Monitoring Of Liver Function Tests Research Articles

Radiation-induced liver disease mimicking liver metastasis after low-dose hepatic irradiation during radiotherapy for gastric mucosa-assisted lymphoid tissue lymphoma: A case report.

Radiation-induced liver disease (RILD) is an established complication of hepatic irradiation that is typically reported in patients receiving high-dose radiotherapy for hepatocellular carcinoma or liver metastases. However, RILD can also occur after unintentional low-dose liver exposure during radiotherapy for other gastrointestinal malignancies when careful precautions are not taken. We report the case of a 44-year-old woman with gastric mucosa-associated lymphoid tissue lymphoma who underwent salvage radiotherapy administered to the entire stomach. One month after completing this radiotherapy, computed tomography and magnetic resonance imaging of the patient's abdomen revealed a 4 cm lesion in the left lateral liver segment, suggestive of metastasis. An ultrasound-guided biopsy was performed, and the histopathological findings were consistent with those of RILD. Conservative management was pursued with close monitoring of liver function tests. The patient's imaging findings and liver enzyme levels normalized approximately 3 months after the initial diagnosis. This case highlights the importance of considering RILD in the differential diagnosis of new hepatic lesions detected after radiotherapy, even in patients with low-dose liver exposure within generally acceptable limits. Careful correlation with the radiotherapy plan is crucial to avoid misdiagnosing RILD as metastatic disease and to guide appropriate management.

Removing the FDA’s Boxed Hepatotoxicity Warning and Liver Function Testing Requirement for Ambrisentan

Endothelin receptor antagonists are first-line therapy for pulmonary arterial hypertension (PAH). The first 2 agents approved in the class, bosentan and ambrisentan, initially carried boxed warnings for hepatotoxicity and required monthly liver function tests (LFTs) as part of a risk evaluation and mitigation strategy (REMS); however, in 2011, as further safety data emerged on ambrisentan, the boxed hepatotoxicity warning and LFT requirements were removed. To analyze changes in the use of and LFT monitoring for ambrisentan and bosentan after changes to the ambrisentan labeling and REMS. This serial cross-sectional study used data from 3 longitudinal health care insurance claims databases-Medicaid, Optum's deidentified Clinformatics Data Mart, and Merative Marketscan-to perform an interrupted time series analysis of prescription fills and LFTs for patients taking ambrisentan and bosentan. Participants were patients filling prescriptions for ambrisentan and bosentan from July 1, 2007, to December 31, 2018. Data analysis was performed from April 2021 to August 2023. Removal of the boxed warning for hepatotoxicity and the REMS LFT monitoring requirements on ambrisentan in March 2011. The primary outcomes were use of ambrisentan (ie, individuals with at least 1 dispensing per 1 000 000 individuals enrolled in the 3 datasets) vs bosentan and LFT monitoring (ie, proportion of initiators with at least 1 ordered test) before initiation and before the first refill. A total of 10 261 patients received a prescription for ambrisentan during the study period (7442 women [72.5%]; mean [SD] age, 52.6 [17.6] years), and 11 159 patients received a prescription for bosentan (7931 women [71.1%]; mean [SD] age, 47.7 [23.7] years). Removal of the ambrisentan boxed hepatotoxicity warning and LFT monitoring requirement was associated with an immediate increase in the use of ambrisentan (1.50 patients per million enrollees; 95% CI, 1.08 to 1.92 patients per million enrollees) but no significant change in the use of bosentan. There were reductions in recorded LFTs before drug initiation (13.1% absolute decrease; 95% CI, -18.2% to -8.0%) and before the first refill (26.4% absolute decrease; 95% CI, -34.4% to -18.5%) of ambrisentan but not bosentan. In this serial cross-sectional study of ambrisentan, labeling changes and removal of the REMS-related LFT requirement were associated with shifts in prescribing and testing behavior for ambrisentan but not bosentan. Further clinician education may be needed to maximize the benefits of REMS programs and labeling warnings designed to ensure the safe administration of high-risk medications.

Factors Influencing Liver Abnormalities in Psoriatic Arthritis Patients: A Comprehensive Study.

The aim of this study was to establish the incidence of liver abnormalities in psoriatic arthritis patients and identify the factors that contributed to this condition. This is a longitudinal cohort study. Psoriatic arthritis (PsA) patients with liver enzymes abnormalities were identified. Our control group consisted of PsA patient from the same cohort who had no history of liver abnormalities. Factors associated with liver abnormalities were identified using univariate and multivariate analysis. A total of 247 of PsA patients were included and out of those, 99 developed liver enzymes abnormalities. The mean age of the patients was 56 years old (±13.5) with 56.1% female and 39.4% Indian descendants. The univariate logistic regression demonstrated that disease duration of PsA (OR=1.06, 95% CI=1.01 - 1.10, p=0.012), diabetes mellitus (OR=2.16, 95% CI=1.26 - 3.70, 0.005) and non-alcoholic fatty liver disease (NAFLD) (OR=3.90, 95% CI = 1.44 - 10.53, p=0.007) were associated with abnormal liver function in PsA patients. No association was found with both conventional synthetic disease-modifying antirheumatic drugs or biologics. Liver enzymes abnormalities in PsA patients were linked to disease duration, diabetes mellitus and NAFLD. For these high-risk populations, vigilant monitoring of liver function tests is vital for early detection and intervention.

Autoimmune Hepatitis Management: Recent Advances and Future Prospects

Autoimmune hepatitis (AIH) is a varied inflammatory chronic liver disease. AIH’s prevalence varies and has increased recently. Diagnosis involves the discovery of histologic features following liver biopsy and serologic testing. Clinical features vary, and up to 40% of patients may be asymptomatic. Evaluating thiopurine methyltransferase (TMPM) activity before treatment is crucial for an optimal response. The primary treatment goal is biochemical remission, normalized serum IgG, and liver enzymes. Induction therapy typically involves azathioprine and corticosteroids. Close monitoring of liver function tests and serum immunoglobulin levels is essential. Medications can be tapered after achieving biochemical remission. Liver transplantation may be required for refractory disease or cirrhosis. Further therapeutic approaches are needed, particularly for non-responders to first-line treatments.

Incidence of amoxycillin-clavulanic acid associated hepatotoxicity in an Australian children's hospital.

Amoxycillin/clavulanic acid is the most common antimicrobial cause of drug-induced liver injury in adults. It is a less common cause of severe drug-related hepatotoxicity in children despite its frequent use. We studied the incidence, characteristics and predictive factors for amoxycillin/clavulanic acid hepatoxicity in children. Retrospective cohort study of children who received oral or intravenous amoxycillin/clavulanic acid at a quaternary children's hospital over a 5-year period. Children were included if they had liver function tests (LFTs) determined at baseline, during and within 3 months after the treatment course. Causality was assessed using the Naranjo criteria for adverse drug reactions and Roussel Uclaf Causality Assessment Method. Of 3271 children prescribed amoxycillin/clavulanic acid, 374 were included. Forty-nine (13%) had LFT abnormalities related to amoxycillin/clavulanic acid. Fourteen (3.6%) fulfilled Common Terminology Criteria for Adverse Events (CTCAE) grade 2 criteria with clinically significant hepatotoxicity. Age <2 years, sepsis, post-gastrointestinal surgical indications, prolonged treatment course of >7 days and higher cumulative amoxycillin (>10 g) and clavulanic acid dose (>1 g) were predictive of hepatotoxicity. The median time to resolution of LFT abnormalities was 4 weeks (range 3-7). The incidence of amoxycillin/clavulanic acid related LFT abnormalities (CTCAE Grade 2 or above) in children was 3.6%. A prolonged treatment course >7 days, high cumulative amoxycillin (10 g) and clavulanic acid (>1 g) doses, those aged <2 years, and patients with sepsis or post-gastrointestinal surgery were predictive of a higher likelihood of abnormal LFTs. LFT monitoring should be considered in children receiving ≥7 days of treatment, particularly in those with other predisposing factors.

Prolonged Itraconazole Therapy as Sole Treatment for Patients with Allergic Fungal Rhinosinusitis.

Currently, the mainstay of treatment for allergic fungal rhinosinusitis (AFRS) is surgical debridement along with topical or systemic steroids. However, prolonged systemic steroid therapy comes with side effects and is also sometimes contraindicated. Systemic antifungals have been used earlier as an adjunct to steroids or in refractory cases, but they have not been used as the sole primary treatment. To study the effectiveness of sole Itraconazole therapy in patients with AFRS by comparison of clinical, radiological, and biochemical parameters before and after treatment. Thirty-four patients diagnosed with localized sino-nasal AFRS were recruited and started on the tablet Itraconazole 200 mg orally twice daily for 3 months with q2weekly monitoring of liver function tests. The baseline clinical, radiological, and biochemical parameters were then compared with those after completion of 3 months of Itraconazole therapy. There was significant difference between all the parameters-clinical: SNOT-22 score (p < 0.001) and Meltzer endoscopy score (p < 0.001), radiological: Lund-Mackay score (p = 0.004) and 20-point CT score (p = 0.002), and biochemical: serum total IgE (p < 0.001), Aspergillus-specific IgE (p < 0.001), and absolute eosinophil count (p < 0.001). The clearance of the disease was more in anterior sinuses than the posterior ones. Prolonged Itraconazole can be given as sole therapy in AFRS, especially in patients for whom steroids are contraindicated or in those who are awaiting surgery. It can result in symptomatic and radiological improvement, but surgery still remains the definitive treatment option for AFRS for complete clearance of disease. 3 Laryngoscope, 134:545-551, 2024.

Retrospective analysis of risk factors for levofloxacin-induced liver injury

Levofloxacin is used as a first-line drug for the treatment of Legionella pneumonia. However, the relatively high incidence of drug-induced liver injury (DILI) remains a clinical problem. Based on the available patient data, this study aimed to identify the risk factors for DILI before levofloxacin administration. Multiple logistic regression analyses suggested that male sex (odds ratio [OR], 6.975; 95% confidence interval [CI], 1.737–28.000; p = 0.006), elevated C-reactive protein level (OR, 1.182; 95% CI, 1.089–1.283; p = 0.0006), and high haemoglobin level (OR, 1.640; 95% CI, 1.226–2.195; p = 0.001) before administration of levofloxacin were risk factors for DILI. Possible treatment with alternative drugs should be considered in male patients with elevated C-reactive protein and haemoglobin levels. Moreover, close monitoring of liver function tests when levofloxacin is administered may prevent the development and severity of DILI.

Hepatitis E Vaccination in Pakistan: Where Do We Stand

Hepatitis E is not something new when it comes to hepatology practice. We have been hearing it for years just like any other hepatitis but the troublesome dilemma is that we didn't have any vaccination for it until few years recently and the main treatment was conservative. It is obviously guided by monitoring of liver function tests. The magnitude of the problem is colossal and can trigger catastrophe. About 12 million people are the victims of Hepatitis B or C in our country and around 150,000 new cases are emerging annually. Hepatitis E has been affecting 3.3 million people all over the world. The numbers are huge in Pakistan where people do indulge in poor hygiene and&#x0D; the sanitation system is dismal serving as a root of all infective diseases and Hepatitis E is one of them.1

S3334 An Atypical Presentation of Propylthiouracil-Associated Fulminant Hepatitis in a Patient With Thyroid Storm

Introduction: Propylthiouracil (PTU) is an antithyroid agent used in thyrotoxicosis which is known to have hepatotoxic complications typically within weeks to months of administration. We present a case in which PTU liver injury was observed to occur within 48 hours of administration in a patient with underlying liver disease. Case Description/Methods: A 59 y.o. F with diet-controlled DM presented with palpitations and diarrhea. She was hypertensive and tachycardic in the ED; physical exam was unremarkable. Her laboratory workup was significant for TSH < 0.01 mcIU/mL with FT4 3.2 ng/dL, TSI positive at 353%. Liver function tests (LFTs) showed ALP 277, Tbili 2.4, DBili 1.5, ALT 76, and AST 98. An echocardiogram showed an EF of 35%. The patient was diagnosed with thyroid storm and started on PTU (received 800mg over 24hrs) and propranolol. On day 2, her LFTs showed ALT 450 and AST 890, and PTU was stopped. The next day, she became encephalopathic and developed acute liver failure with an INR of 4.1. General surgery was consulted for thyroidectomy. However, she was deemed unsuitable for surgery given her increased pre-operative risk. She was started on a NAC drip for DILI. Other etiologies for fulminant liver failure were ruled out including Hep A, B, and C, autoimmune hepatitis, and portal vein thrombosis. Liver biopsy showed acute steatohepatitis with necrosis, hepatocanalicular cholestasis, and periportal and pericellular fibrosis. After stopping PTU, patient’s LFTs normalized. On day 14, after potassium iodide preparation, the patient successfully underwent total thyroidectomy. Microscopic evaluation of thyroid tissue revealed multinodular hyperplasia. 6 weeks post-discharge she is asymptomatic with normal LFTs, TFTs and EF. Discussion: PTU is a thionamide used to manage hyperthyroidism. It causes DILI in approximately 1 in 10,000 people. Onset is often within 2-12 weeks of initiation. In our patient, fulminant hepatic failure developed within 48 hours of initiation. The findings of her core needle liver biopsy noted above indicated a DILI superimposed on baseline liver disease. This baseline liver disease may have been related to thyroid disease, NASH or congestive hepatopathy which may have predisposed her to an exaggerated response to PTU. Fortunately, our patient recovered and had a successful total thyroidectomy. This case illustrates that PTU-associated DILI may present atypically and with short latency. Close monitoring of LFTs and early surgical evaluation may prevent fulminant liver failure.

S2956 Delayed Onset Drug-Induced Acute Liver Failure Caused by Glatiramer Acetate (GA) in Multiple Sclerosis Requiring Liver Transplantation

Introduction: Glatiramer acetate (GA) has been used for multiple sclerosis (MS) since 1996. Regular liver function test monitoring is not required for the medication because there have not been any reported cases of liver toxicity.1Here, we report the first case of delayed onset GA-induced ALF requiring liver transplantation. Case Description/Methods: A 59-year-old woman with well-controlled MS presented to the emergency department with three weeks of jaundice and dark-colored urine. Initial labs showed AST 2527 IU/L (81x ULN), ALT 2512 IU/L (81x ULN), total bilirubin 22.7 mg/dL (19x ULN), ALP 210 IU/L (2x ULN), INR 2.65. Further workup showed normal ceruloplasmin, alpha-1-antitrypsin, and IgG. Hepatitis, HSV, VZV, T-spot, HIV, ANA, anti-mitochondrial antibody, anti-LKM antibody were negative. Anti-smooth muscle antibody was 1:40. Her liver enzymes were normal one year prior to presentation, and she had no family history of autoimmune or liver disease. Computed tomography abdomen/pelvis showed patent vasculature and no evidence of cirrhosis. MRI/MRCP showed no biliary obstruction. Her only medication was GA, which she had been taking since 2008. Physical exam was notable for mild asterixis, and she was started on IV N-acetyl cysteine for 3 days. Liver biopsy demonstrated submassive necrosis (70%) consistent with drug induced liver injury (Fig. 1A). GA was thought to be the most likely etiology of her liver injury and was held. Liver transplant was ultimately deferred because her liver enzymes and her mental status improved. She was discharge on day 6. Four days later she developed severe abdominal pain, lethargy and re-presented to the hospital. She was slow to respond, had scleral icterus and asterixis with AST 909 IU/L, ALT 839 IU/L, total bilirubin 27.2 mg/dL, INR 2.94. The patient underwent expedited liver transplant evaluation and was listed on the same day. She successfully underwent deceased donor liver transplant three days later. Liver explant showed mixed zone 1 and 3 liver necrosis (50%) with associated inflammation, mild lobular inflammation and cholestasis (Fig. 1B-D). Discussion: Our case illustrates the first case of GA-induced ALF requiring liver transplantation. Previous reports showed that patients with GA drug-induced-liver injury recovered completely in 1-5 months after drug withdrawal and time of presentation ranges from 1 to 8 months, as opposed to 14 years in our case. Patients on GA should have long term regular liver monitoring.Figure 1.: Histological analysis of pre-transplant and explant liver. A. Hematoxylin and eosin (H&E) stain of the pre-transplant biopsy showed extensive necrosis including zone 3 (x100). B. Gross picture of explant (weight 500.3 gram). The surface showed wrinkles, which were characteristics of acute liver failure with massive hepatocyte necrosis. C. H&E stain of explant showed no viable hepatocytes in the worst area. (x200). D. Masson trichrome stain showed no fibrosis, which confirms the acute process (x200).

The Correlated Risk Factors for Severe Liver Damage Among HIV-Positive Inpatients With Abnormal Liver Tests.

Background:This study investigated the factors correlated with severe liver damage among HIV-infected inpatients.Methods:We retrospectively collected the first hospitalized HIV-infected patients in the Department of Infectious Disease of the First Affiliated Hospital of China Medical University from January 1, 2010, to December 31, 2019. We used multivariate logistic regression to identify the factors associated with severe liver damage.Results:A total of 493 patients with abnormal liver tests were recruited. Among 63 cases (12.8%) with severe liver injury, drug-induced liver injury (DILI) identified by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score as the direct cause was found in 43 cases. Anti-tuberculosis drug (ATD) exposure [adjusted odds ratio (aOR) = 1.835, 95% confidence interval (CI): 1.031–3.268], cotrimoxazole exposure (aOR = 2.775, 95% CI: 1.511–5.096), comorbidity of viral hepatitis (aOR = 2.340, 95% CI: 1.161–4.716), alcohol consumption history (aOR = 2.392, 95% CI: 1.199–4.769), and thrombocytopenia (aOR = 2.583, 95% CI:1.127–5.917) were associated with severe liver injury (all P < 0.05).Conclusions:DILI was the predominant cause of severe liver damage, followed by hepatitis virus co-infection. For patients with alcohol consumption and thrombocytopenia, frequent monitoring of liver function tests should be considered.

Omental Tuberculosis in a Patient with Alcoholic Liver Cirrhosis-the Diagnostic and Treatment Dilemma

Alcoholic cirrhosis is frequently complicated by spontaneous bacterial peritonitis (SBP) due to the translocation of gut bacteria. However, in immigrants to the USA from parts of the world with high tuberculosis burden, a high degree of clinical suspicion of tuberculous peritonitis should be maintained when a patient presents with symptoms similar to SBP. We describe a case of a 45-year-old Nepali man with a history of alcohol abuse who immigrated to the USA six years prior and presented to the hospital with abdominal pain, night sweats, fevers, and a 10 kg weight loss. A CT scan revealed abdominopelvic ascites, liver nodularity suggestive of cirrhosis, and heterogeneous attenuation of the omentum. A CT-guided biopsy of the omentum was done, and the histopathology revealed non-necrotizing granulomas. However, given the demographics of the patient along with his constitutional symptoms, there was high suspicion for abdominal tuberculosis, and a second CT-guided omental biopsy was done and sent for tissue cultures. Due to the delay in getting microbiological confirmation of tuberculosis and persistent fevers, an empiric trial of isoniazid, rifampicin, pyrazinamide, and ethambutol (RIPE) was started with close monitoring of liver function tests. Since the patient’s symptoms improved, the RIPE regimen was continued. Twenty-five days later, tuberculosis was confirmed on omental biopsy tissue culture. This case highlights the diagnostic and treatment challenges associated with omental tuberculosis with liver cirrhosis and suggests a potential role for an empiric trial of RIPE regimen in the appropriate clinical context.

Safety Profile of Tolvaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease constitutes the most prevalent hereditary kidney disease, associated with high rates of morbidity leading eventually to end-stage renal disease. Tolvaptan is a selective vasopressin antagonist and has emerged as a promising therapeutic option for patients with autosomal dominant polycystic kidney disease. The present review summarized current evidence regarding the safety profile of tolvaptan in patients with the disease. Consistent with its pharmacological action, aquaretic adverse events represent the most common side effects of tolvaptan, consisting of polyuria, pollakiuria and polydipsia. Gradual dose titration based on urinary osmolality, as well as dietary interventions aiming to reduce solute excretion, have been proposed as potential strategies to mitigate polyuria. In addition, tolvaptan administration may be complicated by liver injury, characterized by alanine aminotransferase and bilirubin elevations. Hepatotoxicity has been suggested to be triggered by impaired biliary clearance, activation of innate immunity and increased oxidative stress. Frequent monitoring of liver function tests has been shown to be effective in preventing Hy’s Law and liver failure cases. Uric acid elevation due to reduced renal excretion may lead to hyperuricemia and gout, although no drug discontinuations have been linked to these events. Future studies should confirm the safety profile of tolvaptan in large-scale real-world studies, clarify the pathogenetic pathways leading to hepatotoxicity and define its role in special populations, especially pediatric patients.

Incidence of Hepatotoxicity and Factors Associated During Highly Active Antiretroviral Therapy in People Living with HIV in Ethiopia: A Prospective Cohort Study.

IntroductionHepatotoxicity is one of the risk factors associated with treatment non-adherence, which is the main risk factor for drug resistance. Therefore, this study aimed to determine the incidence and risk factors of hepatotoxicity during highly active antiretroviral therapy (HAART) among people living with HIV in Ethiopia.MethodsA prospective cohort study was conducted between April 2007 and January 2011 at Saint Peter Specialized Hospital, Akaki and Kality Health Centers, Addis Ababa, Ethiopia. A total of 316 HIV-infected adult individuals (70 participants were HIV and TB co-infected and 246 were infected with HIV alone) were included in this study. The study participants were followed for a total of 18 months with or without HAART. Socio-demographic data were collected using a structured questionnaire, and venous blood samples were collected for laboratory tests. Logistic regression and Poisson regression were used to determine the independent effect of each variable on hepatotoxicity at baseline and end of follow-up.ResultsOf 316 HIV-infected people, 72 (22.8%) participants had an elevated ALT/AST which was 100% mild-to moderate hepatotoxicity at baseline. Baseline CD4 T-cell count (p = 0.027) and HIV co-infection with TB (p < 0.001) were independently associated with hepatotoxicity at baseline. The overall incidence rate of hepatotoxicity in participants on HAART (21.8 per 100 person-years) was lower than participants who were HAART naïve (33.3 per 100 person-years) (p = 0.009).ConclusionHigh incidence of mild-to-moderate hepatotoxicity and low severe hepatotoxicity were observed in HIV-infected individuals who were on HAART or were HAART naïve. HAART may minimize the occurrence of hepatotoxicity. Although HAART could minimize hepatotoxicity among HIV-infected people, to manage mild and moderate hepatotoxicity liver function test monitoring is required.

HCV GT1b-patient With Alanine Aminotransferase Elevation and Sustained Virologic Response Achieved By grazoprevir/elbasvir Discontinuation

In the present Japanese female patient with alanine aminotransferase (ALT) elevation greater than 500 IU/l during combination therapy with grazoprevir/elbasvir against HCV infection, this therapy was stopped at week 8. However, sustained virologic response was achieved. In the present report, we also focused on ALT elevation and sustained virologic response during and after antiviral therapies. The current case report demonstrates that careful monitoring of liver function tests may be required during direct-acting antiviral therapy against HCV infection because it is now possible to treat patients with polypharmacy, patients with chronic kidney disease, patients with cirrhosis or aged patients. Careful attention should be paid to liver damage as one of the adverse events in the use of HCV nonstructural protein 3/4A protease inhibitors. Of interest, many publications have addressed both ALT elevations during direct-acting antiviral therapy and viral clearance in relatively short treatment durations.

The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis.

Introduction:Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients.Methods:We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as ‘COVID-19’ OR ‘SARS CoV-2’ AND ‘Remdesivir’. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software.Results:Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) (n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40–0.74) p = 0.0001; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38–0.84) p = 0.005; I2 = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19–0.54) p = 0.0001; I2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59–1.54) p = 0.85; I2 = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59–1.11) p = 0.19; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86–1.80) p = 0.25; I2 = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66–1.75) p = 0.77; I2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70–1.68) p = 0.73; I2 = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80–1.08) p = 0.32; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73–2.62) p = 0.32; I2 = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51–2.18) p = 0.89; I2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18–4.01) p = 0.85; I2 = 78%].Discussion & Conclusion:Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested.Plain Language SummaryTen-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo.The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir.There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir.There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women.

Effectiveness and safety of Ciclopirox Olamine compared to that of Luliconazole in management of patients with multi-site dermatophytosis on background itraconazole therapy

Wide spread, inappropriate use of antifungal drugs in dermatophytosis has resulted in rise in minimum inhibitory concentration (MIC) values and reduced response. Hence there is a need for a different antifungal with a novel mechanism of action.This was an open-label, randomised, prospective, interventional, comparative, double-arm study. The patients were treated with either topical ciclopirox olamine or luliconazole twice daily for 6 weeks. All the patients were taking oral itraconazole 100mg twice daily for 4 weeks. Effectiveness endpoints were percentage of patients achieving complete cure, clinical cure and mycological cure at the end of the treatment period from baseline. Safety was assessed by analyzing the AEs and monitoring of liver function tests. 92 patients were included in the study. 44 and 43 patients completed the study in ciclopirox and luliconazole group respectively. 84.09%, 88.63% and 86.36% patients achieved ccomplete, clinical and mycological cure rate in ciclopirox group respectively. 83.72%, 88.37% and 86.04% patients achieved complete, clinical and mycological in luliconazole group respectively. 10.63% patients in the Ciclopirox group and 10.86% in the Luliconazole group reported one or more drug related AE. Nausea, skin rash, head ache and vomiting were AEs reported. The results of this study prove that Ciclopirox is novel antifungal agent which is efficacious and safe in the management of dermatophytosis.

Effectiveness and safety of combination of Itraconazole and Amorolfine in management of patients with recalcitrant multi-site dermatophytosis who failed previous combination antifungal therapy

There is alarming rise in cases of dermatophytosis in India.Standard treatment recommendations are no longer working. Combination of topical and systemic antifungal drugs is one of the most frequently used treatment strategy.This was an open label, prospective, interventional, non-comparative study. Effectiveness endpoints were percentage of patients achieving complete cure, clinical cure and mycological cure at the end of the treatment period from baseline. Safety was assessed by analyzing the AEs and monitoring of liver function tests. 66 patients were included in the study. 75.75%, 86.36% and 81.8% patients achieved complete cure, clinical cure and mycological cure respectively at the end of the study period. There was improvement in each symptom during study duration as observed during each follow up visit on week 2, 4 and 6. Total of 10.60% reported 1 or more drug related AE. Nausea was most common side effect followed by vomiting, headache and edema of face. All the AEs were mild in nature and resolved during study. To conclude the result of this study shows that the combination therapy of oral itraconazole and topical amorolfine represents an improved treatment strategy for patients with recalcitrant multisite tinea infections.

Hepatitis B and C Infections in Patients With Prolonged Hemodialysis Secondary to Chronic Renal Failure.

ObjectiveTo determine the frequency of hepatitis B and C in patients with prolonged hemodialysis suffering from chronic renal failure.MethodsA retrospective study was conducted from January to August 2017 at Tabba Kidney Institute, Karachi. A total of 255 patients on hemodialysis were included in the study by using convenient sampling technique. All the relevant data such as gender, age, duration of hemodialysis and presence of hepatitis B and C were recorded. Data were analyzed using Statistical Package for Social Sciences, version 21 (IBM Corp., Armonk, NY) while binary logistic regression was applied to develop a risk assessment model for the study outcomes.ResultsThe study results showed that 134 (52.5%) patients were on hemodialysis for five years or more, 173 (67.8%) of them suffered from hepatitis B while 124 (48.6%) of them suffered from hepatitis C. The study results further revealed that after controlling for the effects of age and gender, the duration of hemodialysis was significantly associated with both hepatitis B (AOR 1.917, 95% CI 1.111-3.306, p=0.019) and hepatitis C (AOR 2.323, 95% CI 1.395-3.870, p=0.001) among the patients studied.ConclusionThe study concluded that longer duration of hemodialysis in patients with chronic renal failure was significantly associated with both hepatitis B and hepatitis C infections in the study population. A myriad of patient and environmental factors can contribute to this finding in patients with chronic renal insufficiency. Therefore, periodic monitoring of liver function tests and routine surveillance for viral hepatitis can help establish an early diagnosis of infection, potentially improving patient outcomes improving patient outcome.

Clinical Profile, Liver Dysfunction and Outcome of Dengue Infection in Children

Liver involvement in dengue illness is common and can lead to acute liver failure (ALF). No single method can effectively identify patients at risk for disease progression and bad outcome. We aimed to determine the relationship between liver dysfunction, kinetics of liver function tests (LFTs) and severity of hepatitis on the outcome in pediatric dengue illness. We conducted a prospective observational study of hospitalized children (1-12 years) with dengue infection (July 2014-July 2015). Serial monitoring of LFTs was done in confirmed dengue cases. Patients were classified into non-severe (NSD) and severe dengue (SD). Severity of hepatitis was graded: mild, moderate and severe hepatitis. Events were noted during hospitalization. One hundred two children (66, boys), median age 72 (48-96) months, were analyzed (NSD, n = 41; SD, n = 61). Elevated transaminases (92%) was the most common abnormality; aspartate transaminase (AST) and alanine transaminase (ALT) in 87% and 82%, respectively. Maximum abnormalities in LFTs peaked at day 5 (AST, ALT) and day 7 (Alkaline Phosphatase [ALP], gamma-glutamyl transferase) of illness. Elevated transaminases was found to be higher in SD than NSD (100% vs. 80%, P = 0.006). Severe hepatitis developed organ dysfunction such as altered sensorium (P < 0.001), ALF (P < 0.001), acute kidney injury (P < 0.001) and shock (P < 0.001), more commonly than those with mild to moderate hepatitis. Fourteen patients died, two-thirds of whom had severe hepatitis (P < 0.001). Using binary logistic regression, presence of severe hepatitis and shock at presentation was an independent predictor for ALF (odds ratio: 77; 95% confidence interval : 13-457, P < 0.001) and mortality (odds ratio: 55; 95% confidence interval: 4.6-66, P < 0.001), respectively. Many children with dengue have liver involvement. Severe hepatitis in dengue is associated with significant organ dysfunction and poor outcome.