Normal Baseline Liver Function Research Articles

Rare Clinically Significant Idiosyncratic Drug Induced Liver Injury Caused by Low Dose Atorvastatin: Time for a New Approach to Surveillance and Risk Identification

Background: Atorvastatin is a member of the class of cholesterol lowering drugs called statins, which works by inhibiting HMG-CoA reductase, an enzyme involved in cholesterol synthesis in the liver. Statins are used to reduce the risk of cardiovascular events in individuals who have risk factors or a history of cardiovascular disease. While atorvastatin is generally well-tolerated, like all statins, it can have some adverse effects, including Drug induced liver injury (DILI) which is rare and often dose related. However, there is scarcity of reports on symptomatic DILI occurring in patients on low dose statin and normal baseline liver function test. This case adds to the growing body of literature on the potential idiosyncratic, non-dose related adverse effects associated with atorvastatin therapy. Case report: A 69-year-old woman with history of Hypertension, Hyperlipidemia, Prediabetes, Non-Alcoholic Fatty Liver Disease (NAFLD) presented to her Primary care Physician (PCP) for regular follow up. Her Lipid panel in the last 1 year has been suboptimal with her Atherosclerotic Cardiovascular disease (ASCVD) risk score between 12.0-15.1% despite lifestyle modification. Patient was started on 10 mg of Atorvastatin daily after documenting normal baseline liver function test. Fifty-six days later, patient presented to the PCP’s office with symptoms of fatigue, nausea and, right upper abdominal pain for 3 days. She had right upper abdominal tenderness and was mildly icteric. Based on her PCPs suspicion for DILI, she was advised to discontinue atorvastatin and transferred to the emergency room for further evaluation. In the Emergency room her vitals remained stable. Liver Ultrasound showed normal sized liver with features of hepatic steatosis. Laboratory analysis showed elevated alanine aminotransferase (ALT) greater than 16 times Upper limit of normal (ULN), aspartate aminotransferase (AST) greater than 9 times ULN, while alkaline phosphatase (ALP) elevation was less than 2 times ULN suggesting hepatocellular pattern. She was seen by a hepatologist 1 week later and other etiologies of acute hepatitis were ruled out. Over the course of 4 weeks, her symptoms completely resolved and liver function tests continued to improve. Forty-six days after Atorvastatin was discontinued, her aminotransaminases returned to normal levels. Conclusion: Although DILI is usually dose dependent, this case emphasizes the need for constant monitoring of liver function test of patients on low dose statins including patients with normal baseline liver function test. Personalized medical approach involving validated predictive score for DILI may become increasingly important in tailoring statin therapy to minimize the risk of adverse effects.

The efficiency and safety of low-dosage isotretinoin therapy for Chinese acne vulgaris patients.

Acne vulgaris is one of the most common skin conditions in dermatology clinics. Accumulating evidence has implicated oral low-dosage isotretinoin was an effective treatment for acne with fewer side effects. Currently, the data on low-dosage isotretinoin use in Chinese is limited. To investigate the efficiency and safety of low-dosage isotretinoin therapy for Chinese acne patients. Three hundred and eighty-eight patients treated with low-dosage isotretinoin (0.2-0.4 mg/kg/d) and who completed the course (120 mg/kg) were enrolled. Medical information on the severity, duration, adverse effects, and outcome of acne was reviewed. The majority (90.2%, n = 350) of patients achieved complete remission, and on average, patients received 13.5 months of treatment. The time between isotretinoin start and the clear date between the mild and moderate groups was not significantly different (74 ± 24 vs. 84 ± 24 days). However, it took longer to resolve for the severe acne group (112 ± 25 days). Follow-up 1 year after completion of the isotretinoin course, 37/350 (10.6%) patients relapsed, but there was no difference in the severity of acne. There were 133 (34.3%), 40 (10.3%), and 14 (2.6%) patients who developed hypercholesterolemia, hypertriglyceridemia, and high LDL, respectively. Thirty-two (8.2%) and 28 patients (7.2%) had elevated serum levels of alanine and aspartate aminotransferases. No values above grade 2 were detected. This study reaffirms the efficacy and safety of low-dosage oral isotretinoin in Chinese patients with acne vulgaris. Lab investigation could be performed after 2 months of therapy in healthy patients with normal baseline liver function and lipid panel tests.

First line combination of ribociclib and letrozole in patients (pts) with metastatic breast cancer (MBC): Focus on hepatic toxicity in the context of a real–world setting the Italian, multicenter Hermione–8 study.

e13064 Background: The introduction in the clinical practice of CDK4 / 6 inhibitors, in combination with endocrine therapy, has been a breakthrough in the therapeutic scenario of hormone receptor+ve/Human Epidermal growth Factor 2–ve (HR+/HER2–) MBC pts. However, despite the outstanding results in terms of OS and quality of life achieved up to now, it is important to consider that the highly selected population of clinical trials doesn’t always accurately predict the clinical impact of therapies in the general population, hence having real world data is an essential tool to guide physicians in daily clinical practice. Methods: In this observational, multicentre, prospective study, we evaluated the safety profile and the incidence of dose reductions, temporary interruptions and treatment discontinuation due to adverse events, in a real–world cohort of Italian pre or postmenopausal HR+/HER2– MBC pts who received a first line combination of ribociclib and letrozole. Results: A total of 78 MBC patients were included in the analysis. The median duration of treatment was 17 (1–61) months. At the time of ribociclib initiation, 13 (16.7%) pts already presented an altered transaminase value whereas liver metastases were present in 17 pts (21.8%). Ten (12.8%) pts experienced hepatic toxicity while on treatment. The median number of cycles for liver toxicity was 3 (1–18). The most common hepatic event was transaminase level increase in 7 (8.8%) pts. Such event occurred more frequently in the group of pts with normal baseline liver function. Hepatic toxicity was grade 1 in 3 (3.8%) pts, grade 2 in 3 (3.8%) pts, grade 3 in 3 (3.8%) pts and grade 4 in 1 (1.3%) pt. Dose reduction due to hepatic toxicity occurred in 3 (3.8%) pts, in particular one of them needed dose reduction from 600 mg to 400 mg, one from 600 mg to 200 mg whereas treatment discontinuation was applied in the last patient. Median time of treatment interruption due to hepatotoxicity was 29 (14–45) days and 3 (3.8 %) pts discontinued ribociclib due to adverse events. No deaths due to liver failure have been reported. Conclusions: Hermione–8 trial support a manageable safety profile of the combination ribociclib and letrozole in MBC patients treated in a real–world clinical setting, confirming toxicity profile in line with the results presented in the MONALEESA clinical trials. Dose reductions, temporary interruptions and discontinuation of treatment due to adverse events have been limited and seems comparable to the results from MONALEESA trials. [Table: see text]

Laparoscopic liver posterior sectionectomy

Background: Our patient was a 67-year-old male with metastatic right colon cancer to the liver with lesions in segment II and segment VII. He had a BMI of 30, no prior abdominal surgical history, and normal baseline liver function. He had undergone 4 cycles of neoadjuvant FOLFOX with Bevacizumab.

Promoting Surgical Resection through Future Liver Remnant Hypertrophy.

An inadequate future liver remnant (FLR) can preclude curative-intent surgical resection for patients with primary or secondary hepatic malignancies. For patients with normal baseline liver function and without risk factors, an FLR of 20% is needed to maintain postsurgical hepatic function. However, the FLR requirement is higher for patients who are exposed to systemic chemotherapy (FLR, >30%) or have cirrhosis (FLR, >40%). Interventional radiologic and surgical methods to achieve FLR hypertrophy are evolving, including portal vein ligation, portal vein embolization, radiation lobectomy, hepatic venous deprivation, and associating liver partition and portal vein ligation for staged hepatectomy. Each technique offers particular advantages and disadvantages. Knowledge of these procedures can help clinicians to choose the suitable technique for each patient. The authors review the techniques used to develop FLR hypertrophy, focusing on technical considerations, outcomes, and the advantages and disadvantages of each approach. Online supplemental material is available for this article. ©RSNA, 2022.

Variations in Parameters of Hepatotoxicity Induced by Anti TB Treatment with Comorbid Acute Viral Hepatitis

Objectives & background: Drug-induced hepatotoxicity (DIH) is a common side effect of anti-TB drugs. Acute viral hepatitis (AVH) may be confounded with chronic alcoholic hepatitis clinically, biochemically, and histologically (CAH). Place of Study: Rashid Latif Medical College Lahore Duration of Study: March 2019 to January 2021 Methods: This prospective research examined the effect of acute viral hepatitis as a contributing and confounding factor in patients with normal baseline liver function who acquired acute hepatitis while taking short-course anti-TB medication. All acute hepatitis patients' blood was analysed for hepatitis A, B, C, and E markers. Results: In 12 of 80 TB patients who developed viral hepatitis, the hepatitis E virus was present. Indicators of acute viral hepatitis included a delayed onset of acute hepatitis significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and a longer period for abnormal levels to normalise. Conclusions: According to our statistics, 15% of anti-TB hepatotoxic patients had AVH. Before attributing the hepatotoxic impact of anti-TB medications to DIH patients, viral hepatitis should be evaluated and ruled out in all endemic-area patients.

Objectives & background: Drug-induced hepatotoxicity (DIH) is a common side effect of anti-TB drugs. Acute viral hepatitis (AVH) may be confounded with chronic alcoholic hepatitis clinically, biochemically, and histologically (CAH). Place of Study: Rashid Latif Medical College Lahore Duration of Study: March 2019 to January 2021 Methods: This prospective research examined the effect of acute viral hepatitis as a contributing

Background: Diabetes, low nighttime blood pressure, and nonarteritic ischemic optic neuropathy may be associated. Not too many studies present whether this relationship applies to patients. Objective: Diabetes mellitus, low blood pressure at night, and nonarteritic ischemic optic neuropathy were studied in a group of individuals. Methods: The ophthalmology clinic will conduct a cross-sectional research on patients with nonarteritic ischemic optic neuropathy from March 2019 to December 2021. Nonarteritic ischemic optic neuropathy patients were tested for diabetes. Some participants wore ambulatory blood pressure monitors during the trial. Nighttime blood pressure drops are typical, muted, severe, and reverse. Results: Nonarteritic ischemic optic neuropathy was identified in 67 individuals. 587 of 67 patients were selected. 34 patients (50.7%) had diabetes, while 39 (58.2%) had hypertension. 32 people's blood pressure dropped during sleep. Only four (5.9%) saw substantial drops. Conclusions: Diabetes may be linked to nonarteritic ischemic optic neuropathy, but not nocturnal blood pressure declines. Keywords: Optic Neuropathy, Diabetes Mellitus, Hypertension

Incidence of and risk factors for liver damage in patients with HIV-1 mono-infection receiving antiretroviral therapy.

The study aimed to investigate the incidence of and risk factors for liver damage in patients with human immunodeficiency virus type-1 (HIV-1) mono-infection receiving antiretroviral therapy (ART). We retrospectively analyzed the clinical data of patients who were diagnosed with HIV-1 infection and initiated ART from January to December 2017. Among them, 382 patients with HIV-1mono-infection and normal baseline liver function were included in the analysis. The incidence of liver damage at each follow-up point, and possible risk factors for liver damage were evaluated via COX regression survival analyses. The overall incidence of liver damage (grade I-IV) was 27.23% (interquartile range [IQR]: 26.38%-28.72%). Grade I liver damage was most common and accounted for 22.13% of cases (IQR: 21.06%-24.04%), while grade II liver damage accounted for 3.40% of cases (IQR: 3.19%-4.26%). COX regression and survival analyses revealed that baseline body mass index (BMI), alanine aminotransferase (ALT) level, CD4+ T cell count, HIV-1 viral load, and the antiretroviral regimen were significantly correlated with the occurrence of liver damage. Moreover, baseline ALT levels and HIV-1 viral load were identified as independent risk factors for liver damage in patients with HIV-1mono-infection. Liver damage is common in patients with HIV-1mono-infection undergoing ART. Patients with risk factors for liver damage should be well-informed before the initiation of ART, and liver function should be closely monitored during ART even in patients with normal liver function before ART.

Challenging Thyroid Storm in Pregnancy, Case Report

Background: Thyroid storm is a rare complication of hyperthyroidism. It can lead to life-threatening complications such as Arrhythmias, multiorgan failure and disseminated intravascular coagulation (DIC) (1). In pregnant patients can cause spontaneous abortions, fetal demise (2). Aggressive treatment under critical care settings is needed. Clinical Case: We report a case of 24-year-old Indian female twelve weeks pregnant; background of Graves’ disease for five years, was on carbimazole but she discontinued since she became pregnant. Presented to Hamad general hospital with nausea, vomiting and altered mental status for one day. She was afebrile, normotensive, tachypneic, tachycardiac with heart rate of 150bpm, and confused. Investigations showed supraventricular tachycardia aborted by adenosine and amiodarone, TSH was < 0.01mIU/l(0.3-4.2) and FT4> 100 pmol/L(11.6-21.9),normal baseline liver function and complete blood counts. In the emergency department, she was managed for thyroid storm with hydrocortisone, propranolol, propylthiouracil (PTU), iodine solution and cholestyramine. Then suddenly she deteriorated requiring intubation and vasopressor support under care of Medical Intensive Care Unit (MICU) progressed to multiorgan failure; acute liver injury, acute kidney injury and DIC. So, PTU was stopped and started on plasma exchange followed by total thyroidectomy and tracheostomy. US pelvis showed nonviable fetus, so dilation and curettage were done by obstetric team. Afterwards, she markedly improved except her conscious level and kidney function which required Hemodialysis. MRI brain showed small subdural hematoma treated conservatively and Wernicke encephalopathy treated with thiamine with substantial response and spontaneously breathing. Post thyroidectomy she required calcium supplementation and levothyroxine, liver function and coagulation parameters back to baseline. Conclusion: Thyroid storm in pregnancy is a medical emergency with high mortality rate, it needs high index of suspicion and early aggressive management by a multidisciplinary team. Plasmapheresis may be considered for challenging cases as a bridge for definitive therapy. Thyroidectomy may be the only option in selected cases like our case.

Clarithromycin-Associated Acute Liver Failure Leading to Fatal, Massive Upper Gastrointestinal Hemorrhage from Profound Coagulopathy: Case Report and Systematic Literature Review

While erythromycin has caused numerous cases of acute liver failure (ALF), clarithromycin, a similar macrolide antibiotic, has caused only six reported cases of ALF. A new case of clarithromycin-associated ALF is reported with hepatic histopathology and exclusion of other etiologies by extensive workup, and the syndrome of clarithromycin-associated ALF is better characterized by systematic review. A 60-year-old nonalcoholic man, with normal baseline liver function tests, was admitted with diffuse abdominal pain and AST = 499 U/L and ALT = 539 U/L, six days after completing a 7-day course of clarithromycin 500 mg twice daily for suspected upper respiratory infection. AST and ALT each rose to about 1,000 U/L on day-2 of admission, and rose to ≥6,000 U/L on day-3, with development of severe hepatic encephalopathy and severe coagulopathy. Planned liver biopsy was cancelled due to coagulopathies. Extensive evaluation for infectious, immunologic, and metabolic causes of liver disease was negative. Abdominal computerized tomography and abdominal ultrasound with Doppler were unremarkable. The patient developed massive, acute upper gastrointestinal bleeding associated with coagulopathies. Esophagogastroduodenoscopy was planned after massive blood product transfusions, but the patient rapidly expired from hemorrhagic shock. Autopsy revealed a golden-brown heavy liver with massive hepatic necrosis and sinusoidal congestion. Rise of AST/ALT to about 1,000 U/L each was temporally incompatible with shock liver because this rise preceded the hemorrhagic shock, but the subsequent AST/ALT rise to ≥6,000 U/L each may have had a component of shock liver. The six previously reported cases were limited by failure to exclude hepatitis E (4), lack of liver biopsy (2), and uninterpretable liver biopsy (1) and by confounding potential etiologies including disulfiram, israpidine, or recent acetaminophen use (3), clarithromycin overdose (1), active alcohol use (1), and severe heart failure (1). Review of 6 previously reported and current case of clarithromycin-associated ALF revealed that patients had AST and ALT values in the thousands. Five patients died and 2 survived.

2111. Anidulafungin vs. Micafungin Treatment in Adult Patients with Candidemia: A Retrospective Study of Single-Center Experience

BackgroundCandidemia is one of the fatal causes of nosocomial infection, requiring prompt recognition and treatment. Echinocandins are recommended for the treatment of invasive candidiasis and candidemia. Although similar clinical efficacy and safety are well known between caspofungin and micafungin, there are few studies comparing micafungin and anidulafungin. The objective of this study was to evaluate the clinical efficacy and safety between micafungin and anidulafungin treatment for adult patients with candidemia.MethodsThis retrospective cohort study was performed on adult candidemia patients diagnosed from January 2006 through December 2018 at a tertiary medical center, Seoul, South Korea. The study subjects included adult patients ≥19 years with candidemia who were only treated with micafungin or anidulafungin for more than 3 days. Baseline and clinical characteristics were reviewed through electrical medical records. Liver function was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Hepatotoxicity was defined as the elevation of more than CTCAE grade 1 and severe hepatotoxicity was defined as the CTCAE grade 3 or higher elevations.ResultsA total of 98 patients with candidemia was treated with micafungin (n = 46, 46.9%) or anidulafungin (n = 52, 53.1%). In the univariate analysis, there were no significant differences in age, sex, source of candidemia, and comorbidities between the micafungin and anidulafungin groups. Although the clearance time of candidemia after echinocandin treatment was shorter in the anidulafungin than in the micafungin (5.64 ± 2.79 vs. 8.06 ± 5.30 days, P = 0.009) group, there was no significant difference in terms of clinical response (51.9% vs. 46.7%), mycological response (76.9% vs. 67.4%), and mortality (54.3% vs. 55.8%) between these two groups. The overall incidence of hepatotoxicity was similar. Also, there was no difference in the development of hepatotoxicity or severe hepatotoxicity between micafungin and anidulafungin groups for patients with normal baseline liver function test(LFT) and abnormal baseline LFT.ConclusionOur results suggest that clinical efficacy and hepatotoxicity may be similar between micafungin and anidulafungin treatment for adult patients with candidemia.Disclosures All authors: No reported disclosures.

5-Fluorouracil induced liver toxicity in patients with colorectal cancer: role of computed tomography texture analysis as a potential biomarker.

To assess if CT texture analysis (TA) can serve as a biomarker of liver toxicity in patients with colorectal cancer treated with 5-fluorouracil (5-FU)-based chemotherapy. In this IRB-approved, HIPAA-compliant retrospective study, patients with colorectal cancer treated with 5-FU-based regimens during 2008-2010 were identified from institutional electronic database. Total 43 patients (23 women; mean age 56years) with normal baseline liver function tests (LFTs), availability of baseline (pre-chemotherapy) and first follow-up CT (median 1.7months, interquartile range (IQR) 1.5-2.5) performed during chemotherapy were included. Two single-slice ROI of right and left liver lobe were obtained on baseline and first follow-up CT for TA. Texture features [mean, entropy, kurtosis, skewness, mean of positive pixel, standard deviation (SD)] were extracted using a commercially available software (TexRAD; Feedback Medical Ltd, Cambridge, UK). Changes in texture parameters between baseline and follow-up CT were evaluated with Wilcoxon signed-rank test for patients with and without LFT elevation during chemotherapy. Patients with LFT elevation (n = 34; 79%) showed significantly different mean, entropy, skewness, and SD (p values range 0.007-0.047) between baseline and first follow-up CT. No significant changes in features were observed in patients without LFT elevation (n = 9; 21%). In 19 patients (56%), first follow-up CT was performed before elevation of LFTs was observed. This proof-of-concept study shows that there are early changes in liver texture on first follow-up CT in patients with LFT elevation during 5-FU-based chemotherapy for colorectal cancer. In more than 50% of cases, these changes occur before LFT elevation becomes evident on blood tests.

Liver damage in patients living with HIV on antiretroviral treatment with normal baseline liver function and without HBV/HCV infection: an 11-year retrospective cohort study in Guangxi, China

ObjectiveTo characterise the association between duration of exposure to antiretroviral treatment (ART) and liver damage in HIV patients with an initially normal baseline liver function and without hepatitis B virus...

Pazopanib-Induced Liver Injury: A Near TKO From a TKI

A 56 year old man with Renal Cell Carcinoma on Pazopanib was admitted with right upper quadrant (RUQ) abdominal pain and fatigue. He had no significant alcohol use. Vitals were normal, exam revealed scleral icterus, jaundice, and mild RUQ tenderness. Labs were notable for Total bilirubin 4.1 mg/dL, AST 770 U/L, ALT 909 U/L, and ALP 681 U/L. Viral markers for Hepatitis A, B, C, E and Cytomegalovirus (CMV) and autoimmune panel were negative. Serum ceruloplasmin level was 30mg/dl, ferritin 2365ng/ml, and transferrin saturation 65%. Ultrasound with liver doppler was unremarkable. Liver biopsy revealed severe lobular inflammation and portal expansion by lymphocytes, with admixed plasma cells and eosinophils. Stains for fibrosis, iron deposition, and alpha-1 antitrypsin globules were negative. IHC staining was negative for CMV and HSV antigens. He was diagnosed with drug-induced liver injury (DILI) from Pazopanib and started on ursodiol with tapering course of oral prednisone. Liver enzymes gradually improved and completely resolved by week 10.Pazopanib, a Tyrosine Kinase Inhibitor (TKI), is approved for the treatment of Renal Cell Carcinoma (RCC) and Soft Tissue Sarcomas (STS). It targets VEGF receptor and other kinases involved in tumor angiogenesis. The mechanism of TKI induced liver injury remains unclear. Mitochondrial toxicity, inhibition of glycolysis, and apoptosis has been proposed to be the mechanisms of hepatotoxicity. In our case, patient had a score of 7 on the Naranjo probability scale for adverse drug reaction, indicating that Pazopanib is the probable cause of DILI. Although hepatotoxicity with Pazopanib has been reported, only a single case report with accompanying biopsy has been reported in the literature. Both patients in the report had normal baseline liver function tests and significant AST and ALT elevation by week 6 after initiation. Liver biopsies in these patients revealed similar features. With increasing use of TKI agents in oncotherapy, one must be aware of the potential adverse effect of DILI from newer agents such as Pazopanib. The onset of DILI from Pazopanib ranges from 4-12 weeks after initiation. Majority of patients recover completely on drug discontinuation with normalization of liver function and enzymes as seen in our patient, however occasional fatalities have been reported. Thus monitoring liver enzymes on TKI therapies is imperative for early recognition of Pazopanib induced DILI and prompt discontinuation of the drug.

Valproate Acid (Depakote) Induced Hyperammonemic Encephalopathy in the Pediatric Populations

Valproate acid (Depakote) (VPA) is very effective in the treatment of various illnesses including: seizure disorders, migraine headache prophylaxis, neuralgia, and bipolar disorder. The use of VPA frequently results in elevated plasma levels of ammonia. This is seen despite normal baseline liver function test results in such patients. In this case report, we describe two instances of VPA-induced hyper ammonemic encephalopathy in patients who had supra therapeutic levels of VPA. Family physicians, Child Neurologists, Child Psychiatrists and Pediatricians should be aware of this potential complication, and it is highly recommended to check ammonia levels in patients taking VPA who present with a change in mental status. With a rise in off-label use it is even more important that physicians are made aware of this potential complication. Treatment of VPA-induced hyperammonemic encephalopathy is still under investigation. As of yet, administration of L-carnitine is postulated to have a potential benefit in some cases. VPA has numerous drug interactions and toxicities, including pancreatitis, thrombocytopenia, hepatitis and hyperammonemia. Here are we list two case reports of VPA induced hyperammonemic encephalopathy both occurring in patients with no history of any underlying liver pathologies. In both two cases, both patients were under stable conditions, no comatose. In both 2 cases of patients we described, they all have normal or sub therapeutic level of VPA. Because of the wide spectrum of symptoms associated with Valproate Acid induced Hepatic Encephalopathy (VHE), clinician should be aware of hyperammonenia in differential diagnosis with other common symptoms.

Safety and Efficacy of Intermittent Intravenous Administration of High-Dose Micafungin

Background. The use of mold-active azoles for antifungal prophylaxis after allogeneic stem cell transplantation (SCT) is hindered by adverse events and drug–drug interactions. Higher doses of echinocandins administered intermittently may be an alternative in this setting. Methods. This was a single-center, observational 5-year study to characterize the safety and efficacy of intermittent administration of high-dose intravenous micafungin (≥5 doses of ≥300 mg micafungin 2–3 times weekly) in patients with acute leukemia and allogeneic SCT recipients. Results. A total of 104 patients (84 allogeneic SCT recipients and 20 patients with leukemia) received intermittent high-dose intravenous micafungin, 83 (79.8%) as prophylaxis. Large variability in the micafungin dosing regimen was observed; 78 (75%) patients received >75% of their course as 300 mg micafungin 3 times weekly. Liver function tests decreased from baseline to end of treatment (EOT; P < .001). Patients with normal baseline liver function (n = 55 [52%]) maintained similar enzyme levels throughout the study. For patients with abnormal baseline liver function (n = 49 [47%]), liver function tests significantly improved from baseline to EOT (P ≤ .005). Duration and/or micafungin dosing algorithms were not associated with liver toxicity at EOT. There were no significant changes in renal function, and infusion-related reactions or deaths were not observed. Five of 83 (6.0%) patients in the prophylaxis group developed a breakthrough fungal infection. Conclusions. In this largest cohort of patients to date, intermittent administration of high-dose micafungin was well tolerated, without any associated liver or renal function abnormalities, and may be considered an alternative antifungal prophylactic strategy. Prospective studies are needed to further validate these findings.

Safety and Efficacy of Intermittent Intravenous Administration of High-Dose Micafungin.

The use of mold-active azoles for antifungal prophylaxis after allogeneic stem cell transplantation (SCT) is hindered by adverse events and drug-drug interactions. Higher doses of echinocandins administered intermittently may be an alternative in this setting. This was a single-center, observational 5-year study to characterize the safety and efficacy of intermittent administration of high-dose intravenous micafungin (≥5 doses of ≥300 mg micafungin 2-3 times weekly) in patients with acute leukemia and allogeneic SCT recipients. A total of 104 patients (84 allogeneic SCT recipients and 20 patients with leukemia) received intermittent high-dose intravenous micafungin, 83 (79.8%) as prophylaxis. Large variability in the micafungin dosing regimen was observed; 78 (75%) patients received >75% of their course as 300 mg micafungin 3 times weekly. Liver function tests decreased from baseline to end of treatment (EOT; P < .001). Patients with normal baseline liver function (n = 55 [52%]) maintained similar enzyme levels throughout the study. For patients with abnormal baseline liver function (n = 49 [47%]), liver function tests significantly improved from baseline to EOT (P ≤ .005). Duration and/or micafungin dosing algorithms were not associated with liver toxicity at EOT. There were no significant changes in renal function, and infusion-related reactions or deaths were not observed. Five of 83 (6.0%) patients in the prophylaxis group developed a breakthrough fungal infection. In this largest cohort of patients to date, intermittent administration of high-dose micafungin was well tolerated, without any associated liver or renal function abnormalities, and may be considered an alternative antifungal prophylactic strategy. Prospective studies are needed to further validate these findings.

The changes of the ratio of T helper 17 and regulatory T cells in the peripheral blood of patients with anti-tuberculosis drug-induced liver injury and its significance

Objective To observe the changes of the peripheral blood T helper (Th)17 cells/regulatory T cells (Treg) ratio in patients with anti-tuberculosis drug-induced liver injury, and to explore the relationship between Th17/Treg ratio and liver function. Methods Ninety inpatients with the diagnosis of secondary pulmonary tuberculosis (TB) from Affiliated Hospital of Zunyi Medical College from Feb. 2013 to Mar. 2015 were included in this study. All these patients had normal base line liver function. After 2 weeks of anti-TB chemotherapy, 21 patients with alanine transaminase (ALT) and/or aspartate aminotransferase (AST) ≥2×upper limit of normal (ULN) were defined as TB with liver injure group, the other 69 patients with ALT and/or AST<2×ULN were defined as TB with non-liver injured group. Before treatment and two weeks after anti-TB therapy, the peripheral blood Th17/Treg ratios and liver functions of all patients in both groups were detected in order to compare the changes of Th17/Treg ratios pre and post anti-TB chemotherapy and to explore the relationship between Th17/Treg ratio and ALT/AST levels. Student's t test was used for statistical analysis, and Pearson correlation analysis was used for correlation test. Results Before treatment, there was no statistical significance of Th17, Treg and Th17/Treg ratio between groups (P>0.05). The Th17 levels in TB with liver injured group ([2.522±0.388]/mL vs [2.075±0.369]/mL, t=3.633, P 0.05). The Th17 level and Th17/Treg ratio in TB with liver injured group were significantly higher than those in TB with non-liver injured group (t=2.203, P 0.05). Conclusion The changes of Th17/Treg ratio are related with anti-TB drug-induced liver injury in patients with secondary pulmonary tuberculosis. Key words: Tuberculosis, pulmonary; Drug-induced liver injury; Antitubercular; Th17/Treg

Early changes in hepatic function among HIV–tuberculosis patients treated with nevirapine or efavirenz along with rifampin-based anti-tuberculosis therapy

To describe the longitudinal changes in hepatic function among HIV-infected tuberculosis (TB) patients receiving once-daily nevirapine (NVP)- or efavirenz (EFV)-based antiretroviral treatment (ART) along with rifampin-containing anti-TB treatment. This was a nested study within a randomized clinical trial, taking place between May 2006 and June 2008 at the National Institute for Research in Tuberculosis, Chennai, India. Antiretroviral-naïve HIV-infected TB patients were initiated on an intermittent short-course regimen and randomized to receive didanosine and lamivudine with either NVP (400 mg) or EFV (600 mg) once-daily. Blood was analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum alkaline phosphatase (SAP), and bilirubin at baseline, at ART initiation, fortnightly after ART initiation until 2 months, then monthly until 6 months and 6-monthly thereafter. Of the 168 patients included (79% men, median CD4 count 93 cells/mm3, median viral load 242,000 copies/ml), 104 were on EFV-based ART and 64 on NVP-based ART. There was a small but statistically significant elevation in ALT and SAP at 2 weeks and AST at 6 weeks after ART initiation. The proportion of patients with rate-limiting toxicity of liver enzymes was small. None had treatment terminated because of hepatotoxicity. Hepatotoxicity is not a major concern when HIV-infected TB patients, with normal baseline liver function initiate treatment for both infections simultaneously.

Incidence and risk factors for non-alcoholic steatohepatitis in females treated with tamoxifen for breast cancer

Background and study aims Tamoxifen used in the treatment of breast cancer is reported to cause hepatic steatosis. This study aimed to assess the incidence and risk factors of the development of fatty liver disease, resulting from tamoxifen use, in females with breast cancer. Patients and methods Seventy females aged between 28 and 80 years with breast cancer were recruited from Shahid Sadoughi Clinic, Yazd, Iran in 2006–2008. The patients underwent chemotherapy followed by 20 mg tamoxifen daily as postoperative endocrine treatment. Only in patients with normal baseline liver function, negative test for hepatitis C virus (HCV) and hepatitis B surface antigen (HbsAg) and normal liver ultrasonography were included. The development of fatty changes over a 6-months period of treatment was the main outcome measurement assessed by ultrasonography. Results Thirty-five of 70 patients developed fatty change during follow-up, in which nine were in grade one, 20 in grade two and six patients in grade three. Risk factors associated with the development of fatty change were elevation of triglycerides (2.4, 1.2–4.8), elevation of fasting blood sugar (FBS) and low high-density lipoprotein (HDL) (3.4, 1.4–7.8). No relation was found between the development of fatty change and age (1.3, 0.87–2.00), menopause (1.13, 0.69–1.9), previous history of diabetes (2.4, 0.7–8.4), previous chemotherapy regimen and receptors type (c-erbB2, P53, progesterone receptor (PR), oestrogen receptor (ER)) and stage of breast cancer. Further, there was no relation between the development of fatty change and hypercholesterolemia, low-density lipoprotein (LDL), arterial hypertension and body mass index (BMI). Conclusion Tamoxifen was associated with a high risk of development of non-alcoholic steatohepatitis in patients with higher triglycerides and FBS and lower HDL. However, no relationship was found with the level of BMI, LDL, hypertension, overweight and obesity.