Ademetionine in patients with liver disease: a review

The aim of the present review is to have an in-depth analysis of the published scientific literature relating to the clinical use of ademetionine in various etiologies of liver disease. Literature search was performed using electronic databases like Pubmed/Medline/others to identify studies on ademetionine in patients with intrahepatic cholestasis, alcoholic liver disease, non-alcoholic fatty liver disease, drug induced liver injury and viral hepatitis. Ademetionine has been studied in various etiologies of liver disease with varying dosing and durations. In patients with chronic and alcoholic liver disease, ademetionine was found to be beneficial in improving liver enzyme levels, increasing glutathione levels, improving signs and symptoms of fatigue, pruritus and jaundice. Positive effects of ademetionine therapy have also been documented in multiple studies in patients with non-alcoholic fatty liver disease, with improvements observed in triglyceride, total cholesterol, alanine transaminase and asprtate transaminase levels and ultrasound grading of fatty change. In patients with drug induced liver injury, improvements were observed in liver biochemical markers and symptoms such as pruritus, fatigue and jaundice. Ademetionine has also been studied in patients with viral hepatitis with improvement in laboratory markers and signs and symptoms. Published data suggest that there is clinical evidence to substantiate the use of ademetionine across indications. Its use has resulted in sustained improvement in biochemical markers; signs and symptoms of liver disease has been observed in both acute and chronic liver disease. Further data is warranted through clinical studies to focus on specific end points of therapy areas, in existing and new indications

Hepatocellular Carcinoma: Challenges in Indian Scenario

Hepatocellular carcinoma (HCC), a leading solid organ malignancy is on the rise across the world, including India. Its incidence has almost tripled in the last 30 years and it is among the fastest growing malignancy in the USA. It is the third most frequent cause of death from cancer and the eighth most commonly occurring cancer in the world. A disease of multifactorial etiology, HCC poses many challenges. It demands multidisciplinary care involving diagnostic, medical and surgical inputs. A lot of research is ongoing in terms of attempts to improve its treatment and results thereof. Identification of some of the causative factors has resulted in efforts towards its primary prevention as well. Universal immunization against Hepatitis B virus is one such effort in this direction. Identification of role of various molecular pathways is leading to targeted drug developments offering personalized treatment to concerned patients. The authors have been involved in the diagnosis and management of this important liver cancer. This article summarizes the various challenges encountered in the diagnosis and management of HCC in India.Keywords: Hepatocellular carcinoma (HCC), risk factors, staging of HCC, liver transplantation, transarterial chemoembolisation (TACE), transareterial radioembolisation (TARE), targetted therapy, sorafenib

MR Findings of Cortical Blindness Following Cerebral Angiography: Is This Entity Related to Posterior Reversible Leukoencephalopathy?

We describe MR findings in three patients who experienced transient cortical blindness following cerebral angiograms. All angiograms were performed by using the same nonionic contrast medium. On the basis of similar clinical and radiologic findings, we believe that this entity is closely related to and probably has the same pathophysiology as posterior reversible leukoencephalopathy

Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease: a preliminary report

Background and Aims: Hepatotoxicity is a major side-effect of antitubercular drugs (ATD). As these drugs are metabolized in the liver, there is a theoretical risk of increased hepatotoxicity in patients with underlying chronic liver disease (CLD). Ofloxacin has antitubercular activity and has exclusive renal clearance. The aim was to study the efficacy and safety of an ofloxacin-based antitubercular regimen for treating tuberculosis in patients with underlying CLD. Methods: Thirty-one cases were randomly assigned to two drug regimens using WHO dosage schedules: (i) regimen A (n = 15): isoniazid, rifampicin and ethambutol for 2 months, followed by isoniazid and rifampicin for a further 7 months; and (ii) regimen B (n = 16): isoniazid, pyrazinamide, ethambutol and ofloxacin for 2 months, followed by isoniazid, ethambutol and ofloxacin for a further 10 months. Hepatotoxicity was diagnosed if alanine aminotransferase/aspartate aminotransferase increased > fivefold from the baseline or to > 400 IU/L, or if bilirubin increased by > 2.5 mg/dL from the baseline. Results: The response to ATD was achieved in all the patients who completed the therapy. Four (26.6%) patients on regimen A developed hepatotoxicity as compared to none on regimen B (P = 0.043). None of these patients could be restarted on ATD using the same regimen A because of the persistently deranged liver functions. Conclusions: In patients with tuberculosis who have underlying CLD: (i) an ofloxacin-based antitubercular regimen without rifampicin is as effective as a rifampicin-based regimen; and (ii) a combination of isoniazid with rifampicin is more hepatotoxic than a combination with ofloxacin and pyrazinamide

Living donor liver transplant outcomes during the COVID-19 pandemic: does a decrease in case volume impact the overall outcomes?

Background : High-volume centers (HVCs) are classically associated with better outcomes. During the coronavirus disease 2019 (COVID-19) pandemic, there has been a decrease in the regular liver transplantation (LT) activity at our center. This study analyzed the effect of the decline in LT on posttransplant patient outcomes at our HVC. Methods : We compared the surgical outcomes of patients who underwent LT during the COVID-19 pandemic lockdown (April 1, 2020 to September 30, 2020) with outcomes in the pre-pandemic calendar year (April 1, 2019 to March 31, 2020). Results : During the 6 months of pandemic lockdown, 60 patients underwent LT (43 adults and 17 children) while 228 patients underwent LT (178 adults and 50 children) during the pre-pandemic calendar year. Patients in the pandemic group had significantly higher model for end-stage liver disease (MELD) scores (24.39±9.55 vs. 21.14±9.17, P=0.034), Child-Turcotte-Pugh scores (11.46±2.32 vs. 10.25±2.24, P=0.03), and incidence of acute-on-chronic liver failure (30.2% vs. 10.2%, P=0.002). Despite performing LT in sicker patients with COVID-19-related challenges, the 30-day (14% vs. 18.5%, P=0.479), 3-month (16.3% vs. 20.2%, P=0.557), and 6-month mortality rates (23.3% vs. 28.7%, P=0.477) were lower, but not statistically significant when compared to the pre-pandemic cohort. Conclusions: During the COVID-19 pandemic lockdown the number of LT procedures performed at our HVC declined by half because prevailing conditions allowed LT in very sick patients only. Despite these changes, outcomes were not inferior during the pandemic period compared to the pre-pandemic calendar year. Greater individualization of patient care contributed to non-inferior outcomes in these sick recipients

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update Authors Authors and affiliations

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the APASL ACLF Research Consortium (AARC) was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the \u27Golden Therapeutic Window\u27, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here

Identifying the early predictors of non-response to steroids in patients with flare of autoimmune hepatitis causing acute-on-chronic liver failure

Background and aims: Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment.Methods: Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks.Results: Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p \u3c 0.001] to predict non-response. Combination of AARC score \u3e 6, MELD score \u3e 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p \u3c 0.001).Conclusion: Baseline AARC score, MELD score, and the dynamic SURFASA score on day 3 can accurately identify early non-response to steroids in AIH-ACLF