestations of COVID-19 (SARS-CoV-2): A Review.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with many neurological symptoms but there is a little evidence-based published material on the neurological manifestations of COVID-19. The purpose of this article is to review the spectrum of the various neurological manifestations and underlying associated pathophysiology in COVID-19 patients. Method: We conducted a review of the various case reports and retrospective clinical studies published on the neurological manifestations, associated literature, and related pathophysiology of COVID-19 using PUBMED and subsequent proceedings. A total of 118 articles were thoroughly reviewed in order to highlight the plausible spectrum of neurological manifestations of COVID 19. Every article was either based on descriptive analysis, clinical scenarios, correspondence, and editorials emphasizing the neurological manifestations either directly or indirectly. We then tried to highlight the significant plausible manifestations and complications that could be related to the pandemic. With little known about the dynamics and the presentation spectrum of the virus apart from the respiratory symptoms, this area needs further consideration. Conclusion: The neurological manifestations associated with COVID-19 such as Encephalitis, Meningitis, acute cerebrovascular disease, and Guillain Barré Syndrome (GBS) are of great concern. But in the presence of life-threatening abnormal vitals in severely ill COVID-19 patients, these are not usually underscored. There is a need to diagnose these manifestations at the earliest to limit long term sequelae. Much research is needed to explore the role of SARS-CoV-2 in causing these neurological manifestations by isolating it either from cerebrospinal fluid or brain tissues of the deceased on autopsy. We also recommend exploring the risk factors that lead to the development of these neurological manifestations.