Micropropagation of Crotalaria laburnifolia L. – An ethnomedicinally important herbal species

A protocol for in vitro shoot multiplication in Crotalaria labumifolia L. through nodal explants was established. Excision and culture of the nodal segments from in vitro developed shoots on fresh MS medium with concentration of BA (1mg/1) facilitated development of multiple shoots. Subsequent cultures enhanced the rate of shoot proliferation. Shoots cultured on ½ MS medium containing NAA (0.5 mg/1) initiated roots well compared with IBA and this is the most suitable protocol studied in C. labumifolia. The present study is the first report on in vitro regeneration in this species&nbsp

Critical assessment of the efficiency of chitosan biohydrogel beads as recyclable and heterogeneous organocatalyst for C–C bond formation

The effectiveness of neutral pH chitosan hydrogel beads (CSHB) as a green organocatalyst for a variety of C–C bond forming reactions (i.e. aldol reaction, Knoevenagel condensation, nitroaldol (Henry) reaction, Michael addition) has been comprehensively evaluated. Reaction rates, conversions and selectivities were studied as a function of a series of input variables including size, pH and reactive surface area of the beads, catalyst loading, temperature, molecular weight of the biopolymer, concentration, solvent system and molar ratio of reactants. Moreover, the catalytic biohydrogel beads were characterized by a variety of techniques including, among others, SEM, FT-IR, TGA and DSC

Relationship Between Characteristics of Medications and Drug-Induced Liver Disease Phenotype and Outcome

Background & Aims: It is not known if specific characteristics of medication are associated with type of drug-induced liver injury (DILI) or outcome. We examined the relationships among select characteristics of medications and DILI phenotype and outcome. Methods: We analyzed 383 cases of DILI caused by a single orally administered prescription agent from the DILI Network Prospective Study with causalities of definite, highly likely, or probable. Relationship of daily dosage (≥ 50 mg vs. ≤ 49 mg), preponderance of hepatic metabolism (≥50% vs <50%), or Biopharmaceutics Drug Disposition Classification System (BDDCS) class (1–4, based on solubility and metabolism of the drug) were compared with clinical characteristics and outcomes. Results: Compared to cases of DILI in the <50 mg/day group, those associated with daily dosages ≥50 mg had shorter latency (median 38 days vs 56 days; P=.03) and a different biochemical pattern of liver injury (P=.04); no differences in pattern of injury, recovery, severity, or outcome were observed. Patients with DILI caused by medications with or without preponderant hepatic metabolism did not differ in clinical characteristics or outcomes. Compared to other classes of BDDCS, DILI caused by BDDCS class 1 medications had significantly longer latency (P<.001) and greater proportion of hepatocellular injury (P=.001). However, peak liver biochemical values and patients’ time to recovery, disease severity, and outcomes did not differ among the 4 BDDCS classes. Conclusions: Characteristics of medications (dosage, hepatic metabolism, and solubility) are associated with features of DILI such as latency and pattern of liver injury, but not with recovery, severity, or outcome

Reliability of causality assessment for drug, herbal and dietary supplement hepatotoxicity in the Drug‐Induced Liver Injury Network (DILIN)

Background & AimsBecause of the lack of objective tests to diagnose drug‐induced liver injury (DILI), causality assessment is a matter of debate. Expert opinion is often used in research and industry, but its test–retest reliability is unknown. To determine the test–retest reliability of the expert opinion process used by the Drug‐Induced Liver Injury Network (DILIN).MethodsThree DILIN hepatologists adjudicate suspected hepatotoxicity cases to one of five categories representing levels of likelihood of DILI. Adjudication is based on retrospective assessment of gathered case data that include prospective follow‐up information. One hundred randomly selected DILIN cases were re‐assessed using the same processes for initial assessment but by three different reviewers in 92% of cases.ResultsThe median time between assessments was 938 days (range 140–2352). Thirty‐one cases involved >1 agent. Weighted kappa statistics for overall case and individual agent category agreement were 0.60 (95% CI: 0.50–0.71) and 0.60 (0.52–0.68) respectively. Overall case adjudications were within one category of each other 93% of the time, while 5% differed by two categories and 2% differed by three categories. Fourteen per cent crossed the 50% threshold of likelihood owing to competing diagnoses or atypical timing between drug exposure and injury.ConclusionsThe DILIN expert opinion causality assessment method has moderate interobserver reliability but very good agreement within one category. A small but important proportion of cases could not be reliably diagnosed as ≥50% likely to be DILI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111130/1/liv12540.pd

Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C

Background Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C

Acute-on-Chronic Liver Failure: Getting ready for prime-time

Acute on chronic liver failure (ACLF) is a culmination of chronic liver disease and extra-hepatic organ failures, which is associated with a high short-term mortality and immense healthcare expenditure. There are varying definitions for organ failures and ACLF in Europe, North America and Asia. These differing definitions need to be reconciled to enhance progress in the field. The pathogenesis of ACLF is multi-factorial and related to interactions between the immuno-inflammatory system, microbiota and the precipitating factors. Individual organ failures related to the kidney, brain, lungs and circulation have cumulative adverse effects on mortality and are often complicated or precipitated by infections. Strategies to prevent and rapidly treat these organ failures are paramount in improving survival. With the aging population and paucity of organs for liver transplant, the prognosis of ACLF patients is poor, highlighting the need for novel therapeutic strategies. The role of liver transplant in ACLF is evolving and needs further investigation across large consortia. A role for early palliative care and management of frailty as approaches to alleviate disease burden and improve patient-reported outcomes is being increasingly recognized. CONCLUSION: ACLF is a clinically relevant syndrome that is epidemic worldwide and which requires a dedicated multi-national approach focused on prognostication and management. Investigations are underway worldwide to get ACLF ready for prime time. Compensated cirrhosis with \u3e 90% 1-year survival can transition into the decompensated stage with the onset of jaundice, ascites, variceal bleeding and hepatic encephalopathy (HE) (1)Acute on chronic liver failure (ACLF) is associated with rapid deterioration of liver function leading to liver failure, multiple extra-hepatic organ failures and high short-term mortality (2). Even if patients survive the acute insult, they may never return to their pre-episode functional state (3). The term acute decompensation has been used to characterize ascites, gastrointestinal bleeding, hepatic encephalopathy or infections without organ failure(4). There are several gaps in knowledge surrounding ACLF, which will be highlighted in this review. The prevalence of ACLF is difficult to assess due to varying regional definitions (5). ACLF, once thought to occur only in decompensated cirrhosis, has been recognized even in chronic liver disease without cirrhosis (5). ACLF occurs in approximately 10-30% of hospitalized cirrhotic patients (6-8). Because of its acuity, patients are frequently admitted into the intensive care unit (ICU), and every effort is made to stabilize these patients for liver transplantation (LT). This drives healthcare costs(9). Despite this intensive management, ACLF is associated with substantial morbidity and mortality. Because curative LT is only available to \u3c 10% of cirrhotic patients each year and ACLF patients are often delisted, the morbidity and mortality rates remain high, especially with an increasing number of organ failures (10)

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Liver injury from herbals and dietary supplements in the U.S. Drug‐Induced Liver Injury Network

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108649/1/hep27317.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108649/2/hep27317-sup-0001-supptbl1.pd