Mazin Khalid

Clinical efficacy and tolerability of direct-acting antivirals in elderly patients with chronic hepatitis C

Background There is a lack of evidence-based data on aged patients with newer direct-acting antivirals (DAAs) and with shorter duration of treatment regimens involving DAAs with or without ribavirin (RBV) and pegylated interferon (Peg IFN). Patients and methods Medical records of 240 patients treated with DAAs with or without Peg IFN and RBV between January 2013 and July 2015 were retrospectively analyzed. Patients were divided into two groups: patients aged 65 years and older (N=84) and patients aged younger than 65 years (N=156). Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks after treatment, and adverse reactions were compared between the groups. Results No statistically significant difference was observed with end of treatment response (98.8 vs. 98%, P=0.667) and sustained virologic response at 12 weeks after treatment (93.1 vs. 94.1%, P=0.767) between patients aged 65 and older and those younger than 65 years of age. Fatigue was the most common adverse event recorded (32.5%), followed by anemia (19.6%), leukopenia (11.7%), thrombocytopenia (10%), skin rash (8.3%), and headache (7.9%). The RBV dose was reduced in eight (8%) patients and four patients discontinued the RBV treatment because of severe anemia. RBV dose reduction or discontinuation did not reach statistical significance (P=0.913). Increased fibrosis, cirrhosis, aspartate aminotransferase, alanine aminotransferase, hemoglobin, and platelet levels seem to affect the sustained virologic response in the elderly. Twelve (6.28%) patients failed to respond to treatment and the failure rate was not significant (P=0.767) between the groups. Conclusion DAAs with or without IFN and RBV in the standard recommended 12 or 24-week treatment regimens are effective, well tolerated, and may be safely extended to elderly patients infected with chronic hepatitis C.

Hyperacute liver injury following intravenous fluconazole: A rare case of dose-independent hepatotoxicity

Fluconazole is a triazole antifungal medication used in the treatment of various fungal infections. It is available in both oral and parenteral formulations. Liver damage has been reported with fluconazole use, but most commonly it is benign elevated liver transaminases. Acute liver failure (ALF) in fluconazole use is rare, with cases being reported sporadically in literature and large cohorts describing incidence rates of acute liver injury ranging from 0.0 to 31.6/10,000 patients. We present a case of a 45-year-old African-American male with no history of liver disease who presented with superficial candidiasis and superimposed bacterial cellulitis. He was subsequently started on intravenous fluconazole and clindamycin. Shortly after he developed ALF and a drug-induced liver injury (DILI) was suspected. Fluconazole was stopped, and the clinical picture improved shortly afterward, leading to a diagnosis of fluconazole-induced ALF. Patient underwent laboratory and clinical evaluation to exclude competing etiologies of liver injury as well as a standardized assessment for causality and disease severity such as Roussel Uclaf Causality Assessment Method/Council for International Organizations of Medical Sciences score, which concluded a “Highly Probable” DILI, and a Naranjo score identifying adverse drug reaction (ADR) which concluded a “Definite ADR.” Due to the severity of ALF and the routine use of fluconazole in clinical practice, clinicians should be aware that fluconazole can be a causative agent of ALF, even in low-risk populations.

Hypereosinophilic Syndrome Complicated by Eosinophilic Myocarditis With Dramatic Response to Steroid

Introduction. Eosinophilic myocarditis is an infiltrative disease that affects the myocardium leading to various presentations. It can be precipitated by medications, helminthiasis, or hypereosinophilic syndrome. Case. We present the case of a young, male patient who presented with palpitations and dyspnea and was found to have heart failure with reduced ejection fracture of 12%. His past medical history was significant for recent lung problem treated with steroids. Based on his history and laboratory findings, he was started on intravenous steroids for treatment of eosinophilic myocarditis. Within 3 days, his ejection fracture improved to 35%. Conclusion. Given the nonspecific clinical presentations, mimicking other diseases, high index of suspicion is warranted to diagnose eosinophilic myocarditis. This is crucial as early detection and treatment with steroids can lead to a dramatic response.

Drug-Induced Liver Injury: An Institutional Case Series and Review of Literature:

Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the USA. DILI can be broadly classified as Intrinsic and Idiosyncratic. Identifying predictors and at-risk patients are challenging but can have a substantial clinical implication. This case report series demonstrates the importance of valproic acid, fluconazole, and amiodarone as potential hepatoxic agents of drug-induced liver injury leading to acute hepatic failure. The causality in all cases was established by Roussel Uclaf Causality Assessment Method/Council for International Organizations of Medical Sciences score and Naranjo Algorithm. Obesity, hypo-perfusion state, and concurrent hepatotoxic agent might identify at-risk patients. Further studies are required to understand the risk factors.

A Rare Case of Acute Pancreatitis Due to Very Severe Hypertriglyceridemia (>10 000 mg/dL) Successfully Resolved With Insulin Therapy Alone: A Case Report and Literature Review

A 48-year-old male presented to the psychiatric emergency room for dysmorphic mood. He was admitted to medical service for the management of hyponatremia, which was discovered in his initial laboratory workup. After the first day of admission, he developed abdominal pain and fever, and subsequent laboratory work revealed a triglyceride level of 10 612 mg/dL (reference range = 0-194 mg/dL). Computed tomography scan of the abdomen and pelvis revealed a hypodense lesion in the pancreas surrounded by a moderate amount of peripancreatic fluid suggestive of hemorrhagic pancreatitis. Based on the laboratory findings and imaging, we diagnosed acute pancreatitis (AP) secondary to hypertriglyceridemia. The patient was initiated on intravenous fluids and insulin to help decrease the triglyceride level with the plan to initiate apheresis. However, the patient improved on insulin therapy alone, which negated the need for apheresis, and the patient was discharged with fenofibrate with no further complications. While elevated triglycerides are a well-known cause of AP, we sought to assess various treatment options in management, especially considering a severely elevated triglyceride level of >10 000 mg/dL. Along with supportive care in AP, there are additional options in hypertriglyceridemia AP, including heparin, insulin, apheresis, antioxidants, and fibrates. Currently, there are no clear guidelines favoring one therapeutic option over the other.

Valproic acid induced acute liver injury resulting in hepatic encephalopathy- a case report and literature review

ABSTRACT Valproic acid (VPA) is a commonly used agent in the management of seizures and psychiatric disorders. Hyperammonemia is a common complication of VPA with 27.8% of patients having elevated levels – that is unrelated to hepatotoxicity and normal transaminases. Common side effects include obesity, insulin resistance, metabolic disorder and severe forms of hepatotoxicity. Other rare and idiosyncratic reactions have been reported, one of which is presented in our case. A 27-year old patient presented with hyperammonemia and encephalopathy as a consequence of idiosyncratic VPA reaction causing drug-induced liver injury (DILI) with severely elevated transaminases. DILI is commonly overlooked when investigating encephalopathy in the setting of VPA. Physicians should consider DILI in the context of hyperammonemia and transaminitis.

Predictors of hospital stay in normotensive acute pulmonary embolism: a retrospective pilot study

ABSTRACT Introduction: The aim of our study is to determine the clinical, biochemical, and imaging factors that affect the duration of hospital stay in patients admitted with normotensive acute pulmonary embolism. Methods: This was a single-center retrospective study conducted in a community hospital in New York metropolitan area for patients admitted from October 2015 to October 2017. Results: A total of 79 patients were included, the mean age was 55.76 (SD = 17.33), 29 cases were males (37%) and 50 cases were females (63%). Among all patients, 17 cases had short length of stay (LOS) (≤2 days) and 62 cases had long LOS (>2 days). There were statistically significant differences in age (p = .041), presence of lung disease (p = .036), number of comorbidities (p = .043), and pulmonary embolism severity index (PESI) scores (original and simplified; p = .002 and .001, respectively). Logistic regression analysis showed that PESI score significantly predicted long LOS (OR 1.067, 95% CI [1.001, 1.137], p = .048). Similarly, sPESI significantly predicted long LOS (OR 0.223, 95% CI [0.050, 0.999], p = .050). Both regression models were adjusted for age, lung disease, and number of comorbidities. Conclusion: Both original and simplified PESI scores were statistically significant predictors of duration of hospital stay. Patients with multiple comorbidities or with chronic lung disease were also likely to have prolonged hospital stay. None of the cardiac biomarkers affected the duration of hospital stay, neither did the presence of right ventricular dysfunction nor treatment modality.

Spinal gout causing reversible quadriparesis: a case report and literature review

ABSTRACT Gout commonly affects peripheral joints and is rarely found in axial joints, such as the spine and sacroiliac joints. We report a case of a patient that presented with quadriparesis who was empirically treated for spinal gout and a review of relevant literature. A 77-year-old male presented with new-onset quadriparesis that developed over 3 days. MRI imaging was suggestive of tophaceous gout of the cervical spine, but our patient refused a spinal biopsy. He was empirically treated with high-dose steroids and his upper and lower extremities weakness started improving within 3 days and resolved completely. Although spinal gout is uncommon, this case indirectly suggests that gout should be kept as a differential diagnosis when faced with back pain or quadriparesis. This case implies that empiric treatment should be considered when radiographic evidence is suggestive of tophaceous gout of the spine.

Sofosbuvir Based Regimens in the Treatment of Chronic Hepatitis C with Compensated Liver Cirrhosis in Community Care Setting

Background Direct-acting antiviral (DAA) drugs have been highly effective in the treatment of chronic hepatitis C (CHC) infection. We aim to evaluate the treatment response of Sofosbuvir based DAA in CHC patients with compensated liver cirrhosis as limited data exists in the real-world community setting. Methods All the CHC patients with compensated liver cirrhosis treated with Sofosbuvir based DAAs between January 2014 and December 2017 in a community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with the sustained virologic response at 12 weeks posttreatment (SVR12), and adverse reactions were assessed. Results One hundred and twelve patients with CHC infection and concurrent compensated cirrhosis were included in the study. Black patients represented the majority of the study population (64%). Eighty-seven patients were treated with Ledipasvir/Sofosbuvir (LDV/SOF) ±Ribavirin and 25 patients were treated with Sofosbuvir/Velpatasvir (SOF/VEL). Overall, SVR 12 after treatment was achieved in 90% in patients who received one of the two DAA regimens (89.7% in LDV/SOF group and 92% in SOF/VEL group). SVR 12 did not vary based on age, sex, body mass index, baseline HCV viral load, HCV/HIV coinfection, type of genotype, and prior treatment status. Apart from a low platelet count, there were no other factors associated with a statistical difference in SVR 12(p=0.002) between the two regimens. Fatigue (35%) was the most common adverse effect and no patients discontinued treatment due to adverse effects. Conclusion In the community care setting, Sofosbuvir based DAAs are safe, effective with high overall SVR, and well tolerated in patients with CHC patients with compensated liver cirrhosis.

Real-World Clinical Efficacy and Tolerability of Direct-Acting Antivirals in Hepatitis C Monoinfection Compared to Hepatitis C/Human Immunodeficiency Virus Coinfection in a Community Care Setting

Background/Aims Limited data exist comparing the safety and efficacy of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) monoinfected and HCV/human immunodeficiency virus (HIV) coinfected patients in the real-world clinic practice setting. Methods All HCV monoinfected and HCV/HIV coinfected patients treated with DAAs between January 2014 and October 2017 in community clinic settings were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks (SVR12) after treatment, and adverse reactions were compared between the groups. Results A total of 327 patients were included in the study, of which 253 were HCV monoinfected, and 74 were HCV/HIV coinfected. There was a statistically significant difference observed in SVR12 when comparing HCV monoinfection and HCV/HIV coinfection (94% and 84%, respectively, p=0.005). However, there were no significant factors identified as a predictor of a reduced response. The most common adverse effect was fatigue (27%). No significant drug interaction was observed between DAA and antiretroviral therapy. None of the patients discontinued the treatment due to adverse events. Conclusions In a real-world setting, DAA regimens have lower SVR12 in HCV/HIV coinfection than in HCV monoinfection. Further studies involving a higher number of HCV/HIV coinfected patients are needed to identify real predictors of a reduced response.