Pavani Garlapati

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.

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.

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.

A Rare Case of Systemic Lupus Erythematosus with Gastric Ulcer and Acute Pancreatitis: A Case Report and Literature Review

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease which can manifest in many different organ systems. Gastrointestinal (GI) involvement is common in SLE, but the symptoms are usually mild. More severe GI complications including acute pancreatitis and peptic ulcer bleeding are rare but represent a significant risk of morbidity and mortality. We present a case of a 25-year-old Hispanic female with a severe SLE flare. The initial presentation included symptoms of hematemesis and epigastric abdominal pain secondary to both gastric ulceration and acute pancreatitis, an atypical presentation of an SLE flare. The non-specific symptom of abdominal pain makes both acute pancreatitis and gastric ulcer disease a clinical challenge; however, clinicians need to have a high suspicion for these conditions co-existing at the same time due to higher mortality rates.

Metachronous Granular Cell Tumor of the Descending Colon

Granular cell tumors (GCTs) are uncommon tumors. They are believed to be neuronal in origin and are usually found in the head and/or neck area of the body. They have also been reported in various locations of the gastrointestinal (GI) system, usually discovered during routine screening colonoscopy. We report a case of GCT in a 58-year-old asymptomatic African American female as a metachronous tumor of a well-differentiated adenocarcinoma of the sigmoid colon, which was an incidental finding in screening colonoscopy. To our knowledge, this is the first case with GCT identified as a metachronous tumor following an adenocarcinoma of the colon.

Association Between Vitamin D Levels and Treatment Response to Direct-Acting Antivirals in Chronic Hepatitis C: A Real-World Study

Background Low serum vitamin D levels in chronic hepatitis C (CHC) is associated with advanced liver fibrosis; and there remains an imprecise relationship with the treatment response based on the vitamin D levels. Previous studies have shown conflicting results on the vitamin D levels, and association with treatment response in CHC treated with interferon-based regimens. Methods Patients with CHC treated with direct-acting antivirals (DAAs) between January 2016 and December 2017 in the community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with the sustained virologic response at 12 weeks post-treatment (SVR 12) were assessed in CHC patients with deficient, insufficient, and normal levels of vitamin D measured before the initiation of DAA therapy. Results Two hundred and ninety-one patients were included in the study. Direct-acting antivirals included in the study were ledipasvir/sofosbuvir ± ribavirin, ombitasvir + paritaprevir + ritonavir + dasabuvir ± ribavirin, and sofosbuvir/velpatasvir. An overall sustained virologic response was achieved in 95% (n = 276) of patients. SVR 12 rates among patients with vitamin D deficiency, vitamin D insufficiency and normal vitamin D levels were 92%, 96.2%, and 97.2% respectively and was not statically significant (P = 0.214). A total of 71 patients were cirrhotic. The prevalence of vitamin D insufficiency (20 - 29.9 ng/mL) and deficiency (< 20 ng/mL) was significantly higher in cirrhotic patients (P = 0.01). Despite this, pretreatment vitamin D levels did not show any impact on the virologic response. The most common adverse effect observed was fatigue. None of the patients had to discontinue the treatment due to adverse events. Conclusions DAAs are safe and effective with a high overall SVR 12 in CHC and treatment response does not depend on the pretreatment vitamin D levels. The prevalence of both vitamin D insufficiency and deficiency was observed to be higher in cirrhotic cohorts compared to non-cirrhotic counterparts.

Direct-Acting Antivirals in Chronic Hepatitis C Genotype 4 Infection in Community Care Setting

Background Limited data exists comparing the safety, tolerability, and efficacy of direct-acting antivirals (DAAs) in patients with chronic hepatitis C genotype 4 (HCV GT-4) in the community practice setting. We aim to evaluate the treatment response of DAAs in these patients. Methods All the HCV GT-4 patients treated with DAAs between January 2014 and October 2017 in a community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with sustained virologic response (SVR) at 12 weeks post treatment (SVR12), and adverse reactions were assessed. Results Fifty-two patients of Middle Eastern (primarily Egyptian) descent were included in the study. Thirty-two patients were treated with ledipasvir/sofosbuvir (Harvoni®) ± ribavirin, 12 patients were treated with ombitasvir/paritaprevir/ritonavir/dasabuvir (ViekiraPak®) ± ribavirin, and eight patients were treated with sofosbuvir/Velpatasvir (Epclusa®). Ten patients (19.2%) had compensated cirrhosis. Overall, SVR at 12 weeks was achieved in 94% in patients who received one of the three DAA regimens (93.8% in Harvoni® group, 91.7 % in ViekiraPak® group and 100% in Epclusa® group). Prior treatment status and type of regimen used in the presence of compensated cirrhosis had no statistical significance on overall SVR achievement (P value = 0.442 and P value = 0.091, respectively). The most common adverse effect was fatigue (27%). Conclusions In the real-world setting, DAAs are effective and well tolerated in patients with chronic HCV GT-4 infection with a high overall SVR rate of 94%. Large-scale studies are needed to further assess this SVR in these groups.