Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Effect of Low Positive End of Treatment Viral Load with Direct-Acting Antiviral Therapy on Sustained Virologic Response

Background. Direct-acting antivirals (DAAs) are highly effective treatments against hepatitis C virus (HCV), with sustained virologic response (SVR) rates of 93–100% against all genotypes. In most patients, viral load (VL) becomes undetectable four weeks into treatment, but rarely a low positive VL may be observed at the end of treatment (EOT). This study was conducted to determine the effect of low positive EOT VLs with DAA therapies on SVR at 12 and 24 weeks. Methods. A retrospective chart review was conducted from January 2014 to December 2018 on 1256 HCV patients of all genotypes (1–6) who had received DAA therapy at two large hepatology referral centers. Baseline demographic data, along with VL at week four, EOT, and SVR12/24 time points were collected for patients that had positive EOT VL. Treatment outcome for any patient with positive EOT VL was noted. Results. Eight out of 1256 patients treated with varying DAA therapies were observed to have low positive EOT VLs ranging from <15 to 235 IU/mL. One patient had a negative EOT VL, but 23 IU/mL at week four after EOT. All eight patients who had low positive EOT VLs and one patient who had a low positive VL at four weeks after EOT achieved SVR at weeks 12 and 24. One of the eight patients had cirrhosis. The majority of patients were genotype 1a. Conclusion. In the DAA treatment era, low levels of detectable HCV RNA at EOT does not predict treatment failure

Perspective toward complementary & Alternative medicines in the prevention of COVID-19 infection

Background: Across the globe, people are seeking integrative and holistic measures to prevent coronavirus (COVID-19) infection in the form of complementary and alternative medicines (CAM) with or without conventional medicines. This study was done to know the extent of CAM use for COVID-19 prophylaxis and to know beliefs and attitudes of people related to CAM use in India. Methodology: A pretested and prevalidated questionnaire was circulated on social media. Participants, who completed the online form and gave voluntary consent, were included. The questionnaire included demographic details and questions related to CAM use, preferences with reasons, preparations used, perceived role of CAM in prevention, immunity boosting and side effects, sources of information, etc. Results: Out of 514 responses, 495 were analyzed. 47.07% of respondents were males and 52.93% were females. 66.9% were using CAM for COVID-19 prophylaxis. The association between age, gender, and profession with CAM use was statistically significant (P < 0.05). 41.1% reported CAM use in the past. 36.6% of CAM users were taking “Kadha” and 33% were using ayurvedic medicines. Other frequently used CAM preparations were chyavanprash, giloy, tulsi, ginger, pepper, cloves, honey, sudarshanghanvati, arsenic-30, lemon juice, cinnamon, steam inhalation, ashwagandha, swasarivati, coronil, and warm saline water gargles. 46.9% of the CAM users were on self-medication and 52.3% preferred CAM over allopathy. Conclusion: Complementary and alternative medicine utilization for COVID-19 prophylaxis is widespread and self-medication is prevalent. As no specific cure is available in conventional systems, people believe in traditional medicines more than conventional, yet confusion exists. There is a need of increasing awareness regarding side effects, drug–drug interactions, and self-medication

Pulmonary toxicity following bleomycin use: A single-center experience

Background: Bleomycin-induced pulmonary (BIP) toxicity is a notorious entity and cropped up in roughly 10% of cases. The aim of the study is to evaluate BIP at our tertiary care cancer center. Patients and Methods: This is a retrospective, analytical study conducted at a tertiary care center from January 1998 to December 2012. Records of all the patients who were offered bleomycin chemotherapy as an integral part of adriamycin, bleomycin, vinblastine, and dacarbazine or bleomycin, etoposide, and cisplatin regimen in Hodgkin disease (HD) or germ cell tumor (GCT) were studied for the study inclusion criteria. Twenty-two patients treated with bleomycin who had respiratory symptoms and/or abnormal high-resolution computed tomography (HRCT) findings, suggestive of bleomycin-induced lung injury were included in this study. Results and Statistical Analysis: A total of 22 patients met the inclusion criteria for the study cohort. Of 22 patients, 8 were of HD and 14 were of GCT (nonseminomatous GCT [NSGCT] = 10 and seminomatous GCT = 4). Of 22 patients, 14 had symptoms of nonproductive cough, dyspnea and showed HRCT findings of ground glass opacities, diffuse alveolar damage, extensive reticular markings, traction bronchiectasis, and/or nodular densities. Two patients had fever and pleuritic pain. Eight patients were asymptomatic. Symptomatic patients were treated with prednisone at the dose of 0.75–1 mg/kg 4–8 weeks then gradually tapered. Four patients required noninvasive ventilatory support and managed with oxygen, nebulization, and antibiotics. Two patients required mechanical ventilatory support (HD = 1 and NSGCT = 1) and developed multiorgan failure subsequently succumbed to death. Conclusion: BIP is noteworthy lung toxicity as subsequent mortality ranges from 10% to 20% and shrinks survival rate in patients with highly curable malignant conditions. Physicians should be vigilant concerning this impending side effect

Primary Synovial Sarcoma of Kidney: A Rare Differential Diagnosis of Renomegaly

Synovial sarcomas (SS) are classified as subgroup of soft tissue sarcomas affecting mainly extremities of young adults. Primary SS of kidney are very rare tumours with poor prognosis. Though they have characteristic histology and immunohistochemistry (IHC) due to rarity of incidence it is difficult to diagnose them. Sometimes chromosomal rearrangement studies are required to confirm the diagnosis. We are presenting a case of 41-year-old male who was referred to our cancer centre for evaluation of left renal mass. CT scan of abdomen revealed a large left renal mass encasing the aorta. Biopsy of renal mass revealed poorly differentiated sarcoma and IHC was positive for vimentin, CD99, and BCL2 and negative for AE1, epithelial membrane antigen, and leukocyte common antigen. The patient was clinically inoperable as renal mass was encasing the aorta. So he was subsequently offered palliative chemotherapy in form of ifosfamide and adriamycin. CT abdomen shows partial response after 3 cycles of chemotherapy according to RECIST criteria

Primary Vaginal Myeloid Sarcoma: A Rare Case Report and Review of the Literature

Myeloid sarcoma (chloroma, granulocytic sarcoma, or extramedullary myeloid tumour) is an extramedullary mass forming neoplasm composed of myeloid precursor cells. It is usually associated with myeloproliferative disorders but very rarely may precede the onset of leukemia. Here, we are presenting a rare case of primary vaginal myeloid sarcoma in a geriatric female patient without initial presentation of acute myeloid leukemia (AML). A 68-year-old female patient with ECOG Performance Score of 1 presented with pervaginal bleeding for 20 days. On colposcopic examination, she was found to have mass in the anterior fornix of vagina. A punch biopsy specimen revealed chloromatous infiltration of the vagina. LCA (leukocyte common antigen), MPO (myeloperoxidase), and c-kit were strongly positive on IHC (immunohistochemistry). The patient’s routine blood investigations were normal including peripheral smear, lactose dehydrogenase, uric acid, 2D echocardiography, conventional cytogenetics, bone marrow aspiration, and biopsy. The patient was given 4 cycles of decitabine (Decitex, manufactured by Sun Pharmaceutical Industries Limited, India), 20 mg/m2 for 5 days at an interval of 28 days. There was a partial response to decitabine according to RECIST criteria. As decitabine therapy was well tolerated, we are continuing in the same way until disease progression without any complications. The patient is undergoing regular follow-up at our centre