Long‐Term Survivors with Artificial Liver Support in Fulminant Hepatic Failure

Abstract: Clinical ability of artificial liver support (ALS) has been improved greatly in recent years which has allowed us to encounter long‐term survivors with fulminant hepatic failure (FHF) whose liver function has been almost completely lost. This suggests that application of ALS in patients with FHF gains time while awaiting transplantation as well as time for functional recovery and regeneration of the liver graft following receipt of the graft with marginal function and/or size. Thus, ALS will contribute greatly to extending the indications for liver transplantation and increase the number of patients receiving and benefiting from this treatment. On the other hand, introduction of ALS prolongs the duration of intensive treatment which increases the risk of infection and increases medical costs. In addition, when to discontinue intensive treatment of patients whose level of consciousness is maintained only by ALS is controversial. Thus, further investigation will be needed to establish a consensus on indications for long‐term ALS in FHF.     

Liver Injury from Herbal,Dietary, and Weight Loss Supplements: a Review

Herbal and dietary supplement usage has increased steadily over the past several years in the United States. Among the non-bodybuilding herbal and dietary supplements, weight loss supplements were among the most common type of HDS implicated in liver injury. While drug induced liver injury is rare, its consequences are significant and on the rise. The purpose of this review is to highlight case reports of weight loss products such as Hydroxycut and OxyElite Pro as one form of HDS that have hepatotoxic potential and to characterize its clinical effects as well as pattern of liver injury. We also propose future strategies in the identification and study of potentially hepatotoxic compounds in an effort to outline a diagnostic approach for identifying any drug induced liver injury.     

Alcoholic Liver Disease and COVID-19 Pneumonia: A Case Series

The novel coronavirus 2019 (COVID-19) was reported by the World Health Organization in December 2019, and since then it has progressed into a worldwide pandemic, causing significant morbidity and mortality. Gastrointestinal symptoms of COVID-19 and elevated liver chemistries are seen in up to 50% of infected patients. Recent reports have suggested a high mortality rate for COVID-19 in patients with pre-existing liver disease, having an associated mortality of 39.8%. Alcoholic liver disease is a significant cause of morbidity and mortality in New Mexico (USA), and we report here the clinical course and characteristics of three cases of patients with alcoholic cirrhosis who were admitted to our hospital with COVID-19.     

Protection by Glycyrrhizin against Warm Ischemia‐Reperfusion–Induced Cellular Injury and Derangement of the Microcirculatory Blood Flow in the Rat Liver

Background/Aim: The mechanism by which ischemia‐reperfusion (I/R)‐induced derangement of the hepatic microcirculation leads to tissue injury is not fully understood. We postulated that alterations to the hepatic microcirculation, including hemodynamic derangement and increased leukocyte‐endothelium interaction, play a role, and that glycyrrhizin exerts its hepatoprotective effects, in part, by reducing these microcirculatory changes. Materials and Methods: Wistar rats were subjected to 30–60 minutes segmental hepatic ischemia, followed by 120 minutes of reperfusion. Glycyrrhizin was administered prior to ischemia. Using intravital fluorescence microscopy, the administration of fluorescein isothiocyanate–conjugated erythrocytes allowed the measurement of erythrocyte‐velocity (RBC_vel), lobular, and sinusoidal perfusion. Bleb formation was observed by electron microscopy. Blood and tissue were taken for the assessment of liver injury. Results: Glycyrrhizin reduced I/R‐induced liver injury (histology, liver enzymes) and reduced hepatocyte apoptosis (TUNEL, caspase‐3 activity). Glycyrrhizin inhibited hepatocyte bleb formation and reversed the I/R‐induced reductions in lobular perfusion and RBC_vel. Leukocyte rolling and adherence in postsinusoidal venules and neutrophil infiltration were reduced by glycyrrhizin. I/R‐induced elevation in HMGB1 was prevented by glycyrrhizin. Conclusions: Early bleb formation with deranged microcirculatory flow and leukocyte‐endothelium interaction would appear to contribute to I/R‐induced hepatocellular injury. Glycyrrhizin exerts its hepatoprotective effect by preventing these changes, in addition to a direct cellular effect.     

Liver manifestations and complications in inflammatory bowel disease: A review

Hepatobiliary manifestations are common in inflammatory bowel disease (IBD), with 30% of patients presenting abnormal liver tests and 5% developing chronic liver disease. They range from asymptomatic elevated liver tests to life-threatening disease and usually follow an independent course from IBD. The pathogenesis of liver manifestations or complications and IBD can be closely related by sharing a common auto-immune background (in primary sclerosing cholangitis, IgG4-related cholangitis, and autoimmune hepatitis), intestinal inflammation (in portal vein thrombosis and granulomatous hepatitis), metabolic impairment (in non-alcoholic fatty liver disease or cholelithiasis), or drug toxicity (in drug induced liver injury or hepatitis B virus infection reactivation). Their evaluation should prompt a full diagnostic workup to identify and readily treat all complications, improving management and outcome.     

Feasibility and safety of using an automated decision support system for insulin therapy in the treatment of steroid‐induced hyperglycemia in patients with acute graft‐versus‐host disease: A randomized trial

Steroid‐induced hyperglycemia (SIHG) has shown to independently increase the risk for mortality in patients with acute graft‐versus‐host disease, and it is still unclear whether SIHG might be a modifiable risk factor. Therefore, a feasibility trial was carried out aiming to evaluate the performance of a standardized decision support system (GlucoTab [GT]) for insulin therapy in patients with SIHG. A total of 10 hyperglycemic acute graft‐versus‐host disease patients were included and treated either with GT or standard of care during hospitalization. Follow‐up duration was 6 months. Comparing the GT versus standard of care group, 364 versus 1,020 glucose readings were available during a median of 41 days (interquartile range [IQR] 22–89) and 101 days (IQR 55–147) of hospitalization. The median overall glucose levels were 151 mg/dL (123–192) versus 162 mg/dL (IQR 138–193) for GT and standard of care, respectively (P < 0.001); hypoglycemia rates were comparably low. Treatment of SIHG with an algorithm‐based system for subcutaneous insulin was feasible and safe.     

One-Year Outcomes after Ledipasvir/Sofosbuvir Treatment of Chronic Hepatitis C in Teenagers with and without Significant Liver Fibrosis—A Case Series Report

One-year outcomes after therapy with ledipasvir/sofosbuvir (LDV/SOF) in children with chronic hepatitis C (CHC) presenting with and without significant liver fibrosis were analyzed. We included patients aged 12–17 years treated with LDV/SOF, presenting with significant fibrosis (F ≥ 2 on the METAVIR scale) in transient elastography (TE) at the baseline and we compared the outcomes with that of patients without fibrosis. Patients were followed every 4 weeks during the treatment, at the end of the therapy, at week 12 posttreatment, and one year after the end of treatment. Liver fibrosis was established using noninvasive methods: TE, aspartate transaminase-to-platelet ratio index (APRI), and Fibrosis-4 index (FIB-4). There were four patients with significant fibrosis at baseline: one with a fibrosis score of F2 on the METAVIR scale, and three with cirrhosis (F4) at baseline. One year after the end of treatment, the hepatitis C viral load was undetectable in three of them. One patient was lost to follow-up after week 4. In two out of the four patients, a significant improvement and regression of liver fibrosis was observed (from stage F4 and F2 to F0-F1 on the METAVIR scale). In one patient, the liver stiffness measurement median increased 12 weeks after the end of the treatment and then decreased, but still correlated with stage F4. An improvement in the APRI was observed in all patients. In four patients without fibrosis, the treatment was effective and no progression of fibrosis was observed. A one-year observation of teenagers with CHC and significant fibrosis treated with LDV/SOF revealed that regression of liver fibrosis is possible, but not certain. Further observations in larger groups of patients are necessary to find predictors of liver fibrosis regression.     

Classification of the etiologies of acute liver failure in Japan: A report by the Intractable Hepato‐Biliary Diseases Study Group of Japan

The Intractable Liver Diseases Study Group of Japan, supported by the Ministry of Health, Labor and Welfare, established novel diagnostic criteria for “acute liver failure” in 2011. In these criteria, patients without histological findings of hepatitis are included in the disease entity of “acute liver failure”, as in Europe and the USA. In this report, classification criteria for the etiologies of “acute liver failure” in Japan are proposed.     

Reduction of Elevated Cytokine Levels in Acute/Acute‐on‐Chronic Liver Failure Using Super‐Large Pore Albumin Dialysis Treatment: An In Vitro Study

The removal of small water soluble toxins and albumin‐bound toxins in acute liver failure patients (ALF) or acute‐on‐chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e.g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut‐offs should be considered in extracorporeal liver support devices based on albumin dialysis in order to address these problems, as the introduction of super‐large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment albumin dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin‐bound toxins were removed more efficiently using novel large (Emic2) to super‐large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL‐6 and tumor necrosis factor‐α was drastically improved using super‐large pore membranes. The Emic2 membrane predominantly removed IL‐6. In vitro data suggest that the usage of larger pore sized membranes in albumin dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super‐large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified.     

Cardiac Resynchronization Therapy Relieves Intractable Angina Due to Exercise‐Induced Left Bundle Branch Block Without Left Ventricular Systolic Dysfunction: A Detailed Case Study

Exercise‐induced left bundle branch block is rare and can be demonstrated with exercise testing. When the heart rate reaches a certain threshold, the QRS widens into left bundle branch block. This paper describes a patient with exercise‐induced left bundle branch block related angina and dyspnea, who responded to cardiac resynchronization therapy. We documented the potential benefits of cardiac resynchronization therapy with a left ventricular rapid pacing study prior to its implantation. Although exercise‐induced left bundle branch block is not a current indication for cardiac resynchronization therapy in patients such as ours, it could be considered when conventional drug therapy fails.     

Albumin Dialysis in Liver Failure: Comparison of Molecular Adsorbent Recirculating System and Single Pass Albumin Dialysis—A Retrospective Analysis

Despite improvement in critical care, liver failure is still associated with high mortality. Therapeutic concepts are aimed at restoring endogenous liver function or to bridge the time to liver transplantation. In addition to standard medical treatment, extracorporeal liver support with albumin dialysis is used for this purpose. The aim of this study was to analyze the efficacy of single pass albumin dialysis (SPAD) in comparison to the molecular adsorbent recirculating system (MARS) in patients treated at our university hospital intensive care unit between July 2004 and August 2008. In this retrospective analysis we studied patients presenting with liver failure who were treated with albumin dialysis. Laboratory parameters, daily health scoring, the number of transfusions, and mortality were recorded. The (paired) t‐test, Mann–Whitney U‐test, and Wilcoxon test were used for statistical analysis. In all, 163 albumin dialysis treatments, 126 with MARS and 37 with SPAD, in 57 patients were performed. MARS resulted in a significant decrease in bilirubin (?38 ± 66.5 µmol/L from a baseline of 301 ± 154.6 µmol/L), γ‐glutamyltransferase (γ‐GT), alanine aminotransferase, creatinine, and urea. SPAD resulted in a significant decrease in bilirubin (?41 ± 111.2 µmol/L from a baseline of 354 ± 189.4 µmol/L) and γ‐GT, while lactate levels increased. No differences in the need for blood transfusion, health scoring, or mortality between the two treatment modalities were detected. This retrospective analysis suggests equal efficacy of MARS and SPAD; however, prospective assessment to further define the role of SPAD in the treatment of acute or acute‐on‐chronic liver failure is needed.